Antimicrobials

J Clin Oncol, 1996 Mar, 14(3), 901 - 10
Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy; Wexler LH et al.; PURPOSE: To evaluate whether recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients . PATIENTS AND METHODS: Thirty-seven newly diagnosed patients age 1 to 25 years were randomized to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3 . GM-CSF (5 to 15 micrograms/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was > or = 500/microliter on 2 consecutive days . RESULTS: GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P < .0001), but did not significantly affect the grade of granulocyte nadir . No differences were seen in the incidence or types of infectious complications, incidence or duration of hospitalization and antimicrobial therapy, response to chemotherapy, or event-free or overall survival . GM-CSF was associated with more severe and protracted thrombocytopenia (median platelet nadir, 29,500/microliter {range, 3,000 to 288,000} v 59,000/microliter {range, 3,000 to 309,000}, P < .0001; median time to recovery > 75,000/microliter, 16.0 days {range, 0 to 61} v 14.0 days {range, 0 to 38}, P < .0001) . CONCLUSION: GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia . GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications . We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity.

Ann Surg, 1996 Mar, 223(3), 303 - 15
Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections . The Intra-Abdominal Infection Study Group; Solomkin JS et al.; OBJECTIVE: In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections . A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy . SUMMARY BACKGROUND DATA: Intra-abdominal infections result in substantial morbidity, mortality, and cost . Antimicrobial therapy often includes a 7- to 10-day intravenous course . The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity . METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO) . RESULTS: Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group . For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV . Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed . Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV . Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment . CONCLUSIONS: These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations . Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.

South Med J, 1996 Mar, 89(3), 335 - 9
Thoracobiliary fistula; Johnson MM et al.; Thoracobiliary communications in the form of either pleurobiliary or bronchobiliary fistulas are reported complications of many diseases . A strong suspicion in the appropriate clinical setting is necessary to recognize this problem . Bilioptysis is the sine qua non of a bronchobiliary fistula . Diagnostic imaging studies are useful to identify the communication and to delineate its location . Although surgery is the optimal intervention, percutaneous drainage and intravenous antimicrobial therapy may offer the best therapeutic option in patients with metastatic cancer and limited physiologic reserve . We report a unique case of bronchobiliary fistula complicating a uterine leiomyosarcoma with hepatic metastases . Long-term palliation was achieved with percutaneous drainage and appropriate fluid and electrolyte replacement therapy.

J Biol Chem, 1996 Feb 23, 271(8), 4038 - 45
Human enteric defensins . Gene structure and developmental expression; Mallow EB et al.; Paneth cells, secretory epithelial cells of the small intestinal crypts, are proposed to contribute to local host defense . Both mouse and human Paneth cells express a collection of antimicrobial proteins, including members of a family of antimicrobial peptides named defensins . In this study, data from an anchored polymerase chain reaction (PCR) strategy suggest that only two defensin mRNA isoforms are expressed in the human small intestine, far fewer than the number expressed in the mouse . The two isoforms detected by this PCR approach were human defensin family members, HD-5 and HD-6 . The gene encoding HD-6 was cloned and characterized . HD-6 has a genomic organization similar to HD-5, and the two genes have a striking pattern of sequence similarity localized chiefly in their proximal 5'-flanking regions . Analysis of human fetal RNA by reverse transcriptase-PCR detected enteric defensin HD-5 mRNA at 13.5 weeks of gestation in the small intestine and the colon, but by 17 weeks HD-5 was restricted to the small intestine . HD-6 mRNA was detectable at 13.5-17 weeks of gestation in the small intestine but not in the colon . This pattern of expression coincides with the previously described appearance of Paneth cells as determined by ultrastructural approaches . Northern analysis of total RNA from small intestine revealed quantifiable enteric defensin mRNA in five samples from 19 24 weeks of gestation at levels approximately 40-250-fold less than those observed in the adult, with HD-5 mRNA levels greater than those of HD-6 in all samples . In situ hybridization analysis localized expression of enteric defensin mRNA to Paneth cells at 24 weeks of gestation, as is seen in the newborn term infant and the adult . Consistent with earlier morphological studies, the ratio of Paneth cell number per crypt was reduced in samples at 24 weeks of gestation compared with the adult, and this lower cell number partially accounts for the lower defensin mRNA levels as determined by Northern analysis . Low levels of enteric defensin expression in the fetus may be characteristic of an immaturity of local defense, which is thought to predispose infants born prematurely to infection from intestinal microorganisms.

Cancer, 1996 Feb 15, 77(4), 791 - 8
The identification of febrile, neutropenic children with neoplastic disease at low risk for bacteremia and complications of sepsis; Lucas KG et al.; BACKGROUND: The management of pediatric oncology patients with fever and neutropenia assumes that all patients are at risk for bacteremia, and therefore generally involves hospitalization and broad-spectrum parenteral antibiotics for all patients . The determination of which patients are at low risk for having positive blood cultures and for developing complications related to bacteremia is of potential benefit . METHODS: The records of 161 pediatric patients with neoplastic disease hospitalized for 509 episodes of fever and neutropenia between January 1990 and June 1992 were retrospectively reviewed . Clinical features at initial presentation, clinical and microbiologic documentation of infection, and outcome were analyzed . RESULTS: The only presenting clinical features that correlated with an increased likelihood of having positive blood cultures were chills, hypotension, the requirement for fluid resuscitation (P < 0.001), or a diagnosis of leukemia or lymphoma (P < 0.041) . Leukemia patients with relapse admitted for fever and neutropenia were no more likely to have positive blood cultures than those patients in remission . There were ten episodes of fever and neutropenia in which patients were transferred to the intensive care unit (ICU), and two sepsis related deaths . Nine episodes involving ICU management and both deaths were in patients who had persistent fever and an absolute neutrophil count (ANC) of less than 100 after 48 hours of hospitalization (n = 177) . Patients with an ANC of less than 100 after 48 hours were twice as likely to have antibiotic changes, 15 times more likely to receive amphotericin B, and were hospitalized twice as long as patients with an ANC of 100 or higher after 48 hours . CONCLUSIONS: Children hospitalized for fever and neutropenia who have persistent fever and an ANC of less than 100 after 48 hours are at high risk for morbidity and are more likely to require antibiotic changes and antifungal therapy . Children who initially lack signs of sepsis, are afebrile, and have an ANC of 100 or higher after 48 hours are at low risk for complications and could be selectively discharged on antimicrobials after a 48-hour period of inpatient hospitalization.

Transplantation, 1996 Feb 15, 61(3), 427 - 30
Cytolytic therapy for the treatment of bronchiolitis obliterans syndrome following lung transplantation; Kesten S et al.; Bronchiolitis obliterans syndrome (BOS) is a common occurrence following lung transplantation and is one of the most important impediments to long-term graft viability . Cytolytic therapy has been used as treatment for BOS, but there is little data documenting efficacy . Furthermore, these agents have been associated with significant adverse effects . Charts of 15 patients who received an antilymphocyte preparation (ALP) for BOS were reviewed . Forced expiratory volume-1 second (FEV1) and stage of BOS were compared before and after treatment . Complications of ALP were recorded from the charts . Two of 15 patients had an improvement in FEV1, 5/15 exhibited no change, and 8/15 continued to decline . There was no pattern associating stage of BOS with likelihood of response to ALP . All patients received antimicrobial prophylaxis and did not experience infectious complications following administration of the ALP . ALP for the treatment of BOS results in an arrest or improvement of FEV1 in approximately 50% of patients . Infectious complications are uncommon when antimicrobial prophylaxis is administered.

JAMA, 1996 Feb 14, 275(6), 463 - 9
Emerging bacterial zoonotic and vector-borne diseases . Ecological and epidemiological factors; Walker DH et al.; Among the etiologic agents of emerging infectious diseases are several bacterial organisms that naturally reside in animal and arthropod hosts . The most compelling emerging bacterial zoonotic and vector-borne diseases in the United States are Lyme disease; a Southern erythema migrans-like illness; human monocytic ehrlichiosis; human granulocytic ehrlichiosis; a novel cat flea-associated typhus group rickettsiosis; bartonelloses of immunocompetent and immunocompromised persons, particularly with AIDS; and sylvatic plague . Some of these antimicrobial-treatable infections are life threatening . During the acute stage of illness when antimicrobial agents are most effective, the flulike clinical signs and symptoms and available laboratory tests frequently do not point to a particular diagnosis . Epidemiological factors determined by the ecology of the bacteria are often the most useful diagnostic clues . The recognition of these evolving problems emphasizes the need for development of better laboratory diagnostic methods, for surveillance for and tracking of disease, and for continued research into factors contributing to transmission of the organisms . The continual appearance of previously unidentified bacterial infections requires prospective national strategies for timely recognition of the syndrome, identification of the agent, establishment of criteria and methods for diagnosis, optimization of the treatment regimen, and determination of successful approaches to prevention and control.

JAMA, 1996 Feb 14, 275(6), 452 - 7
Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family; Bifani PJ et al.; OBJECTIVE--To determine whether isolates of Mycobacterium tuberculosis from New York and elsewhere that are resistant to four or more primary antimicrobial agents and responsible for widespread disease in the 1990s represent a newly emerged clone or a heterogeneous array of unrelated organisms . SETTING--New York City area and selected locations in the United States . PATIENTS--M tuberculosis isolates from 1953 patients in New York and multidrug-resistant isolates from six patients from other US communities . DESIGN--Convenience sample of all M tuberculosis strains (M tuberculosis isolates resistant to rifampin, streptomycin, isoniazid, and ethambutol, and sometimes ethionamide, kanamycin, capreomycin, or ciprofloxacin) submitted to the Public Health Research Institute Tuberculosis Center since 1991 and samples submitted to the Centers for Disease Control and Prevention from throughout the United States . The samples submitted were representative of the New York City strains of M tuberculosis . MAIN OUTCOME MEASURE--Characterization of resistant M tuberculosis strains studied by IS6110 and polymorphic GC-rich repetitive sequence (PGRS) hybridization patterns, multiplex polymerase chain reaction (PCR) analysis, and automated DNA sequencing of genes containing mutations associated with resistance to rifampin (rpoB), isoniazid (katG and inhA locus), and streptomycin (strA and rrs) . RESULTS--Multidrug-resistant M tuberculosis isolates were recovered from 253 New York City patients and had the same or closely allied IS6110 and PGRS patterns, multiplex PCR type, and gene mutations associated with resistance to rifampin, isoniazid, and streptomycin . Isolates with these same molecular characteristics were recovered from patients in Florida and Nevada, health care workers in Atlanta, Ga, and Miami, Fla, and an individual who recently moved from New York City to Denver, Colo, and caused disease or skin test conversion in at least 12 people in a nursing home environment . CONCLUSIONS--The results document the molecular origin and spread of progeny of a closely related family of multidrug-resistant M tuberculosis strains that have recently shared a common ancestor and undergone clonal expansion . The multidrug-resistant phenotype in these organisms arose by sequential acquisition of resistance-conferring mutations in several genes, most likely as a consequence of antibiotic selection of randomly occurring mutants in concert with inadequately treated infections . Dissemination of these difficult-to-treat bacteria throughout New York City and to at least four additional US cities has adverse implications for tuberculosis control in the 21st century.

J Biol Chem, 1996 Feb 9, 271(6), 2935 - 40
Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils; Chertov O et al.; Reports that interleukin-8 (IL-8) induces the infiltration of neutrophils followed by T-cells into injection sites led us to postulate that by stimulation of neutrophil degranulation IL-8 may cause the release of factors with chemoattractant activity for T-lymphocytes . Extracts of human neutrophil granules were chromatographed to isolate and purify T-lymphocyte chemoattractant factors . Two major peaks of T-cell chemotactic activity were purified by C18 reversed phase high pressure liquid chromatography (HPLC) . The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3 . Purified defensins HNP-1 and HNP-2 (kindly provided by Dr . R . I . Lehrer, UCLA) were also potent chemoattractants for human T-cells, while HNP-3 was inactive . The second peak of T-cell chemoattractant activity was also further purified to homogeneity by C4 reversed phase HPLC and identified by NH2-terminal sequence analysis as CAP37/azurocidin, a protein with sequence homology to serine proteases . 0.1 100 ng of defensins and 1.0 100 ng/ml CAP37 were able to stimulate in vitro T-cell chemotaxis . Neutrophil activating factors, i.e . IL-8, phorbol 12-myristate 13-acetate/ionomycin, and formylmethionylleucylphenylalanine each induced the release of CAP37 and defensins from neutrophil granules . Subcutaneous administration of defensins or CAP37/azurocidin into BALB/c mice resulted in a moderate neutrophil and mononuclear cell infiltrate by 4 h, which was greater by 24 h at the site of injection . Additionally, subcutaneous injection of defensins into chimeric huPBL-SCID mice resulted in significant infiltration by human CD3+ cells within 4 h . These results identify the antimicrobial proteins, CAP37/azurocidin and defensins HNP-1 and HNP-2, as potent neutrophil-derived chemoattractants for T-cells . These proteins represent primordial antimicrobial peptides which may have evolved into acute inflammatory cell-derived signals that mobilize immunocompetent T-cells and other inflammatory cells.

Proc Natl Acad Sci U S A, 1996 Feb 6, 93(3), 1221 - 5
Structure-activity analysis of thanatin, a 21-residue inducible insect defense peptide with sequence homology to frog skin antimicrobial peptides; Fehlbaum P et al.; Immune challenge to the insect Podisus maculiventris induces synthesis of a 21-residue peptide with sequence homology to frog skin antimicrobial peptides of the brevinin family . The insect and frog peptides have in common a C-terminally located disulfide bridge delineating a cationic loop . The peptide is bactericidal and fungicidal, exhibiting the largest antimicrobial spectrum observed so far for an insect defense peptide . An all-D-enantiomer is nearly inactive against Gram-negative bacteria and some Gram-positive strains but is fully active against fungi and other Gram-positive bacteria, suggesting that more than one mechanism accounts for the antimicrobial activity of this peptide . Studies with truncated synthetic isoforms underline the role of the C-terminal loop and flanking residues for the activity of this molecule for which we propose the name thanatin.

Food Addit Contam, 1996 Feb-Mar, 13(2), 211 - 9
The production of pig tissue sulphadimidine reference material; Crooks SR et al.; The production of stable homogeneous reference materials containing the antimicrobial agent sulphadimidine in pig tissue is described . These were commissioned by the Community Bureau of Reference (BCR), established by the Commission of the European Communities, to promote improvements in analytical accuracy and to ensure uniformity of results determined by member states . Sulphadimidine-containing tissue powders (400 vials each of muscle, liver and kidney) were prepared by orally dosing pigs with drug, producing lyophilized tissue powders and blending these with negative tissues from unmedicated animals to achieve target concentrations . Details of the production process, the stabilizing procedure developed and the analytical assessments of homogeneity and stability are given.

Nahrung, 1996 Feb, 40(1), 1 - 7
Detection of inhibitors in milk by microbial tests . A review; Suhren G et al.; The demands concerning microbial inhibitor tests were subjected to marked changes during the last decades: It started with the claim of being able to detect contaminated milk which might cause problems during fermentation processes ('technological safety') . Due to the present day attention drawn to toxic and allergic hazards for numerous antimicrobials Maximum Residue Limits (MRLs) or safe/tolerance levels are fixed ('toxicological safety') . This means a variety of demands underlying permanent changes with respect to the 'detection pattern' which cannot be fulfilled by a single test . Within an Integrated Detection System microbial inhibitor tests play an important role as screening methods for those antimicrobials which can be detected with satisfactory sensitivities . This paper deals with some features of microbial inhibitor tests such as detection limits, performance susceptibility for interference factors, qualitative determination and standardization.

Acta Med Port, 1996 Feb-Mar, 9(2-3), 79 - 85
{Pneumonia in an internal medicine service}; Alvares E et al.; A retrospective study was performed in 107 patients with pneumonia in a total of 2231 who were admitted in a Medicine ward, of an University Hospital in Lisbon during 1990 . From the studied patients, 50 (46,7%) were females and 57 (53,3%) males . The mean age was 70,7 +/- 15,3 years, with a mean of 12.8 admission days . In the past history it was identified 43 (40%) patients with respiratory illness . In this, the chronic obstructive airways disease were the more prevalent disease in 22 (20.5%) patients . In the other chronic debilitating diseases, registered in 90 (84.1%), we reported in 58 (54.2%) patients among cardiovascular illness, hypertension (H) in 17 (15.8%) cases and H with diabetes mellitus II (DMII) in 14 (13.1%) . The most common radiographic pattern was bronchopneumonia in 56 (52.3%) cases and in the respiratory functional study, the partial respiratory insufficiency occurred in 25 (23.4%) cases . In blood test at admission, it was found anaemia in 35 (32.7%) patients, leukocytosis in 72 (67.3%), elevated sedimentation rate in 70 (65.4%), renal dysfunction in 12 (11.2%) and hyperglycemia in 67 (62.6%) . Concerning therapeutics, the ampicillin was the most used antimicrobial therapy in 50 (46.7%) cases and the oxygenotherapy was necessary in 45 (42%) . Only 29 (27.1%) needed bronchodilators and 3 (2.8%) required mechanical ventilatory support . The evolution was good in 76 (71%) cases and 31 (29%) patients died . The authors conclude that the pneumonia is a frequent disease in the Internal Medicine Clinics, either as admission cause either as complication of other comorbid medical condition and has a high mortality rate . The most important factors for the prognosis were the age of patients and previous diseases . The aim of the authors is to enhance prevention infection in lower respiratory tract, principally in the weak constitutions patients and the prescription of the appropriate therapy according with the judgment presumption and if possible with the isolated microorganism . Identify with the retrospective study, important elements in the clinical process for interpretation of diagnosis and therapeutic attitude and to learn with the preceding experience for future orientation.

Ann Med, 1996 Feb, 28(1), 23 - 30
New prospects in the prevention of otitis media; Heikkinen T et al.; Otitis media is the most common bacterial infection in children, accounting for a substantial economic burden to the health care system . Together with concern for long-term developmental sequelae, prevention of otitis media has become a high priority area of research . A wide range of factors has been associated with an increased risk of acute otitis media . Most of these factors, however, predispose to upper respiratory tract infection which, in turn, can be considered the most important risk factor for acute otitis media . Conventionally, antimicrobial prophylaxis, tympanostomy tubes and adenoidectomy have been used for prevention of otitis media . At present, the vaccine approach seems to hold the greatest promise for ultimate prevention of otitis media . In addition to the bacterial vaccines, vaccines against the most common viruses predisposing to acute otitis media may also prove valuable in the prevention of otitis media.

J R Coll Surg Edinb, 1996 Feb, 41(1), 1 - 6
Continuing search for solutions to trauma associated infections; Polk HC Jr; The surgeon's unending efforts to control infection in the surgical patient have reopened old avenues in the last years of this century . While there remains much to be learned about ideal antibiotic use, much contemporary energy is devoted to a clarification of the host's non-specific antimicrobial defense system, looking for the salient and critical defect and evaluating putative therapies . The laboratory bench yields a myriad of defects and likely solutions; the clinical scenario has been far less forgiving, and a raft of well-planned and executed clinical trials have produced half an answer . The wisest current strategy in surgical infection control is a judicious critique of failed clinical trials and the prospective development of precise reassessment, seeking a definable valuable outcome . We must continue to monitor the laboratory bench and should apply these concepts to the recalcitrant pneumonia that has been the most common cause of death in surgical patients for the past 30 years.

Inflamm Res, 1996 Feb, 45(2), 62 - 7
Evaluation of the effects of defensins on neutrophil functions; Yomogida S et al.; Defensins are known to be the microbicidal components of neutrophil granules, which contribute to oxygen-independent antimicrobial mechanisms . In this study, we have examined the effect of defensins on neutrophil functions, such as adhesion, superoxide anion generation, phagocytosis and chemotaxis . Guinea-pig defensins increased the expression of CD11b, CD11c and CD54 (intercellular adhesion molecule ICAM-1) on human neutrophils, and induced adhesion of guinea-pig and human neutrophils . When the effect of guinea-pig defensins on superoxide anion generation was examined, defensins inhibited superoxide anion generation during phagocytosis of complement-opsonized particles . Furthermore, defensins inhibited complement-dependent phagocytosis . However, they did not inhibit the binding of complement-opsonized particles to neutrophils, suggesting that defensins possibly inhibit complement-dependent phagocytosis by affecting the ingestion step but not the binding step . Defensins exhibited neither chemotactic nor chemokine activity . Interestingly, 10-20% of total defensins were released extracellularly from phagocytosing neutrophils . Together these observations indicate that, in addition to their antimicrobial activity, defensins may have the ability to modulate the functions of neutrophils at sites of infection or inflammation.

Aliment Pharmacol Ther, 1996 Feb, 10(1), 119 - 22
Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy); Yousfi MM et al.; BACKGROUND: Multi-drug regimens are generally required to reliably cure Helicobacter pylori infection . Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater . METHODS: We evaluated a 14-day combination regimen for H.pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d . and ranitidine 300 mg b.d . (MRC) instead of omeprazole . Ranitidine alone was continued for an additional 4 weeks . H . pylori status was determined by rapid urease testing, histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy . RESULTS: Twenty-seven patients with documented peptic ulcer disease and H . pylori infection were treated . Five had previously failed macrolide-based antimicrobial therapy; none had received metronidazole . All ulcers were healed at week 6 except one patient taking naproxen; his H . pylori infection was cured . Overall, H . pylori infection was cured in 78% (95% CI = 58-91%) . In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I . = 66-97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured . In contrast, four of five patients with metronidazole-resistant isolates were cured (80%) . In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89%, 95% C.I . = 65-99%) . Mild side effects were reported by 27%, including diarrhoea and altered taste . Compliance averaged 98% . CONCLUSION: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin-sensitive isolates . Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.

Aliment Pharmacol Ther, 1996 Feb, 10(1), 105 - 9
The effect of omeprazole on gastric juice viscosity, pH and bacterial counts; Goddard AF et al.; BACKGROUND: In vitro studies have shown that pH is an important determinant of mucus structure and function, but the relationship in vivo is unclear . Omeprazole increases intragastric pH and also allows bacterial overgrowth . In this study we have assessed the effect of omeprazole on gastric juice viscosity and examined the influence of pH and bacterial overgrowth on the resulting change . METHODS: Gastric juice specific viscosity, pH and total bacterial counts were measured in nine healthy male volunteers before and after omeprazole 20 mg twice daily for 1 week . The effect of incubation at pH 2 and 7 was also determined . Viscosity changes were compared with changes in pH and bacterial counts . RESULTS: Mean viscosity fell (P < 0.05) following treatment, though there was a wide range in viscosity both before and after treatment . The decrease was reproduced by incubation of pre-treatment juice at pH 7 but not pH 2 . The fall in viscosity was correlated (P < 0.05) with change pH . CONCLUSION: Omeprazole decreases gastric juice, and hence gastric mucus, viscosity by increasing intragastric pH . This could be important if it allows improved penetration of antimicrobials to Helicobacter pylori within the mucus layer.

Pharmacol Res, 1996 Feb, 33(2), 127 - 34
Pharmacological activities of Chelidonium majus L . (Papaveraceae); Colombo ML et al.; Chelidonium majus L . (Papaveraceae) has a long history as being useful for the treatment of many diseases in European countries . This plant is of great interest for its use also in Chinese herbal medicine . The plant contains, as major secondary metabolites, isoquinoline alkaloids, such as sanguinarine, chelidonine, chelerythrine, berberine and coptisine . Other compounds structurally unrelated to the alkaloids have been isolated from the aerial parts: several flavonoids and phenolic acids . C . majus extracts and its purified compounds exhibit interesting antiviral, antitumour and antimicrobial properties both in vitro and in vivo.

J Ethnopharmacol, 1996 Feb, 50(2), 97 - 102
Antimicrobial activities of southern Nepalese medicinal plants; Taylor RS et al.; In an ethnopharmacological screening of selected medicinal plants used in Nepal, methanol extracts from 20 plant species were assayed for activity against eleven strains of bacteria and four strains of fungi . Duplicate assays were conducted with and without exposure to ultraviolet (UV)-A radiation to test for light-activated or light-enhanced activity . Fifteen of the extracts showed activity against bacteria and fourteen showed activity against fungi . Five extracts were active only when exposed to UV-A light, and the antibiotic or antifungal effect of five extracts was enhanced upon exposure to light . Two of the most active extracts were from plants used to treat diarrhoea and dysentery . Bark from both Terminalia alata (Combretaceae) and Mallotus phillppensis (Euphorbiaceae) was active against Gram-positive and Gram-negative bacteria.

J Ethnopharmacol, 1996 Feb, 50(2), 91 - 6
Studies on the cytotoxicity, antimicrobial and DNA-binding activities of plants used by the Ese'ejas; Desmarchelier C et al.; Thirty-nine extracts of 13 plants used traditionally as medicinal by the Ese'ejas were studied in order to determine their cytotoxic effect in the brine shrimp . Infusions showed no toxicity . Those plants that tested positive for methanolic and dichloromethane extracts were assayed for DNA-binding activity . Cytotoxicity was not due to the presence of compounds that interact with DNA . Antimicrobial activity of plants used to treat infectious diseases was also performed for the decoctions . These proved to be active against some of the test microrganisms used in the assay.

J Clin Periodontol, 1996 Feb, 23(2), 140 - 2
Effect of chlorhexidine on the adherence properties of Porphyromonas gingivalis; Grenier D; Chlorhexidine is a bisbiguanide compound that possesses substantive and antibacterial properties . The aim of the present investigation was to evaluate the effect of chlorhexidine on the adherence of Porphyromonas gingivalis to epithelial cells and erythrocytes . Both pretreatment of bacterial cells with chlorhexidine (> 20 micrograms/ml) and incorporation of chlorhexidine in an adherence assay markedly affected the ability of P . gingivalis to adhere to epithelial cells . Chlorhexidine also strongly inhibited hemagglutination by P . gingivalis . It is suggested that chlorhexidine binds to cells, altering the structural conformation of the outer membrane and reducing adherence . This ability of chlorhexidine to prevent bacterial adherence may represent an additional mechanism by which this antimicrobial agent exerts its beneficial clinical effect when used as an adjunct to periodontal therapy.

Phytochemistry, 1996 Feb, 41(3), 735 - 8
Antimicrobial abietane diterpenoids from Plectranthus elegans; Dellar JE et al.; Two novel abietane diterpenoids have been isolated from the aerial material of Plectranthus elegans and identified as 11-hydroxy-12-oxo-7,9(11),13-abietatriene and 7 alpha,11-dihydroxy-12-methoxy-8,11,13-abietatriene . Their structures were determined through rigorous use of spectroscopic methods . Both inhibited spore germination of the fungus Cladosporium cucumerinum, in direct bioautography, at a dose of 1 microgram . The new diterpenes also inhibited the growth of Gram-positive bacteria, in the concentration range 10-40 micrograms ml-1 in broth dilution assay . No effect was observed against Gram-negative bacteria . The ecological implications of these findings are discussed.

Infect Control Hosp Epidemiol, 1996 Feb, 17(2), 119 - 28
Antimicrobial use in long-term-care facilities; Nicolle LE et al.; There is intense antimicrobial use in long-term-care facilities (LTCF), and studies repeatedly document that much of this use is inappropriate . The current crisis in antimicrobial resistance, which encompasses the LTCF, heightens concerns of antimicrobial use . Attempts to improve antimicrobial use in the LTCF are complicated by characteristics of the patient population, limited availability of diagnostic tests, and virtual absence of relevant clinical trials . This article recommends approaches to management of common LTCF infections and proposes minimal standards for an antimicrobial review program . In developing these recommendations, the article acknowledges the unique aspects of provision of care in the LTCF.

J Chemother, 1996 Feb, 8(1), 37 - 42
Type frequency and antimicrobial susceptibility of Mycobacterium avium-intracellulare complex strains isolated in Italy from AIDS and non-AIDS patients; Fattorini L et al.; Typing of the glycopeptidolipid antigens performed by thin layer chromatography on 59 Mycobacterium avium-intracellulare (MAC) strains isolated in Italy from AIDS patients showed that the most frequent types were 1, 4, 3, 8, and 21 (24, 19, 14, 14 and 8% of the strains, respectively) . Among non-AIDS patients, types 1, 4 and 8 were also frequently found . The antimicrobial susceptibility tested in agar and/or liquid media to a panel of drugs indicated in clofazimine and rifabutin effective agents against both AIDS and non-AIDS strains . The data obtained show that MAC type distribution in Italy appears to be different from that reported for other countries . No major differences in drug susceptibility between AIDS and non-AIDS related strains were found.

Ann Pharmacother, 1996 Feb, 30(2), 130 - 2
Antimicrobial liquid formulations: a blind taste comparison of three brands of penicillin VK and three brands of amoxicillin; Chan DS et al.; OBJECTIVE: To rate the perception of taste, texture, smell and aftertaste of various brands of penicillin VK and amoxicillin . DESIGN: Oral, liquid formulations of three brands of penicillin VK (PenVee K, V-Cillin-K, VeeTids) and three brands of amoxicillin (Amoxil, Trimox, Wymox) were evaluated for smell, texture, taste, and aftertaste by 30 volunteers in a blind study . Each category was scored on a scale of 1 to 5 . The order in which the drugs were sampled was randomized for the first three groups of five participants . The order then was reversed for the remaining three groups of participants . SETTING: A 537-bed US Army teaching hospital . PARTICIPANTS: Participants included 30 healthy adult volunteers from the Departments of Pediatrics, Nursing, and Pharmacy . MAIN OUTCOME MEASURES: Drugs received cumulative scores in each category, as well as an overall total score ranking . The data were analyzed using one-way ANOVA for repeated measures with a post hoc Duncan's multiple range test to determine significant differences between individual means . RESULTS: Overall, Trimox and Amoxil scored significantly higher than the remaining drugs . Although V-Cillin-K scored highest in the smell category, its score was significantly below those of Trimox and Amoxil in the texture, taste, aftertaste, and overall categories . Overall, the three penicillin VK solutions scored lower than the three amoxicillin suspensions, with PenVee K ranking the lowest . Among the penicillin VK solutions, V-Cillin-K scored significantly higher overall than the other two penicillin VK solutions . CONCLUSIONS: Overall, all three amoxicillin oral, liquid suspensions that were studied scored significantly better than the three penicillin VK solutions.

Antimicrob Agents Chemother, 1996 Feb, 40(2), 477 - 80
Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori; Versalovic J et al.; Twelve clarithromycin-resistant Helicobacter pylori isolates (100% of resistant isolates examined) from seven different patients each contained an A-->G transition mutation within a conserved loop of 23S rRNA . A-->G transition mutations at positions cognate with Escherichia coli 23S rRNA positions 2058 and 2059 were identified . Clarithromycin-susceptible H . pylori isolates from 14 different patients displayed no polymorphisms in a conserved loop within domain V of 23S rRNA . The study is the first to report mutations in H . pylori associated with resistance to an antimicrobial agent used in established peptic ulcer treatment regimens.

Antimicrob Agents Chemother, 1996 Feb, 40(2), 437 - 42
How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?
Ji B, Lounis N, Truffot-Pernot C, Grosset J.
Although the MICs of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, or KRM-1648 (KRM), for Mycobacterium avium complex (MAC) were significantly lower than those of other drugs, its in vivo activity was very weak . Beginning 28 days after inoculation, beige mice that had been infected intravenously with 1.87 x 10(7) CFU of MAC 101 were administered KRM alone, clarithromycin (CLARI) alone, or CLARI plus KRM six times weekly for 16 weeks . In contrast to the mice treated with CLARI-containing regimens, the mortality and the mean spleen weights of mice treated with KRM alone (either 10 or 20 mg/kg of body weight per dose) did not differ significantly from those of untreated mice, their numbers of CFU were very much greater than pretreatment values, and multiplication of MAC was only slightly inhibited . Although monotherapy by KRM selected KRM-resistant mutants, the selection was very weak; the mean number of CFU and the frequency of KRM-resistant mutants increased by no more than 1 order of magnitude after 16 weeks of treatment with KRM at 20 mg/kg per dose . Selection of CLARI-resistant mutants was inhibited but not completely prevented by treatment of the mice with CLARI plus KRM . These results indicate that KRM displayed only a weak bacteriostatic effect against the isolate tested in the beige mouse model; its ability to enhance the antimicrobial effect of CLARI or to prevent emergence of CLARI-resistant mutants was very limited.

Antimicrob Agents Chemother, 1996 Feb, 40(2), 314 - 19
Activity of trovafloxacin (CP-99,219) against Legionella isolates: in vitro activity, intracellular accumulation and killing in macrophages, and pharmacokinetics and treatment of guinea pigs with L . pneumophila pneumonia; Edelstein PH et al.; The activity of trovafloxacin against 22 clinical Legionella isolates was determined by broth microdilution susceptibility testing . The trovafloxacin concentration required to inhibit 90% of strains tested was < or = 0.004 micrograms/ml, in contrast to 0.032 micrograms/ml for ofloxacin . In guinea pig alveolar macrophages, trovafloxacin achieved intracellular levels up to 28-fold over the extracellular concentration, which was similar to the levels obtained with erythromycin . Trovafloxacin (0.25 micrograms/ml) reduced bacterial counts of two L . pneumophila strains grown in guinea pig alveolar macrophages by > 2 log10 CFU/ml, without regrowth, under drug-free conditions over a 3-day period; trovafloxacin was significantly more active than ofloxacin or erythromycin (0.25 to 1 microgram/ml) in this assay . Single-dose (10 mg of prodrug CP-116,517-27 per kg of body weight given intraperitoneally {i.p.}, equivalent to 7.5 mg of trovafloxacin per kg) pharmacokinetic studies performed in guinea pigs with L . pneumophila pneumonia revealed peak serum and lung trovafloxacin levels to be 3.8 micrograms/ml and 5.0 micrograms/g, respectively, at 0.5 h and 4.2 micrograms/ml and 2.9 micrograms/g, respectively, at 1 h . Administration of a lower prodrug dose (1.4 mg of trovafloxacin equivalent per kg i.p.) gave levels in lung and serum of 0.4 microgram/g and 0.4 microgram/ml, respectively, 1 h after drug administration . The terminal half-lives of elimination from serum and lung were 0.8 and 1.1 h, respectively . All 15 infected guinea pigs treated for 5 days with CP-116,517-27 once daily (10 mg/kg/day i.p., equivalent to 7.5 mg of trovafloxacin per kg/day) survived for 10 days after antimicrobial therapy, as did all 15 guinea pigs treated with ofloxacin once daily (10 mg/kg/day i.p.) for 5 days . None of 13 animals treated with saline survived . In a second experiment with animals, trovafloxacin (1.4 mg/kg/day i.p . for 5 days) protected all 16 guinea pigs from death, whereas all 15 animals treated with saline died . Trovafloxacin is an effective antimicrobial agent against Legionella in vitro and in vivo, with the ability to concentrate in macrophages and kill intracellular organisms.

Phytochemistry, 1996 Feb, 41(2), 537 - 44
Antimicrobial isoflavanones from Desmodium canum; Monache GD et al.; Bioassay-directed fractionation of Desmodium canum resulted in the isolation and characterization of three antimicrobial isoflavonones . These compounds, namely, desmodianones A, B and C, were assigned the structures 5,7,2'-trihydroxy-6,6"-dimethyl-6"-(4-methylpent-3- enyl)pyrano(2",3";4',5')isoflavanone, 5,2',4'-trihydroxy-7-methoxy-6-methyl-8-(3-methylbut-2-enyl)-is oflavanone, and 5,7,2',4'-tetrahydroxy-6-methyl-5'-(3,7-dimethylocta-2,6-dienyl )-isoflavanone, respectively.

Am J Health Syst Pharm, 1996 Feb 1, 53(3), 285 - 8
Using pharmacists' documentation of clinical activities to reclaim employees and reposition the department; McDaniel MR et al.; The use of documentation on pharmacist clinical activities to encourage greater hospital investment in a department is described . From 1983 through 1988, the number of full-time-equivalent (FTE) positions in the pharmacy department at a 468-bed medical center was reduced from 63 to 39.4 . To cope with the challenge of a sharply reduced staff, the department established a permanent pharmacy-nursing task force, developed a pharmacy strategic plan, used total quality management, recruited the best staff possible when openings appeared, and held staff retreats . In addition, measures were taken to begin documenting all pharmacist clinical activities online . As data were accumulated, it became clear that more pharmacist involvement in patient care areas was needed and that more resources would be necessary to achieve that . Presentations were made to hospital administration to demonstrate the existing and potential contributions of the department; the presentations drew heavily on the clinical documentation . Formal reports were also submitted . As a result, the department received approval for a pharmacist career ladder, an increase of 1.6 pharmacist FTEs for the evening shift, a large salary-range adjustment for staff pharmacists, and an increase of 1 pharmacist FTE to focus on antimicrobial use . A pharmacy department successfully used documentation of its clinical activities to make a case to administration for reclaiming some of the pharmacist FTEs lost through downsizing.

J Clin Microbiol, 1996 Feb, 34(2), 471 - 3
Comparison of three methods for recovery of yeasts from hands of health-care workers; Strausbaugh LJ et al.; This study compared three methods for the detection of yeasts on the hands of 30 nurses: (i) direct finger impressions on inhibitory mold agar plates, (ii) bag washes in brain heart infusion broth, and (iii) bag washes in brain heart infusion broth supplemented with gentamicin and vancomycin . The antimicrobial agent-supplemented bag wash method identified the greatest number of yeast carriers and yielded the most yeast isolates, especially non-C . albicans Candida spp.

Singapore Med J, 1996 Feb, 37(1), 39 - 43
Murine typhus: a forgotten cause of febrile illness in Singapore; Loh KC et al.; We report 6 cases of marine typhus presented to us within a period of 3 months . The diagnoses were made based on the Weil-Felix reaction in the context of supportive clinical and epidemiological features, and response to appropriate antimicrobial therapy . This review serves to remind us that murine typhus is still an important cause of acute febrile illness in Singapore, especially among the migrant Indian workers.

Antonie Van Leeuwenhoek, 1996 Feb, 69(2), 161 - 69
Protein engineering of lantibiotics; Kuipers OP et al.; Whereas protein engineering of enzymes and structural proteins nowadays is an established research tool for studying structure-function relationships of polypeptides and for improving their properties, the engineering of posttranslationally modified peptides, such as the lantibiotics, is just coming of age . The engineering of lantibiotics is less straightforward than that of unmodified proteins, since expression systems should be developed not only for the structural genes but also for the genes encoding the biosynthetic enzymes, immunity protein and regulatory proteins . Moreover, correct posttranslational modification of specific residues could in many cases be a prerequisite for production and secretion of the active lantibiotic, which limits the number of successful mutations one can apply . This paper describes the development of expression systems for the structural lantibiotic genes for nisin A, nisin Z, gallidermin, epidermin and Pep5, and gives examples of recently produced site-directed mutants of these lantibiotics . Characterization of the mutants yielded valuable information on biosynthetic requirements for production . Moreover, regions in the lantibiotics were identified that are of crucial importance for antimicrobial activity . Eventually, this knowledge will lead to the rational design of lantibiotics optimally suited for fighting specific undesirable microorganisms . The mutants are of additional value for studies directed towards the elucidation of the mode of action of lantibiotics.

Indian Pediatr, 1996 Feb, 33(2), 117 - 9
Diarrhea management in some Jhuggi clusters of Delhi; Taneja DK et al.; PIP: In India, a survey was conducted of 6285 persons living in 1090 households in the Jhuggi clusters of Sanjay Amar Colony, Hathi Park, and Jai Prakash Colony in New Delhi to identify diarrhea management practices at home and at a health facility and to determine knowledge levels about preparation of oral rehydration solution (ORS) and sugar salt solution (SSS) . 183 (2.9%) persons experienced diarrhea in the previous 2 weeks . 68.3% were younger than 5 years old . 13.1% of all diarrhea cases had blood in their stool . Oral rehydration therapy (ORT) was provided to 3.3% in ORS form, 10.4% in SSS form, 5.5% as dal water, and 5.5% as shikanji . Correct preparation of SSS via finger pinch, scoop, or spoon and glasses was performed in 36.6% of households . Only 11.5% could correctly measure the water needed to make 1 liter of ORS . The first action against the diarrhea was often taken on day 2 (13.1%) and day 3 (18%) . 55.7% of diarrhea cases sought treatment at a private practice . 7.1% went to a government health facility . 79.1% of cases taken to a medical practitioner received a drug (e.g., antidiarrheals and antimicrobials) . Yet, antimicrobials were indicated in only 13.1% of diarrhea cases taken to a health facility . These cases had dysentery . Only 31.3% received ORS or home-available fluids . Government health facilities were more likely to provide ORT than private practitioners (61.5% vs . 27.4%) . All diarrhea cases experiencing dehydration received ORT or intravenous fluids . These findings stress the need for reorientation training of physicians on appropriate case management of diarrhea and rational use of drugs in cases of acute diarrhea . Families also need training in correct preparation and use of ORT and in restriction on the use of drugs .

Fiziol Zh Im I M Sechenova, 1996 Feb, 82(2), 71 - 8
{The opiate-like and antimicrobial bioactivities of food protein peptides}; Kharchenko EP; At least four food peptides were found to possess opiate-like and antibacterial properties, lys-arg-fen-ala-glu being the most active one . These peptides seem to be able to become accumulated in high concentrations in indigestion and induce an intestinal spasm and constipation.

Trends Biotechnol, 1996 Feb, 14(2), 60 - 5
Novel antimicrobial compounds identified using synthetic combinatorial library technology; Blondelle SE et al.; The recent emergence of combinatorial chemistry has greatly advanced the development of biologically active lead compounds . It is anticipated that combinatorial library technology will add great value to the fight against drug-resistant bacterial strains, which pose increasingly serious health hazards . Owing to the need to use complex cell-based assays and, in turn, to screen free compounds in solution, the potential use of combinatorial libraries in the field of infectious diseases has not yet been fully explored . Despite these limitations, a number of new antimicrobial and/or antifungal compounds have been successfully identified from pools of millions of other compounds.

J Interferon Cytokine Res, 1996 Feb, 16(2), 159 - 68
Kinetics and dose dependence of macrophage colony-stimulating factor-induced proliferation and activation of murine mononuclear phagocytes in situ: differences between lungs, liver, and spleen; Held TK et al.; Alveolar macrophages (AM) play an important role in antimicrobial defense mechanisms of the lung . It therefore seems reasonable to use macrophage colony-stimulating factor (M-CSF) to enhance local resistance mechanisms . However, little is known about the in vivo activity of M-CSF on macrophages in various organs . We determined the effect of a single subcutaneous dose of M-CSF (10, 50, 100, and 500 ng, respectively) on the number and functional status of AM as well as of macrophages in liver and spleen of mice . Organs were investigated immunohistochemically on days 1 and 3 after injection using monoclonal antibodies specific for F4/80, Ia antigen, and MAC-1 . We found a significant increase in the number of F4/80+ AM, Kupffer cells, and splenic macrophages reaching its maximum 24 h after injection of low doses (10 and 50 ng per mouse, respectively) of M-CSF and decreasing to a level seen in untreated mice at 72 h after M-CSF in liver and spleen, whereas at a dose of 50 ng per mouse the number of AM remained high . In contrast, the numbers of AM, Kupffer cells, and splenic macrophages did not increase significantly when high doses were used (500 ng) . The expression of Ia antigen and MAC-1 was increased on macrophages in the spleen but not on AM or Kupffer cells . TNF-alpha was elevated in bronchoalveolar (BAL) fluid after 3 h and IL-6 at 6, 12, and 24 h after M-CSF injection in dose-dependent manner . Nitric oxide production was not increased after injection of M-CSF . Our results point to regional differences in the response of macrophages to M-CSF . These may caused by differences in the M-CSF-induced production of TNF-alpha and IL-6 . These findings may be important for the therapeutic use of M-CSF in microbial infections.

J Chemother, 1996 Feb, 8 Suppl 2, 71 - 82
The penetration of novel intravenous cephalosporins into the lung; Baldwin DR; Relating the concentrations of active antimicrobial at the potential site of infection to MIC, may give some indication of clinical efficacy . Where relatively insusceptible pathogens are involved, site concentrations are likely to be important predictors of efficacy . Unfortunately, there are sources of errors in measurement which make the values obtained imprecise . Despite this, broad trends are beginning to emerge, especially with bronchial biopsy concentrations . In bronchial biopsies, cephalosporins reach approximately 35 to 55% of simultaneous serum concentrations, in whole lung tissue 15 to 50% and in ELF 15 to 35% . The observed site to serum ratios are consistent with the permeability characteristics of cephalosporins and the barriers to movement of drugs into sites of infection . There is evidence that inflammation may alter the barriers to infection and for the cephalosporins site penetration may be higher . Further work is necessary to establish a clear relationship between site concentrations in the lung and clinical efficacy.

Tuber Lung Dis, 1996 Feb, 77(1), 19 - 26
Clarithromycin against Mycobacterium avium complex infections; Heifets LB; The turning point in antimicrobial therapy of Mycobacterium avium infections came with the development of two new macrolides, clarithromycin and azithromycin . Controlled clinical trials, the first ever conducted with any agent among patients with M . avium infection, indicated the high efficiency of clarithromycin, in either acquired immune deficiency syndrome (AIDS) patients having a disseminated infection or non-AIDS patients with localized pulmonary disease . Monotherapy with clarithromycin resulted in elimination of bacteremia in almost all patients with disseminated infection, which is inevitably followed by a relapse of bacteremia in patients who survived long enough to reach this event . The strains susceptible to clarithromycin isolated before therapy contained 10(-8) or 10(-9) resistant mutants, and the relapses of bacteremia were caused by multiplication of these pre-existing mutants . Clarithromycin-resistance was associated with a mutation in the 23S rRNA gene . Cross-resistance between clarithromycin and azithromycin was confirmed with laboratory mutants and clinical isolates . At least two methods for determining the susceptibility of the M . avium isolates to clarithromycin are available: one is minimum inhibitory concentration (MIC) determination on Mueller-Hinton agar (pH 7.4) supplemented with 10% Oleic acid-albumin-dextrose catalase, the other is MIC determination in 7H12 broth, also at pH 7.4 . The breakpoints for 'susceptible' for these methods are < or = 8.0 micrograms/ml and < or = 2.0 micrograms/ml, respectively . The breakpoints for 'resistant' are > 128 micrograms/ml for the agar method and > 32.0 micrograms/ml for the broth method . The predictability value of MIC determination was confirmed by comparing the test results with the patients' clinical and bacteriological response to therapy . The remaining major problem in the therapy of the M . avium infections is a selection of companion drugs to be used in combination with clarithromycin (or azithromycin) to prevent the emergence of the macrolide-resistance . A number of clinical trials are now in progress to find a solution to this problem.

FEMS Immunol Med Microbiol, 1996 Feb, 13(2), 95 - 9
In vitro and in vivo induction of nitric oxide by murine macrophages stimulated with Bordetella pertussis; Torre D et al.; Nitric oxide (NO) exhibits potent antimicrobial activity in vitro . The function of NO in host defenses in vivo, however, is presently unclear . Experiments were undertaken to determine the production of NO in vitro from murine peritoneal and alveolar macrophages, and murine macrophage cell line (J774A.1) stimulated with Bordetella pertussis or pertussis toxin (PT) . In addition, we determined circulating levels of NO in the sera and bronchoalveolar lavage (BAL) fluids of mice infected intranasally with B . pertussis . The results of this study showed that in vitro murine peritoneal macrophages induce production of NO in response to B . pertussis and PT . In addition, murine macrophage cell line, J774A.1 also induces NO production after stimulation with B . pertussis . NO production was also detected in alveolar macrophages from mice infected intranasally with B . pertussis . Finally, a significant increment of circulating levels of NO was noted, in the sera but not in the BAL fluids, of mice infected intranasally with B . pertussis.

Curr Opin Immunol, 1996 Feb, 8(1), 8 - 13
Innate immunity in higher insects; Hoffmann JA et al.; The hallmark of the innate immune response of higher insects is the rapid and transient synthesis of a battery of broad spectrum antimicrobial peptides by the fat body . The control of the genes encoding these peptides involves cis-regulatory promoter elements homologous to sequences functional in mammalian acute-phase genes . Study of immune-deficient mutants of Drosophila has indicated that distinct pathways control the antibacterial and antifungal responses in this species . Novel receptors potentially involved in the initiation of the immune response have been recently characterized.

Pharmazie, 1996 Feb, 51(2), 76 - 83
On the synthesis of pyridazomycin congeners . Part 2: L-alpha-Amino acids bearing a terminal azinium or diazinium system; Easmon J et al.; The synthesis of a variety of novel compounds structurally related to the antimicrobial natural product pyridazomycin via alkylation of appropriate azine and diazine derivatives is reported . Based on the results of preliminary antimicrobial tests the dependence of antimicrobial activity from several structural features of pyridazomycin is discussed.

Arzneimittelforschung, 1996 Feb, 46(2), 210 - 2
In vitro activity of a new rifamycin derivative against Mycobacterium leprae; Dhople AM et al.; The antimicrobial effects of T9 (3-(4-cinamyl-1-piperazinyl)iminomethyl rifamycin SV) alone and in combination with ofloxacin, against strains of M . leprae were evaluated, using an in vitro cell-free culture system . The minimum inhibitory concentrations (MICs) of T9 against rifampin-sensitive and rifampin-resistant strains of M . leprae were 0.1 microgram/ml and 0.4 microgram/ml, respectively . Furthermore, in common with rifabutin, but not with rifamycin, T9 demonstrated synergy with ofloxacin against both rifampin-sensitive rifampin-resistant strains of M . leprae . The results suggest that T9, in combination with ofloxacin as part of multidrug regimens, warrants further evaluation as treatment for patients with leprosy.

Arch Pathol Lab Med, 1996 Feb, 120(2), 199 - 203
Autopsy verification of Encephalitozoon intestinalis (microsporidiosis) eradication following albendazole therapy; Joste NE et al.; Microsporidian infections are increasingly recognized as an important cause of morbidity for persons infected with the human immunodeficiency virus . Encephalitozoon (formerly Septata) intestinalis is a recently described microsporidian that causes intestinal and disseminated infections in severely immunocompromised patients with acquired immunodeficiency syndrome . Several studies suggest that albendazole is an effective therapy for E intestinalis infection . However, relapses of symptoms and reappearance of microsporidian spores in diagnostic specimens have been reported following treatment in some cases . Because these results are based on examination of feces or cytologic specimens with an inherent sampling bias, it would be ideal to have autopsy data on the complete tissue evaluation of major organ systems of patients who had antemortem E intestinalis infection treated with albendazole . This report describes an acquired immunodeficiency syndrome patient with diarrhea and wasting syndrome associated with E intestinalis infection . Treatment with albendazole produced relief of his clinical symptoms and eliminated microsporidian spores in his feces . Following his death from other causes, an autopsy was performed . Comprehensive microscopic examination of all major organs revealed no evidence of residual microsporidian infection, suggesting parasitologic cure of E intestinalis with albendazole . The postmortem finding of complete clearance of microsporidia from body tissues is significant for future albendazole treatment of patients infected with E intestinalis and provides strong support for the value of the autopsy in evaluating the therapeutic efficacy of antimicrobials in emerging infections.

Vnitr Lek, 1996 Feb, 42(2), 133 - 5
{Empirical antimicrobial therapy of respiratory infections}; Musilova J; Respiratory infections cause a significant morbidity and mortality . Ideally, the treatment should be directed against the identified pathogen and its sensitivity to antibiotics . In many situations, however, the pathogen is unknown and the infections are treated empirically . Author briefly reviews the current empirical therapeutical recommendations based on the age of patient, comorbidity and the type of infection (acute bronchitis, exacerbations of chronic bronchitis, community acquired pneumonia, nosocomial pneumonia and pneumonia in immunocompromised patients.

Curr Eye Res, 1996 Feb, 15(2), 225 - 8
Effects of polyhexamethylene biguanide and chlorhexidine on four species of Acanthamoeba in vitro; Tirado-Angel J et al.; We determined the relative minimal inhibitory and minimal amoebicidal concentrations of chlorhexidine digluconate and polyhexamethylene biguanide for four species of Acanthamoeba . The amoebae were grown in peptone-glucose-yeast extract broth for 72 h in tissue culture flasks . Either washed trophozoites (approximately 10(5)) or cysts (approximately 10(5)) were incubated in the enrichment broth in 96 well microtiter trays . Antimicrobial concentrations of the biguanides were determined from microscopic examinations of methylene blue uptake and from subcultures . In general, killing was time dependent . Minimal amoebicidal concentrations at 24 h ranged from 50 to 100 mg/ml and to as low as 25 mg/ml by 72 h . Trophozoites were killed more rapidly than cysts . Both biguanides had similar levels of activity . A synergistic combination of chlorhexidine and polyhexamethylene biguanide (total concentration 25 mg/ml) was most evident for A . castellanii and A . polyphaga . Cysts of A . culbertsoni and A . hatchetti stained more rapidly after exposure to the combination of biguanides than to the single biguanides, but there were no statistically significant differences in the final numbers of dead or stained cysts after exposure to the combination or to the single biguanides.

J Periodontol, 1996 Feb, 67(2), 130 - 9
Repopulation of periodontal pockets by microbial pathogens in the absence of supportive therapy; Shiloah J et al.; This clinical study evaluated the reinfection incidence by Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi) in periodontal pockets following scaling and root planing (SRP) and intra-pocket irrigation with antimicrobial agents in a patient population who did not receive supportive maintenance therapy . The number of target organisms was determined utilizing DNA probes . Forty-one (41) inflamed pockets > or = 5 mm with attachment loss and containing at least one target species were selected in 6 adult patients . Following a baseline clinical and bacterial examination, all patients received thorough SRP . In addition, 1 to 2 teeth in each patient were randomly assigned to each of the following 4 treatment modalities: 1) control group, no irrigation; 2) saline group, irrigation with 2 cc of 0.85% saline; 3) tetracycline group, irrigation with 2 cc of aqueous tetracycline HCl, 50 mg/ml (5%); and 4) chlorhexidine group, irrigation with 2 cc, respectively . All selected sites were non-adjacent . No additional therapy was rendered during the entire 1-year observation period . Clinical parameters and microbial analyses were recorded again at 1 week, and 1, 3, 6, 9, and 12 months post-treatment . The effect of antimicrobial irrigation on the reinfection rate of sites by Aa, Pg, and Pi was compared with that of the control groups (1 and 2) by ANOVA . No statistically significant differences were observed among the irrigation treatment groups with regard to any of the clinical or bacterial parameters studied . Therefore, the 4 treatment groups were combined into a single group whereby the rate of bacterial repopulation following extensive scaling and root planing could be ascertained . The infection incidence of sites at baseline (of total sites), 1 week and 12 months (of sites originally infected at baseline) was 14/41, 3/14, and 7/14 for Aa; 33/41, 6/33, and 12/33 for Pg; and 37/41, 3/37, and 12/37 for Pi, respectively . Thus, half or fewer of the originally infected sites became reinfected at 12 months despite lack of maintenance therapy . The results suggest that 1) a single episode of pocket irrigation with antimicrobial agents following thorough scaling and root planing did not affect the rate of repopulation of periodontal pockets by the tested pathogens; 2) thorough scaling and root planing has a lasting suppressive effect on selected periodontal pathogens for the majority of sites in patients with adult periodontitis; 3) pre-operative probing depth, the amount of gingival fluid flow and the composition of the subgingival microflora may serve as predictors for reinfection in the absence of maintenance care; and 4) reinfection of the treated sites by Aa, Pg, and/or Pi may constitute a risk factor that diminishes the effect of therapy in the absence of supportive maintenance care.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1996 Feb, 81(2), 141 - 7
Recurrent aphthous stomatitis . An update; Ship JA; Recurrent aphthous ulceration or recurrent aphthous stomatitis is the most common oral mucosal disease known to human beings . Despite much clinical and research attention, the causes remain poorly understood, the ulcers are not preventable, and treatment is symptomatic . The most common presentation is minor recurrent aphthous stomatitis: recurrent, round, clearly defined, small, painful ulcers that heal in 10 to 14 days without scarring . Major recurrent aphthous stomatitis lesions are larger (greater than 5 mm), can last for 6 weeks or longer, and frequently scar . The third variety of recurrent aphthous stomatitis is herpetiform ulcers, which present as multiple small clusters of pinpoint lesions that can coalesce to form large irregular ulcers and last 7 to 10 days . Diagnosis of all varieties is usually made after clinical examination . Many local and systemic factors have been associated with these conditions, and there is evidence that there may be a genetic and immunopathogenic basis for recurrent aphthous ulceration . Management of this condition depends on the clinical presentation and symptoms and includes analgesic, antimicrobial, and immunomodulatory drugs . As dental clinicians and researchers become better trained in oral medicine and stomatology, it is anticipated that the pathophysiology, prevention, and treatment of recurrent aphthous ulceration will improve in the future.

J Dent Res, 1996 Feb, 75(2), 736 - 42
Ins and outs of antimicrobial resistance: era of the drug pumps; Jenkinson HF; Over the past five years, concerns have heightened over the escalating numbers of pathogenic micro-organisms isolated that are resistant to many antibiotics and drugs . This phenomenon poses major problems in the treatment of patients with hospital- or community-acquired infections caused by bacteria, fungi, or parasitic organisms . Microbial cells have acquired resistances to specific antibiotics and drugs by mechanisms that include antibiotic inactivation, target alteration, or drug exclusion . More recently, the importance of another mechanism, that of drug expulsion, has been recognized as contributing significantly to antibiotic and drug resistance in microbes . Drug expulsion, mediated by membrane-associated drug efflux pumps, can protect cells from a range of toxic compounds and therefore may confer single-step multidrug resistance . It is imperative that new drugs be designed or discovered that will poison the pumps or bypass the efflux mechanisms.

Clin Transplant, 1996 Feb, 10(1 Pt 1), 20 - 3
Role of granulocyte colony stimulating factor (G-CSF) in reversing neutropenia in renal allograft recipients; Peddi VR et al.; Neutropenia in solid organ transplant recipients may be caused by immunosuppressive therapy, antimicrobial therapy, as well as bacterial and viral infections . Filgrastim, a human granulocyte colony stimulating factor (G-CSF) is used for the reversal of neutropenia . Although its influence is principally restricted to neutrophil progenitors, the safety of G-CSF in terms of percipitating or aggravating allograft rejection and its efficacy in reversing neutropenia in kidney and combined kidney and pancreas transplant patients has not been studied or reported . In this study we retrospectively analyzed the use of G-CSF between March 1992 and May 1994 at the University of Cincinnati Medical Center, in patients who received either a kidney or a combined kidney and pancreas transplant . A total of 25 patients developed 35 episodes of neutropenia and received an average of 2.9 doses of G-CSF per episode . The mean WBC nadir was 2.6 x 10(3)/cu mm with an average peak WBC count of 15.5 x 10(3)/cu mm following treatment (p = < 0.00001) . The average number of days to peak WBC after initiation of treatment was 4.6 days . The mean pre-treatment serum creatinine level was 2.3 mg/dl and the peak serum creatinine in the week following treatment remained the same . We conclude that G-CSF is an effective treatment in reversing neutropenia in renal transplant recipients and does not precipitate or aggravate allograft rejection.

Am J Infect Control, 1996 Feb, 24(1), 1 - 6
Risk factors for infectious complications after abdominal surgery for malignant disease; Velasco E et al.; BACKGROUND: The emergence of nosocomial infection as a serious complication after intraabdominal operations for cancer prompted us to identify major independent risk factors associated with postoperative infection . METHODS: Risk factors were studied in single and multivariate analyses . Variables considered were remote infection, antimicrobial prophylaxis, preoperative stay, chemotherapy, radiotherapy, weight loss, elective versus emergency operation, wound class, duration of operation, drains, sex, age, and physical status . RESULTS: During 24 months, 236 patients were entered in the study . The overall postoperative infection rate was 45.7%; the surgical site infection rate was 22.4% . Multivariate analysis identified three independent variables: duration of operation longer than 5 hours (odds ratio 6.41, 95% confidence interval 3.28 to 12.54), presence of remote infection at operation (odds ratio 3.76, 95% confidence interval 1.76 to 8.03), and preoperative stay longer than 22 days (odds ratio 2.03, 95% confidence interval 1.04 to 3.95) . The relative risk of infection increased from 3.0 when one risk factor was present to 7.3 when all three risk factors were present . CONCLUSIONS: The predictive power of our final multivariate risk index clearly groups these patients according to differing risk for postoperative infection . This classification contributes substantially to the effectiveness of infection control strategies to prevent the occurrence of postoperative infection in the high-risk population of patients with cancer.

Mol Immunol, 1996 Feb, 33(3), 265 - 8
Structural analysis of human natural resistance-associated macrophage protein 1 promoter; Kishi F et al.; Natural resistance-associated macrophage protein gene 1 (Nramp1) was isolated as a candidate for the mouse gene locus Lsh/Ity/Bcg, which regulates macrophage activation for antimicrobial activity against intracellular pathogens . To investigate the structural and functional organization of the human homologue, NRAMP1, the overlapping genomic clones encompassing NRAMP1 were isolated . These clones spanned approximately 35 kb in size and the nucleotide sequence of 3779 bp of the 5' flanking region has been determined . The transcription start site was mapped by primer extension analysis . A TATA box element and the transcription regulatory elements in the acute phase reaction were found.

J Pediatr, 1996 Feb, 128(2), 237 - 40
Microbial dynamics of persistent purulent otitis media in children; Brook I et al.; Repeated aspirations (for a period of 36 to 55 days) of the exudate through an open perforation were performed in seven children with acute otitis media that did not respond to antimicrobial therapy . Penicillin-resistant organisms were present in all but one of the first two aspirates . Failure to respond to antimicrobial therapy was associated with the emergence of resistant anaerobic and aerobic bacteria in the third and fourth cultures . The infection was cured in all instances after administration of antimicrobial agents effective against these bacteria.

J Photochem Photobiol B, 1996 Feb, 32(3), 165 - 70
The UVR wavelength dependence for lomefloxacin photosensitization of human skin; Young AR et al.; Lomefloxacin is a new fluoroquinolone with effective broad-spectrum antimicrobial activity . However, in common with other structurally related drugs, skin photosensitization reactions have been reported . The wavelength dependence for such photosensitization has been investigated on the previously unexposed buttock skin of 12 normal healthy human volunteers of skin types I and II . Using geometric square root of 2 dose increments, baseline 24 h minimal erythema doses were assessed at 300, 320, 330, 340, 350 and 360 nm, and with broad-band UVA . In addition, dose-response curves were constructed for erythema as measured by a reflectance device . Subjects received single daily oral doses of 400 mg lomefloxacin at specified times for 4 days . At 2 h after the final dose, new areas of buttock skin were irradiated to assess changes in minimal erythema dose and erythema dose-response . Convolution of the erythema action spectra obtained pre- and on-drug with a terrestrial solar spectrum showed that, although the UVA sensitivity on-drug was enhanced, most of the erythemally effective solar energy was still in the UVB region . An action spectrum derived for lomefloxacin skin photosensitization showed peak activity at 320 nm, the same spectral region as that for maximal absorption of the drug . There was no evidence of skin photosensitization at 300 nm.

Arch Surg, 1996 Feb, 131(2), 192 - 9
Impact of different classes antimicrobial agents on plasma endotoxin activity; Nitsche D et al.; OBJECTIVE: To investigate the influence of different classes and doses of antibiotics on endotoxin release in gram-negative infection in a rat model of intra- abdominal infection . DESIGN: Immediately after intraperitoneal inoculation of Escherichia coli (5 x 10(7) colony-forming units/kg), anesthetized Wistar rats were treated with a single intravenous dose of an antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxacin (3 mg/kg or 6 mg/kg), imipenem (7 mg/kg or 14 mg/kg), or gentamicin (5 mg/kg) . An untreated control group received 0.9% sodium chloride instead of antibiotic . Plasma endotoxin activity, blood bacteria count, and mean arterial pressure were monitored at 60-minute intervals for 5 hours . At the end of the experiment, lavage was performed to determine the bacteria count in the peritoneal cavity . RESULTS: In the untreated group, the blood bacteria count increased rapidly . Five hours after therapy, the plasma endotoxin activity in the cefotaxime group was higher by a factor of 3.6 than in the untreated group . Compared with the cefotaxime group, endotoxin activity was approximately 26% lower in the ciprofloxacin (3 mg/kg) group, 35% lower in the imipenem groups, and 38% lower in the gentamicin group . The lowest endotoxin levels were in the high-dose ciprofloxacin group . Bacteria counts in the peritoneal cavity were lowest in the gentamicin and high-dose ciprofloxacin groups . Except in the high-dose ciprofloxacin group, the endotoxin increase in the therapy groups was associated with a significant (P < .05) decrease in mean arterial pressure . CONCLUSIONS: In the early phase of therapy, antibiotic-induced endotoxin release is influenced by the mode of action of the agent class . This is not the sole influence in every class . With quinolones, this effect is also influenced considerably by dosage, ie, by pharmacodynamics.

Am J Gastroenterol, 1996 Feb, 91(2), 239 - 45
Cost-effectiveness of treatment regimens for the eradication of Helicobacter pylori in duodenal ulcer; Vakil N et al.; BACKGROUND: Eradication of Helicobacter pylori with antimicrobials was recommended by a recent NIH consensus panel for all infected patients with peptic ulcer disease . The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials . METHODS: A decision analysis tree was developed with three regimens that are widely used regimens for the eradication of H . pylori: 1) 2-wk triple drug therapy (metronidazole, bismuth, tetracycline with H2 receptor antagonist), 2) 2-wk omeprazole and amoxicillin, and 3) 2-wk omeprazole and clarithromycin . Traditional H2 receptor antagonist therapy was used for comparison . A 2-yr time period was chosen for study to allow sufficient time for relapse and to evaluate its effect on the treatment strategy . Probabilities for eradication, compliance, and metronidazole resistance were determined from published data, and assumptions were tested by sensitivity analysis . RESULTS: Standard 2-wk triple drug therapy was the least expensive strategy ($720), and conventional H2 receptor antagonist therapy was the most expensive ($1791) . Costs with 2-wk therapy with omeprazole and clarithromycin ($768) were lower than with omeprazole and amoxicillin ($1028) . CONCLUSIONS: Treatment to eradicate H . pylori in infected patients with duodenal ulcer is a less expensive strategy than traditional therapy with H2 receptor antagonists . Triple drug therapy is the optimal regimen in areas where metronidazole resistance rates are < 36% and compliance is > 53% . Omeprazole and amoxicillin is not cost-effective unless eradication rates are greater than 74% . Dual drug therapy with omeprazole and clarithromycin is effective in regions where metronidazole resistance is high or where it is anticipated that there would be poor compliance with the more complicated triple drug therapy regimen.

Mayo Clin Proc, 1996 Feb, 71(2), 179 - 83
Concise review for primary-care physicians; Swanson JA et al.; Acute otitis media (AOM) in young children consumes a substantial amount of medical care services provided by primary-care physicians . A recent increase in the number of young children with AOM prompted a review of the associated risk factors . Eustachian tube dysfunction, bacterial colonization, and host inflammatory response form the basis for the development of AOM . Signs and symptoms of AOM in young children are often nonspecific and subtle, particularly in infants . Physical examination and pneumatic otoscopy verify the diagnosis . New modalities including tympanometry and acoustic reflectometry may be helpful . Amoxicillin remains the drug of choice for AOM, despite recent trends in microbial resistance . Second- and third-line antimicrobial agents might be considered in selected clinical settings . Young children with recurrent episodes of otitis media must be monitored closely . Preventive measures and medical or surgical intervention should be considered in order to minimize the long-term medical and developmental effects of AOM.

J Inorg Biochem, 1996 Feb, 61(2), 143 - 54
Cobalt(II), nickel(II), and copper(II) complexes of sulfanilamide derivatives: synthesis, spectroscopic studies, and antibacterial activity . Crystal structure of {Co(sulfacetamide)2(NCS)2}; Blasco F et al.; The synthesis and characterization of new coordination compounds of Co(II), Ni(II), and Cu(II) with sulfacetamide (N-{4-(amino-fenil)sulfonil}acetamide) is reported . The complex {Co(sulfacetamide)2(NCS)2} crystallizes in the triclinic space group P-1 . The cell dimensions are a = 7.80(2) A, b = 8.327(9) A, c = 9.568(3) A, alpha = 90.5(1) degrees, beta = 90.5(1) degrees, gamma = 97.8(2) degrees, V = 616(1) A3, Z = 2, and Dx = 1.689 g/cm3 . The final conventional R-factor = 0.039 (Rw = 0.039) for 3535 "observed" reflections and 173 variables . The Co(II) is surrounded in a regular octahedral arrangement by two Nthyocianato from the NCS, two Namino and two Oacetamido atoms from the sulfacetamide . Each sulfacetamide, acting as a bidentate ligand, chelates two Co(II) ions as a bridge through the Namino and the Oacetamido atoms . IR, Reflectance Diffuse, EPR, and magnetic properties of the obtained complexes are discussed . The complexes were screened for their activity against E . Coli and S . aureus, showing an appreciable antimicrobial activity compared with the ligands.

J Am Vet Med Assoc, 1996 Feb 1, 208(3), 404 - 7
Use of antimicrobial-impregnated polymethyl methacrylate beads for treatment of chronic, refractory septic arthritis and osteomyelitis of the digit in a bull; Trostle SS et al.; A 6-year-old 895-kg Angus bull was evaluated for a 6-month history of left hind limb lameness that was refractory to antimicrobial treatment . On physical examination, there was soft-tissue swelling associated with the lateral digit . Radiography revealed septic arthritis of the distal interphalangeal joint and osteomyelitis of the distal and middle phalanges . Treatment included debridement and lavage . Bacteriologic culture of debrided tissues yielded aerobic and anaerobic organisms . Antimicrobials were administered parenterally and locally in the form of antimicrobial-impregnated polymethyl methacrylate beads . The limb also was placed in a cast to promote ankylosis . The bull recovered, and the digit was salvaged.

J Pediatr Hematol Oncol, 1996 Feb, 18(1), 90 - 4
Opportunistic osteomyelitis in the jaws of children on immunosuppressive chemotherapy; Hovi L et al.; PURPOSE: Four children with an osteomyelitic process in the jaw bones while on cytotoxic chemotherapy were treated by radical surgery and antimicrobial chemotherapy . PATIENTS AND METHODS: Symptoms (local swelling and pain in the jaw, necrotic gingivitis, and spontaneous loss of teeth) appeared 3 weeks, 4 weeks, and 8 months after diagnosis of leukemia, and 8 days posttransplant in a patient with severe aplastic anemia . Three had the process in the mandible and one in the maxilla . Specific diagnoses of Aspergillus flavus, Saccharomyces cerevisiae, and Actinomyces species were obtained histologically from surgical samples . Treatment was radical surgery to remove all infected and necrotic tissue: removal of a substantial part of the mandible and loss of seven to eight permanent teeth in those with mandibular lesions . Actinomycosis was treated with penicillin for 2 years . The patients with fungal lesions received amphotericin B for 2, 5, and 6 months, with adjuvant itraconazole, fluconazole, or 5-fluorocytosine for 9-12 months . Anti-cancer chemotherapy was continued . RESULTS: All the bony lesions healed . The patient with acute myeloid leukemia died in relapse 1 year postdiagnosis; her aspergillus osteomyelitis had been inactive for 8 months . The other three patients are alive and well 1.9, 2.1, and 1.9 years after termination of antimicrobial therapy . CONCLUSIONS: We emphasize the necessity of specific diagnosis from appropriate surgical samples and conclude that in patients undergoing chemotherapy bony lesions caused by opportunistic microorganisms may be curable with aggressive surgery and prolonged medication.

JAMA, 1996 Jan 24-31, 275(4), 300 - 4
The challenges of emerging infectious diseases . Development and spread of multiply-resistant bacterial pathogens; Tenover FC et al.; Resistance is an emerging problem in human medicine and the effects of resistance are being noted on an ever-increasing scale . Whether it is treatment of nosocomial bacteremia in New York City or community-acquired dysentery in Central Africa, multiresistant organisms are diminishing our ability to control the spread of infectious diseases . Clearly, the rate at which resistant organisms develop is not solely a function of the use of antimicrobials in humans, but is also highly influenced by the use of these agents in veterinary medicine, animal husbandry, agriculture, and aquaculture, as has been emphasized at recent meetings sponsored by organizations such as Rockefeller University and the American Society for Microbiology, and in the report on bacterial resistance recently issued by the US Office of Technology Assessment . We have entered an era where both physicians and patients must take on the responsibility to use antimicrobials wisely and judiciously . Just as in the days at the turn of the century when the public was an integral part of establishing quarantines for infectious diseases, now again the public's cooperation must be sought for this latest threat to public health . The multiresistant organisms of the 1990s are a grim warning of the possibility of the postantibiotic era.

JAMA, 1996 Jan 17, 275(3), 234 - 40
Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in Hospitals . A challenge to hospital leadership; Goldmann DA et al.; OBJECTIVE--To provide hospital leaders with strategic goals or actions likely to have a significant impact on antimicrobial resistance, outline outcome and process measures for evaluating progress toward each goal, describe potential barriers to success, and suggest countermeasures and novel improvement strategies . PARTICIPANTS--A multidisciplinary group of experts was drawn from the following areas: hospital epidemiology and infection control, infectious diseases (including graduate training programs), clinical practice (including nursing, surgery, internal medicine, and pediatrics), pharmacy, administration, quality improvement, appropriateness evaluation, behavior modification, practice guideline development, medical informatics, and outcomes research . Representatives from appropriate federal agencies, the Joint Commission on Accreditation of Healthcare Organizations, and the pharmaceutical industry also participated . EVIDENCE--Published literature, guidelines, expert opinion, and practical experience regarding efforts to improve antibiotic utilization and prevent and control the emergence and dissemination of antimicrobial-resistant microorganisms in hospitals . CONSENSUS PROCESS--Participants were divided into two quality improvement teams: one focusing on improving antimicrobial usage and the other on preventing and controlling transmission of resistant microorganisms . The teams modeled the process a hospital might use to develop and implement a strategic plan to combat antimicrobial resistance . CONCLUSIONS--Ten strategic goals and related process and outcome measures were agreed on . The five strategic goals to optimize antimicrobial use were as follows: optimizing antimicrobial prophylaxis for operative procedures; optimizing choice and duration of empiric therapy; improving antimicrobial prescribing by educational and administrative means; monitoring and providing feedback regarding antibiotic resistance; and defining and implementing health care delivery system guidelines for important types of antimicrobial use . The five strategic goals to detect, report, and prevent transmission of antimicrobial resistant organisms were as follows: to develop a system to recognize and report trends in antimicrobial resistance within the institution; develop a system to rapidly detect and report resistant microorganisms in individual patients and ensure a rapid response by caregivers; increase adherence to basic infection control policies and procedures; incorporate the detection, prevention, and control of antimicrobial resistance into institutional strategic goals and provide the required resources; and develop a plan for identifying, transferring, discharging, and readmitting patients colonized with specific antimicrobial-resistant pathogens.

Structure, 1996 Jan 15, 4(1), 47 - 54
The structure of the substrate-free form of MurB, an essential enzyme for the synthesis of bacterial cell walls; Benson TE et al.; BACKGROUND: The repeating disaccharide and pentapeptide units of the bacterial peptidoglycan layer are connected by a lactyl ether bridge biosynthesized from UDP-N-acetylglucosamine and phosphoenolpyruvate in sequential enol ether transfer and reduction steps catalyzed by MurA and MurB respectively . Knowledge of the structure and mechanism of the MurB enzyme will permit analysis of this unusual enol ether reduction reaction and may facilitate the design of inhibitors as candidate next-generation antimicrobial agents . RESULTS: The crystal structure of UDP-N-acetylenolpyruvylglucosamine reductase, MurB, has been solved at 3.0 A and compared with our previously reported structure of MurB complexed with its substrate enolpyruvyl-UDP-N- acetylglucosamine . Comparison of the liganded structure of MurB with this unliganded form reveals that the binding of substrate induces a substantial movement of domain 3 (residues 219-319) of the enzyme and a significant rearrangement of a loop within this domain . These ligand induced changes disrupt a stacking interaction between two tyrosines (Tyr190 and Tyr254) which lie at the side of the channel leading to the active site of the free enzyme . CONCLUSIONS: The conformational change induced by enolpyruvyl-UDP-N- acetylglucosamine binding to MurB results in the closure of the substrate-binding channel over the substrate . Tyr190 swings over the channel opening and establishes a hydrogen bond with an oxygen of the alpha-phosphate of the sugar nucleotide substrate which is critical to substrate binding.

Eur J Biochem, 1996 Jan 15, 235(1-2), 394 - 403
Surface location and orientation of the lantibiotic nisin bound to membrane-mimicking micelles of dodecylphosphocholine and of sodium dodecylsulphate; Van Den Hooven HW et al.; The interaction of nisin, a membrane-interacting cationic polypeptide, with membrane-mimicking micelles of zwitterionic dodecylphosphocholine and of anionic sodium dodecylsulphate was studied . Direct contacts have been established through the observation of NOEs between nisin and micelle protons . Spin-labeled DOXYL-stearic acids were incorporated into the two micellar systems . From the paramagnetic broadening effects induced in the 1H-NMR spectrum of nisin it is concluded that the molecule is localized at the surface of the micelles . The interactions of nisin with zwitterionic and with anionic micelles resemble each other as do the nisin conformations {van den Hooven, H . W., Doeland, C . C . M., van de Kamp, M., Konings, R . N . H., Hilbers, C . W . & van de Ven, F . J . M . (1995) Eur J . Biochem . 235, 382-393} . The hydrophobic residues are immersed into the micelles and oriented towards the center, whereas the more polar or charged residues have an outward orientation . The micellar systems are considered to model the first step in the mechanism of antimicrobial action of nisin, this step is the binding of nisin to the cytoplasmic membrane of target bacteria . Detailed information on this initial binding step is obtained . Hydrophobic and electrostatic interactions appear to be involved in the nisin-micelle contacts . It is suggested that subtilin, a lantibiotic structurally related to nisin, has a comparable membrane interaction surface.

Eur J Biochem, 1996 Jan 15, 235(1-2), 382 - 93
Three-dimensional structure of the lantibiotic nisin in the presence of membrane-mimetic micelles of dodecylphosphocholine and of sodium dodecylsulphate; Van Den Hooven HW et al.; The lantibiotic nisin is a cationic, polycyclic bacteriocin of 34 residues, including several unusual dehydro residues and thioether-bridged lanthionines . The primary target of its antimicrobial action is the cytoplasmic membrane . Therefore the conformation of nisin when bound to membrane-mimicking micelles of zwitterionic dodecylphosphocholine and of anionic sodium dodecylsulphate was determined with high-resolution NMR spectroscopy . Structures were calculated on the basis of NMR-derived constraints with the distance-geometry program DIANA and were further refined by restrained energy minimization using X-PLOR . The conformation of nisin complexed to both types of micelles is the same, irrespective of the different polar head-groups of the detergents . The structure consists of two structured domains: an N-terminal domain (residues 3-19) containing three lanthionine rings, A, B and C; and a C-terminal domain (residues 22-28) containing two intertwined lanthionine rings numbered D and E . These domains are flanked by regions showing structural variability . Both domains are clearly amphipathic, a property characteristic for membrane-interacting polypeptides . The structures of the ring systems are better defined than those of the linear segments . The four-residue rings B, D and E of nisin all show a beta-turn structure, which is closed by the thioether linkage . The backbones of the rings B and D form type 11 beta-turns . Ring E resembles a type I beta-turn . Preceding the intertwined rings D (residues 23-26) and E (25-28) another type-II beta-turn is found formed by the residues 21-24, so that the C-terminal domain consists of three consecutive beta-turns . The structures of nisin in the micellar systems differ significantly from the previously determined (and now partially recalculated) structure in aqueous solution {van de Ven, F . J . M., van den Hooven, H . W., Konings, R . N . H . & Hilbers, C . W . (1991) Eur J . Biochem . 202, 1181-1188} in the first lanthionine ring around dehydroalanine 5.

Eur J Biochem, 1996 Jan 15, 235(1-2), 267 - 74
Nisin Z, mutant nisin Z and lacticin 481 interactions with anionic lipids correlate with antimicrobial activity . A monolayer study; Demel RA et al.; Monomolecular layers of lipids at the air/water interface have been used as a model membrane to study membrane interactions of the lantibiotic nisin . The natural lantibiotics nisin A and nisin Z proved to have a high affinity for the anionic lipids phosphatidylglycerol and bis(phosphatidyl)glycerol (cardiolipin) . The interaction with zwitterionic phopholipids or neutral lipids is very low at surface pressures higher than 32 mN/m . Nisin, nisin mutants and lacticin 481 show a remarkable correlation between anti-microbial activity and anionic lipid interaction . The results indicate that primarily the N-terminal part (residues 1-22) penetrates into the lipid phase . Reduction of the flexibility at positions 20-21 has a negative effect on monolayer interaction and activity . The C-terminal part is probably responsible for ionic interactions of nisin in monomeric or oligomeric form with anionic lipids . In mixtures of anionic and zwitterionic lipids maximal interactions are found at approximately 70 mol/100 mol anionic lipid . Gram-positive bacteria, which form the main target for nisin, are characterized by a high content of anionic lipids in the membrane . Monolayers formed of lipid extracts of bacteria sensitive to nisin were more strongly penetrated than those of bacteria relatively insensitive to nisin.

Ugeskr Laeger, 1996 Jan 15, 158(3), 261 - 4
{Bacteremia in the county of Ribe}; Scheel O et al.; The Department of Microbiology at the Central Hospital of Esbjerg, established in 1987, serves the five hospitals in Ribe county, Denmark . From early on, the department has endeavoured to guide the hospital's antimicrobial policy . In order to investigate whether this involvement had any measurable impact on the antimicrobial resistance pattern in our region, we compared the resistance patterns of 212 strains isolated from the blood of bacteraemic patients in 1988 to those of 317 strains isolated in 1992 . No increase in antibiotic resistance was revealed . This is noteworthy since new specialties have been established at the Central Hospital during this period, with an increased number of patients requiring antimicrobial therapy . It is important to survey the antibiotic resistance pattern closely, and that this is done locally.

Vet Rec, 1996 Jan 13, 138(2), 39 - 40
Actinobacillus suis septicaemia in two foals; Nelson KM et al.; A 24-hour-old Hackney ony filly developed signs of weakness, depression and a poor suck reflex, with harsh lung sounds over both fields, and a 48-hour-old Arabian colt from a normal birth which had sucked vigorously developed loose stools and became depressed, weak and anorectic . Both foals had serum IgG concentrations greater than 800 mg/dl, but each had a severe neutropenia with a left shift, and blood cultures from both of them yielded Actinobacillus suis . The A suis isolates had different antimicrobial susceptibility patterns and, in the case of the Arabian, the isolate was resistant to commonly used broad spectrum antimicrobial agents.

Biochem Biophys Res Commun, 1996 Jan 5, 218(1), 408 - 13
A novel antimicrobial peptide from Bufo bufo gargarizans; Park CB et al.; A potent and structurally novel antimicrobial peptide was isolated and characterized from the stomach tissue of Bufo bufo gargarizans, an Asian toad . The 39-amino acid peptide, named buforin I, was purified to homogeneity by heparin-affinity column and reverse-phase HPLC . The amino acid sequence of buforin I was identical in 37 of 39 amino-terminal residues of Xenopus histone H2A . The buforin I showed strong antimicrobial activities in vitro against a broad-spectrum of microorganisms and was found to be more potent than magainin 2 . In addition, a 21-amino acid peptide, named buforin II, which was derived from buforin I, showed more potent antimicrobial activities than buforin I.

Yao Xue Xue Bao, 1996, 31(6), 425 - 30
{Synthesis and antimicrobial activities of tetrahydro-2H-1,3,5-thiadiazine-2-thiones}; Chen GQ et al.; Ten 3-benzyl-5-substitued tetrahydro-2H-1,3,5-thiadiazine-2-thiones were synthesized and seven of them are reported for the first time . The structures of the compounds have been elucidated by UV, IR, H-NMR and elemental analysis . The in vitro activity of the compounds against 6 kinds of bacteria and 2 kinds of fungi was tested . The antimicrobial activities of all compounds are more potent than sulfadiazine sodium and less potent than norfloxacini . All compounds were found to be more active against gram-negative and less active against gram-positive bacteria and weak against fungi.

Akush Ginekol (Sofiia), 1996, 35(4), 49 - 50
{The therapeutic potentials of the vaginal antimicrobial preparation Chlorchinaldin}; Zlatkov V et al.; The aim of this study is the clinical testing of the vaginal wide-range, antimicrobial, quinolone--Chlorchinaldin/0,2/by POLFA, which has a strong antibacterial, antifungal, trichomonal and keratoplastic effect . The medicine was used on 43 patients with complaints of aggravated fluor . The clinical, colposcopic and microbiologic study showed: candidiasis--in 16 trichomoniasis--in 8, bacterial vaginalis--in 3 and anaerobic vaginitis--in 2 patients . The rest of the women (14) had various aerobic microbial findings . The treatment was daily using one vaginal tablet, every night for 10 days . A control examination was carried out one week after the any of therapy . The results showed a positive clinical effect, since in 67.4% there were negative microbiological findings . The lack of effect in cases with bacterial vaginosis and anaerobic vaginitis was painted out . These results give reason to believe that the wide antimicrobial range of Chlorchinaldin B will be complementary to the currently used drugs in the treatment of vaginal infections.

J Clin Dent, 1996, 7(2 Spec No), 46 - 9
Quanticalc assessment of the clinical scaling benefits provided by pyrophosphate dentifrices with and without triclosan; White DJ et al.; The Quanticalc (QC) dental scaler permits a quantitative assessment of the work used by professionals in calculus removal through the measurement of force dynamics and scaling strokes applied in calculus debridement . The purpose of this study was to use the QC to compare the clinical effects of two 5% pyrophosphate dentifrices on dental calculus in subjects following six-months' product use . Three-hundred forty-six subjects participated in a six-month, double-blind tartar control clinical trial involving traditional Volpe-Manhold Index (VMI) evaluations . Following the six-month VMI examinations, the subjects had a QC prophylaxis (scaling force measurements) . The three dentifrice treatment groups included a control dentifrice (NaF only, Crest); NaF dentifrice containing 5.0% pyrophosphate (Crest Tartar Control); and NaF dentifrice containing 5.0% pyrophosphate plus 0.28% triclosan (antimicrobial) . Subjects were balanced by baseline (pretest) VMI scores at the start of the trial . QC examinations revealed statistically significant reductions in total force and stroke number used by the therapist to scale the six anterior VMI teeth for subjects using the pyrophosphate tartar control dentifrices as compared to control dentifrice . The reduction in scaling effort amounted to almost 3 kg per scaling for subjects . QC results paralleled VMI reductions of calculus on the teeth and demonstrated that the use of 5% pyrophosphate dentifrices, with or without triclosan antimicrobial, results in significant reductions in the total (developed) force and strokes required by therapists in regular calculus debridement at a six-month interval . The clinical benefits of tartar control toothpastes may not only include reductions in cosmetically objectionable supragingival calculus, but in reducing professional effort in calculus debridement during regular prophylaxis.

J Clin Dent, 1996, 7(4), 90 - 5
Comparison of the clinical anticaries efficacy of a 1500 NaF silica-based dentifrice containing triclosan and a copolymer to a 1500 NaF silica-based dentifrice without those additional agents: a study on adults in Israel; Mann J et al.; Recent years have seen much work in the development of dentifrices containing the antimicrobial agent triclosan, a broad spectrum antibacterial agent manufactured for use in oral products by the Ciba-Geigy Corporation . Studies have shown that the incorporation of this agent into dental products, in combination with a PVM/MA copolymer (the non-proprietary designation for a polyvinylmethyl ether/maleic acid copolymer), can provide several important dental therapeutic benefits, including an antigingivitis effect . A considerable amount of the research on the therapeutic benefits of such dentifrices has been reported in the literature . The present study is a component of a large-scale program of clinical research to investigate the anticaries effectiveness of fluoride dentifrices containing 0.3% triclosan and 2.0% PVM/MA copolymer . The study included two treatment groups, each consisting of adults living near the Kiryat Gat area in Israel, who were assigned to the use of one of the following sodium fluoride (NaF) dentifrices: 1) a dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer in a 0.331% NaF/silica (1500 ppm F) base; or 2) a dentifrice containing 0.331% NaF/silica (1500 ppm F) . Conducted in accordance with the guidelines for caries clinical studies published by the Council on Dental Therapeutics of the American Dental Association, the study employed clinical diagnostic criteria as described in the August, 1987 National Institute of Dental Research (NIH/NIDR) publication . Dental radiographs were not employed . Principal comparisons of the dentifrices tested were implemented through the construction of 90% confidence intervals for the ratio of mean 3-year caries increments using Fieller's Theorem . Of those subjects who met the initial inclusion/exclusion criteria for this study, 1,296 were available for the 36-month examination . DFS (resp., DFT) increments over this period were 5.21 (1.30) for the triclosan/copolymer dentifrice, and 5.23 (1.39) for the dentifrice without those additives . The confidence interval calculations for both incremental DFS and DFT support the conclusion that a dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer in a 0.331% NaF/silica (1500 ppm F) base provides a level of anticaries efficacy which is "at least as good as" that provided by a dentifrice containing 1500 NaF/silica, without those additive agents . As such, the results of this clinical study clearly indicate that the addition of triclosan and a copolymer to a 1500 NaF/silica dentifrice does not compromise its anticaries efficacy.

J Clin Dent, 1996, 7(4), 85 - 9
Comparison of the clinical anticaries efficacy of an 1100 NaF silica-based dentifrice containing triclosan and a copolymer to an 1100 NaF silica-based dentifrice without those additional agents: a study on adults in California; Feller RP et al.; Recent years have seen much work in the development of dentifrices containing the antimicrobial agent triclosan, a broad spectrum antibacterial agent manufactured for use in oral products by the Ciba-Geigy Corporation . Studies have shown that the incorporation of this agent into dental products, in combination with a PVM/MA copolymer (the non-proprietary designation for a polyvinylmethyl ether/maleic acid copolymer), can provide several important dental therapeutic benefits, including an antigingivitis effect . Much research on the therapeutic benefits of such dentifrices has been reported in the literature . The present study is a component of a large-scale program of clinical research to investigate the anticaries effectiveness of fluoride dentifrices containing 0.3% triclosan and 2.0% PVM/MA copolymer . The study included two treatment groups, each consisting of adults living within a 50 mile radius of Loma Linda, California, who were assigned to the use of one of the following sodium fluoride (NaF) dentifrices: 1) a dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer in a 0.243% NaF/silica (1100 ppm F) base; or 2) a dentifrice containing 0.243% NaF/silica (1100 ppm F) . Conducted in accordance with the guidelines for caries clinical studies published by the Council on Dental Therapeutics of the American Dental Association, the study employed clinical diagnostic criteria as described in the August, 1987 National Institute of Dental Research (NIH/NIDR) publication . Dental radiographs were not employed . Principal comparisons of the dentifrices tested were implemented through the construction of 90% confidence intervals for the ratio of mean 3-year caries increments, using Fieller's theorem . Of those subjects who met the initial inclusion/exclusion criteria for this study, 1,542 were available for the 36-month examination . DFS (resp., DFT) increments over this period were 2.07 (0.63) for the triclosan/copolymer dentifrice, and 2.16 (0.68) for the dentifrice without those additives . The confidence interval calculations for both incremental DFS and DFT support the conclusion that a dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer in a 0.243% NaF/silica (1100 ppm F) base provides a level of anticaries efficacy which is "at least as good as" that provided by a dentifrice containing 1100 NaF/silica without those additive agents . As such, the results of this clinical study clearly indicate that the addition of triclosan and a copolymer to a 1100 NaF/silica dentifrice does not compromise its anticaries efficacy.

Antibiot Khimioter, 1996, 41(11), 7 - 13
{The effect of solar ultraviolet on the system of microorganisms-higher plant antibiotics, a natural phenomenon and a new approach to enhancing the efficacy of antibiotics}; Smirnov VV et al.; Under the effect of solar radiation some antibiotics of plant origin (phenylheptatriin, bakuchiol and others) showed antimicrobial phototoxicity differing by the spectrum and activity from the antibiotic action . The highest in vitro antimicrobial phototoxicity was observed with polyacetylene phenylheptatriin: the activation effect of solar radiation on it was due to UV-A and developed in gaseous phase or to a lesser extent in dispersed liquid phase . For comparison, 18 currently used antibiotics of various chemical structure were investigated and no phototoxicity under the effect of solar radiation with respect to the tested microbes was detected . In nature the phenomenon of antimicrobial phototoxicity of plant secondary metabolites due to the effect of solar radiation is probably of large scale . The study of the phenomenon is a new trend in biology (plant antibiotics and phytoncides, phytoimmunity, ecological and evolutionary microbiology, etc.) and a new approach to increase the efficacy of some antibiotics and to develop principally novel photochemotherapeutics for the treatment of infections in humans, animals and plants.

Biochem Cell Biol, 1996, 74(2), 283 - 7
Accumulation of natural and synthetic betaines by a mammalian renal cell line; Randall K et al.; Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria . All betaines accumulated less than glycine betaine . Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80% . Most substituted glycine betaine analogues accumulated to 2-5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels . Inhibition studies to distinguish the betaine ports were performed by the addition of proline . Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was . As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated . Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress . High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation . Because alpha-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.

Morfologiia, 1996, 110(6), 14 - 24
{The tissue and cell defense mechanisms of the oral mucosa}; Bykov VL; The modern concepts of tissue and cell defense mechanisms in oral mucosa are discussed . These mechanisms include (a) physical barriers (of epithelium and lamina propria), (b) non-specific antimicrobial humoral factors, (c) non-specific cellular defense mechanisms, (d) specific immune humoral and cell-mediated defense mechanisms, (c) saliva, containing both non-specific and specific antimicrobial factors . Special reference is given to antigen-presenting dendritic cells and various lymphocyte subpopulations both in epithelium and in lamina propria . The interaction of different cell and tissue defense mechanisms and their regional variations are briefly characterized.

Folia Microbiol (Praha), 1996, 41(4), 321 - 8
Antimicrobial activities of Streptomyces pulcher, S . canescens and S . citreofluorescens against fungal and bacterial pathogens of tomato in vitro; el-Abyad MS et al.; Thirty-seven actinomycete species isolated from fertile cultivated soils in Egypt were screened for the production of antimicrobial compounds against a variety of test organisms . Most of the isolates exhibited antimicrobial activities against Gram-positive, Gram-negative, and acid-fast bacteria, yeasts and filamentous fungi, with special attention to fungal and bacterial pathogens of tomato . On starch-nitrate agar, 14 strains were active against Fusarium oxysporum f.sp . lycopersici (the cause of Fusarium wilt), 18 against Verticillium albo-atrum (the cause of Verticillium wilt), and 18 against Alternaria solani (the cause of early blight) . In liquid media, 14 isolates antagonized Pseudomonas solanacearum (the cause of bacterial wilt) and 20 antagonized Clavibacter michiganensis ssp . michiganensis (the cause of bacterial canker) . The most active antagonists of the pathogenic microorganisms studied were found to be Streptomyces pulcher, S . canescens (syn . S . albidoflavus) and S . citreofluorescens (syn . S . anulatus) . The antagonistic activities of S . pulcher and S . canescens against pathogenic fungi were assessed on solid media, and those of S . pulcher and S . citreofluorescens against pathogenic bacteria in liquid media under shaking conditions . The optimum culture conditions were determined.

Cytogenet Cell Genet, 1996, 75(4), 240 - 2
Six antimicrobial peptide genes of the cathelicidin family map to bovine chromosome 22q24 by fluorescence in situ hybridization; Castiglioni B et al.; Six phage clones containing gene members of the family of antimicrobial peptides named cathelicidins, were mapped to bovine chromosome 22q24, by means of fluorescence in situ hybridization . The mapping data suggest the clustering of cathelicidins into a CATHL@ locus, in a similar manner as for beta-defensins, another family of antimicrobial peptides, defining the locus DEFB@ mapped to 27q13-->q14.

Int J Clin Pharmacol Res, 1996, 16(2-3), 73 - 6
Drug interaction between cyclosporine and two antimicrobial agents, josamycin and rifampicin, in organ-transplanted patients; Capone D et al.; In the post-transplant period, antimicrobial agents are often coadministered with cyclosporine (CsA) to treat the infections occurring in the immunosuppressed patients . These agents produce drug interactions with cyclosporine and can increase or reduce the blood concentration of the immunosuppressant . We report two cases of drug interaction between cyclosporine and two antimicrobial agents, josamycin and rifampicin, coadministered in a kidney-transplanted and a liver-transplanted patient, respectively . Josamycin increased the CsA blood levels by inhibiting the CsA metabolism through the hepatic cytochrome P450 enzymes . Conversely, rifampicin decreased the CsA blood levels by stimulating the same enzymatic system . When using these agents it is necessary to adjust the CsA doses to avoid risks of CsA toxicity or allograft rejection.

Quintessence Int, 1996 Jan, 27(1), 19 - 25
Clinical effect of subgingival tetracycline irrigation and tetracycline-loaded fiber application in the treatment of adult periodontitis; Trombelli L et al.; A controlled clinical trial was carried out to compare the clinical effect of combined antimicrobial-mechanical treatment modalities on moderate-to-deep periodontal pockets in patients with adult periodontitis . Twelve patients having at least three nonadjacent sites of periodontitis were included in the split-mouth study . Gingival Index, Plaque Record, bleeding on probing, probing depth, attachment level, and recession depth were recorded immediately before treatment . In the control site, supragingival and subgingival scaling was performed with an ultrasonic scaler . One experimental site received supplemental irrigation with 15 mL of a 100-mg/mL tetracycline solution, while the other received a tetracycline-loaded fiber after mechanical instrumentation . Fibers were left in place for 10 days . Reevaluation 30 and 60 days after treatment showed that all three treatment modalities were effective in improving clinical parameters . No adjunctive effect on the healing response was obtained by augmenting mechanical debridement with tetracycline.

Bull World Health Organ, 1996, 74(6), 553 - 9
Food fermentation: a safety and nutritional assessment . Joint FAO/WHO Workshop on Assessment of Fermentation as a Household Technology for Improving Food Safety; Motarjemi Y et al.; An assessment of the food-safety and nutritional aspects of lactic acid fermentation for the preparation of weaning food at the household level was carried out during a Joint FAO/WHO Workshop held in Pretoria, South Africa, in December 1995 . In particular, lactic acid fermentation was evaluated as a part of food preparation processes involving other operations such as soaking, cooking, and the germination of cereal grains . The use of germinated cereals is of particular interest since they can be used to prepare semi-liquid porridges of high nutrient density . After reviewing the present state of knowledge concerning the antimicrobial effects of the lactic acid in fermented foods, and the nutritional benefits of fermentation and the use of germinated cereals, the Workshop made an inventory of gaps in current knowledge and priorities for further research . High priority areas for research include the following: the effect of lactic acid fermentation on viruses, parasites, certain bacteria, and mycotoxins; certain physiological and nutritional effects of the consumption of fermented foods; the characterization and optimization of fermentation processes and the development of appropriate fermentation starters; and risk mitigation using the Hazard Analysis Critical Control Point system, the health education of food handlers, and efforts to change the consumer perception of fermented foods.

Scand J Infect Dis Suppl, 1996, 101, 14 - 6
Melioidosis; a treatment challenge; Chaowagul W; Ceftazidime has reduced the mortality of severe disease by half, but melioidosis remains a difficult and expensive infection to treat . Empirical treatment of septicemia with aminoglycosides combined with penicillin, ampicillin, or second-generation cephalosporins is ineffective . The response to appropriate antibiotic treatment is slow, and most patients require a minimum of 2 weeks of high-dose parenteral treatment . Large abscesses should be drained if possible . Ceftazidime remains the drug of choice, but co-amoxyclav is an effective alternative (although treatment failure rates are slightly higher), and preliminary experience with imipenem is encouraging . The relapse rate following 8 weeks of treatment is approximately 28%, and this is reduced to 9% with 20 weeks of treatment . The relapse rate is determined by the extent of the infection and not the underlying predisposing condition . Resistance to all treatment antimicrobials has been documented, but this has not proved a major problem to date . Patients who survive the acute phase of melioidosis require life-long follow-up.

Scand J Infect Dis Suppl, 1996, 101, 9 - 13
Antibiotics, cytokines, and endotoxin: a complex and evolving relationship in gram-negative sepsis; Horn DL et al.; Compelling experimental evidence now exists that antimicrobial agents induce the release of endotoxin from Gram-negative bacteria during the process of bacteriolysis . Different antimicrobial classes, particularly those which act upon the outer membrane of bacteria, vary in the amount of free endotoxin released from Gram-negative organisms . Despite this in vitro evidence, clinically important consequences of antibiotic-induced endotoxin release have yet to be consistently documented . Complexities in the host-pathogen interactions during actual infection with Gram-negative bacteria may account for the difficulties in demonstrating this phenomena in vivo . This brief review analyses these interactions and defines clinical settings where antibiotic-induced endotoxin release may prove to be clinically relevant.

Nephrol Dial Transplant, 1996, 11 Suppl 9, 31 - 3
Chemotherapy and immunomodulation in the elderly; Fraschini F et al.; Ageing brings about an impairment of all body functions . Any antimicrobial and oncological treatment must take into account the senescent condition of the patient . Aged people are considered an immunodepressed population and oncotherapy has envisaged the use of components of the immune system . Our hope is to dispose shortly such neuroimmunomodulators as to be able to activate the impaired immune system which is present in the elderly.

Antibiot Khimioter, 1996, 41(10), 22 - 7
{Comparison of the results of determining antibiotic sensitivity on AGV medium and on Mueller-Hinton and isosensitest agars}; Kozlov RS et al.; To evaluate the adequacy of AGV agar for antimicrobial susceptibility testing, the susceptibility of a range of bacteria to 10 antimicrobials on AGV, Mueller-Hinton and isoSensitest agars, all supplemented with 5 per cent lyzed horse blood was determined . Disc tests were used . In general, AGV agar gave identical susceptibility results to Mueller-Hinton and isoSensitest agars for common gram positive and gram negative bacteria with most of the tested microbials excluding sulphonamides and trimethoprim . With those latter antimicrobials inhibition zones for susceptible organisms were not formed on AGV agar whereas large zones were present on Mueller-Hinton and isoSensitest agars . This discrepancy probably can be explained by the presence of high levels of thymidine in AGV agar; too high to be corrected even by the addition of 5 per cent lysed horse blood . AGV agar is possible to use for susceptibility testing with most of the microbials excluding trimethoprim and sulphonamides.

Ann Chir Main Memb Super, 1996, 15(4), 238 - 43
{A case of arthritis of the wrist caused by Mycobacterium marinum . Review of the literature}; Flisch CW et al.; The authors report the case of a woman aquarium keeper who developed septic arthritis of her right wrist due to Mycobacterium marinum . Clinical status and history, histopathologic and microbiologic characteristics are reviewed and discussed . The authors emphasize the importance of urgent and aggressive surgery combined with antimicrobial chemotherapy.

Neuropharmacology, 1996, 35(9-10), 1271 - 7
Evidence that a hybrid molecule of norfloxacin and biphenylacetic acid is a potent antagonist at the GABAA receptor; Imanishi T et al.; The combination of some fluorinated quinolone antimicrobials and certain non-steroidal anti-inflammatory drugs (NSAIDs), such as fenbufen, has been reported to elicit serious convulsions in humans . Fluoroquinolones, including norfloxacin (NFLX) and NSAIDs synergistically inhibit GABAA receptors . The mechanism(s) of the synergism, however, at present remains unclear . In the present study, the hypothesis that NFLX and biphenylacetic acid (BPA), an active metabolite of fenbufen, undergo an intermolecular interaction to produce a more potent GABAA antagonist, was investigated by examining the effects of two hybrid molecules of NFLX linked with BPA on GABA-evoked whole cell currents, recorded from rat hippocampal neurons using the perforated-patch clamp technique . Hybrid-1, with a -CONH(CH2)3- chain between NFLX and BPA, inhibited the GABA response more potently than co-treatment with NFLX and BPA . In contrast, hybrid-2 with a -CONH- chain between NFLX and BPA, exhibited only a weak inhibition of the GABA response . The characterization of the inhibition of the GABA response in the presence of hybrid-1 was similar to that of the combination of NFLX and BPA regarding the following: (1) there was a rightward parallel shift of the concentration-response curve of GABA at lower concentrations and a suppression of the maximal response to GABA at higher concentrations; (2) it was voltage-independent; and (3) there was no influence on the reversal potential of the GABA response . These results therefore suggest that NFLX and BPA interact with the GABAA receptor at nearby sites and thus suppress the GABA response.

Microbiol Immunol, 1996, 40(12), 899 - 905
Rapid increase of pneumococcal resistance to beta-lactam and other antibiotics in isolates from the respiratory tract (Nagasaki, Japan: 1975-1994); Rikitomi N et al.; The susceptibility of 101 pneumococcal isolates from the respiratory tract during 1991-1994 was examined and compared with the susceptibility of isolates over the period of 1975-1990 . A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents . During 1991-1994, 38% of all the isolates were resistant to penicillin . The rates of resistance during this period were 16-23% for three newer cephalosporins, 18% for imipenem, 69% for tetracycline, 31% for erythromycin, 20% for chloramphenicol and 9% for clindamycin . The use of antibiotics within one month prior to pneumococcal isolation was correlated with penicillin resistance (P < 0.05) . Serotyping of the isolates by antiserum revealed differences in predominant types between penicillin-resistant (19F, 23F,4) and -susceptible isolates (15, 4, 11A) . Our data suggests that anti-pneumococcal antibiotics should be carefully chosen on the basis of susceptibility tests.

Zentralbl Chir, 1996, 121(9), 768 - 72; discussion 772-3
{Clinical experience with a new antimicrobially coated InterGard-IgK/AM vascular prosthesis in surgical treatment of deep wound infection with involvement of the synthetic bypass: report of 2 cases}; Manouguian S; We report 2 cases of infected vascular prosthesis, where the infected alloplastic material was removed and the revascularisation of the lower extremity was done by implantation of the new antimicrobial surface-coated InterGard prosthesis in the area of the former infected graft . An extra-anatomical bypass was not promising in these cases . Clinical, bacteriological and granulocyte-scintigraphic examinations have provided no evidence for persisting infection 12 and 11 months after implantation of this prosthesis . We are aware that the postoperative observation periods are too short to allow definitive assessment . Nevertheless we still consider that this prosthesis means a new and promising option in the treatment of infected vascular graft.

Antibiot Khimioter, 1996, 41(9), 60 - 7
{A method of sequential (intravenous and oral) use of ofloxacin in the treatment of patients with infections of organs of the peritoneal cavity}; Savitskaia KI et al.; Clinico-laboratory estimation of the efficacy and tolerance of ofloxacin used in succession, at first intravenously and then orally, in the treatment of 15 patients with infection of the abdominal cavity was performed . It was shown that after the use for a period of 10 years ofloxacin preserved its high antimicrobial activity against gram-positive and gram-negative organisms with multiple drug resistance and remained superior to the majority of broad spectrum antimicrobial agents by the number of susceptible isolates . The successive use of ofloxacin proved to be highly efficient . The total efficacy of the drug amounted to 80 percent and no side effects were recorded . The analysis of the microbiological state of the antiinfectious resistance system (AIRS) showed that the dysbiotic lesions on the mucosa of the upper respiratory tracts and large intestine detected in all the patients before the treatment with ofloxacin remained after the treatment . However, a change in the microflora responsible for dysbacteriosis was observed . The investigation of the immunological status of the AIRS suggested that the good and satisfactory results of the therapy with ofloxacin could to a significant extent be due to the proportion of the active neutrophils.

Antibiot Khimioter, 1996, 41(9), 11 - 2
{Use of ofloxacin in infections which do not readily respond to treatment}; Zalaudek G; The properties of ofloxacin such as a new mechanism of action, broad spectrum and high antimicrobial activity, 100-percent bioavailability and rapid penetration to the body tissues, etc . which defined the antibiotic high efficacy in the therapy of infections difficult for the treatment with other antibacterial drugs are presented . The intensive use of ofloxacin within the last years was no accompanied by an increase in the resistance of the main pathogens to it . High concentrations of ofloxacin provided in the nasa sinuses and the antibiotic broad spectrum including the majority of gram-positive and gram-negative microbes conditioned its high therapeutic efficacy in the treatment of chronic sinusitis and otitis . Successful treatment of tuberculosis resistant of other drugs with ofloxacin supplementing the standard 3-component combination of rifampicin, isoniazid and pyrazinamide was shown possible . By its bioavailability ofloxacin proved to be superior to ciprofloxacin and its oral dose of 200 mg was equivalent by the efficacy to the oral dose of 500 mg of ciprofloxacin . The usual regimen of the ofloxacin use in the treatment of severe infections was 400 mg intravenously twice a day . The further oral use in a dose of 400 mg once a day was possible after the infectious process stabilization.

Boll Chim Farm, 1996 Jan, 135(1), 18 - 23
Syntheses and pharmacological properties of new 2-aminobenzimidazole derivatives; Nawrocka W; The paper reports the structures, syntheses and pharmacological properties of new compounds having a 2-aminobenzimidazole group . They exhibit various activities: histamine H1- and H2-receptors blocking activities, antilipidemic and platelet antiaggregatory, anti-inflammatory and analgesic properties, antimicrobial, fungicidal, parasiticide, antiarrythmic activity and muscle relaxant, comparable to those of drugs used in therapy.

Diagn Microbiol Infect Dis, 1996 Jan, 24(1), 37 - 41
Antimicrobial susceptibility testing of Helicobacter pylori . Comparison of E-test, broth microdilution, and disk diffusion for ampicillin, clarithromycin, and metronidazole; Hachem CY et al.; The optimal method for the determination of the minimum inhibitory concentration (MIC) of antimicrobials against Helicobacter pylori has not been established . The epsilometer agar diffusion gradient test (E-Test; AB Biodisk, Solna, Sweden) was compared with broth microdilution, the reference method, and disk diffusion for the antimicrobial susceptibility testing of 122 clinical isolates of H . pylori to ampicillin, clarithromycin, and metronidazole . Isolates were considered to be resistant when the MIC values was > 8 micrograms/ml for either ampicillin or metronidazole and > 2 micrograms/ml for clarithromycin . For an individual isolate, the MICs for ampicillin and clarithromycin determined by broth microdilution and the E-test were highly reproducible, with replicate results being within +/- 1 log2 dilution . The correlation between the MICs determined by E-test and broth microdilution was excellent for both ampicillin and clarithromycin (90.1% and 88.5% were within +/- log2 dilution, and 98.3% and 96.7% of the values were within +/- 2 log2 dilution, respectively) . In no instance did the interpretation of "sensitive" or "resistant" differ . Conversely, only 70.5% of the E-test results of metronidazole were within +/- 1 log2 dilution of the broth microdilution results . In addition, 15 (12.3%) of the H . pylori isolates interpreted as resistant by the E-test were sensitive by the broth microdilution method . All discrepancies occurred when the E-test MIC values fell between 8 and 32 micrograms/ml . The results of the ampicillin and clarithromycin disk diffusion assay correlated 100% with the results of the broth microdilution . However, these data suggest that when the E-test MIC results of metronidazole yield values between 8 and 32 micrograms/ml, the MIC should be reevaluated by another method.

J Nat Prod, 1996 Jan, 59(1), 62 - 5
Chlorochimaphilin: a new antibiotic from Moneses uniflora; Saxena G et al.; A study of the antimicrobial compounds from Moneses uniflora resulted in the isolation of a novel compound, 8-chloro-2,7-dimethyl-1,4-naphthoquinone (8-chlorochimaphilin) (1), together with chimaphilin (2) and 3-hydroxychimaphilin (3) as the antimicrobial components . 2,7-Dimethyl-1,3-dihydroxynaphthyl 4-O-alpha-L-rhamnopyranoside (4) and 2,7-dimethoxy-1,4,8-trihydroxynaphthalene (6) were also isolated and identified.

Vestn Ross Akad Med Nauk, 1996, (9), 30 - 3
{Design of topically resorptive interferon drugs}; Shchekanova SM et al.; The current data on the development and design of topically resorptive interferon drugs are summarized . In many cases it is advisable to use topically resorptive interferon agents which allows them to topically affect a clinical process, to avoid negative sequelae seen when high-dose interferon is unjustifiably systematically given, by reducing its use to a minimum . Interferon is known to be one of the best antiviral agent, besides, it produces marked antimicrobial and antitumor effects . Whether interferon as a component of drugs can be stabilized by axillaries of various chemical nature which act as stabilizers, promoters, and carriers is dealt with . The topically resorptive formulations designed in terms of biopharmaceutical factors are described . The advantages of topically resorptive agents over other drugs are shown and hence they can be widely used in practical medicine.

Khirurgiia (Sofiia), 1996, 49(4), 9 - 11
{The pathophysiological and intensive care-resuscitation aspects of septic shock}; Vasilev D et al.; Sepsis and septic shock continue to be the most common causes of death and multiple organ failure among patients in intensive care units . The standard therapeutic regimens include surgical removal of the source of sepsis, antimicrobial therapy, optimizing oxygenation, volume resuscitation, and treatment with catecholamines . The ever extending knowledge of the pathophysiological role played by cytokines and nitrous oxide in septic shock promote the efforts to control their synthesis and pharmacologic action in clinical situations . New therapeutic approaches have become available, including the administration of high doses immunoglobulins, monoclonal antibodies against endotoxin, pentoxilfyline and nitrous oxide inhibitors . Based on the encouraging findings, controlled clinical studies are undertaken to assay with precision their clinical efficacy.

Prog Mol Subcell Biol, 1996, 15, 154 - 89
Clotting and immune defense in Limulidae; Muta T et al.; The blue blood of the horseshoe crab contains a sophisticated defense system very sensitive to pathogens or foreign materials . The hemocytes circulating in the hemolymph detect trace amounts of LPS molecules on the invading microorganisms and respond quickly to release the granular components into the external milieu . The coagulation system composed of three serine protease zymogens, factor C, factor B, and proclotting enzyme, and a clottable protein, coagulogen, is activated by LPS to form insoluble coagulin gel . The coagulation system also responds to beta-(1,3) glucan through the activation of unique heterodimeric serine protease zymogen, factor G . The pathogens are, thus, engulfed in the gel and subsequently killed by antimicrobial substances with various specificities, which are also released from cells . The horseshoe crab has developed two kinds of serine protease zymogens as biological sensors, factor C and factor G, which are responsive to LPS and beta-(1,3) glucan on the surface of Gram-negative bacteria and fungi, respectively . These are possible invaders for horseshoe crabs and also for most animals including humans . This novel heterodimeric serine protease zymogen, factor G, may open a new way to develop an innovative assay system to quantitate beta-(1,3) glucans . Furthermore, these LPS and beta-(1,3) glucan sensitive factors could be utilized as a unique tool to analyze other biological reactions caused by LPS or the glucan . Although the coagulation reaction in horseshoe crabs is famous, it is not the only defense mechanism of this animal . Many agglutinins are present either in hemolymph plasma or in the cell . The hemolymph plasma also has cytolytic activity against foreign cells . These cellular and humoral defense systems, in concert, defend themselves from invading foreign organisms . Such a sophisticated defense system has allowed the horseshoe crab to survive for more than 200 million years on the earth . Horseshoe crabs are often called inverted question markliving fossils." However, they are not fossils . They are living.

Transpl Int, 1996, 9 Suppl 1, S399 - 402
Costs of drugs used after renal transplantation; Hilbrands LB et al.; There are no detailed data on the relative contributions to overall health care costs of the various drugs that are commonly used in renal transplant patients . We performed a cost analysis in 122 patients, using the medical records and our hospital administration service as data sources, for all health care-related costs during the first year after renal transplantation . During the first 3 months all patients were on cyclosporine (CsA) and prednisone . Subsequently, they were randomly allocated to CsA monotherapy or to conversion from CsA to azathioprine . Cost of drugs comprised about 25% of total health care expenses . In CsA-treated patients, the following costs per patient per year were calculated: CsA, DFL 9929 (1 DFL is about US$0.60; 67.5% of total drug costs); antilymphocyte agents, DFL 2613 (17.8%); other immunosuppressive drugs, DFL 455 (3.1%); antimicrobial agents, DFL 687 (4.7%); antihypertensive drugs, DFL 467 (3.2%); remaining drugs, DFL 554 (3.8%) . Conversion from CsA to azathioprine resulted in a decrease in mean drug costs for the remainder of the first posttransplant year of DFL 4597 (P < 0.01) . Although the incidence of acute rejections tended to be higher after steroid withdrawal than after conversion (39% versus 26%, not significant), the costs of anti-rejection therapy, hospitalization, and laboratory services did not differ . We conclude that CsA is the main determinant of overall drug costs . When compared to CsA monotherapy, conversion from CsA to azathioprine at 3 months after transplantation may result in subsequent cost savings of about DFL 5000 per patient per year without a higher incidence of rejection or graft loss.

Cancer Detect Prev, 1996, 20(6), 590 - 6
Modulation of nitrate-nitrite conversion in the oral cavity; van Maanen JM et al.; The formation of nitrite from ingested nitrate can give rise to the induction of methemoglobinemia and endogenous nitrosation resulting in the formation of carcinogenic N-nitroso compounds . We investigated the possibility of modulation of the conversion of nitrate into nitrite in the oral cavity in order to seek ways of reducing the formation of the deleterious nitrite . We investigated the effectiveness of several mouthwash solutions with antibacterial constituents on the reduction of nitrate into nitrite in the oral cavity . In 15 studied subjects, the mean percentage of salivary nitrate reduced to nitrite after ingestion of 235 mg (3.8 mmol) nitrate was found to be 16.1 +/- 6.2% . The use of an antiseptic mouthwash with active antibacterial constituent chlorhexidine resulted in an almost complete decrease of the mean percentage of reduced nitrate, to 0.9 +/- 0.8% . Mouthwash solutions with antibacterial component triclosan or antimicrobial enzymes amyloglucosidase and glucose oxidase did not affect the reduction of nitrate into nitrite . A toothpaste with active components triclosan and zinc citrate with synergistic antiplaque activity was also without effect . Use of a pH-regulating chewing gum resulted in a rise in the pH in the oral cavity from 6.8 to 7.3 . At 30 min after nitrate ingestion, this rise was accompanied by a significant increase in the salivary nitrite concentration, which might be explained by the pH being close to the optimal pH for nitrate reductase of 8 . In conclusion, a limited number of possibilities of modulation of the conversion of nitrate into nitrite in the oral cavity are available.

Medicina (B Aires), 1996, 56(2), 115 - 8
{Serum bactericidal rate . Methodological proposal to predict the efficacy of antimicrobial therapy}; Riera EB et al.; Several in vitro techniques have been developed, which are able to quantify the bactericidal activity of a determined antibacterial drug against an infective agent . The Serum Bactericidal Rate (SBR) is proposed as a complementary technique for the determination of the "killing curve", the serum bactericidal test or the minimal bactericidal concentration . SBR takes into account the most advantageous features of both of them . SBR is based on quantifying at different times the survival of the bacterial inoculum exposed to the patient's serum . Thus, bactericide speed is evaluated in the first hours of contact with the microorganism (as in the "killing curve"), but taking into account drug concentrations which have been reached by the patient (as in the serum bactericidal test) . Preliminary assays suggest that SBR may have greater capacity to discriminate an infectious agent in answer to different therapeutic schemes than other determinations, although prospective studies are required to evaluate its predictive value.

Retina, 1996, 16(5), 383 - 7
Recurrent ocular toxoplasmosis in patients treated with systemic corticosteroids; Morhun PJ et al.; PURPOSE: The authors discuss a possible relationship between systematic corticosteroid use and reactivation of ocular toxoplasmosis . METHODS: Patients were identified who developed foci of recurrent toxoplasmic retinochoroiditis while being treated with systemic corticosteroids . Case histories were reviewed retrospectively . RESULTS: During a 10-year interval, three patients were identified at the University of California, Los Angeles, who had been receiving systemic corticosteroid therapy (dose range, 0.27-1.23 mg/kg/day) when they developed recurrent toxoplasmic retinochoroiditis . Disease occurred at intervals of 20 days to approximately 1 year after start of corticosteroid therapy . Lesions were typical in appearance, course, and manner in which they responded to antimicrobial therapy . CONCLUSION: Recurrent toxoplasmosis in patients receiving corticosteroid therapy probably is uncommon . These cases do not confirm a causal relationship between corticosteroid use and initiation of disease recurrence.

Acta Vet Hung, 1996, 44(2), 153 - 63
The role of feed protein quality in reducing environmental pollution by lowering nitrogen excretion . III . Strategies of feeding: a review; Hegedus M; To meet the requirements of pigs a better supply of amino acids can be achieved by using ileal digestibility data of feed ingredients in least-cost feed formulation . Digestibility of amino acids can be improved by addition of multienzyme products, antimicrobial additives and probiotics . Protein accretion may be positively influenced by beta-adrenergic agonists . An adequate ratio of protein to dietary energy is essential to achieve optimal protein utilization . Nitrogen output can be minimized by improving feed efficiency and by eliminating antinutritional substances with adequate processing . The use of the ideal protein concept helps to minimize nitrogen excretion . Management and animal hygiene also have a significant impact on the overall nitrogen balance in animal production.

Eur J Surg Suppl, 1996, (576), 50 - 2
Duration of antibiotic treatment in surgical infections of the abdomen . Postoperative peritonitis; Bohnen JM; Postoperative peritonitis is potentially lethal and is usually caused by leakage of gut contents . Successful management depends on early diagnosis and treatment which require clinical suspicion and aggressive diagnostic imaging . Treatment consists of fluid and nutritional resuscitation, peritoneal toilet, control of gut leakage and initiation of antimicrobial therapy . Since delay in diagnosis is common, antimicrobial treatment is usually begun when the infection has become well developed . Experimental evidence has shown that in some settings antimicrobial agents do not perform as well in later stages of infection but whether this applies to peritonitis is not known . The optimal duration of antimicrobial therapy has not been studied specifically in postoperative peritonitis . Arguments for prolonged treatment include the potential for greater killing of bacteria in patients who have severe infections . Arguments against prolongation of therapy include the lesser role of antibiotics compared with operative management, doubt about the value of antibiotics' ability to kill bacteria at later stages of infection and the significant number of infective and non-infective complications of drug therapy . Limitation of antimicrobial treatment to no more than seven days is advocated . Persistent clinical signs, fever, or leucocytosis should prompt a search for a drainable focus of infection in the abdomen or treatable site elsewhere.

Eur J Surg Suppl, 1996, (576), 33 - 5
Duration of antibiotic treatment in surgical infections of the abdomen . The future: randomised prospective studies; Solomkin JS; The important questions are: what is the most efficient, least costly, and least hazardous way of providing antimicrobial therapy to postoperative patients? These questions, and the answers, are integral to the practice of medicine . I discuss a few pitfalls associated with antibiotic studies and suggest potential solutions . I urge doctors interested in these problems to focus on establishing the hospital systems needed to provide continuous feedback, rather than sporadic information driven by collegial requests.

Eur J Surg Suppl, 1996, (576), 24 - 8
Cardiovascular adverse effects of antimicrobials in complex surgical cases; Kuenneke M et al.; Previously undescribed adverse effects of antibiotics on the cardiovascular system were described in complex surgical cases . Hypotension, bradycardia and tachycardia were seen in a randomised clinical trial, and confirmed in a randomised experiment with piglets, and in a study with isolated vascular tissue that was exposed simultaneously to antibiotics, endotoxin, and later on histamine at histamine H1-receptors . These findings may influence indications and duration for antimicrobial therapy, and support the concept of "minimal" postoperative antibiotic therapy in emergency abdominal operations.

Eur J Surg Suppl, 1996, (576), 19 - 23
Duration of antibiotic treatment in surgical infections of the abdomen . Pharmacokinetic basis for short courses of antimicrobial therapy; Wittmann DH; Pharmacokinetics relate to distribution of drugs between various body compartments; pharmacodynamics pertain to antimicrobial action at the site of infection . In this review the pharmacokinetic/pharmacodynamic justification for short courses of antibiotics is presented . A simplified pharmacokinetic model for most antimicrobials divides the body into a central compartment, the bloodstream, and a peripheral compartment consisting of extravascular fluid . The latter is the site of most infections . Adequate drug concentrations have to be achieved and sustained within the peripheral compartment to kill bacteria, or at least to inhibit bacterial growth and enhance killing by host defence mechanisms . Laboratory data with standardised bacterial inocula suggest that bacteria need to be exposed to either the minimal inhibitory concentration (MIC) or the minimal bactericidal concentration (MBC) for 16-24 hours to inhibit growth or to kill 99.9% of bacteria, respectively . Antimicrobials that yield tissue compartment concentrations in excess of the MIC or MBC, therefore, may be equally effective, and eliminate bacteria within 16-24 hours, once operation has reduced the bacterial inoculum . From this standpoint pharmacokinetics variables such as the time above MIC, which express the antibiotic-microbial-time relationship, become more important . The duration of administration, therefore, must be tailored by clinical judgement to the magnitude of the remaining bacterial inoculum, and the condition of the patient . Pharmacokinetics indicate that courses of treatment can be shortened.

Acta Otolaryngol Suppl, 1996, 525, 68 - 72
Antimicrobial ear drop medication therapy; Suzuki K et al.; Ear drop medication, which delivers a concentrated drug directly to the lesion, is a useful therapeutic approach in that it provides enhanced efficacy at the affected site while avoiding the side effects accompanying systemic administration of the drug . In the present study we evaluated the effectiveness of three recently developed antibacterial agents with no proven ototoxicity: cefmenoxime (CMX), fosfomycin (FOM), and ofloxacin (OFLX) . The bacterial eradication rate, the bacterial persistence rate, and the fungal infection rate were 91.4%, 2.9% and 5.7% for CMX, 71.2%, 20.9% and 7.0% for FOM, and 88.4%, 4.7% and 7.0% for OFLX, respectively . For lomefloxacin (LFLX) (with one week of treatment), the eradication rate and the persistence rate were 80.2% and 19.8%, respectively . It is advisable to limit the duration of treatment with the same otic drug; using the drug for more than 4 weeks at the most should be avoided.

J Biochem (Tokyo), 1996 Jan, 119(1), 85 - 94
A cysteine protease inhibitor stored in the large granules of horseshoe crab hemocytes: purification, characterization, cDNA cloning and tissue localization; Agarwala KL et al.; A cysteine protease inhibitor with an apparent Mr = 12,600, designated limulus (L)-cystatin, was isolated from hemocyte lysates of the Japanese horseshoe crab (Tachypleus tridentatus), using two steps of chromatography, including dextran sulfate-agarose, and carboxymethylated papain-agarose . L-cystatin inhibits amidolytic activity of papain by forming a noncovalent 1:1 complex with an equilibrium constant (Ki) of 0.08 nM . It also inhibits cathepsin L (Ki = 0.17 nM) and ficin (Ki = 0.52 nM), but not argingipain (a bacterial cysteine protease) and calpains . A cDNA for L-cystatin was isolated and the open reading frame coded for a mature protein of 114 amino acids, of which 99 residues were confirmed by peptide sequencing . L-cystatin shows significant sequence identities to members of the family 2 cystatin, such as bovine colostrum cystatin (33%) and human cystatin S (31%) . Northern blotting revealed expression of the mRNA in hemocytes and slightly in heart but expression was negligible in hepatopancreas, intestine, stomach, and muscle . Immunoblotting revealed the localization to be in the large granules of hemocytes . Furthermore, L-cystatin has an antimicrobial activity against Gram-negative bacteria, which is much stronger than that of chicken egg white cystatin . These data suggest that the large granule-derived L-cystatin serves synergistically to accomplish an effective defense against invading microbes, together with other defense molecules that are released in response to external stimuli.

Semin Gastrointest Dis, 1996 Jan, 7(1), 41 - 8
Whipple's disease; Marth T et al.; Whipple's disease (WD) is a rare systemic disease caused by infection with the recently identified actinomycetes, Tropheryma whippelii . The disorder affects mostly middle-aged men, and the major clinical features are weight loss, arthropathy, and diarrhea; other symptoms, caused by systemic infection, are not infrequent . The diagnosis is usually established by duodenal biopsy, which shows the pathognomonic periodic acid Schiff-positive infiltrates in the lamina propria . In addition, RT-polymerase chain reaction of tissue specimens can be used to verify the presence of T whippelii . In most cases, patients can be successfully treated by prolonged administration of antimicrobials, such as trimethoprim-sulfamethoxazole . The unusual chronic-relapsing course of the disease, the predisposition of middle-aged, HLA-B27-positive men for WD, and other characteristics of the disease imply that host factors are involved in the etiopathogenesis of WD . Indeed, it has been shown that patients with WD have suppressed delayed-type hypersensitivity responses in vivo and decreased in vitro T-cell responses, eg, to phytohemagglutinin and concanavalin A . In addition, serum-suppressor factors and shifts in T-cell subpopulations have been found . Perhaps most importantly, WD macrophages have a decreased ability to degrade intracellular microorganisms and patients have reduced numbers of circulating cells expressing CD11b, a cell adhesion and complement receptor molecule on macrophages involved in the activation of intracellular killing of pathogens . Most of those immunologic alterations also occur in patients with longstanding clinical remission, suggesting that this subtle host-defense defect plays an important role in disease pathogenesis.

Allergol Immunopathol (Madr), 1996 Jan-Feb, 24(1), 25 - 8
{Asthma and cyclic neutropenia}; Salazar Cabrera AN et al.; We report a male with history of recurrent infections (recurrent oral aphtous disease {ROAD}, middle ear infections and pharyngo amigdalitis) every 3 weeks since he was 7 months old . At the age of 3 years cyclic neutropenia was diagnosed with cyclic fall in the total neutrophil count in blood smear every 21 days and prophylactic antimicrobial therapy was indicated . Episodic events every 3 weeks of acute asthma and allergic rhinitis were detected at the age of 6 years old and specific immunotherapy to Bermuda grass was given during 3 years with markedly improvement in his allergic condition but not in the ROAD . He came back until the age of 16 with episodic acute asthma and ROAD . The total neutrophil count failed to 0 every 21 days and surprisingly the total eosinophil count increased up to 2,000 at the same time, with elevation of serum IgE (412 Ul/mL) . Specific immunotherapy to D.pt . and Aller.a . and therapy with timomodulin was indicated . After 3 months we observed clinical improvement in the asthmatic condition and the ROAD disappeared, but the total neutrophil count did not improve . We present this case as a rare association between 2 diseases with probably no etiological relationship but may be physiopatological that could help to understand more the pathogenesis of asthma.

Rev Med Interne, 1996, 17(7), 571 - 5
{Actinomycosis and non-Hodgkin's malignant lymphoma: fortuitous association?}; Guerci AP et al.; Two cases of actinomycosis associated with non Hodgkin's lymphoma (NHL) are reported . In one case, low grade NHL was diagnosed many years after actinomycosis because of the persistence of abdominal lymphadenopathy in spite of antibiotic therapy . In the second case, hepatic metastasis were initially suspected until actinomycosis diagnosis was made by percutaneous liver biopsy under scanography . High grade NHL was diagnosed by laparotomy and liver biopsy performed 6 weeks after the onset of antibiotic therapy as no improvement in hepatic lesions was obtained . These two case reports outline the difficulties encountered in the diagnosis of actinomycosis and the indication of a repeat biopsy when actinomycosis does not respond to antimicrobial therapy because of the possibility of concomitant malignancy.

Eur Surg Res, 1996, 28(5), 351 - 60
Effect of intraperitoneal antimicrobials on the concentration of bacteria, endotoxin, and tumor necrosis factor in abdominal fluid and plasma in rats; Rosman C et al.; The efficacy of intraperitoneal instillation of antimicrobial agents in eliminating the bacterial contaminant in patients with generalized peritonitis remains controversial . We determined the effect of intraperitoneal instillation of taurolidine or imipenem on mortality, and on the concentration of bacteria, endotoxin, and tumor necrosis factor (TNF) in rats with intraperitoneally injected bacteria . Thirty rats were inoculated intraperitoneally with two enteric bacterial strains, followed by either taurolidine, saline, or imipenem . Abdominal fluid and blood were analyzed at different time intervals . The survival rate was highest in the imipenem group (p < 0.05) . The bacterial concentration in abdominal fluid in the taurolidine and imipenem group was lower than in the saline group (p < 0.005), but the concentration in the imipenem group was lowest (p < 0.005) . The endotoxin concentration in abdominal fluid and plasma in the taurolidine group was lower than in the other two groups (p < 0.05) . The TNF concentration in abdominal fluid and plasma in the taurolidine group was lower than in the saline group (p < 0.05), whereas the concentration in the imipenem group was higher (p < 0.005) . We conclude that topically applied taurolidine in rats with intraperitoneally injected bacteria may have a weak antibacterial effect, and lowered concentrations of endotoxin and TNF . Topically applied imipenem had a profound bactericidal activity but induced endotoxin and TNF release.

Epidemiol Rev, 1996, 18(1), 10 - 28
Child-care practices: effects of social change on the epidemiology of infectious diseases and antibiotic resistance; Holmes SJ et al.; The increasing number of mothers of young children in the work force and the resultant escalated use of child-care facilities has had a marked effect on the epidemiology of infectious diseases in young children . Children attending child care are at high risk for respiratory and gastrointestinal tract illnesses . The high prevalence of infectious diseases in the child-care setting is accompanied by high usage of antibiotics, which in turn has resulted in spread of antibiotic-resistant organisms . The infectious disease standards of the American Public Health Association/American Academy of Pediatrics guidelines were developed to prevent and limit transmission of infectious diseases in the child-care setting . Adherence to these standards is essential but will not completely eliminate the increased risk of infectious diseases in child-care settings . New challenges need to be addressed to assure that optimal health promotion and disease prevention is practiced in child-care settings . We approach the 21st century with a vast amount of medical knowledge, molecular technology, highly effective vaccines, and powerful antimicrobial agents . However, at the same time we face many unsolved serious problems, such as preventing or controlling the emergence and spread of antibiotic-resistant organisms that adversely affect our ability to treat infectious diseases . Further research is needed concerning the relations between child care, the use of antibiotics, and transmission of antibiotic-resistant organisms in order to design and implement the most effective strategies for preventing or controlling antibiotic resistance . The potential risk for transmission of HIV in the child-care setting also needs to be recognized, and procedures to prevent transmission of blood-borne pathogens need to be followed . Monitoring compliance with national standards for child-care facilities, dissemination of information concerning infectious diseases and use of antibiotics, and development and use of new vaccines are strategies which should be used to help protect the health of children in child-care environments.

Acta Neurochir (Wien), 1996, 138(7), 835 - 9
Short course antimicrobial therapy in intracranial abscess; Jamjoom AB; In this study, the author attempts to question the necessity of prolonged antimicrobial treatment for intracranial abscess . The C reactive protein (CRP) was measured serially in 26 patients with intracranial abscess . All patients had undergone surgery and were treated with antimicrobial therapy . The CRP was elevated in 20 (77%) patients and its return to normal after treatment correlated with a good recovery . In 3 (12%) patients a persistently high CRP level postoperatively coincided with reformation of the abscess . A transient rise in the CRP value during decrease to normal was due to deep venous thrombosis in 2 (8%) patients . The return of the CRP to normal in conjunction with improvement of the patient's clinical condition and evidence of resolution of the abscess on CT scan were used as a guideline to stop antibiotics early . The antimicrobial therapy of the patients in this series ranged from 11-30 (mean 20) days and the follow up from 6-36 (median 21) months; there have been no recurrences.

Scand J Infect Dis, 1996, 28(3), 275 - 8
Detection and identification of non-tuberculous mycobacterial infections in 6,472 tuberculosis suspected patients; Bahrmand AR et al.; Between March 1993 and March 1994, 82 patients with infection by non-tuberculous mycobacteria (NTM) and 443 patients with tuberculosis (TB) were registered among 6,472 patients with suspected tuberculosis . Skin-test reactivity to purified protein derivative (PPD) in patients demonstrated indurations of 10-14 mm or more for the majority of patients in both groups . Most patients with NTM infection had abnormal chest roentgenograms showing sporadic infiltrations, nodular abscesses, and cavities resembling TB radiological evidence . The similarity in age range, PPD skin reaction, and radiological evidence in patients infected with NTM or Mycobacterium tuberculosis (MTB) can mislead the physician . Some NTM species were recovered more often than others . Mycobacterium fortuitum from 22 clinical specimens (26.8%); Mycobacterium gastric 19 (23.1%); and Mycobacterium terrae complex 15 (18.3%) . The antimicrobial drug susceptibility tests of the isolated organisms showed that 42 (9.5%) isolates of MTB were resistant to isoniazid and 31 (7.0%) to streptomycin . a few strains (1.3%) were identified as being resistant to a combination of 3 primary drugs . These findings suggest that drug-resistant mycobacterial infections are becoming an important problem in the region.

J Biomater Sci Polym Ed, 1996, 7(11), 1005 - 15
Cytotoxicity tests for antimicrobial agents using cultured skin substitutes fixed at interface of air and culture medium; Kuroyanagi Y et al.; The present study is focused on a new cytotoxicity test using cultured dermal and epidermal sheets, which are fixed at the air and medium interface as a wound surface model . The cultured dermal sheet is composed of human fibroblasts and a collagen matrix, and the cultured epidermal sheet is composed of human keratinocytes and a collagen matrix . Each cultured sheet was fixed at the air and medium interface, over which a piece of test specimen was placed . The in vitro system created, provides a mimetic wound surface since during wound repair, fibroblasts are embedded in an extracellular matrix, while keratinocytes migrate and proliferate on provisional granulation tissue . The results thus obtained in this cytotoxicity test are useful for determining the efficacious amount of antimicrobial agent used in clinical cases.

Pharmacol Ther, 1996, 69(1), 79 - 83
The chemotherapeutic effects of H+/K+ inhibitors on Helicobacter pylori infection; Logan RP; Helicobacter pylori's powerful urease enzyme is essential for colonisation and adaptation to the acid milieu of the stomach . Eradication of infection with "standard triple therapy" abolishes the chronic immunological and inflammatory responses to H . pylori and, thus, cures gastritis and peptic ulcer . In vitro, proton pump inhibitors (PPI) are active against H . pylori with minimum inhibitory concentrations that compare favourably with bismuth salts . PPIs are also potent urease inhibitors, but because PPIs are also active against urease-negative mutant Helicobacter spp., it is unlikely that urease inhibition alone accounts for their anti-H . pylori activity . Early reports suggested that omeprazole monotherapy was able to eradicate H . pylori . This has not been confirmed by more comprehensive studies, which have shown that treatment with omeprazole is associated with a shift of infection from the antrum to the corpus . The explanation for this observation is unclear, but does not appear to be due to bacterial overgrowth . Raising the intragastric pH with a PPI lowers the minimum inhibitory concentration of the many antimicrobials, while decreasing the acid storage pool increases the intramucosal concentration . Dual therapy (omeprazole with either amoxycillin or clarithromycin) is a more logical and highly effective alternative to standard triple therapy, with fewer side effects and better patient compliance . However, H . pylori eradication regimens based on a PPI and two antimicrobials will be the first-line treatment for H . pylori gastritis and peptic ulcer in the future.

J Infect, 1996 Jan, 32(1), 17 - 21
An audit of the clinical features and use of antimicrobials in adult diarrhoea; Laing RB et al.; We reviewed the case records of 128 adult patients hospitalized with diarrhoea . A relevant stool pathogen was isolated from 45, a diagnosis of culture-negative or non-specific gastroenteritis (NSGE) was made in 40 and the remaining 43 patients had no enteric infection . A history of fever or bloody stools was more common in those with culture-positive gastroenteritis than it was in those with NSGE or other diarrhoeal illness . The mean duration of diarrhoea prior to admission was significantly shorter in those with all forms of gastroenteritis than it was in the remainder . Epirical treatment with ciprofloxacin was commenced in 46% of all cases of gastroenteritis, of which 51% were found to have a relevant pathogen on stool culture . Patients with NSGE were just as likely to be treated with ciprofloxacin as those who were subsequently found to have culture-positive gastroenteritis . A history of abdominal tenderness or bloody stools did not discriminate for treatment with empirical ciprofloxacin in any patient group . Patients with positive stool cultures were more likely to be given ciprofloxacin if they were febrile but the same was not true for the other patients . In the patients reviewed, a significantly higher proportion of those with culture-positive diarrhoea presented with a history of fever or bloody stools . Despite this, the empirical use of ciprofloxacin in suspected infective gastroenteritis appeared to be only partially guided by the clinical features.

Infection, 1996 Jan-Feb, 24(1), 76 - 9
Polymerase chain reaction control of antibiotic treatment in dermatoborreliosis; Muellegger R et al.; Assessment of the efficacy of an antibiotic drug used in patients with various manifestations of dermatoborreliosis is crucial . Clinical judgement alone (resolution of the present dermatologic lesion, prevention of later major or minor sequelae) is not sufficient in erythema migrans and acrodermatitis chronica atrophicans . Thus, laboratory tests are desirable to prove the benefit of an antimicrobial agent . It was intended to establish a constant parameter--besides the clinical picture--for assessing the efficacy of antibiotic treatment in patients with dermatoborreliosis in terms of eradication of Borrelia burgdorferi from the site of infection . Polymerase chain reaction (PCR) was therefore performed from pretreatment biopsy specimens from lesional skin of 36 erythema migrans patients (m:f = 15:21, mean age 49 years) and seven acrodermatitis chronica atrophicans patients (m:f = 0:7, mean age 59 years), respectively . After antibiotic therapy with minocycline (100 mg, orally twice daily, 14 days) for erythema migrans, and ceftriaxone (2 g, intravenously once daily, 14 days) for acrodermatitis chronica atrophicans another punch biopsy was obtained and analysed by PCR . In pretreatment specimens, B . burgdorferi-specific DNA was amplified by PCR in 23/36 erythema migrans patients (69%), and in 5/7 acrodermatitis chronica atrophicans patients (71%) . After antibiotic therapy, PCR yielded negative results in all of these cases . Clinically, all patients showed complete recovery or at least marked improvement of lesions at this time . PCR appears to be a reliable parameter for the assessment of the efficacy of antibiotic treatment in dermatoborreliosis.

Infection, 1996 Jan-Feb, 24(1), 60 - 3
In vitro susceptibility of thirty Borrelia strains from various sources against eight antimicrobial chemotherapeutics; Baradaran-Dilmaghani R et al.; Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were evaluated of the antimicrobial chemotherapeutics amoxicillin, azithromycin, cefotaxime, ceftriaxone, doxycycline, penicillin G sodium, roxithromycin, and trimethoprim-sulfamethoxazole for 30 Borrelia strains from various sources (skin, cerebrospinal fluid, ticks) . Of these strains 29 were Lyme disease agents of the species Borrelia afzelii (n = 12), Borrelia burgdorferi sensu stricto (n = 4), Borrelia garinii (n = 13), and one was the relapsing fever strain Borrelia turicatae (n = 1) . Tests were performed in microtiter plates by broth dilution . MIC was determined after 72 hours of incubation by comparing growth control with the antibiotic dilutions by means of dark field microscopy . Strains tested were susceptible against amoxicillin, azithromycin, cefotaxime, ceftriaxone, doxycycline, and penicillin G sodium, partly susceptible to roxithromycin, and resistant to trimethoprim-sulfamethoxazole . No statistically significant differences in MIC and MBC were seen among the different antibiotics with the various Borrelia species.

J Enzyme Inhib, 1996, 10(2), 93 - 103
Piperastatin A, a new selective serine carboxypeptidase inhibitor produced by actinomycete . I . Taxonomy, production, isolation and biological activities; Murakami S et al.; Piperastatin A (structure, N-formyl-allo Ile-Thr-Leu-Val-Pip-Leu-Pip, Pip = hexahydropyridadine-3-carboxylic acid; molecular weight, 809), a new inhibitor of serine carboxypeptidase was discovered in the fermentation broth of Streptomyces lavendofoliae MJ908-WF13 . It was purified by activated charcoal chromatography, YMC gel ODS-A chromatography and centrifugal partition chromatography (CPC) by monitoring its inhibitory activity against carboxypeptidase Y (CP-Y), and finally obtained as colourless needles . Piperastatin A is a competitive inhibitor of the enzyme with Ki = 52 +/- 6.2 nM . Piperastatin A is a highly specific inhibitor of the serine carboxypeptidases, CP-Y and platelet deamidase with little effect on related enzymes, has no antimicrobial activity and has low toxicity.

Eur Respir J, 1996 Jan, 9(1), 37 - 41
Do quantitative cultures of protected brush specimens modify the initial empirical therapy in ventilated patients with suspected pneumonia?
Rodriguez de Castro F, Sole-Violan J, Aranda Leon A, Blanco Lopez J, Julia-Serda G, Cabrera Navarro P, Bolanos Guerra J.
The real contribution of the protected specimen brush (PSB) to guide the choice of antimicrobial therapy in ventilated patients with severe pneumonia is not well established . This study aimed to assess how data obtained by PSB changed the initial empirical therapy . One hundred and ten ventilated patients with suspected pneumonia were entered into a prospective study . All patients underwent fibreoptic bronchoscopy within the first 24 h after clinical suspicion of pneumonia . Specimens were obtained by PSB and were processed for quantitative cultures using standard methods . When patients were started on empirical antibiotics, a standard therapeutic regimen was followed . The decision to introduce, withdraw, maintain, or modify antibiotic therapy, according to the PSB culture results, was left to the attending physician . Pneumonia was the final diagnosis in 45 (41%) of the 110 patients . Pneumonia was excluded in 47 (43%) patients and in the remaining 18 (16%) the diagnosis was uncertain . The initial therapeutic plans were considered to be adequate in 40 patients (36%) and inadequate in 37 cases (34%) . In 17 patients (15%), therapeutic changes were made based on the results of PSB cultures . In one case appropriate antibiotics were introduced; in nine cases the therapeutic regimen was reduced to select a narrower and rational therapy; and in seven patients therapy was changed because the prescribed antimicrobial agents were ineffective against the organisms recovered . This study shows that therapeutic changes were made based on the results of PSB cultures in 38% of the patients with pneumonia . In contrast, the PSB technique has no impact on antimicrobial therapy of patients without pneumonia.

Clin Infect Dis, 1996 Jan, 22(1), 124 - 8
Persistent diarrhea in travelers; DuPont HL et al.; Most patients with traveler's diarrhea can be efficiently treated with available pharmacological agents . A more difficult problem is the persistent diarrhea (lasting > or = 14 days) that occurs in approximately 3% of travelers who have acute diarrhea . In the initial evaluation of these patients, ideally three stool samples should be obtained for examination for pathogens . If an agent is not identified or the patient has not responded to specific therapy, he or she may be empirically treated with an antimicrobial drug directed toward common bacterial enteropathogens, if such treatment has not already been administered . For those patients whose conditions do not respond, antiprotozoal therapy may be employed empirically . If diarrhea continues, then an endoscopic evaluation is indicated, and specific treatment can be given if an agent or condition is identified . A proportion of patients will continue to have diarrhea following empirical therapy and a gastroenterologic workup . These individuals are best given symptomatic treatment and reassured that the prognosis is good.

Biosci Biotechnol Biochem, 1996 Jan, 60(1), 152 - 3
Potent allelochemical falcalindiol from Glehnia littoralis F . Schm; Satoh A et al.; A potent allelochemical in Glehnia littoralis F . Schm . was investigated . Falcalindiol was isolated from G . littoralis; 859.9 mg/kg of fresh root and 62.5 mg/kg of fresh aerial parts . Its structure was elucidated by spectroscopic methods, and the antimicrobial activities of falcalindiol were evaluated by the paper disk method against several microorganisms . The plant growth inhibition of falcalindiol was also investigated.

Kansenshogaku Zasshi, 1996 Jan, 70(1), 80 - 6
{Serological assay for diagnosis of verotoxin-producing Escherichia coli (VTEC) infection in the patients with diarrhea}; Kobayashi K et al.; A total of 239 serum samples from 136 persons were used for bacterial agglutination assay (BA) against predominant three O-antigens of VTEC . All VTEC isolates from stools of 30 patients were only O157:H7 serotype (these patients are called group I) . The levels of positive BA antibody titers (over 1:160) to O157-antigen were recognized in each patients as follows . The VTEC isolated patients with HUS or without HUS in group I were all of 13 (100%) and 14 (82.4%) in 17 patients, respectively . And 21 (65.6%) patients of group II (HUS patients with stool negative cultures, or stool cultures were not performed in 32 patients), and 6 (15.0%) patients of group III (family members of group I and II; 40 persons), were also recognized . In group IV (patients with diarrhea due to other pathogen than VTEC; 11 patients), and V (clinically healthy persons; 23 persons), none were recognized as positive BA antibody titers . All patients in the group II except one who had a positive BA antibody titer to O111, were not recognized to O111 and O26 . A few VTEC-positive patients without gastrointestinal syndrome did not have significant agglutinating titers to O157-antigen on the days after VTEC isolation . However, almost all patients with diarrhea due to VTEC and HUS, and with VTEC but no HUS, had a level of positive BA antibody titer on the 5 day after onset of diarrhea . These results suggest that this serological assay is a very simple and useful tool for diagnosis of VTEC infection when VTEC are not detected by culture method due to antimicrobial treatment, or due to the lapse of many days after onset of diarrhea.

Shock, 1996 Jan, 5(1), 4 - 16
Update on current therapeutic approaches in burns; Shirani KZ et al.; Burn injury results in a rapid loss of intravascular volume as wound edema forms, which reduces the circulating blood volume and generates the need for fluid therapy to combat hypovolemia . Fluid resuscitation of a burn patient is usually carried out with isotonic, sodium- and chloride-containing fluids, such as lactated Ringer's solution . The initial 24 h resuscitation volume is based on the burn size and body weight of the patient . Following a successful resuscitation, the burn patient develops stereotypic neurohormonal and metabolic responses that, depending on the extent of injury, last for several weeks or months . Breathing of incomplete products of combustion by the fire victim produces inhalation injury, the incidence of which rises with increasing burn size and the severity of which is proportional to the duration of exposure . Systemic hypoxia from carbon monoxide toxicity causes early death; chemical airway injury increases mortality and predisposes to subsequent pneumonia that further reduces survival . The diagnosis of inhalation injury is made by bronchoscopy and/or xenon scan and therapy involves support of ventilation . Thermal destruction of the cutaneous mechanical barrier and the presence of nonviable avascular burn eschar as well as impairment of other host defenses render the burn patient susceptible to local as well as systemic infections . Care following resuscitation is focused on topical antimicrobial therapy, burn wound excision, and wound closure by grafting . Nutritional support and the prevention and control of infection are constant themes in burn patient management . A progressive improvement in general care of the acutely injured patient, prevention of shock, effective means of maintaining organ function, prevention and control of burn wound and other infections, and physiologically based metabolic support have significantly increased burn patient survival in recent decades.

Acta Cardiol, 1996, 51(3), 279 - 85
Infective endocarditis and occult splenic abscess caused by Brucella melitensis infection: a case report and review of the literature; Saadeh AM et al.; This report describes a patient with prosthetic aortic valve endocarditis caused by Brucella melitensis infection with an initial relapse after apparent recovery due to associated occult splenic abscess . In spite of a prolonged period of recovery (6 months) achieved with splenectomy and antibrucella antimicrobial therapy, a second relapse occurred and cure was achieved after replacement of the infected prosthetic valve and prolonged courses of antibrucella antimicrobial therapy . There is controversy on the optimal therapy of such cases, but this report suggests that successful management requires a combination of medical and early surgical therapy.

Genomics, 1996 Jan 1, 31(1), 95 - 106
Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships; Bevins CL et al.; Defensins, a family of antimicrobial peptides isolated from several mammalian species, have a proposed functional role in innate host defense . In humans, certain defensin genes are expressed in phagocytic cells of hematopoietic origin, while others are expressed in Paneth cells, epithelial cells of the small intestine . In this study, we determined the chromosomal localization of the human defensin (HD) genes expressed in Paneth cells, HD-5 and HD-6 . Analysis of a panel of human/hamster hybrids localized both HD-5 and HD-6 to chromosome 8 . Southern blot analysis of DNA from cell lines that contain either chromosome 8 deletions or duplications further localized these two genes to 8p21-pter . Fluorescence in situ hybridization analysis of metaphase chromosomes using an HD-5 probe further supported the regional map assignment . Previous studies had localized the hematopoietic genes to chromosome 8p23, and the current work is consistent with both the enteric and the myeloid defensin genes being located at the same cytogenetic region of chromosome 8 . In addition, the evolutionary relationships of this gene family were addressed using dot matrix sequence analysis . From this analysis, a model for the possible evolutionary history of the human defensin genes is proposed . According to this model, an early duplication of a primordial defensin gene yielded the ancestral genes of present day HD-5 and HD-6 . The model further suggests that a subsequent unequal meiotic crossover event had generated an additional gene, comprised of a hybrid of sequences from the two parental genes, and that this hybrid gene then served as the ancestor to present day hematopoietic defensin genes.

Acta Microbiol Pol, 1996, 45(1), 55 - 65
Physiological and biochemical changes induced by osmolality in halotolerant aspergilli; Mahdy HM et al.; Aspergillus ventii and Aspergillus parasiticus halotolerant and alkali-resistant fungi were isolated from hypersaline soil of Wadi El-Natroun, Egypt by using a complex medium of high salt concentration (20% NaCl {w/v}) . They were able to grow and resist the salt stress to about 20-25% NaCl and the alkaline condition tentatively to pH about 10.5 . The presence of high salt concentration distorts the sporogenesis and stunt the conidiophores as well as inhibits the antimicrobial agent(s) and some extracellular hydrolytic enzymes (lipase(s) and amylase(s)) . The application of some exogenous compatible solutes particularly trehalose, alpha-ketoglutarate and glycerol improves the growth and increases the resistance to salt stress (osmolality) of the two fungal isolates to about 27.5-29% NaCl (w/v) . Results of the biochemical analysis (total soluble proteins, carbohydrates and lipids) PAGE and TLC of amino acid analysis support the suggestion that each species of Aspergillus has a specific mechanism for adaptation.

Scand J Infect Dis, 1996, 28(2), 155 - 7
Antibiotics and increased temperature against Borrelia burgdorferi in vitro; Reisinger E et al.; In 1917, spirochaetal neurosyphilis was treated successfully with malariotherapy in combination with salvarsan or bismuth . Malariotherapy for spirochaetal Lyme disease has been discussed, but the mechanism of an antispirochaetal effect remains unclear . We cultured Borrelia burgdorferi at different temperatures, alone and in combination with antibiotics . Our data demonstrate that growth of the strains PKo and ATCC 35210 (B31) was impaired at temperatures of 37 degrees C and inhibited at 39 degrees C and 40 degrees C, respectively . Strain ATCC 35211, however, grew well up to 39 degrees C but did not multiply at 40 degrees C . A bactericidal effect was seen at 41 degrees C for the strains B31 and PKo and at 42 degrees C for all strains . The susceptibility of all strains to penicillin and ceftriaxone was increased up to 16-fold by an elevation of temperature from 36 degrees C to 38 degrees C . These in vitro data suggest that elevated body temperature may be beneficial during antimicrobial treatment of Lyme disease . This may be particularly important in tissues where high concentrations of antibiotics are difficult to achieve.

Blood Purif, 1996, 14(2), 179 - 87
Mechanisms regulating cytokine release from peritoneal macrophages during continuous ambulatory peritoneal dialysis; Fieren MW; The proinflammatory cytokines interleukin-1 (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are key mediators of the body's response to infection . Peritoneal macrophages from continuous ambulatory peritoneal dialysis (CAPD) patients isolated during peritonitis have an increased capacity to secrete IL-1 beta and TNF alpha . This peritoneal macrophage activation for IL-1 beta and TNF alpha release is a two-stage process . In contrast, peritonitis macrophages and infection-free macrophages stimulated in vitro with bacteria generate a decreased amount of the anti-inflammatory prostanoids . Exogenous and endogenous prostaglandin E2 (PGE2) was found to inhibit the release of TNF alpha rather than IL-1 beta from peritoneal macrophages, indicating that the synthesis and secretion of these cytokines is distinctly regulated by PGE2 . In addition to macrophage products, acting in an autocrine fashion cytokine production and release may be regulated by secretory products of other cells in the peritoneal cavity including lymphocytes and mesothelial cells, which have the capability to produce various mediators . No evidence was found that the NO system is an important part of the antimicrobial arsenal of peritoneal macrophages.

Prog Med Chem, 1996, 33, 99 - 145
Recent advances in the chemistry and biology of carbapenem antibiotics; Coulton S et al.; The discovery of the olivanic acids and thienamycin aroused considerable interest amongst medicinal chemists and microbiologists around the world . The susceptibility of these agents to metabolic degradation has, however, been a major obstacle in their development . For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1 . The enormous success of Primaxin for the treatment of a range of life-threatening bacterial infections provided the impetus for the discovery of totally synthetic, non-natural carbapenem derivatives that combine the broad spectrum of antimicrobial activity with stability to enzymatic degradation . This has indeed been realised in the development of meropenem; it possesses the broad spectrum of activity and resistance to beta-lactamases that are embodied in imipenem as well as displaying increased stability to human dehydropeptidases . Most recent research has focused upon the development of carbapenem antibiotics which combine broad spectrum antimicrobial activity and metabolic stability with oral absorption, for the treatment of community-acquired infections . Indeed, the pro-drug esters of the tricyclic carbapenems represent the first significant advance in this respect . However, the increased use of carbapenem antibiotics would undoubtedly accelerate the emergence of carbapenem-hydrolysing enzymes . The ultimate challenge could therefore be the design and synthesis of carbapenem derivatives that are resistant to these metallo-beta-lactamases . Due to the enormous problems encountered in the development of the carbapenem antibiotics, this area of research has, in the past, been described as a battlefield that did not bode well for the future {181} . Primaxin and meropenem proved however that these problems were not insurmountable, and are therefore a testimony to the persistence and dedication of those scientists in their war against bacterial infection.

Med Trop (Mars), 1996, 56(1), 95 - 8
{Burundi: knowledge and practices of physicians and nursing personnel about acute respiratory infections in children}; Baribwira C et al.; In order to detect problems in the management of acute respiratory infection in children and to optimize training, a survey was undertaken in 1993 including 9 pediatricians, 27 general practitioners, and 58 nurses in Bujumbura, Burundi . A questionnaire including 15 main items was used . Findings showed a poor understanding of risk factors in 62% of the population, especially among general practitioners and nurses . Clinically 79% were able to make a proper diagnosis of pneumonia . Overtreatment of coryza using antimicrobial, mucolytic, and cough drugs was suspected in 88.8% . Findings were similar with regard to management of pneumonia . Wheezing was treated in accordance with WHO recommendations in only 18% of cases . For acute respiratory infection, 53.6% used penicillin A, 18% used penicillin G, 15.9% used cotrimoxazole and 2.9% used macrolides . The duration of antimicrobial therapy was unnecessarily long for 49.4% . While 70.5% of the population (100% of pediatricians) considered the state of their knowledge and practices to be sufficient, 93.6% (55.6% of pediatricians) indicated that specific training in this field would be useful . This survey suggests that training is needed for health care workers at all levels specifically in the management and prevention of acute respiratory infection in children.

EXS, 1996, 75, 323 - 45
Adaptive evolution of lysozyme: changes in amino acid sequence, regulation of expression and gene number; Prager EM; Adaptive evolution of lysozyme has involved remodelling of amino acid sequences and changes in patterns of gene expression and in gene number . Following an outline of the phenomena likely to be indicative of adaptive evolution and how one can assess them, this chapter focuses on four cases in which lysozyme c has been recruited as a digestive enzyme in the stomachs of creatures needing to retrieve nutrients from microorganisms in fermented food . For each case-ruminant artiodactyls, leaf-eating monkeys, a leaf-eating bird, and fruit flies-the factors likely to be of primary importance in lysozyme's adaptation are examined . Additional examples of apparent adaptation for digestion or antimicrobial defense in animals as diverse as mice, moths, and molluscs are summarized . This chapter considers also the case of three internally clustered residues which among galliform bird lysozymes c occur either as Thr 40, Ile 55, and Ser 91 (TIS) or as Ser 40, Val 55, and Thr 91 (SVT) . Reconstruction and testing of six possible intermediate proteins and development of the concept of a neutral corridor of protein traits are described.

Wiad Parazytol, 1996, 42(1), 3 - 27
{Anti-infective defence strategies and methods of escape from entomologic pathogens under immunologic control of insects}; Jarosz J; Insect immunity comprises a complex of several distinct systems, both haemocytic and humoral in nature, that cooperate together in a more or less coordinated way to provide protection of the body cavity from invading microorganisms . Insects can respond to infections by a selective synthesis of haemolymph immune proteins that are responsible for antibacterial immunity . Antibacterial activity of insect blood is attributable to innate compounds such as lysozome, and to induced polypeptides or small basic proteins absent in non-immunized insects . The cecropins and attacins in Lepidoptera, and diptericins in Diptera are the inducible antibacterial immune proteins well defined biochemically . Bacterial pathogens and some parasites of insects, preferably entomogenous rhabditid nematodes, have developed the mechanism by which they may counteract insect immunity . This phenomenon is realized either by escaping immune reactions or by degrading antimicrobial factors of haemolymph in an active process . Passive resistance of parasites to insect immunity is a result of a strong evolutionary pressure on parasites to develop mechanisms to escape insect immune reactions or to minimize their effectiveness through changes in the parasite itself . Active resistance to the insect non-self response system involves a partial or total destruction of immune proteins by extracellular proteinases released during parasitism.

J Clin Microbiol, 1996 Jan, 34(1), 1 - 9
Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans; Aguero-Rosenfeld ME et al.; We investigated the appearance and evolution of immunoglobulin M (IgM) and IgG antibodies to Borrelia burgdorferi in 46 patients with culture-proven erythema migrans (EM) . All patients received antimicrobial treatment and were prospectively evaluated for up to 1 year . A total of 257 serially collected serum samples were tested by commercial IgG-IgM enzyme-linked immunosorbent assay and separate IgM and IgG immunoblots (IBs) . At the baseline, 33% of the patients had a positive ELISA result and 43% of the patients had a positive IgM IB result by using the criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors for the interpretation of IB results . Positive serology at the baseline and the rate of seroconversion correlated directly with disease duration and/or evidence of dissemination prior to treatment . At days 8 to 14 after the baseline, 91% of patients had a positive ELISA result and/or IgM IB result . Peak IgM antibody levels were seen at this time in patients with localized or disseminated disease . The most frequent IgM bands at the baseline and the peak were of 24 kDa (OspC), 41 kDa, and 37 kDa . Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors . The persistence of antibodies was directly related to disease duration and/or dissemination prior to treatment . Since IgM antibodies to the 24- and 41-kDa antigens remained detectable for long periods, 38% of IgM IBs were still positive at 1 year postbaseline . IgM to antigens of 39, 58, 60, 66, or 93 kDa, conversely, were most often seen in sera obtained within 1 month postbaseline . Their presence may be of assistance in confirming a recent infection with B . burgdorferi in individuals living in areas where Lyme disease is endemic.

Nephron, 1996, 72(4), 708 - 11
Fibroadhesive form of tuberculous peritonitis: chyloperitoneum in a patient undergoing automated peritoneal dialysis; Huang CH et al.; Chyloperitoneum is a rare condition in patients undergoing peritoneal dialysis . We report here a patient who developed chylous ascites during the course of tuberculous peritonitis . The diagnosis was confirmed by cultures of dialysate and peritoneal biopsy, and laparoscopy revealed severe hyperemia and intestine adhesion . Intrinsic lymphatic obstruction and superimposed peritoneal fibrosis together might be responsible for the pathogenesis of this special presentation . Although in most cases of continuous ambulatory peritoneal dialysis, the causes of chyloperitoneum remained unknown, we suggest, from the experience of this case, that tuberculous peritonitis, especially the fibroadhesive form, should be highly suspected in any dialysis cases with chyloperitoneum . Laparoscopy should be initiated early, particularly when the culture is negative for common pathogens or when the patient responds poorly to the usual antimicrobial agents.

Nephron, 1996, 72(4), 679 - 82
Acne: a potential side effect of cyclosporine A therapy; el-Shahawy MA et al.; A renal transplant recipient who developed severe acne 6 months after transplantation is described . Maintenance immunosuppression consisted of cyclosporine A (CsA), azathioprine and prednisone . Tapering the prednisone dose to as low as 5 mg/day, in addition to topical tetracycline, Retin-A cream, and systemic antimicrobial therapy failed to control the progression of the skin lesions . Despite therapy with isotretinoin (Accutane), the lesions continued to progress with nodulocystic transformation (acne conglobata) and isotretinoin was discontinued after 4 months . However, the condition continued to worsen with the development of a systemic illness with daily fever, diaphoresis, and depression . High fever (103 degrees F) with shaking chills prompted hospitalization . Withdrawal of CsA resulted in rapid and continuous improvement of the skin lesions . After 12 months of follow-up, the lesions significantly resolved except for residual areas of scarring . No episodes of acute allograft rejection occurred . In conclusion, we suggest that CsA therapy may be associated with the development of acne . Nodulocystic transformation (acne conglobata) may occur despite the use of isotretinoin . Finally, withdrawal of CsA may lead to resolution of the skin disease and should, therefore, be considered as a therapeutic option for severe and treatment-resistant cases.

Br J Clin Pract, 1996 Jan-Feb, 50(1), 50 - 1
Tuberculous mastitis: a rare disease; Al Soub H et al.; Two cases of tuberculous mastitis are described . This disease remains rare . While routine laboratory investigations are not helpful in its diagnosis, fine needle aspiration to allow histologic examination of tissue and culture is essential--both to differentiate tuberculous mastitis from pyogenic breast abscess and breast carcinoma, and to guide antimicrobial therapy . Antituberculous drugs in combination with aspiration or surgical drainage are usually associated with an excellent outcome.

Perit Dial Int, 1996, 16 Suppl 1, S340 - 6
Significance, epidemiology, and prevention of peritoneal dialysis catheter infections; Burkart JM; Catheter infections are a major cause of morbidity, catheter loss, and transfer to hemodialysis . These infections are mainly due to S . aureus . To date, treatment is less than optimal . Therefore, the primary goal should be prevention of catheter infections . Prevention is based on improving catheter design and implantation technique while using careful exit-site care . Prophylaxis with antimicrobials such as intranasal mupirocin or the use of silver-impregnated catheters appears promising as a way to reduce the risk of developing S . aureus infections . To optimize patient outcome, one must focus on these preventive measures.

Drugs, 1996, 51 Suppl 1, 1 - 5
Emerging resistance to antimicrobial agents in gram-positive bacteria . Pneumococci; Appelbaum PC; The prevalence of penicillin-resistant pneumococci is increasing worldwide . Methods for susceptibility testing, as well as in vitro susceptibility of penicillin-susceptible and -resistant strains to new and existing agents (including oral and parenteral streptogramins), are described . For all specimens except CSF, oxacillin screening followed by determination of penicillin minimum inhibitory concentrations (MICs) is satisfactory . For CSF, simultaneous testing of penicillin and cefotaxime or ceftriaxone by E-test is necessary . Of all available oral beta-lactams, amoxicillin yields the lowest MICs against penicillin-susceptible and -resistant pneumococci, and is the drug of choice for the treatment of otitis media . Cefotaxime and ceftriaxone yield MICs that are low enough to permit therapy of meningitic and nonmeningitic infections (the former in combination with vancomycin) . The higher the strain's benzylpenicillin (penicillin G) MIC, the more likely it is that simultaneous resistance to nonrelated compounds such as tetracyclines, macrolides, and cotrimoxazole (trimethoprim/ sulfamethoxazole) will occur . None of the available quinolones should be used for therapy of pneumococcal infections . Of new and experimental drugs, some of the new quinolones, trovafloxacin, and oral and parenteral streptogramins are promising agents . Imipenem is epileptogenic, but meropenem has potential in the therapy of meningitis . Problematical infections caused by penicillin-resistant pneumococci include meningitis and otitis media . The optimal therapy of the latter two diseases has not yet been clearly delineated.

Scand J Gastroenterol Suppl, 1996, 214, 56; discussion 57 - 60
Treatment of Helicobacter pylori infection by topical administration of antimicrobial agents; Satoh K; A technique has been developed in which a combination of bismuth subnitrate, amoxycillin and metronidazole is instilled into the stomach via a nasogastric tube and removed after 1 hour, thereby avoiding the side-effects often seen with triple therapy . This technique has achieved eradication of H . pylori in 24 of 25 patients with non-ulcer dyspepsia . A modified version of the technique was used in six patients, and eradication achieved in each case.

Scand J Gastroenterol Suppl . 1996;215:118.
Italian omeprazole triple therapy--a 1-week regimen; Bazzoli F; Eradication of Helicobacter pylori infection is increasingly recognized as an appropriate therapeutic option, although it may prove difficult to achieve . Variable results, possibly due to side-effects, poor patient compliance and antimicrobial resistance, have been reported with traditional bismuth triple therapy . The combination of highly effective antisecretory drugs, such as omeprazole, and antimicrobial agents are providing a useful alternative to such traditional triple therapy.

Scand J Gastroenterol Suppl, 1996, 215, 70 - 3
Current indications for Helicobacter pylori eradication therapy; Tytgat GN; Two questions need to be answered before the eradication of Helicobacter pylori infection can be discussed . Firstly, can the infection be cured, and if so, is the cure permanent or transient? Secondly, what is the long-term clinical outcome of H . pylori infection? Current indications for the eradication of H . pylori infection can be divided into three categories: well-established, equivocal and experimental . Peptic ulcer disease in patients positive for H . pylori is a well-established indication for eradication of the organism . H . pylori-positive dyspepsia and the need for prolonged treatment with non-steroidal anti-inflammatory drugs are equivocal indications . MALT (mucosa-associated lymphoid tissue)-lymphoma, hypertrophic/hyperplastic gastritis, atrophic gastritis with or without premalignant mucosal alterations, and the need for prolonged powerful acid-suppressive therapy, in patients positive for H . pylori are all experimental indications . The decision to recommend H . pylori eradication therapy should not be taken lightly . Despite the risks associated with antimicrobial therapy, however, the benefits from cure of the infection are such that antimicrobial therapy is being increasingly favoured, and the reasoning behind withholding eradication therapy is becoming more difficult to understand in the light of current knowledge.

Scand J Gastroenterol Suppl, 1996, 215, 22 - 31
Pathogenic properties of Helicobacter pylori; Moran AP; Helicobacter pylori possesses factors that allow it to colonize the gastrointestinal mucosa and persist at that site . Here it produces adverse pathological changes, and thereby causes disease . Colonization factors: animal models have shown that motility and the production of urease are essential for colonization by H . pylori . The ability of an organism to adhere to host structures is often considered pivotal in colonization . A number of adhesins associated with H . pylori have been described, which may imply that adherence is a multistep process and that different adhesins mediate adherence to different sites in the gastric tissue . Persistence factors: H . pylori lipopolysaccharide (LPS) possess low immunological activity, thereby minimizing the local inflammatory response and contributing to the persistence of the infection . There is also evidence that the LPS affects the qualitative nature of gastric mucin and stimulates pepsinogen secretion . Whether survival during exposure to antimicrobial agents is aided by the development of coccoid forms with intact membranes and polyphosphate energy reserves is not yet known . Putative disease-inducing factors: these include the vacuolating cytotoxin that is capable of inducing gastric ulceration in mice, ammonia products that induce vacuolation, and phospholipases that may affect the hydrophobicity of the mucosa . Mimicry of Lewis blood group antigens on the surface of H . pylori may also contribute to pathogenesis . Characteristics of certain strains, such as the expression of a cytotoxin-associated gene (cagA) and the ability to induce rapid chemiluminescence in neutrophils, are associated with the induction of peptic ulceration.

Farmaco, 1996 Jan, 51(1), 75 - 8
Synthesis and antimicrobial activity of benzo{a}dihydrocarbazole and benzotetrahydrocyclohept{1,2-b}indole derivatives; Macchia M et al.; A certain number of benzodihydrocarbazoles and benzotetrahydrocycloheptindoles were synthesized and tested for their antimicrobial activity . Compounds substituted on the nitrogen of the tetracyclic systems with a dimethylaminopropyl chain showed an antibacterial activity directed almost exclusively towards Gram-positive bacteria, while their N-unsubstituted analogs were completely inactive.

Farmaco, 1996 Jan, 51(1), 59 - 63
Synthesis of some novel pyrazoline and cyanopyridine derivatives as antimicrobial agents; Patel P et al.; Substituted chalcones 2a-j prepared by the treatment of 4'(p-chlorophenylsulphonamido)acetophenone 1 with araldehydes, on condensation with hydrazine hydrate in ethanol and acetic acid provided the desired pyrazolines of the type 3a-j and 4a-j . The same chalcones 2a-j made to react with malononitrile in the presence of ammonium acetate yielded cyanopyridines 5a-j . The structure was confirmed by elemental analyses, IR, NMR and MS spectral studies . The pharmacological profile of the compounds synthesised is described . Most of the compounds displayed their maximum activity against E . coli . Compounds 2b, 2d, 5b, 5d, 5e, 5h and 5i have been selected for their agrochemical screening by DuPont Agricultural Products, U.S.A.

Farmaco, 1996 Jan, 51(1), 53 - 8
Synthesis of 1,2-disubstituted benzimidazole-5(6)-carboxamides and evaluation of their antimicrobial activity; Goker H et al.; A series of 14, N'-(N,N-dialkylaminoethyl)-benzimidazole-5(6) or 5-carboxyamides (1-14), having several substituents on the azole and benzene nuclei, were prepared and evaluated in vitro for antimicrobial activity . The precursor benzimidazolecarboxylic acids (15-27) were prepared via oxidative condensation of diaminobenzoic acids and several aldehydes with cupric ion . Compounds 11-14 were prepared by selective regioisomer synthesis . All carboxamides were prepared from the corresponding acids and N,N-dialkylethylenediamine . Antibacterial and antifungal activities were determined as MIC values . Of the synthesized compounds 1-10, 6 and 10 were found to be the most favourable . In order to clarify the effect of the substituents at N1 on antimicrobial activity, 12 was prepared by p-chlorobenzyl substitution of compound 6, and increased activity was shown . Compounds 13 and 14, which were prepared by replacement with more bulky alkyl groups on the tert-N atom than 12, gave the best results.

Annu Rev Med, 1996, 47, 355 - 64
Bartonella (Rochalimaea) infections: beyond cat scratch; Schwartzman W; Five species of Bartonella have been found to infect humans, henselae, quintana, elizabethae, bacilliformis, and vinsonii . The most common of these in North America are Bartonella quintana and Bartonella henselae, the agents of trench fever, bacillary angiomatosis, and parenchymal peliosis, and in the case of B . henselae cat-scratch disease . B . bacilliformis is endemic in Peru and Ecuador, where it causes oroya fever or Carrion's disease . New methods of diagnosing Bartonella infections have resulted in increased recognition of the many manifestations of these infections . Early recognition is crucial, as these are potentially fatal opportunistic infections that usually respond rapidly to appropriate antimicrobial therapy.

J Virol Methods, 1996 Jan, 56(1), 33 - 40
Sensitive method for the detection of infectious HIV in semen of seropositive individuals; Vernazza PL et al.; The aim of the study was to develop a sensitive culture method for the detection of HIV in semen . Antimicrobials were evaluated to suppress bacterial and fungal contamination of HIV cultures . Toxicity of seminal plasma was reduced using a short incubation of seminal fluid with culture cells . The detection rate was determined by adding known amounts of diluted primary virus isolates to uninfected cells . The sensitivity of the method was determined in a cohort of 33 HIV seropositive men . The use of a virus transport medium with high doses of antibiotics reduced contamination of HIV cultures . Toxicity of seminal plasma on culture cells was limited when seminal fluid was incubated with culture cells for only 90 min . Detection levels for cell-associated virus and cell-free virus from semen were 12 infected cells per ejaculate and 100 infectious units per milliliter of seminal fluid, respectively . Cell-associated HIV could be recovered from 18 semen samples of 33 HIV positive men (55%) . Recovery of cell-free virus from seminal fluid was infrequent . It is concluded that the method is highly sensitive for the detection of HIV from semen . However, the recovery rate of infectious cell-free virus in seminal fluid from clinical samples is infrequent.

Pediatr Infect Dis J, 1996 Jan, 15(1), 54 - 7
Detection of Bordetella pertussis by polymerase chain reaction and culture in the nasopharynx of erythromycin-treated infants with pertussis; Edelman K et al.; BACKGROUND: Pertussis is a highly contagious respiratory disease and the most serious effects occur in young infants . Recently it has been shown that rapid and highly specific PCR can be a useful diagnostic tool for detection of pertussis infection . To our knowledge there are no previous studies concerning the disappearance of Bordetella pertussis DNA from the nasopharynx during antimicrobial treatment . METHODS: We studied prospectively how rapidly live B . pertussis organisms and DNA of these bacteria disappear from the nasopharynx during erythromycin therapy in unvaccinated infants . Eighty-five nasopharyngeal swabs obtained from nine erythromycin-treated infants with pertussis on consecutive days during hospitalization were tested by PCR and culture . The PCR products were further analyzed by Southern hybridization . RESULTS: On the fourth day of treatment 56% of the samples were positive by culture and 89% by PCR, whereas after 7 days the rates were 0 and 56%, respectively . In seven of nine patients PCR remained positive for 1 to 7 days longer than culture . The follow-up study also showed the semiquantitative nature of the PCR assay . The intensity of the PCR products in agarose gel usually weakened with time during erythromycin therapy . CONCLUSIONS: The results of this study show that PCR assay can achieve the specific diagnosis of pertussis infection in a large proportion of infants even when antimicrobial treatment has killed the organisms and culture is no longer positive.

Eur J Surg, 1996 Jan, 162(1), 15 - 21
Antimicrobial prophylaxis in surgery in Belgian hospitals: room for improvement; Kurz X et al.; OBJECTIVE . To evaluate the current practice of surgical antimicrobial prophylaxis in Belgium . DESIGN . Prospective multicentre incidence study . SETTING . 58 of the 206 acute hospitals in Belgium . SUBJECTS . 19746 patients who had operations between October 1992 and June 1993, with detailed analysis of 7983 procedures for which the antimicrobial regimens were known . RESULTS . Antibiotic prophylaxis was given before 14099 (71%) of the 19746 operations . It was given in 57% of the procedures for which prophylaxis is generally not recommended, but it was not used in 14% of procedures for which it is generally recommended, nor in 14% of all contaminated procedures . Duration of operation superseded degree of wound contamination, ASA (American Society of Anesthesiologists) score, and degree of urgency as a predictor of the use of prophylaxis . Prophylaxis was prolonged by more than 2 days postoperatively after 23% of the procedures and by more than 4 days in 8% . Five types of regimens accounted for 80% of all prophylaxis, but overall 234 different regimens were prescribed . Large differences were found in hospital university affiliation status . In general, trends were favourable compared with a study in 1986 . CONCLUSION . Although there was improvement compared with 1986, antimicrobial prophylaxis in surgery could still be more appropriate in terms of indication, duration, and rational choice of drugs.

Schweiz Med Wochenschr Suppl, 1996, 76, 28S - 33S
{Treatment of severe infections: should one always administer an aminoglycoside?}; Cometta A et al.; Until recently, aminoglycoside antibiotics were the cornerstone for the treatment of severe infections . The rationale for using combination therapy containing beta-lactams and aminoglycosides was not only to broaden the antimicrobial spectrum but also to achieve enhanced bacterial killing by synergism and to prevent the emergence of antibiotic resistance . However, with the advent of new potent broad-spectrum and highly bactericidal antibiotics, the necessity of combining beta-lactams with aminoglycosides should be reassessed . This review questions the use of aminoglycosides in three severe infections frequently observed in intensive care units, nosocomial pneumonia, nosocomial sepsis and severe diffuse peritonitis . A review of the literature suggests that the addition of an aminoglycoside to a broad-spectrum beta-lactam does not improve the outcome in nosocomial pneumonia and severe diffuse peritonitis . However, the lack of large prospective studies in severe sepsis or septic shock makes it impossible to draw any conclusion about the addition of an aminoglycoside, and the administration of these agents must be decided on an individual basis.

Rev Med Interne, 1996, 17(1), 25 - 33
{Pneumocystis carinii pneumonia in AIDS: retrospective analysis of 80 documented cases (1985-1993)}; Morlat P et al.; Eighty initial episodes of HIV-associated Pneumocystis carinii pneumonia (PCP) diagnosed at Bordeaux hospital between 1985 and 1993 are reported (57 were men and 23 women) . PCP revealed HIV infection in 29 patients (36%) . Others cases were patients with poor medical follow up (10%), with a CD4+ lymphocyte count above 200/mm3 at last follow-up (9%), non compliant with PCP prophylaxis (9%), or using aerolized pentamidine (AP+) (20%) . The main clinical symptoms were fever (90%), dyspnea (68%), non productive (63%) and productive (17%) cough . Radiographic infiltrates were purely interstitial (59%), acinar and interstitial (25%), purely acinar (5%) and absent (11%) . Thirty-eight percent of AP+ had upper lobe preferential involvement and 13% a pleural effusion . In all cases, Pneumocystis carinii was detected in bronchoalveolar lavage . Extrapulmonary localizations of pneumocystosis were noticed (eye, liver, spleen, ascitis) in two AP+ . Mean CD4+ count was 54/mm3 in patients not having received aerolized pentamidine (AP-) and 22/mm3 in AP+ . P24 antigenemia was positive in 53% (AP-) and 88% (AP+) . PaO2 LDH and albuminemia were similar in both groups . Antimicrobial therapy (Cotrimoxazole in 91% of the cases) was combined with corticosteroids in 45% and mechanic ventilation in 19% . After 30 days of follow-up, 17 deaths were observed (21%) and 14 attributed to PCP: mortality was worse in AP+ (31%) than in AP- (19%) . The main conclusions of our study are the followings: HIV related PCP is still in 1995 frequent and severe; atypical features should not rule out diagnosis; preventive measures are neither sufficient nor efficient . PCP remains in 1995 a priority in HIV related public health and therapeutical research.

Pharm Res, 1996 Jan, 13(1), 91 - 6
Pharmacokinetic-pharmacodynamic modeling of the antibiotic effect of piperacillin in vitro; Nolting A et al.; PURPOSE . It was the aim of the present study to investigate the in vitro antimicrobial effects of the beta-lactam antibiotic piperacillin on Escherichia coli using concentration-time profiles similar to those encountered in vivo . METHODS . An in vitro dilution model was used to expose E . coli to various piperacillin concentration profiles . The antimicrobial effect was evaluated by determination of the number of bacteria over time . RESULTS . A modified Emax-model was found appropriate to describe the pharmacodynamic effect . This model was linked with the respective piperacillin concentrations to provide a suitable pharmacokinetic-pharmacodynamic (PK-PD) model . The average growth half-life in absence of piperacillin was 28 min and the maximum kill half-life was 25 min . The EC50 for the various dosing regimens averaged 5.2 micrograms/mL and was independent of dose . These parameters were used the simulate the bacterial effects of commonly administered doses or dosing regimens in humans . CONCLUSIONS . Based on the in vitro data a more frequent administration of piperacillin will be more efficacious . The proposed PK-PD-model allows a more detailed evaluation of dosing regimens than the use of minimum inhibitory concentrations.

Urol Int, 1996, 56(2), 100 - 4
Clinical experience with inflatable and malleable penile implants in 104 patients; Anafarta K et al.; Penile prosthesis was implanted for erectile impotence of mainly organic origin in 104 patients . The AMS Dynaflex penile prosthesis was inserted in 39 cases, the AMS Malleable 600 prosthesis in 61 and the AMS Ultrex Plus prosthesis in 4 . In 1 patient receiving a malleable prosthesis both rods had to be removed owing to erosion into the urethra and reimplantation was performed at the same operation . Only 1 patient who underwent implantation of the Dynaflex device had mechanical failure that necessitated surgical revision . After implantation of the new prosthesis both patients had satisfactory intercourse . One Dynaflex penile prosthesis, implanted into a juvenile-onset diabetic, became infected and required removal . Another complication was secondary to spontaneous erosion (noninfected) in 1 patient with malleable prosthesis who suffered loss of only one rod and who is still satisfied with the result . The overall complication rate in our series has been approximately 4% . The rest of the patients report satisfaction with the ability to move the penis voluntarily permitting normal sexual activities as well as normal appearance in the flaccid position . According to our experience, careful preoperative assessment from the views of both patient and device selection along with patient education, and strictly obeying the rules of sterility during implantation and applying systemic and local antimicrobial prophylaxis are essential in obtaining a successful result in prosthesis implantation for the individual patient.

Probl Tuberk, 1996, (2), 43 - 5
{Immunotropic activity of antimicrobial agents used in tuberculosis}; Aleksandrova AE et al.; Mice with experimental tuberculosis were given isoniazid, rifampicin, erythromycin, cefotaxime, ofloxacin . Erythromycin, cefotaxime and ofloxacin enhanced macrophage activity if their course did not exceed 2-4 weeks . Isoniazid and rifampicin for a short time inhibited macrophage activity then stimulated it . These findings led the authors to the conclusion that erythromycin, cefotaxime and ofloxacin must be used only in short courses.

Cutis, 1996 Jan, 57(1 Suppl), 13 - 9
Rationale for the development of new topical treatments for acne vulgaris; Gibson JR; The development of new topical anti-acne therapies reflects the need for medications that address the requirements and concerns of an increasingly mature and demanding acne patient population . Some of the topical agents currently under investigation in the United States include several alpha-hydroxy acids (AHAs), the retinoids tazarotene and adapalene, and azelaic acid . All of these agents appear to exert their effect on acne through some effect on the process of keratinization and/or the thickness of the stratum corneum . Azelaic acid also has significant antimicrobial activity relevant to its efficacy in acne vulgaris . While azelaic acid has already been used successfully in many parts of the world for several years, the potential roles of the new retinoids in acne therapy are just beginning to be clarified . The properties of AHAs suggest that they may also be of value in the treatment of acne, but further systematic evaluation is needed.

Int J STD AIDS, 1996, 7 Suppl 1, 23 - 7
Treatment and prophylaxis of Mycobacterium avium complex; Young LS; The most common pathogens involved in disseminated bacterial infection in people with acquired immunodeficiency syndrome (AIDS) are organisms of the Mycobacterium avium-intracellulare complex (MAC) . Azithromycin and clarithromycin, a new azalide and macrolide, respectively, are among the most potent monotherapies for MAC bacteraemia, Although many bloodstream isolates demonstrate increased minimum inhibitory concentrations after 4 months of treatment . Current recommended prophylaxis, based on the results of two randomized, double-blind, prospective studies, is rifabutin 300 mg daily for people with AIDS with < 100 CD4 lymphocytes/mm3 . In the beige mouse model, we have shown that both azithromycin and clarithromycin prevent MAC bacteraemia following repetitive oral challenge . Clinical trails are now underway to confirm these effects in man; comparative treatments include placebo, rifabutin and an azalide/macrolide plus rifabutin . While combinations might be more effective and reduce the emergence of resistance, the spectre of cytochrome P-450 drug interactions necessitates careful study before combination prophylactic approaches are accepted . Such interactions are associated with rifabutin and some macrolides, although azithromycin may be less problematic in this respect as it appears to have little potential to interact with other antimicrobial agents.

S D J Med, 1996 Jan, 49(1), 27 - 8
Antibiotics before surgery; Kaatz B; The antimicrobial era (along with greater surgical skill and precision) has brought us relative safety for procedures that previously were fraught with danger . Civil War amputation surgeries, for example, had an extraordinarily high incidence of infections and mortality . Staying aware of and avoiding the small, but real, risks associated with surgical antibiotic prophylaxis will help sustain the advances we enjoy today.

J Antimicrob Chemother, 1996 Jan, 37(1), 93 - 103
In-vitro effects of cefodizime on leucocyte functions and colony formation from granulocyte-monocyte progenitors; Shin WS et al.; Infections in immunocompromised patients are often difficult to treat, even with currently available antimicrobial agents . An understanding of the effects of antibiotic therapy on the host's immune response is therefore important when deciding on the clinical management of such patients . Antimicrobial agents which lack immunodepressive effects and/or potentiate the immune response are the goal of current research into the treatment of infections in immunocompromised patients . The effects of cefodizime (1-250 micrograms/mL) in vitro on some functional activities of leucocytes and on colony formation by granulocyte monocyte progenitors were studied to investigate the effects of the antibiotic on the host's immune response . A marked enhancement in the lymphocyte transformation reaction was observed in cells exposed to cefodizime . This effect was dose-dependent . Cefodizime had no significant effect on antibody-dependent cell cytotoxicity or on natural killer cell-mediated cytotoxicity . The chemotactic activity of neutrophils was not influenced by the presence of cefodizime (P > 0.05) . The phagocytic activity of neutrophils was significantly increased by cefodizime (P > 0.01) . Cefodizime significantly stimulated, in a dose-dependent manner, colony formation by granulocyte-monocyte progenitors (P < 0.01) . Results suggest that cefodizime has certain stimulatory effects on immunocompetent cells such as enhancing the transformation reaction of lymphocytes, neutrophil phagocytosis and colony formation by granulocyte-monocyte progenitors . Further studies are required to clarify the mechanisms responsible for these effects.

J Antimicrob Chemother, 1996 Jan, 37(1), 7 - 32
Drug chirality: a consideration of the significance of the stereochemistry of antimicrobial agents; Hutt AJ et al.; Approximately 25% of drugs are marketed as either racemates or mixtures of diastereoisomers . Such stereoisomers frequently differ in terms of their biological activity and pharmacokinetic profiles and the use of such mixtures may contribute to the adverse effects of the drug particularly if they are associated with the inactive or less active isomer . In recent years drug stereochemistry has become a significant issue for both the pharmaceutical industry and the regulatory authorities . The significance of stereoisomerism in antimicrobial agents is addressed in this review using examples drawn from the beta-lactams, as being representative of semisynthetic agents, and the quinolones, as examples of synthetic agents . Within these two groups of compounds it is clear that stereochemical considerations are of significance for an understanding of concentration effect relationships, selectivity in both action and inactivation and for an appreciation of the mode of action at a molecular level . In the case of some agents the use of a single isomer is precluded due to their facile epimerization, e.g . carbenicillin, in the case of others there are potential advantages with the use of single isomers, e.g . ofloxacin . However, in the case of latamoxef, a compound which undergoes in-vivo epimerization with a half-life similar to its apparent serum elimination half-life the situation is by-no-means clear cut . These agents emphasise the importance of considering each compound individually, i.e . on a case-by-case basis, before deciding to use a single isomer or stereoisomeric mixture.

J Antimicrob Chemother, 1996 Jan, 37(1), 151 - 4
Comparative in-vitro activity of sparfloxacin and eight other antimicrobial agents against clinical isolates of non-tuberculous mycobacteria; Sanchez-Carrillo C et al.; The in-vitro activity of sparfloxacin and eight other antimicrobial agents against 64 non-tuberculous mycobacteria (non-MAI) (40 rapidly growing and 24 slowly growing) was compared with those of ciprofloxacin, ofloxacin, amikacin, tobramycin, cefoxitin, imipenem, clarithromycin and doxycycline . Sparfloxacin presented the same activity as ciprofloxacin, being highly active against rapidly growing mycobacteria and showing good in-vitro activity against slowly growing mycobacteria . Amikacin was very active against rapidly growing mycobacteria and clarithromycin presented good activity against all mycobacteria tested . These results suggest that sparfloxacin is a valid agent to be considered in the treatment of Mycobacterium spp . infections.

J Antimicrob Chemother, 1996 Jan, 37(1), 117 - 26
In-vitro activity of levofloxacin against clinical isolates of Legionella spp, its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia; Edelstein PH et al.; The activities of levofloxacin and ofloxacin against 22 clinical legionella isolates was determined by microbroth dilution susceptibility testing . Growth inhibition of two Legionella pneumophila strains grown in guinea pig alveolar macrophages by levofloxacin, ofloxacin, or erythromycin was also determined . The drug concentrations required to inhibit 90% of strains tested was 0.032 mg/L for levofloxacin or ofloxacin, and was 0.016 mg/L for ciprofloxacin . BYE alpha broth significantly inhibited the activities of all three drugs tested, as judged by the susceptibility of control Escherichia coli strains . Levofloxacin (0.25 mg/L) reduced bacterial counts of two L . pneumophila strains grown in guinea pig alveolar macrophages by 1 log10, but regrowth occurred over a 3 day period; levofloxacin (1 mg/L) reduced bacterial counts by 2-3 log10 cfu/mL . Levofloxacin was significantly more active than erythromycin, and as active as ofloxacin or ciprofloxacin in this assay . Pharmacokinetic and therapy studies of levofloxacin and ofloxacin were performed in guinea pigs with L . pneumophila pneumonia . For the pharmacokinetic study, levofloxacin was given (10 mg/kg) by the intraperitoneal route to infected guinea pigs; mean peak plasma and lung concentrations were 3.4 mg/L and 1.4 micrograms/g, respectively, at 0.5 h and 2.6 mg/L and 0.6 micrograms/g at 1 h . The terminal half-life phase of elimination from plasma and lung was c . 1 h . All 15 infected guinea pigs treated with levofloxacin (10 mg/kg/day given ip once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 14 guinea pigs treated with the same dose of ofloxacin . None of 13 animals treated with saline survived . Levofloxacin is effective against L . pneumophila in vitro and in a guinea pig model of legionnaire's disease . Levofloxacin should be evaluated as a treatment of human legionnaires' disease.

Food Addit Contam, 1996 Jan, 13(1), 13 - 9
Evaluation of a multiple bioassay technique for determination of antibiotic residues in meat with standard solutions of antimicrobials; Calderon V et al.; A multiple bioassay technique (FSIS-USDA) has been evaluated with standard solutions of 38 antibiotics and sulphonamides . Activity patterns at five levels were obtained when antibiotic solutions were assayed on seven plates prepared with different media and microorganisms . A different activity pattern was obtained for the main antibiotic groups: tetracyclines, beta-lactam antibiotics, macrolides and aminoglycosides . Sulphonamides were not detected at levels at under 100 micrograms/ml . This technique, as a post-screening test for antibiotic residues, can be used after a screening test to identify antibiotic groups to which more specific techniques can be applied for full identification and quantification.

J Vet Med Sci, 1996 Jan, 58(1), 61 - 5
Growth inhibitory effects of bovine lactoferrin to Toxoplasma gondii parasites in murine somatic cells; Tanaka T et al.; Lactoferrin (LF) is known to have broad spectrum antimicrobial properties . In regards to its defense mechanism against parasitic infection, it has shown phagocytic activity in the destruction of amastigotes, an intracellular parasitic form of Trypanosoma cruzi in macrophages . The effect of bovine lactoferrin on the intracellular growth Toxoplasma gondii parasites was examined in murine macrophage and embryonal cells . Co-cultures of host cells with the parasites were supplemented with either lactoferrin, apo-lactoferrin, holo-lactoferrin or transferrin in the culture media for varying periods . The growth activity of intracellular parasites in the host cells was determined by the measurement of selective incorporation of 3H-uracil . Supplement of lactoferrin had no effect on the penetration activity of the parasites, while development of intracellular parasites was inhibited linearly in concentration of lactoferrin . Supplement of apo-lactoferrin and holo-lactoferrin, but not transferrin showed similar effects . These suggest that lactoferrin induces the inhibitory effects on the development of intracellular parasites . Pretreatment of lactoferrin to the macrophages, however, did not show any inhibitory effects . Whereas, mouse embryonal cells preincubated with lactoferrin suppressed the intracellular growth . Thus, the action of lactoferrin to macrophages would be different from that of mouse embryonal cells.

J Clin Periodontol, 1996 Jan, 23(1), 7 - 11
The effects of antimicrobial mouthrinses on de novo plaque formation at sites with healthy and inflamed gingivae; Ramberg P et al.; The objective of the present investigation was to evaluate to what extent mouthrinses containing triclosan and chlorhexidine may modify the amount of de novo plaque that forms on tooth surfaces adjacent to healthy and inflamed gingival units . 10 volunteers were recruited . On day 0, gingival crevicular fluid (GCF) was obtained at predetermined sites and gingivitis (GI) was assessed . A careful oral prophylaxis was given to each of the volunteers who subsequently abstained from all mechanical plaque control measures for the following 18 days . During the first 4 days (rinse phase I), they rinsed with either 0.12% chlorhexidine, 0.06% triclosan or placebo solution . Clinical examinations (GCF, GI) were repeated and the amount of plaque formed determined on days 4, 7 and 14 . On day 14, the participants received a new professional tooth cleaning after which rinse phase II was initiated . During this 2nd phase, the participants rinsed for 4 days with the same mouthwash preparation and in the same manner as during rinse phase I . The examinations were repeated on day 18 . Each participant received a comprehensive oral prophylaxisis and was instructed to perform meticulous mechanical plaque control during the following 4 weeks . A 2nd experimental period was then initiated . A total of 3 experimental periods were repeated until all subjects had rinsed with the 3 different mouthwash preparations . The results demonstrated (i) that significantly more plaque formed at sites with gingivitis than at surfaces adjacent to healthy gingival units and (ii) pre-existing gingivitis significantly increased the amount of de novo plaque that formed in subjects who rinsed with mouthwash preparations containing chlorhexidine and triclosan.

Scand J Rheumatol, 1996, 25(2), 112 - 4
An aseptic inflammation of the clavicle in a patient with Crohn's disease . A potential manifestation of the SAPHO syndrome; Kotilainen PM et al.; A female patient with Crohn's disease developed an septic osteoarticular involvement of the left clavicle and sterno- and acromioclavicular regions . Repeated surgical revisions combined with a broad-spectrum antimicrobial treatment could not prevent the progress of the disease . However, the patient started to improve after the diagnosis of the SAPHO (synovitis, acne, pustulosis, hyperostosis and osteomyelitis) syndrome was made and the dose of her immunosuppressive therapy increased . This patient reminds of the existence of extraintestinal aseptic infections in association with inflammatory bowel disease (IBD) . Moreover, it may provide further evidence on the significant association between SAPHO and IBD.

Int J Syst Bacteriol, 1996 Jan, 46(1), 259 - 64
Nocardia pseudobrasiliensis sp . nov., a new species of Nocardia which groups bacterial strains previously identified as Nocardia brasiliensis and associated with invasive diseases; Ruimy R et al.; We studied five strains of a new Nocardia taxon recently identified among Nocardia brasiliensis strains associated with invasive diseases (R . J . Wallace, Jr., B . A . Brown, Z . Blacklock, R . Ulrich, K . Jost, J . M . Brown, M . M . McNeil, G . Onyi, V . A . Steingrube, and J . Gibson, J . Clin . Microbiol . 33:1528-1533, 1995) to determine their taxonomic status . Several characteristics of these organisms, including the presence of chemotype IV cell walls, nocardomycolic acids, a predominant menaquinone similar to that of Nocardia asteroides ATCC 19247T (T = type strain), and G+C contents ranging from 67 to 68 mol%, are characteristics of the genus Nocardia . Phylogenies based on small-subunit ribosomal DNA sequences clearly confirmed that all five strains belong to the genus Nocardia and occur on a single branch that is clearly distinct from N . brasiliensis . This branch forms a clade with Nocardia vaccinii, Nocardia nova, Nocardia otitidiscaviarum, and Nocardia seriolae . The five new strains exhibited high levels of DNA relatedness with each other, as determined by DNA-DNA hybridization experiments (S1 nuclease procedure), but not with N . brasiliensis strains or with strains of the four phylogenetically related Nocardia species mentioned above . The five new strains differ from N . brasiliensis in the following characteristics: mycolic acid pattern, decomposition of adenine, nitrate reduction, and antimicrobial agent susceptibilities . Therefore, we propose that these strains belong to a new species, Nocardia pseudobrasiliensis . The type strain is strain ATCC 51512, which was isolated from a leg abscess on a patient suffering from ulcerative colitis.

Am J Obstet Gynecol, 1996 Jan, 174(1 Pt 1), 206 - 10
Randomized investigation of antimicrobials for the prevention of preterm birth; Cox SM et al.; OBJECTIVE: Occult amniotic fluid infection has emerged as a possible cause of many heretofore unexplained preterm births . We sought to determine whether antimicrobial therapy is effective in preventing preterm delivery . STUDY DESIGN: A double-blind, placebo-controlled, randomized trial was conducted to study the efficacy of ampicillin-sulbactam and amoxicillin-clavulanic acid in women hospitalized for preterm labor between 24 and 34 weeks' gestation . During this investigation no tocolytics or steroids were used . RESULTS: Thirty-nine women with preterm labor received antimicrobial therapy and 39 received placebos . The mean gestational ages at study entry were 29.8 +/- 0.4 weeks (SEM) and 30.6 +/- 0.3 weeks in the antimicrobial and placebo groups, respectively (not significant) . Similarly, the mean gestational ages at delivery were 34.2 +/- 0.7 and 34.1 +/- 0.6 weeks, respectively (not significant) . Other index values of pregnancy outcome, for example, birth weight, neonatal morbidity, and prenatal death, were not significantly improved by antimicrobial therapy given to the mother in preterm labor . CONCLUSION: We find that antimicrobial therapy given to women in preterm labor is ineffective in the prevention of preterm birth.

Am J Med Sci, 1996 Jan, 311(1), 9 - 16
Reasons for the emergence of antibiotic resistance; Tenover FC et al.; The ability of many different species of bacteria, including those that cause diseases in humans, to resist the inhibitory action of antimicrobial agents has become a global problem . Resistance continues to spread not only in nosocomial pathogens but in several key community-acquired organisms as well . Appropriate control measures for such resistant organisms depend in part on the pathways by which resistance has arisen . Unfortunately, these pathways differ greatly from organism to organism and setting to setting . In addition, although the epidemiology of resistant organisms sometimes is similar to that of susceptible organisms of the same kind, in some situations it may be quite different . In this article, the authors highlight some of the pathways leading to the development of resistance in bacteria, the importance of antimicrobial use, and the relevance of these mechanisms to measures for the control of resistant bacteria in hospital and community settings.

Infect Immun, 1996 Jan, 64(1), 161 - 6
Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection; Murray HW et al.; Euthymic C57BL/L ep/ep (pale ear {PE}) mice halt the visceral replication of intracellular Leishmania donovani but fail to properly resolve infection . A previous study identified an isolated defect in tissue granuloma formation in these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production, and macrophage antimicrobial activity in vitro were all intact . New in vivo results reported here suggest a considerably more complex immune defect, with evidence indicating (i) enhanced control over L . donovani after transfer of normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha, (iv) absent responses to exogenous treatment with recognized antileishmanial cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating factor {GM-CSF}) not corrected by transfer of C57BL/6 spleen cells, and (v) a deficient response to antimony chemotherapy . Defective hepatic granuloma formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4 administration . While treatment with IL-2 and GM-CSF modified the tissue reaction and induced selected effector cells to encase tissue macrophages, no antileishmanial activity resulted . Together, these observations suggest that the failure of PE mice to resolve visceral L . donovani infection likely represents expression of multiple suboptimal immune responses and/or partial defects, probably involving a combination of T-cell dysfunction, a Th2 cell response, and target cell (macrophage) hyporesponsiveness.

Clin Radiol, 1996 Jan, 51(1), 39 - 41
Antibiotic prophylaxis in patients undergoing radiological procedures who are at risk of infective endocarditis--do radiologists know what they are doing?
Chakraverty S, Baker EM, D'Souza R, Hide IG, Chippindale AJ.
The British Society for Antimicrobial Chemotherapy has published guidelines recommending that all patients with prosthetic heart valves, or those with a previous history of bacterial endocarditis, should receive prophylactic antibiotics before procedures likely to cause a bacteraemia, due to the potential risk of bacterial endocarditis . The guidelines are widely available, notably in the British National Formulary . Two separate and independent surveys of radiologists in this Region showed that there was poor awareness of these guidelines and their implications for radiology departments.

Biochem J, 1996 Jan 1, 313 ( Pt 1), 141 - 7
Rapid identification of compounds with enhanced antimicrobial activity by using conformationally defined combinatorial libraries; Blondelle SE et al.; We have combined the strength of our synthetic combinatorial library approach for the rapid identification of highly active compounds with prior knowledge of the relationship between the antimicrobial activities of individual peptides with specific induced conformations in order to identify new peptides with enhanced activity relative to a starting known antimicrobial sequence . In the current study, conformationally defined combinatorial libraries were generated based on an 18-mer antimicrobial peptide known to be induced into an alpha-helical conformation in a lipidic environment . Not only were novel sequences readily identified with 10-fold increases in activity, but detailed information about the structure-activity relationships of the peptides studied was also obtained during the deconvolution process . By using circular dichroism spectroscopy it was found that the individual 18-mer peptides could be induced into alpha-helical conformations on interaction with the cell lipid layer and/or sialic acids, which could result in bacterial cell lysis due to perturbation of the lipid packing of the cell wall.

Am Fam Physician, 1996 Jan, 53(1), 227 - 32
Renal and electrolyte complications associated with antibiotic therapy; Kasama R et al.; Adverse effects of antibiotics generally are minimal, but it is necessary to remain vigilant for potentially serious sequelae, such as unusual forms of renal failure, acidosis and electrolyte abnormalities . Avoiding potentially nephrotoxic drug combinations and monitoring drug levels of nephrotoxic agents such as vancomycin and aminoglycosides should be routine . However, with prolonged use of certain antibiotics, levels of electrolytes, creatinine and blood urea nitrogen should be periodically checked . Elderly and debilitated patients or patients with preexisting renal insufficiency are at particularly high risk for unexpected complications from antimicrobial therapy . All antibiotics have the potential to cause acute interstitial nephritis, which may be manifested by acute renal failure.

Pediatrics, 1996 Jan, 97(1), 59 - 64
Benefit of primary prophylaxis before 18 months of age in reducing the incidence of Pneumocystis carinii pneumonia and early death in a cohort of 112 human immunodeficiency virus-infected infants . New York City Perinatal HIV Transmission Collaborative Study Group; Thea DM et al.; OBJECTIVE . To determine the effectiveness of primary prophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection . METHODS . We conducted a retrospective analysis of a cohort of infants followed from birth at six metropolitan hospitals and one outpatient clinic for pregnant, drug-using women in New York City . Outcomes measured were histologically confirmed PCP and/or death . The potential confounding effect of the infant's stage of illness, as determined by CD4 count, was controlled by including all CD4 determinations as time-dependant covariates in a Cox proportional hazards analysis . Cases were censored at PCP onset, death, loss to follow-up, and 18 months of age . RESULTS . One hundred twelve HIV-infected children were enrolled at birth between 1986 and 1993 . Sixty of these were tracked beyond 18 months of age; of the others, 21 died before this age, 4 were considered lost to follow-up, and 27 had not reached 18 months of age at the last visit . Only 3 cases (4%) of confirmed PCP occurred among the 70 children who received primary PCP prophylaxis before 18 months of age, compared with 12 cases (28%) among 42 children not receiving PCP prophylaxis at any point before 18 months of age . The Kaplan-Meier estimated incidence of PCP in the first year among children not receiving prophylaxis was 25% (95% confidence interval {CI}, 12 to 39) . Using Cox methods, the unadjusted risk of PCP among infants not receiving prophylaxis, relative to those receiving it, was 4.1 (95% CI, 1.1 to 15); the relative risk was 4.4 (95% CI, 1.2 to 17) adjusting for the percentage of CD4-positive lymphocytes and 5.1 (95% CI, 1.3 to 20) adjusting for the absolute number of CD4-positive cells . Eight of 26 deaths were caused by PCP, and the likelihood of early death was significantly diminished if PCP prophylaxis was given (relative risk controlling for absolute CD4 cells, 2.57; 95% CI, 1.1 to 6.1) . CONCLUSIONS . We report evidence that primary antimicrobial PCP prophylaxis is highly effective in decreasing the frequency of PCP and early death in infants with perinatal HIV infection . These findings support the revised National Pediatric HIV Resource Center and Centers for Disease Control and Prevention guidelines for PCP prophylaxis in children.

Geriatrics, 1996 Jan, 51(1), 37 - 40, 43
Renal failure: why today's patients live better and longer; Chan R et al.; The clinical courses of two older patients with progressive renal failure associated with hypertension are described . Their underlying disorders are similar, but there are stark contrasts between medical therapies available now and 50 years ago . Such advances include the development of antihypertensive drugs and antimicrobial medications that have reduced the incidence of renal failure . In addition, recombinant erythropoietin and calcitriol have decreased the morbidity associated with chronic renal failure . Finally, technologic breakthroughs in dialysis have made a once-fatal condition eminently treatable.

Postgrad Med, 1996 Jan, 99(1), 95 - 102, 105-7
Community-acquired pneumonia . What's needed for accurate diagnosis; File TM Jr et al.; Characteristic clinical findings of fever, cough, and rhonchi, together with a new infiltrate on chest films and documentation of a pathogen, establish a diagnosis of infectious pneumonia . Several factors have had an impact on the approach to diagnosis of community-acquired pneumonia by the primary care physician . These include the expanding number of possible pathogens as well as their increasing resistance to antimicrobial therapy . Although the clinical presentation may suggest a specific cause, findings often overlap too much for reliable identification of the specific agent on clinical grounds alone . Isolation of the microorganism or determination of the presence of a specific antigen or antibody is necessary . However, even after extensive studies are performed, the pathogen remains unidentified in 30% to 50% of cases . The primary care physician therefore needs to balance reasonable use of diagnostic tests with empirical therapy.

Postgrad Med, 1996 Jan, 99(1), 109 - 10, 113-4, 117-9, passim
Community-acquired pneumonia . Cost-effective antimicrobial therapy; Cunha BA; At present, three antibiotics (doxycycline, ofloxacin {Floxin}, and azithromycin {Zithromax}) provide optimal therapy for both typical and atypical community-acquired pneumonias . These agents permit a monotherapeutic approach and are also ideal for intravenous-to-oral switch therapy, which results in great cost savings for an institution and an earlier discharge for the patient . The era of oral therapy has been ushered in because of economic imperatives . Fortunately, bioavailability of these three antibiotics is essentially the same when administered intravenously or orally . Moderately to severely ill patients may be safely and effectively treated via the oral route alone; however, most patients who require admission to the hospital are initially given intravenous therapy, after which a change is made to an oral antibiotic equivalent as soon as possible.

J Fam Pract, 1996 Jan, 42(1), 69 - 78
Quinolones: a practical review of clinical uses, dosing considerations, and drug interactions; Borcherding SM et al.; A review of the literature on quinolones reveals numerous clinically relevant points regarding indications, dosing considerations, and drug interactions . Quinolones are useful in the treatment of several infectious diseases . Unfortunately, indiscriminate use of these valuable antimicrobials has resulted in increased patterns of resistance . It is important to consider carefully the site of infection and the potential pathogens in each patient before dosing . Quinolones have excellent oral absorption, with peak serum concentrations approaching those achieved with intravenous administration . When prescribing quinolones, the dose should be based on estimated creatinine clearance . Quinolones are associated with several clinically significant drug interactions . Some of these agents are well-documented inhibitors of hepatic metabolism of theophylline, caffeine, and warfarin . It has been well documented that divalent and trivalent cations in antacids, sucralfate, and some other products significantly reduce the absorption of quinolones . Avoidance or proper management of these interactions is required to ensure optimal safety and efficacy.

Gastroenterology, 1996 Jan, 110(1), 72 - 83
Initial endoscopy or empirical therapy with or without testing for Helicobacter pylori for dyspepsia: a decision analysis; Silverstein MD et al.; BACKGROUND & AIMS: Empirical therapy has been proposed for initial management of dyspepsia . The aim of this study was to evaluate initial endoscopy, empirical therapy, and testing for Helicobacter pylori in the management of patients with a new onset of dyspepsia . METHODS: Decision analysis was used to compare the direct medical charges in the first year after the onset of dyspepsia for patients managed by initial endoscopy or empirical therapy, with or without initial testing for H . pylori . RESULTS: Medical care charges were $2162.50 for initial endoscopy and $2122.60 for empirical therapy, a difference of 1.8% . For a 55-year-old adult, life expectancy was 23.49 years for initial endoscopy compared with 23.48 years for empirical therapy . Empirical therapy has lower charges than initial endoscopy when H2-receptor antagonists are used to prevent recurrence of dyspepsia . Initial noninvasive testing for H . pylori has lower charges than initial endoscopy if patients with dyspepsia with H . pylori receive antimicrobial therapy without endoscopy but would have higher charges if patients with H . pylori routinely have endoscopy . CONCLUSIONS: Surprisingly, the choice of optimal management strategy was a "toss-up." Only modest savings may result from practice guidelines that recommend empirical therapy in the management of patients with dyspepsia.

Mol Cell Biol, 1996 Jan, 16(1), 359 - 68
The interferon-inducible p202 protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities; Min W et al.; The antimicrobial, immunomodulatory, and cell growth-regulatory activities of the interferons are mediated by interferon-inducible proteins . One of these is p202, a nuclear protein that is encoded by the Ifi 202 gene from the interferon-activatable gene 200 cluster . Overexpression of p202 in transfected cells slows down cell proliferation . As shown earlier, p202 binds to the hypophosphorylated form of the retinoblastoma susceptibility protein . Here we report that p202 inhibits the activities of the NF-kappa B and the AP-1 enhancers both in transiently transfected cells and in transfected stable cell lines overexpressing p202 . Furthermore, p202 binds the NF-kappa B p50 and p65 and the AP-1 c-Fos and c-Jun transcription factors in vitro and in vivo . NF-kappa B, c-Fos, and c-Jun participate in the transcription of various cellular and viral genes, and thus p202 can modulate the expression of these genes in response to interferons.

FEBS Lett, 1995 Dec 27, 377(3), 519 - 22
Molecular analysis of the sheep cathelin family reveals a novel antimicrobial peptide; Mahoney MM et al.; Cathelin-related genes are characterized by the presence of a prepro sequence which is highly conserved both within and between species . 3' RACE analysis on sheep bone marrow RNA, using a primer based on a conserved cathelin family coding region, demonstrated the presence of at least three ovine cathelin-related cDNAs . One of these encodes a novel prepropeptide with a predicted C-terminal cleavage product RGLRRLGRKIAHG-VKKYGPTVLRIIRIAG . The chemically synthesized form of this 29 amino acid peptide is shown to be a thermostable, broad spectrum, bactericidal agent.

Biochem Pharmacol, 1995 Dec 22, 50(12), 2105 - 7
Alkali cation transport through liposomes by the antimicrobial fusafungine and its constitutive enniatins; Levy D et al.; Fusafungine is a peptide antibiotic mixture composed of several enniatins and active against Gram-positive bacteria . Ionophoric properties of fusafungine have been studied in liposomes by measuring protoncation exchange by both fluorescence and 31P-nuclear magnetic resonance (NMR) and have been compared to those of its constituent enniatin peptides . Fusafungine, as well as enniatins, transport cations through a mobile carrier mechanism selective for K+ vs . Na+ and involving two antibiotic molecules . The transport efficiencies of the various enniatins appear to be related to their hydrophobicity, in agreement with a previously proposed "sandwich" transport model . The ionophoric properties of crude fusafungine may be involved in its antibiotic action and its local therapeutic properties.

J Med Chem, 1995 Dec 22, 38(26), 5015 - 22
Chemistry and antimicrobial activity of caryoynencins analogs; Yamaguchi M et al.; Caryoynencins (1) are antibiotics isolated from liquid cultures of a plant pathogen, Pseudomonas caryophylli, and are unstable C18 carboxylic acids with a conjugated dienetetrayne structure . Enyne analogs of caryoynencins were synthesized from monosilylated 1,3-butadiyne 2 (n = 2), 1,3,5-hexatriyne 2 (n = 3), and 1,3,5,7-octatetrayne 2 (n = 4) by alkynyl metal addition to 2,4-hexadienal (3) followed by allylic rearrangement and deprotection . Tetraynol 5 (n = 4) thus obtained was resolved by enzyme reactions . The conjugated dienetetrayne compounds are mixtures of 3E,5E- and 3E,5Z-isomers, which equilibrate by room light . 13C-NMR chemical shifts of polyynes obey simple rules, which can be used for signal assignments . Antimicrobial activities of conjugated enynes and related compounds were examined . The tetrayne analog 6 (n = 4) possesses potent antibacterial and antifungal activities, while triyne and diyne analogs 6 (n = 3 and 2) are less active . Chirality does not affect the activities . An isomeric enyne compound, 2,4-tetradecadiene-7,9,11,13-tetrayn-6-ol (8), showed potent activity against Tricophyton.

Toxicology, 1995 Dec 15, 104(1-3), 9 - 16
Potential metabolism and cytotoxicity of N-(3,5-dichlorophenyl)succinimide and its hepatic metabolites in isolated rat renal cortical tubule cells; Henesey CM et al.; N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide and antimicrobial agent that produces nephrotoxicity in rats . The contribution of the kidney, if any, to the mechanism of toxicity of NDPS is not known . Therefore, the ability of isolated renal cortical tubule cells to metabolize NDPS and some of its known hepatic metabolites was studied . The cytotoxic potential of these compounds was also assessed . Renal cortical tubule cells were isolated by collagenase digestion and were incubated with the test compounds (2 mM) for 3 h . Metabolite formation was monitored by reversed phase HPLC and cell viability was assessed using trypan blue exclusion . The isolated kidney cells do not appear to metabolize NDPS or any of its known hepatic metabolites . In addition, none of these compounds were directly cytotoxic to the renal cells . However, the cells were susceptible to mercuric chloride (1 mM) and chloroform (125 or 200 mM) . Intracellular glutathione levels were unaltered by the presence of NDPS in the incubations . These results suggest that NDPS and its metabolites are not directly toxic to the kidney and are not converted into the ultimate nephrotoxic species by the kidney . Extrarenal metabolism may, therefore, be critical to the expression of NDPS-induced nephrotoxicity.

Transplantation, 1995 Dec 15, 60(11), 1211 - 4
Enhancement of nonspecific resistance by liposome-encapsulated immunomodulators does not affect skin graft rejection in mice; ten Hagen TL et al.; Administration of liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidyl ethanolamine (LE-MTPPE) or interferon-gamma (LE-IFN-gamma), or co-encapsulated MTPPE and IFN-gamma (LE-(MTPPE/IFN-gamma)) resulted in a dramatic increase of the nonspecific antimicrobial resistance in mice, as shown before . This kind of treatment is especially of use in immunocompromised hosts who are prone to severe infections . Application of these immunomodulators might protect these patients, e.g., transplant recipients, from opportunistic infections . However, accelerated rejection of the graft, resulting from augmentation of the antimicrobial defense in a nonspecific way, has to be avoided . In this study, the effect of treatment with LE-MT-PPE, LE-IFN-gamma, or LE-(MTPPE/IFN-gamma) on skin graft rejection in mice was investigated . It was found that prophylactic treatment of skin-grafted mice with immunomodulating formulations did not influence rejection of the graft . Moreover, in T cell-depleted mice, which showed a prolonged graft survival compared with immunocompetent recipients, the administration of immunomodulators did not change the survival time of the grafts compared with T cell-depleted mice that did not receive immunomodulators . The results clearly show that, in this experimental setting, application of the antimicrobial resistance-enhancing formulations (LE-MTPPE, LE-IFN-gamma, and LE-(MTPPE/IFN-gamma)) is allowed in graft-bearing recipients, without influencing graft survival.

Biochim Biophys Acta, 1995 Dec 13, 1240(2), 149 - 58
Magainin-induced cytotoxicity in eukaryotic cells: kinetics, dose-response and channel characteristics; Haimovich B et al.; Magainin 1 and magainin 2 are broad-spectrum antimicrobial and antifungal peptides initially purified from Xenopus laevis skin glands . The mechanism of cytotoxicity of the naturally occurring magainin 2 and a potent all-D amino acid analogue, MSI-238, was examined for eukaryotic cells using flow cytometric analysis with propidium iodide (PI) . Exposure to MSI-238 resulted in cell death within seconds to minutes, depending on the concentration of the peptide . Several cell types were examined including a mouse fibroblast cell line Balb/3T3 and a Rous sarcoma virus Balb/3T3-transformed cell line, SRD/3T3, primary chick embryo fibroblasts and cells derived from a human ovarian carcinoma, OVCA-3 . The K0.5 values determined from 5 min exposures ranged from 24 to 80 micrograms/ml for MSI-238 and approximately 600 micrograms/ml for magainin 2 . Molecular properties of MSI-238 induced channels were studied in excised membrane patch recordings from Balb/3T3 and SRD/3T3 cells . At low concentrations of 0.1 micrograms/ml, occasional, brief, multiple-level current fluctuations were seen suggesting channels with multiple, rapidly changing conductance levels . At 5 or 10 micrograms/ml of MSI-238, the current fluctuations were larger in magnitude and occurred more frequently producing a general disruption of the membrane similar to the effects of melittin on membranes.

J Crit Illn, 1996 Jan, 11(1), 55 - 62
Techniques for noninvasive diagnosis of lower respiratory tract infections . Which tests to order, when to consider invasive procedures; Washington JA; Although sputum culture and Gram's staining have been the traditional methods for determining the cause of lower respiratory tract infections, oropharyngeal contamination and improper sputum collection can limit their usefulness . Nevertheless, these noninvasive techniques remain a rapid means of gathering diagnostic clues . Alternative approaches include acid-fast sputum stains, direct immunofluorescence examination, enzyme immunoassays, DNA probes, and serologic testing . However, for critically ill patients, invasive procedures (such as bronchoscopy and thoracentesis) can provide more definitive diagnoses to guide selection of antimicrobial therapy.

Proc Natl Acad Sci U S A, 1995 Dec 5, 92(25), 11801 - 5
Topoisomerase IV is a target of quinolones in Escherichia coli; Khodursky AB et al.; We have demonstrated that, in Escherichia coli, quinolone antimicrobial agents target topoisomerase IV (topo IV) . The inhibition of topo IV becomes apparent only when gyrase is mutated to quinolone resistance . In such mutants, these antibiotics caused accumulation of replication catenanes, which is diagnostic of a loss of topo IV activity . Mutant forms of topo IV provided an additional 10-fold resistance to quinolones and prevented drug-induced catenane accumulation . Drug inhibition of topo IV differs from that of gyrase . (i) Wild-type topo IV is not dominant over the resistant allele . (ii) Inhibition of topo IV leads to only a slow stop in replication . (iii) Inhibition of topo IV is primarily bacteriostatic . These differences may result from topo IV acting behind the replication fork, allowing for repair of drug-induced lesions . We suggest that this and a slightly higher intrinsic resistance of topo IV make it secondary to gyrase as a quinolone target . Our results imply that the quinolone binding pockets of gyrase and topo IV are similar and that substantial levels of drug resistance require mutations in both enzymes.

Biochemistry, 1995 Dec 5, 34(48), 15614 - 8
Antimicrobial peptide pores in membranes detected by neutron in-plane scattering; He K et al.; Antimicrobial peptides isolated from the host defense systems of animals have been shown to exert their activity directly on the lipid bilayer of cell membranes, but the antimicrobial mechanisms are not clear, due chiefly to the difficulty of discerning the high-order structures formed by these peptides in membranes . Previously we have shown that these peptides insert into the membrane when their concentrations exceed a lipid-dependent critical value . With neutron in-plane scattering we now show that inserted alamethicin creates aqueous pores approximately greater than 18 A in diameter . The density of pores is consistent with the assumption that all of the alamethicin is involved in pore formation . Pores were not detected below the critical concentration . Thus concentration-dependent pore formation appears to be the molecular mechanism of antimicrobial action.

FEBS Lett, 1995 Dec 4, 376(3), 225 - 8
cDNA sequences of three sheep myeloid cathelicidins; Bagella L et al.; Several myeloid antimicrobial peptide precursors have been shown to consist of a N-terminal proregion similar to a protein named cathelin and a structurally varied C-terminal antimicrobial domain . Proteins with these features have been named cathelicidins . In this paper we report the cDNA sequences of three ovine cathelicidins of 155, 160 and 190 residues, respectively, with cationic C-terminal sequences corresponding to putative antimicrobial domains . These are structurally varied and include a Cys-rich sequence of 12 residues, which is similar to the bovine antimicrobial cyclic dodecapeptide, a novel 29 residue sequence named SMAP-29 with a possible alpha-helical conformation, and a 60 residue sequence named Bac7.5, which appears to be a new member of the Pro- and Arg-rich group of mammalian antimicrobial peptides.

FEBS Lett, 1995 Dec 4, 376(3), 130 - 4
Structures of genes for two cathelin-associated antimicrobial peptides: prophenin-2 and PR-39; Zhao C et al.; We characterized genes for prophenin (PF)-2 and PR-39, two cathelin-associated antimicrobial peptides found in porcine leukocytes . Both contained 4 exons and 3 introns and were compact, contiguous and highly homologous . Exons I-III encoded most of their cathelin domains . Exon IV specified the final few cathelin residues, including its conserved C-terminal valine, followed by the mature PR-39 peptide or a PF-2 precursor . The highly conserved 5' flanking sequences of this gene family contained NF-kappa B, IL-6, GM-CSF and NF-1 binding motifs and the introns were unusually conserved . These data suggest that the panoply of porcine cathelin-associated antimicrobial peptides arose relatively recently via gene reduplications and exon shuffling, and that in vivo expression of cathelin-associated antimicrobial peptides may respond to mediators generated early during infection.

J Hosp Infect, 1995 Dec, 31(4), 295 - 304
A comparative study of nosocomial and community-acquired strains of Escherichia coli causing bacteraemia in a Danish University Hospital; Olesen B et al.; In a previous study we found a considerably higher mortality rate in patients with nosocomial (NO) compared with community-acquired (CA) Escherichia coli bacteraemia . To establish whether this was due to host differences or to differences in the infecting bacteria, we compared 205 NO with 172 CA bacteraemic isolates of E . coli with respect to serotype, virulence factors and antimicrobial susceptibility . Overall the six most frequent O antigens were O18ac, O6, O1, O2, O15 and O75, respectively . The six most frequent capsular antigens were K1, K5, K52, K2, K7 and K34, respectively . No major differences were found regarding O-antigens, capsular antigens, production of haemolysin, P-fimbriation, serum sensitivity or antimicrobial susceptibility . Surprisingly we found 17 strains of serotype O15:K52:{H1} of both NO (eight) and CA (nine) origin with similar phenotypic characteristics to a strain causing a CA outbreak in London 1986-1987 . Possibly the Danish and the English strains belong to the same clone . Our findings argue against the existence of a distinct NO flora . NO E . coli bacteraemia strains seem to originate primarily from the patients' own flora.

J Clin Pharm Ther, 1995 Dec, 20(6), 341 - 4
Compatibility of a commercially available low-density polyethylene eye-drop container with antimicrobial preservatives and potassium ascorbate; Barnes AR; The compatibility of the 7 ml size of Steri-Dropper, a commercially available low-density polyethylene sterile eye-drop container, was studied for use with solutions containing the antimicrobial preservatives benzalkonium chloride and phenylmercuric acetate . For benzalkonium chloride, there was no difference between the Steri-Dropper and the glass eye-drop bottles throughout the study period of 84 days . However, there was less phenylmercuric acetate present in the Steri-Dropper compared to the glass containers by the end of the study . The suitability of the Steri-Dropper bottle was also studied for use with potassium ascorbate eye drops; these degraded more in Steri-Dropper compared to glass containers and a yellow discoloration of the product was also seen in these containers . The Steri-Dropper bottle is therefore potentially compatible with dispensed formulations containing benzalkonium chloride and, for short periods only, with phenylmercuric acetate . The container would only be suitable for use with oxygen-sensitive drugs for short periods . Further validation of the suitability of the Steri-Dropper bottle would be required for use with any specific formulation.

J Clin Pharm Ther, 1995 Dec, 20(6), 313 - 5
Aerosolized dornase alpha (rhDNase) in cystic fibrosis; Bates RD et al.; Advances in the treatment and management of respiratory and pancreatic disorders has increased the life expectancy of patients with cystic fibrosis to 28 years (1) . Despite the use of potent antibiotics and chest physiotherapy, persistent bacterial infection of the lung is the major cause of morbidity and mortality in these patients (2) . This occurs, in part, because of the production of copious amounts of pulmonary secretions . It has been found that these secretions contain high amounts of human DNA (3-8) . This high DNA concentration causes two problems . First, it increases the viscosity of sputum . This, in conjunction with reduced mucociliary clearance, decreases the removal of sputum . Second, the DNA binds to aminoglycosides, which decreases their antimicrobial efficacy (9, 10) . Until recently there was no effective drug to decrease the viscosity of sputum in patients with cystic fibrosis . Dornase alpha (Pulmozyme) is the first drug to offer a safe and effective method to treat excessive DNA in sputum . In vitro studies demonstrated that rhDNase greatly decreased the viscosity of sputum by decreasing the concentration of DNA in a concentration-dependent manner (11).

J Pharm Biomed Anal, 1995 Dec, 14(1-2), 121 - 9
Automated analytical systems for drug development studies . Part IV . A microdialysis system to study the partitioning of lomefloxacin across an erythrocyte membrane in vitro; Knaub SR et al.; An automated system utilizing microdialysis sampling, intermittent dosing, and liquid chromatographic analysis was assembled in order to study the partitioning of lomefloxacin, a fluoroquinolone antimicrobial, into human erythrocytes in vitro . The apparent erythrocyte:buffer partition coefficient was found to be approximately 2.0 with this system and by a manual method . The value was concentration-dependent; lower partition coefficients were observed at lomefloxacin concentrations less than 1 microgram ml-1 . At all concentrations, values obtained by microdialysis were statistically indistinguishable from those obtained by a conventional manual method . The results indicate that erythrocyte partition coefficients can be measured successfully with the microdialysis system . Furthermore, microdialysis sampling eliminates the tedious methodology associated with traditional erythrocyte partitioning studies, including sample clean-up . Due to automated intermittent dosing and on-line LC analysis, the system operates unattended.

Zentralbl Bakteriol, 1995 Dec, 283(2), 208 - 14
Clinical studies on the use of antibiotic- and antiseptic-bonded catheters to prevent catheter-related infection; Bach A; Central venous catheter-related infections are common despite adherence to hygienic guidelines for insertion and maintenance of these devices . It has been suggested that coating of intravascular catheters with antimicrobial agents, either antibiotics or antiseptics, could reduce the incidence of catheter-related infections . Recent studies have demonstrated the efficacy of antibiotic-coated and antiseptic-impregnated catheters in reducing bacterial colonisation and infection . Preliminary results of pilot studies indicate that silver impregnation of intravascular catheters may be effective . At present, these antimicrobial-bonded catheters seem to be an important addition to the choice of preventive strategies, but their definitive role and possible disadvantages such as induction of resistance still have to be clearly delineated.

Zentralbl Bakteriol, 1995 Dec, 283(2), 201 - 7
Review of animal studies on antimicrobial catheters to prevent catheter-related infections; Bach A; Various experimental models have been developed to investigate the pathogenesis of intravascular catheter-related infections . Catheters are implanted either subcutaneously or intravenously, and the test animals are inoculated via either the subcutaneous tissue near the catheter exit site or the bloodstream . Catheters containing antimicrobial agents were investigated in various test models and their efficacy in inhibiting bacterial colonisation and reducing catheter-related infections was demonstrated.

Zentralbl Bakteriol, 1995 Dec, 283(2), 175 - 86
Polymer materials for the prevention of catheter-related infections; Kohnen W et al.; Catheter-related infections are major problems in medicine because of severe consequences for the patient, prolongation of hospitalization, and increasing therapy costs . Beside progress in hygienic measures, development of catheters with antiinfective properties seems to be a promising approach to the prevention of such infections . Two approaches for infection-resistant catheter materials have been developed: materials with antiadhesive properties and materials with antimicrobial properties . Antiadhesive polymers shall prevent the adhesion of microorganisms to the medical device . However, up to now there has been no material which would lead to a complete inhibition of adherence ("zero adherence") . Materials with antimicrobial properties contain antimicrobial substances which are incorporated into the biomaterial or bound to the polymer surface . These devices seem to be effective in the prevention of "early onset infections" . In this paper, an overview of the development and efficiency of antiadhesive or antimicrobial polymers is given.

Planta Med, 1995 Dec, 61(6), 559 - 60
Lanigerol: a new antimicrobial icetexane diterpene from Salvia lanigera; El-Lakany AM et al.; Roots of Salvia lanigera Poir . yielded a new icetexane {10,12-dihydroxy-9(10-->20)-abeo-8,11,13-abietatriene}, named lanigerol, which had activity (MIC 1 mg/ml) against Gram-positive bacteria.

J Antimicrob Chemother, 1995 Dec, 36(6), 911 - 25
The effects of quinolones on the adherence of type-1 fimbriated Escherichia coli to mannosylated agarose beads; Breines DM et al.; Bacterial adherence is reported to be antagonized by several classes of antibiotics including quinolones, beta-lactams and tetracyclines, based primarily on in-vitro studies in which bacterial cells are exposed to antimicrobials, incubated in the presence of uroepithelial cells (UECs) and assessed for adherence by light microscopy . Some problems associated with the use of this approach, include low sensitivity, high variability and, in the case of adherence of mannose-sensitive Escherichia coli interference by mannose-containing uromucoid . To avoid these problems, mannosylated agarose beads (MABs) were used as a model for UECs . Adherence of E . coli strain AAEC356, which is constitutive for type-1 fimbrial expression, was maximal with 3 x 10(4) beads/mL and 1 x 10(8) bacterial cells/mL co-incubated for 35 min at 37 degrees C . Those bacterial cultures showed 40-60% adherence to MABs but only 4-10% adherence to UECs . This study reports a novel method to detect mannose-sensitive bacterial adherence, using MABs, in order to determine the effects of quinolones, cefdinir and tetracycline on E . coli adherence . Cefdinir and the quinolones ciprofloxacin, enoxacin and PD131628 caused significant reductions in the adherence of AAEC356 to UECs at concentrations equivalent to 1/2 x MIC, while up to 1 x MIC of these antibiotics had no significant effect on adherence to MABs . A direct comparison of UEC to MAB-based techniques showed that PD131628, at concentrations equivalent to 1/16x, 1/4x, 1/2x and 1 x MIC, had no effect on bacterial adherence to MABs, while reductions of 34%, 38%, 87% and 85% respectively were seen in adherence to UECs . The anti-adherent effect mediated by quinolones may not therefore be related to the specific interaction between type-1 fimbriae and mannosylated receptors . While quinolones and cefdinir had no effect on overall bacterial adherence to MABs, there was a decrease in the ability of alpha-methyl-D-mannoside (alpha-MM) to inhibit competitively this adherence . Concurrent exposure of PD131628 or cefdinir with tetracycline prevented this, suggesting that protein synthesis is required for this effect.

J Antimicrob Chemother, 1995 Dec, 36(6), 899 - 909
Antifungal drug susceptibility testing . Working Party of the British Society for Antimicrobial chemotherapy; Rogers TR et al.; This article describes the current situation with regard to intrinsic and acquired resistance to antifungal compounds and progress with the development of standardized methods of susceptibility testing for amphotericin B, flucytosine, and the azoles . Recommendations for testing of isolates from patients destined to receive antifungal drug treatment, or in whom therapeutic failure or relapse is suspected, are presented.

Boll Chim Farm, 1995 Dec, 134(11), 620 - 3
Synthesis and antimicrobial activities of some dithiocarbamate derivatives of Kojic acid; Erol DD et al.; The synthesis of new some dithiocarbamate derivatives of kojic acid are reported . The structures of these compounds are supported by their IR and 1H-NMR spectra, as well as by elemental analysis . The new compounds were tested for their antimicrobial activities.

Boll Chim Farm, 1995 Dec, 134(11), 616 - 9
Behaviour of hexahydrobenzodipyrazolones towards chloroacetylation, aminoalkylation, Grignard reagent and their antimicrobial activity; Metwally MA et al.; Treatment of 2,3a,4,6,7a,8-hexahydrobenzo {1,2-c; 4,5-c} dipyrazole-3,7-dione (1) with chloroacetyl chloride gave the 2,6-bis (chloroacetyl) derivative (2), which on treatment with acetic anhydride pyridine afforded (3) . Compound (2) when heated with pyridine afforded (1) . Compound (1) underwent Mannich reaction with piperidine or morpholine and formaldehyde to give the 2,6-bis (piperidino or morpholinomethyl) derivatives (4a,b) . Hydroxymethylation of (1) with formaldehyde gave the 2,6-bis (hydroxylmethyl) derivative (4), which on heating with piperidine afforded (4a), Reaction of 2,3a,4,6,7a,8-hexahydro- 2,6-bis (phenylsulphonyl) benzo {1,2-c; 4,5-c} dipyrazole-3,7-dione (7) with phenylmagnesium bromide gave dodecahydro-3,3,4a,7,7,8a-hexaphenyl-2,6- bis (phenylsulphonyl) benzo {1,2-c; 4,5-c} dipyrazole (8) . Derivatives of hexahydrobenzodipyrazolone (9a-g) have been subjected to general screening for their antimicrobial activity.

Mil Med, 1995 Dec, 160(12), 609 - 11
Vascular infections: exceeding the threshold; Cox TR; During fiscal year 1988, our hospital infection control practitioner identified a 400% increase in the incidence of vascular surgery nosocomial infections . The six graft and six amputation infections were validated as nosocomial against hospital definitions adopted from the Centers for Disease Control . Our Infection Control Committee mandated an audit of the infected vascular surgery patients using a case/control design to identify and examine associated variables that may need attention . The significant finding was microbial resistance to prophylactic antibiotics used during surgery (p > 0.0001, Fisher's exact) . The use of vancomycin as a prophylactic antimicrobial agent for all major vascular cases was recommended to the surgeons.

J Physiol Pharmacol, 1995 Dec, 46(4), 463 - 9
Susceptibility of Helicobacter pylori to antimicrobial agents: effect of ebrotidine and ranitidine; Piotrowski J et al.; Convincing evidence now exists that infection with H . pylori is a primary factor in the pathogenesis of gastric disease, and new therapy regimens include a combination of H2 blockers with antimicrobial agents . In this study, was assessed the effect of ebrotidine and ranitidine on the in vitro anti-H . pylori activity of amoxicillin, erythromycin, tetracycline, and metronidazole . The assays of the antiulcer drugs alone gave MIC value of 150 mg/L for ebrotidine and 1600 mg/L for ranitidine . Inclusion of ebrotidine in the antimicrobial agent assays evoked at its optimal concentration of 75 mg/L a 28% enhancement in the MIC of metronidazole, 2.5-fold enhancement in the MIC of erythromycin, 2-fold in amoxicillin and 1.7-fold in tetracycline, while ranitidine caused noticeable changes in the MIC values of the tested antimicrobial agents only a the dose of 1600 mg/L . The results demonstrate that ebrotidine enhances anti-H . pylori activity of antimicrobial agents at doses well below that of ranitidine.

Gastroenterol Clin North Am, 1995 Dec, 24(4), 923 - 36
Hepatotoxicity of antimicrobial, antifungal, and antiparasitic agents; Reddy KR et al.; Several antibiotics are known to be hepatotoxic . Apart from subtle, reversible, and often inconsequential abnormalities, cholestasis is the predominant presentation that has a protracted and disabling course . Hepatitis, like illness, is characteristic of some drugs, and chronic liver disease may evolve . It is important to recognize if a patient has an adverse reaction to a drug because continuing use of the drug in the face of hepatitis can have disastrous consequences . Chronic liver disease may ensue and progress onto cirrhosis; this has typically been seen following use of isoniazid and nitrofurantoin . Cholestatic liver disease can progress into a chronic form of a ductopenic state; this is particularly seen after antibiotic-related cholestasis.

Clin Infect Dis, 1995 Dec, 21 Suppl 3, S265 - 76
Antimicrobial chemotherapy for legionnaires' disease: a review; Edelstein PH; Controlled trials of antimicrobial chemotherapy for legionnaires' disease have not been performed, although erythromycin and tetracycline appear to be effective therapies . Laboratory data indicate that the activities of the fluoroquinolone and newer macrolide/azalide agents against Legionella pneumophila are superior to that of erythromycin, and case reports substantiate that the activities of these agents are at least equal . Results of clinical treatment with and laboratory testing of macrolides, tetracyclines, co-trimoxazole, chloramphenicol, aminoglycosides, fluoroquinolones, beta-lactam agents, and streptogramins are reviewed . The drugs of choice for the treatment of legionnaires' disease in immunocompromised or severely ill patients should be one of the fluoroquinolone antimicrobials rather than erythromycin.

Clin Infect Dis, 1995 Dec, 21 Suppl 3, S226 - 37
Diagnosis and treatment of nosocomial pneumonia in patients in intensive care units; Chastre J et al.; The optimal management strategy for ventilator-dependent patients who develop symptoms suggestive of lung infection remains controversial . Our personal bias is that using bronchoscopic techniques to obtain protected-brush and bronchoalveolar lavage specimens from the affected area in the lung permits physicians to devise a therapeutic strategy that is superior to one based only on clinical evaluation . These bronchoscopic techniques, when they are performed before new antibiotics are administered, enable physicians to identify most patients who need immediate treatment and to select optimal therapy, in a form that is safe and well tolerated by patients . Furthermore, they frequently permit physicians to withhold antimicrobial treatment from patients without infection, thereby minimizing the risk of emergence of resistant microorganisms in the intensive care unit . Despite many advances in antimicrobial therapy, successful treatment of patients with nosocomial pneumonia remains a complex undertaking, and ultimately further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.

Clin Infect Dis, 1995 Dec, 21 Suppl 3, S213 - 17
Effectiveness of control programs for pneumonia among children in China and Fiji; Shimouchi A et al.; This article summarizes the implementation and efficacy of the World Health Organization's standard case management program for pediatric pneumonia in three counties in China and in the Western Division of Fiji . The information provided through this program was simple enough to be understood by parents and health care workers with a basic educational background . The program reduced mortality from pneumonia even when implemented through the existing health care system in a relatively poor county in China . The factors important in the success of the program included improved recognition of the signs of childhood pneumonia by parents, earlier presentation of children with these signs to health care facilities, availability of antimicrobial agents at the primary health care level, and rational decisions by health care workers about the use of these agents.

Int J Pept Protein Res, 1995 Dec, 46(6), 480 - 6
Design of 16-residue peptides possessing antimicrobial and hemolytic activities or only antimicrobial activity from an inactive peptide; Thennarasu S et al.; We have explored the possibility of generating peptides having antimicrobial and hemolytic activities or only antimicrobial activity, from a 16-residue peptide, GFFALIPKIISSPLFK, corresponding to the N-terminal region of the toxin pardaxin . This peptide does not exibit these activities, although it can permeabilize model membranes . Peptides were synthesized wherein either A4 or P7 were substituted by K and S11 replaced by K . Peptides in which P7 and S11 were replaced with K, (AK) and A4 and S11 replaced with K and A instead of P at position 7, (KA) showed potent antimicrobial and hemolytic activities . However, the peptide where S11 and A4 were replaced with K, (KP) showed pronounced antimicrobial activity with very weak hemolytic activity . Circular dichroism studies indicated that peptides AK and KA had a strong propensity to occur in a helical conformation, whereas KP did not . Peptides AK and KA were very effective in permeabilizing model membranes, whereas KP was relatively ineffective . Our studies thus suggest the requirements for a peptide to have only antimicrobial activity and also that selectivity in activity can be rationalized on the basis of biophysical principles . Thus, by judicious positioning of amino acids, especially positively charged ones, it should be possible to generate biologically active peptides without taking recourse to a combinatorial approach.

Infect Dis Clin North Am, 1995 Dec, 9(4), 965 - 85
Management of the transplant recipient with pulmonary infection; Houston SH et al.; Pneumonia is a common and potentially fatal complication of transplantation . The clinical approach to this problem requires a multipronged attack . Thorough evaluation of the donor and recipient reduces the risk of infection while pointing to likely infectious complications to be anticipated posttransplant . Careful attention to infection control measures with emphasis on handwashing, high efficiency particulate air filtration, and aggressive outbreak investigation minimizes nosocomial pneumonias . Appropriate use of vaccines and prophylactic antimicrobial therapies decreases posttransplant morbidity and mortality . Once pneumonia occurs, a rapid, thorough diagnostic evaluation increases the likelihood of survival for the individual patient and focuses attention on environmental risks that may pose a hazard to the other transplant recipients in the clinician's institution.

Infect Dis Clin North Am, 1995 Dec, 9(4), 811 - 22
Infection in the organ transplant recipient . An overview; Kontoyiannis DP et al.; Considerable progress has been made in elucidating the factors involved in the pathogenesis of infection in the organ transplant patient . One of the general principles that has emerged is that the risk of clinical infection, particularly opportunistic infection, is determined largely by the interaction between the patient's net state of immunosuppression and the epidemiologic exposures the patient encounters . The two major factors that determine the net state of immunosuppression are the nature of the exogenous immunosuppressive therapy that is administered and whether or not infection is present with one or more of the immunomodulating viruses (particularly cytomegalovirus, Epstein-Barr virus, and the hepatitis viruses) . Finally, the therapeutic prescription for the transplant patient has two components--an immunosuppressive component to prevent and treat rejection and an antimicrobial component, which is linked to the intensity of the immunosuppressive therapy required, to make this safe . This reflects the recognition that the two major barriers to successful transplantation, rejection and infection, are closely tied together by the current requirement for lifelong immunosuppressive therapy . Progress in one area will have beneficial effects on the other.

J Interferon Cytokine Res, 1995 Dec, 15(12), 1047 - 51
Potential application of human interferon-alpha in microbial infections of the oral cavity; Fujioka N et al.; We have been evaluating the potential use of interferon-alpha (IFN-alpha) against fungal infections of the oral cavity . IFN-alpha has been reported to enhance the antifungal activity of neutrophils . This cytokine is also known to synergize with interleukin-1 in enhancing a number of immunomodulatory responses . To study cytokine involvement in oral defense mechanisms against microbial infection, we first demonstrated the presence of antimicrobial interleukins (IL)-1 alpha, IL-1 beta, and IL-8 in the saliva, which can all augment the microbicidal activity of neutrophils, and the presence of epithelial cells and neutrophils in oral lavage fluid from healthy volunteers . Immunostaining for cytokines produced by these cells showed that the candidate producers of both IL-1 alpha and IL-8 are epithelial cells, but those of IL-1 beta remained inconclusive . We next found that IFN-alpha enhanced IL-1 alpha-augmented neutrophil-mediated anticandidal action while marginally enhancing IL-8- and IL-1 beta-mediated reactions . These results suggest that IFN-alpha is a potential agent for treating oral mycosis by cooperating with endogenous cytokine(s) in the saliva, in addition to its intrinsic antiviral action.

Am J Dent, 1995 Dec, 8(6), 352 - 7
Root caries: prevention and chemotherapy; Jones JA; PURPOSE: Root caries is a problem of importance among dentate elderly . Greater life expectancies at both birth and age 65, combined with improvements in tooth retention across all age groups, have resulted in an increasing number of Americans who have retained their teeth into old age . This increase in numbers of teeth combined with the increase in the percent of teeth with recession has in turn resulted in older persons with more root surfaces at risk for caries than ever before . The purpose of this article is to review the literature on the prevention and chemotherapeutic approach to root caries . METHODS: A review of the literature and synthesis of this information resulted in recommendations for the improved root caries risk assessment and the development of clinical examination protocols and strategies for prevention and treatment . RESULTS: Clinicians can better identify persons at risk for root caries in their practice . People who are older, have moderate to severe periodontal bone loss and gingival recession, are impaired, have poor oral hygiene, take multiple medications, have partials, have retained root tips and the recently unemployed or retired are all at increased risk for root caries . Examination strategies should include the use of at least annual bite-wing radiographs (vertical bite-wings in persons with significant attachment loss) and careful examination of the proximal tooth surfaces . Once identified as low, moderate or high risk, daily and professionally applied fluoride therapies should be combined with dietary modifications, and in high risk individuals, antimicrobial agents for both the remineralization of early lesions and prevention of further root caries.

J Periodontol, 1995 Dec, 66(12), 1047 - 55
Inhibition of neutrophil and monocyte defensive functions by nicotine; Pabst MJ et al.; To learn more about the effects of smokeless tobacco on the defensive functions of neutrophils, we studied the influence of nicotine on these cells in vitro, looking at their bactericidal activity against oral pathogens, and at their ability to produce microbicidal reactive oxygen species (oxygen radicals) . Exposure of human blood neutrophils to nicotine (0.01% to 0.1%) inhibited their ability to kill Actinomyces naeslundii, Actinobacillus actinomycetemcomitans, and Fusobacterium nucleatum . Although these concentrations of nicotine are high, such concentrations are relevant to phagocytes in the gingival sulcus, because smokeless tobacco contains 0.5% to 3.5% nicotine by dry weight . Nicotine had no such inhibitory effect when the killing assay was performed in an anaerobic environment, implying that nicotine preferentially affected oxygen-dependent killing mechanisms . To further investigate the effects of nicotine on production of oxygen radicals, neutrophils were primed with lipopolysaccharide and triggered with f-met-leu-phe or phorbol ester in the presence of nicotine . Nicotine inhibited production of superoxide anion (measured by reduction of cytochrome c) and hydrogen peroxide (measured by oxidation of phenol red) . Nicotine inhibition of superoxide production was reversible by washing away the nicotine . By observing that nicotine inhibited the reduction of cytochrome c by reagent potassium superoxide, we determined that nicotine directly absorbed superoxide . In addition, by examining nicotine inhibition of the uptake of oxygen by neutrophils, we determined that nicotine also interfered with the production of oxygen radicals by these cells . Nicotine also inhibited production of superoxide and interleukin-1 beta by monocytes . Nicotine did not affect the viability of neutrophils and monocytes, as determined by their ability to exclude trypan blue dye . Inhibition of the aerobic antimicrobial functions of neutrophils and monocytes by nicotine may alter the microbial ecology of the oral cavity, and this might be one mechanism by which nicotine compromises the oral health of users of tobacco products.

J Dairy Sci, 1995 Dec, 78(12), 2797 - 806
Lipolysis and biohydrogenation of soybean oil in the rumen in vitro: inhibition by antimicrobials; Van Nevel C et al.; This experiment attempted to lower rumen lipolytic activity, biohydrogenating activity, or both using antimicrobial compounds . In vitro incubations were carried out with rumen fluid, 80 mg of soybean oil, and .5 g of commercial concentrates as substrate . Unless stated otherwise, the final concentrations of the additives in the incubation was 20 ppm . Lipolysis and biohydrogenation were determined by separation of triacylglycerols and FFA by TLC; the fatty acid composition of each was determined by GLC before and after incubation and with or without additive . With some of the antibiotics, lipolysis was inhibited 10 to 20%, and the most potent inhibitors were ionophores and amoxicillin . Biohydrogenation (including C18:1) decreased only for lasalocid, but no additive could prevent hydrogenation of linolenic acid liberated from triacylglycerols . Some additives decreased hydrogenation of linoleic acid, but only slightly . Lipolytic activity decreased VFA production more than the other potent additives (amoxicillin, avoparcin, lasalocid sodium, monensin, and salinomycin sodium) . This result could indicate a more specific toxic effect on lipolytic microbes . Finally, different antimicrobials influenced fermentation patterns differently (VFA proportions and CH4 production), but shifts were always in accordance with stoichiometric principles.

J Dairy Sci, 1995 Dec, 78(12), 2645 - 52
The effect of mammary gland expression of human lysozyme on the properties of milk from transgenic mice; Maga EA et al.; Transgenic mice were used as model systems to evaluate the impact of human lysozyme expression in the mammary gland . We previously generated two lines of transgenic mice that express human lysozyme mRNA in the mammary gland under the tissue-specific and developmentally correct control of the bovine gene promoter for alpha s1-casein . Concentrations of human lysozyme protein in milk of transgenic mice varied from .25 to .71 micrograms/microliters of milk . Human lysozyme secreted into mouse milk retained its antimicrobial activity, as determined by a denaturing polyacrylamide gel activity assay . The physical and functional properties of the milk were also altered, because mouse milk containing human lysozyme had a 35% decrease in rennet clotting time, a smaller median micelle size (157 nm vs . 172 nm), and a 2.5- to 3-fold greater gel strength than control milk . From these results, we conclude that the use of transgenic animals producing lysozyme in the milk is feasible and potentially useful to the dairy industry.

Ann Pharmacother, 1995 Dec, 29(12), 1202 - 7
Dosing adjustment of 10 antimicrobials for patients with renal impairment; Preston SL et al.; OBJECTIVE: To describe a program of creatinine clearance-based dosage adjustment of 10 renally eliminated antimicrobial agents and to discuss the utility of such a program in a hospital as a method of quality assurance (by ensuring that patients with renal impairment receive generally accepted dosage adjustments), based on pharmacodynamic principles . METHODS: Consecutive patients prescribed any of 10 targeted renally eliminated antibiotics were included . Recommendations for dosage adjustment were made to the prescriber based on a calculated creatinine clearance . Additional adjustments in drug therapy were performed, including dosage recommendations of nontargeted drugs, simplification of antibiotic regimens, and conversion of intravenous to oral therapy . A cost analysis was performed . RESULTS: During a 6-month study period, 160 dosage changes (7.6% of total number screened) were recommended in 137 patients receiving the targeted antimicrobial agents . Prescribers accepted 147 recommendations (91.9%) . A dosage change recommendation was necessary more than 12% of the time for acyclovir, ceftazidime, and imipenem/cilastatin . A cost avoidance of $11,702.08 was realized . Ancillary drug recommendations that were offered and accepted during the program realized a cost avoidance of $6613.75 . CONCLUSIONS: This dosage adjustment program using pharmacodynamic principles was successful in optimization of dosing, potential minimization of morbidity caused by excessive dosing, and demonstration of direct and potentially indirect cost avoidance . A dosing program for patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.

J Dermatol, 1995 Dec, 22(12), 935 - 8
In vitro and in vivo antibiotic susceptibility of Lyme disease Borrelia isolated from the ixodid tick in Japan; Fujita H et al.; Antimicrobial susceptibility of the Lyme disease Borrelia, strain HP1 vi, isolated from the tick ixodes persulcatus in Hokkaido, Japan, was determined in vitro and in vivo . A broth dilution technique was used to determine the minimum inhibitory concentrations (MICs) and minimum borreliacidal concentrations (MBCs) of five antimicrobial agents . Strain HP1 vi was most susceptible to minocycline (MBC, 0.2 micrograms/ml) . The other antimicrobial agents tested, aspoxicillin, cefmetazole sodium, imipenem cilastatin sodium, and panipenem betamipron, had higher MBCs of 12.5 micrograms/ml, 25 micrograms/ml, > 25 micrograms/ml, and > 25 micrograms/ml, respectively . In vivo antibiotic susceptibility study using a ddY mouse model demonstrated that minocycline and amoxicillin were effective; minocycline had a lower 50% effective dose (ED50) value (6.25 mg/kg) than amoxicillin (30 mg/kg).

Farmaco, 1995 Dec, 50(12), 893 - 4
Synthesis and antimicrobial activity of some 2-(2-oxobenzothiazole-3-yl)-1-arylethanone derivatives; Simsek R et al.; The synthesis of new 2-(2-oxobenzothiazole-3-yl)-1-arylethanone derivatives is reported . The structure of these products is supported by their UV, IR and 1H-NMR spectra, as well as by elemental analysis . The new compounds were tested for antimicrobial activity.

Drugs, 1995 Dec, 50(6), 984 - 90
Current guidelines for the eradication of Helicobacter pylori in peptic ulcer disease; Rauws EA et al.; Pharmacological suppression of gastric acid secretion has traditionally been the most rational approach to healing ulcers successfully . However, ulcers initially healed using antisecretory therapy have a tendency to relapse after treatment is withdrawn . This tendency is altered definitively by eradication of Helicobacter pylori . Antimicrobial therapy should be given to all patients with documented duodenal and gastric ulcer associated with H . pylori infection . The optimal therapeutic regimen to eradicate H . pylori is still not completely clear . The requirement for treatment to be effective in more than 90% of patients makes monotherapy and dual therapy inappropriate . Bismuth-based triple therapy (bismuth, tetracycline and metronidazole) is highly efficacious if the H . pylori strain is sensitive to metronidazole and the patient is compliant, but adverse effects often occur . Triple therapy consisting of omeprazole and 2 antimicrobials (clarithromycin and/or amoxicillin and/or metronidazole) and quadruple therapy (bismuth-based triple therapy plus omeprazole) are both very effective and patient compliance may be better because of the shortened (1 week) course . Preliminary data indicate that the efficacy of the regimen is not influenced by imidazole resistance . Eradication of H . pylori prevents complications and relapse of peptic ulcer disease and is a cost-effective option compared with maintenance acid-suppressive therapy.

Cytometry, 1995 Dec 1, 21(4), 374 - 7
Rapid detection of antimicrobial activity using flow cytometry; Durodie J et al.; Different antibiotic classes vary considerably in their modes of action and hence in their effects on the bacterial cell . Flow cytometry was used to analyse E . coli cells treated with five antibiotics differing in their modes of action . The ratio of protein content, as measured by fluorescence, to forward light scatter (i.e., FL1:FSC) provided a simple and reliable way of detecting within 2 h of treatment antimicrobial activity at a 0.5 minimum inhibitory concentration . This ability to detect antimicrobial activity rapidly offers considerable advantages in drug research for the rapid detection of novel antimicrobials and may, with further development, find a use in the clinic for rapid susceptibility testing as an aid to the selection of therapy.

Bull Pan Am Health Organ, 1995 Dec, 29(4), 322 - 7
Attitudes of Bolivian pharmacists in dealing with diarrhea cases; Zamora Gutierrez AD et al.; To help learn about the recommendations made by Bolivian pharmacists dealing with diarrhea cases, 498 pharmacies in three Bolivian cities (Cochabamba, El Alto, and La Paz) were visited by female interviewers who indicated they were seeking treatment for a child with diarrhea . Ninety-eight of the Cochabamba pharmacies were also visited by a male interviewer who indicated he was suffering from diarrhea and was seeking treatment . In response, fewer than 2% of the pharmacists recommended using oral rehydration salts (ORS), increasing fluid intake, or consulting a physician . Most recommended antimicrobials, antidiarrheals, or some combination of the two . At 329 (66%) of the pharmacies, oral rehydration salts were unavailable, and those that did have such salts rarely offered them to customers . At the time of the survey, pharmacists were not integrated into the Bolivian National Health Secretariat's training program for control of diarrheal diseases . Steps have since been taken to resolve this matter.

Oral Microbiol Immunol, 1995 Dec, 10(6), 382 - 4
Distribution of biotypes and antimicrobial susceptibility of Actinobacillus actinomycetemcomitans; Avila-Campos MJ et al.; Eighty isolates of Actinobacillus actinomycetemcomitans from 30 Brazilian periodontitis patients were examined to determine the distribution of biotypes and in vitro antimicrobial susceptibility . Seventy-seven percent of the isolates belonged to biotype X . All A . actinomycetemcomitans isolates were susceptible to cefoxitin, imipenem and tetracycline.

Toxicol Lett, 1995 Dec, 82-83, 233 - 7
The role of nitric oxide in cell injury; Brune B et al.; Nitric oxide (NO) is a pathophysiological mediator with unique signal transducing properties . Signaling mechanisms are categorized as cGMP-dependent or cGMP-independent . Multiple interactions of NO with oxygen, superoxide, and transition metals determine the biological activity . Cyclic GMP-independent responses of NO account for the antimicrobial, the cytostatic, and the cytotoxic capacity of NO . Cytotoxicity is not only directed to harmful cells but also affects the NO-producing cell in a self-destructing loop . For macrophages and pancreatic beta-cells (RINm5F), we established NO-mediated apoptotic cell death . Endogenously generated or exogenously applied NO causes DNA cleavage after endonuclease activation . NO-mediated accumulation of the tumor suppressor p53 precedes apoptotic cell death.

Tuber Lung Dis, 1995 Dec, 76(6), 570 - 4
Isolation and characteristics of Mycobacterium avium complex from water and soil samples in Uganda; Eaton T et al.; SETTING: Mycobacterium avium complex organisms have not been isolated from late stage AIDS patients in Uganda . This could possibly be due to the absence of M . avium complex in the Uganda environment . OBJECTIVE AND DESIGN: Determine whether M . avium complex organisms could be isolated from water and soils collected in the living environment of Ugandan AIDS patients . RESULTS: Representatives of the M avium complex were isolated from 3 of 7 (43%) water and 3 of 7 (43%) soil samples collected in Kampala, Uganda . The average number of colony-forming units per ml water was 3.3 and average colony-forming units per gram of soil was 7825 . In terms of growth characteristics, antimicrobial susceptibility patterns, and the presence or absence of plasmids and IS901, Ugandan M . avium complex isolates were similar to those isolated from the US and European AIDS patients and their environment . CONCLUSIONS: M . avium complex organisms sharing genetic and physiological characteristics of M . avium complex isolates recovered from patients with AIDS can be isolated from water and soil samples in Uganda.

Antimicrob Agents Chemother, 1995 Dec, 39(12), 2641 - 4
Use of time-kill methodology to assess antimicrobial combinations against metronidazole-susceptible and metronidazole-resistant strains of Helicobacter pylori; Coudron PE et al.; Optimal therapy for Helicobacter pylori infection to date, consists of metronidazole, bismuth, and tetracycline . This combination, however, is less effective against metronidazole-resistant organisms . We used a time-kill kinetic methodology to assess the bactericidal effects of selected agents, alone and in combination, to a metronidazole-susceptible and a metronidazole-resistant strain of H . pylori . single, double, and triple agents showed increasing bactericidal activity . The combination of metronidazole, bismuth, and tetracycline showed maximal killing effect (no detectable regrowth) against the susceptible strain, but against the resistant strain this combination showed less killing . The time-kill methodology may therefore offer an in vitro approach to the initial selection of agents to be evaluated for the treatment of H . pylori infections.

Phytochemistry, 1995 Dec, 40(6), 1803 - 8
Prenylated isoflavanone from Erythrina eriotricha; Nkengfack AE et al.; Bioassay-directed fractionation of a methylene chloride extract of the root bark of Erythrina eriotricha resulted in the isolation of a novel isoflavanone, named eriotrichin B, and the five known pterocarpans, isonorautenol, erybraedin A, erybraedin C, erybraedin D and erybraedin E . The structure of the new compound has been investigated by extensive spectroscopic studies, including 2D NMR and chemical evidence . The in vitro antimicrobial spectrum and potencies of the isolated compounds are also reported.

J Clin Microbiol, 1995 Dec, 33(12), 3341 - 4
Mucormycosis caused by Rhizopus microsporus var . microsporus: cellulitis in the leg of a diabetic patient cured by amputation; West BC et al.; Mucormycosis accompanied the development of bacterial infection in the leg of a diabetic African-American man . Local injury, diabetic ketoacidosis, renal insufficiency, and antimicrobial therapy were factors that contributed to the pathogenesis of the mucormycosis . The cellulitis was caused in part by Rhizopus microsporus var . microsporus and was cured by amputation . We report this unusual case of mucormycosis to emphasize the value of fungal identification, to illustrate a dramatic and successful clinical result, and to draw attention to an apparent role for bacterial infection and its treatment in the pathogenesis of mucormycosis . It is the third case report of mucormycosis in a human in which R . microsporus var . microsporus was definitively identified as the etiologic agent.

Immun Infekt, 1995 Dec, 23(6), 209 - 15
{Rational use of antimycotics against yeast infections}; Hof H et al.; In clinical medicine mere colonization with yeasts is often hardly to be discriminated from true infection . Thus, a clear-cut separation of preventive from therapeutic use of antimycotics is not possible in practical medicine . The problem is that on the one hand one has no exact diagnosis of yeast infection, but on the other hand best therapeutic results are obtained when the drugs are given as early as possible . In comparison to the huge number of antibacterial compounds, the members of antimicrobials are limited . For prophylaxis, one can use the polyenes, such as amphotericin B and nystatin, or the azoles, such as fluconazole or itraconazole . Thereby the azoles act not only locally at the site of application but are absorbed and thus are distributed to remote sites, where the non-resorbable polyenes never arrive . Among the azoles, fluconazole has the advantage that resorption is independent from an acid pH in the stomach, whereas itraconazole resorption is variable in severely ill persons with neutralized gastric fluid . For therapeutic use systemically applied amphotericin B has certain disadvantages . Because of toxic reactions an optimal dose cannot be given; furthermore in some sites insufficient concentrations are achieved, particularly in the kidney and also in the CSF . In contrast, the azoles possess better pharmacologic and toxicologic properties . Resistance to antimycotics is principally possible but still rare, so that in practice a routine testing is not necessary . Candida glabrata as well as Candida krusei are primarily resistant to fluconazole.

Immun Infekt, 1995 Dec, 23(6), 205 - 8
{Antimicrobial oligopeptides--an important factor in non-specific defense against infection}; Haegele B et al.; For survival of plants, animals as well as main in a nature full of aggressive microbes, endogenous antibiotics play an essential role, which is not yet fully appreciated in medicine and science . For example in the granules of polymorphonuclear granulocytes and macrophages or even of specialized epithelial cells such as Paneth cells in the crypts of the intestinal mucosa, oligopeptides are produced with a wide range of antimicrobial activity . According to their chemical structures and modes of action they can be grouped into various different families . The physiological role of these agents on the surface of skin and mucosa or within host tissue is only incompletely understood.

Geburtshilfe Frauenheilkd, 1995 Dec, 55(12), 707 - 10
{Efficacy of various methods for preoperative vaginal antisepsis}; Enzelsberger H et al.; In a prospective clinical study we investigated 115 patients prior to vaginal surgical interventions to determine the antimicrobial efficacy of six different procedures for vaginal antisepsis . To sample the microorganisms we used a cotton swab moistened with a neutralising fluid . Immediately after the time of action of the antiseptic procedures (3 minutes), providone-iodine solution, applied undiluted or diluted 1:10, yielded the strongest median reduction of the vaginal flora (log RF 3.60 and 2.68, respectively) . Of three detergents with antiseptic efficacy, octenidine 0.1% was the most efficient formula (log RF 2.32) . After 30 minutes the log reduction factors (log RF) of almost all procedures (log RF 2.79-3.25) were in a fairly close range, excepting chlorohexidine 0.05% (log RF 2.07) . Overall, the antiseptic detergents showed a marked residual effect, which was less pronounced, if at all, with providone-iodine solutions . A germ-reducing effect of povidone-iodine vaginal suppositories, applied 2 to 3 hrs prior to surgery, was not confirmed, while additional findings indicated that providone-iodine solution applied with the help of a vaginal douche yields a similarly strong germ reduction as the application by means of a ball swabs.

J Clin Pathol, 1995 Dec, 48(12), 1122 - 5
Quality assessment of Microbe Base antimicrobial susceptibility data; Limb DI et al.; AIMS--To assess the quality of centres contributing antimicrobial susceptibility data to a centralised database . METHODS--Twelve organisms were distributed to 31 regional microbiology laboratories contributing data to a centralised susceptibility database . Participants were asked to determine susceptibilities to certain antibiotics by their routine method and return the data to the Department of Microbiology, Royal Hallamshire Hospital, Sheffield, for analysis . RESULTS--Results for the overwhelming majority of organism/antibiotic combinations were in agreement with expected results . Reasons for discrepancies included the non-bimodal distribution of susceptibilities, the use of different content discs, and, more importantly, minimum inhibitory concentrations falling close to breakpoint values . CONCLUSIONS--It is inevitable that any large multicentre database will contain a degree of inaccurate data . This study has highlighted several areas where discrepant results have occurred and has enabled Glaxo Laboratories to approach individual laboratories to address this problem . This study emphasises the value and consistency of Microbe Base as the largest database, of its kind, nationally.

J Antibiot (Tokyo), 1995 Dec, 48(12), 1435 - 9
Macrosphelide, a novel inhibitor of cell-cell adhesion molecule . I . Taxonomy, fermentation, isolation and biological activities; Hayashi M et al.; Potent anti-adherent activity was detected in fermentation extracts of microbial strain FO-5050 . Active compounds designated macrosphelide A and B were isolated and the structure was determined to be 16-membered macrolide antibiotics possessing three ester bonds in the ring structure . Macrosphelide A dose-dependently inhibited the adhesion of HL-60 cells to LPS-activated HUVEC monolayer (IC50, 3.5 microM); macrophelide B also inhibited HL-60 adhesion but to a lesser extent (IL50, 36 microM) . Macrosphelide A did not show any antimicrobial and cytocidal activities at the concentration of 1000 micrograms/ml and 100 micrograms/ml, respectively.

Indian J Med Res, 1995 Dec, 102, 261 - 6
Antimicrobial susceptibility pattern & biotyping of Helicobacter pylori isolates from patients with peptic ulcer diseases; Sharma S et al.; Antimicrobial susceptibility of 50 local isolates of Helicobacter pylori from patients with acid peptic diseases was investigated to commonly used antibiotics . The maximum resistance was (66%) detected to metronidazole (MIC > 8 micrograms/ml) . The frequency of resistance to ampicillin, erythromycin, ciprofloxacin was in the range of 20-28 per cent; least resistance was observed to tetracycline (10%) . The gradient disc diffusion method was found to give reproducible results and also correlated with agar dilution method for minimum inhibitory concentration (MIC) . Study of the enzymatic activity of H . pylori isolates showed that all isolates had urease, catalase, oxidase, esterase-lipase, and naphthol-AS-beta-1-phosphohydrolase enzymes and were consistently negative for ten other enzymes tested . Majority of the isolates expressed alkaline phosphatase (17/18), esterase (17/18) and acid phosphatase (14/18) . The acid phosphatase had the maximum mean enzymatic activity . There was no difference in enzymatic activity between H . pylori isolates from ulcer and gastritis patients . H . pylori isolates could be typed into five biotypes . Type III was found to be more common (44.4%) . This study supports the existence of the strain variations among H . pylori on the basis of the enzyme profiles.

Biopolymers, 1995 Dec, 36(6), 793 - 801
Interaction of mastoparan-B from venom of a hornet in Taiwan with phospholipid bilayers and its antimicrobial activity; Park NG et al.; Mastoparan B (MP-B), an amphiphilic alpha-helical peptide newly isolated from the hornet Vespa basalis, was studied in comparison with mastoparan (MP), in terms of interaction with the phospholipid bilayer and of hemolytic and antimicrobial activity . The amphiphilic structure of MP-B has more hydrophilic amino acid residues in the hydrophilic surface than that of MP . Although each peptide had a considerably different effect on the interaction with lipid bilayers (e.g., their conformation in the presence of acidic and of neutral lipids and dye-release ability from the encapsulated liposomes), on the whole the interaction mode was similar . MP-B caused a change in the shape of erythrocytes from normal discoid to a crenated form (named echinocytes) . MP exhibited strong activity against gram-positive bacteria but not against gram-negative ones . Contrary to this, MP-B showed both strong activity against gram-positive bacteria and potent activity against gram-negative bacteria . Whereas both peptides have almost the same residues on the hydrophobic side, the difference in the hydrophilic surface area on the molecules seems to lead to the subtle change in its interaction with membranes, resulting in the alteration of biological activity.

Kekkaku, 1995 Dec, 70(12), 673 - 8
{Mechanism of bacterial regrowth at the sites of infection in Mycobacterium avium complex-infected mice during treatment with chemotherapeutic agents}; Sato K et al.; Although various antimicrobial drugs show appreciable bactericidal activity in the early phase (2 to 4 weeks after infection) of Mycobacterium avium complex (MAC) infections in mice, no drug, as far as we know, can continue to exert the growth inhibiting activity against the bacteria at the site of infection in the progressed stage . Here, we studied the mechanisms of the bacterial regrowth which usually starts around 2-4 weeks after infection . First, the changes in the level of TNF-alpha, IFN-gamma, IL-6 and IL-10 in the lungs and spleen during the course of MAC infections was examined . Tissue levels of TNF-alpha and IL-10 increased around weeks 2 to 4, then rapidly decreased thereafter, and returned to the normal levels by week 8, while levels of IFN-gamma and IL-6 remained very low throughout the observation period . In this experiment, the bacterial CFUs rapidly decreased during the first 2 weeks of the treatment with a rifamycin derivative, KRM-1648, and thereafter the regrowth of the organisms was observed even in mice treated continuously with KRM-1648, although the rate of bacterial growth in the treated mice was much lower than in untreated control mice . Second, effect of either anti-TGF-beta or anti-IL-10 antibody on intracellular growth of MAC in human monocytes cultured in vitro in the medium with or without addition of TNF-alpha or IFN-gamma were examined . Anti-TGF-beta and anti-IL-10 antibodies potently reduced the bacterial growth in monocytes . Effects of TNF-alpha and IFN-gamma in reducing the bacterial growth was potentiated by the addition of either anti-TGF-beta or anti-IL-10 antibody . Third, anti-IL-10 antibody augmented to some extent the chemotherapeutic efficacy of KRM-1648 against MAC infection, when the drug was given to mice at weeks 2 and 4 after infection . From these results, it is suggested that IL-10 derived from MAC-infected macrophages in response to stimulation with some bacterial components, such as lipoarabinomannan, might downregulate the antimicrobial function of host macrophages against MAC.

J Trop Med Hyg, 1995 Dec, 98(6), 465 - 8
Effective acidification of traditional fermented foods; Simango C; This study was carried out to investigate the survival rates of strains of enteropathogenic Escherichia coli in lactic and acetic acids and to compare them with their survival rates in sour porridge . The fermented and unfermented porridges were prepared in the laboratory . The fermented porridge had both lactic and acetic acids; unfermented porridge was adjusted to the pH of sour porridge with lactic and acetic acids . The sour porridge, the unfermented porridge adjusted to the pH of sour porridge with lactic and acetic acids and the unfermented porridge were inoculated with six strains of enteropathogenic E . coli . The inoculated porridges had a final concentration of 10(6)-10(7) colony-forming units (c.f.u.) per ml of food . Few of the strains of enteropathogenic E . coli were detected 48 hours after inoculation in sour porridge . All the strains were detected 48 hours after inoculation in unfermented porridges adjusted to the pH of sour porridge with lactic and acetic acids but decreased in numbers of surviving cells by about 2 log10 c.f.u . per ml of food . All the strains survived in unfermented porridge for 48 hours and increased in numbers . These results show that lactic and acetic acids have antimicrobial properties but they are not as effective as sour porridge in inhibiting the growth and survival of enteropathogenic E . coli . The inhibitory property of sour porridge is due to a combination of many substances including lactic and acetic acids.

Nat Genet, 1995 Dec, 11(4), 441 - 3
Familial cylindromatosis (turban tumour syndrome) gene localised to chromosome 16q12-q13: evidence for its role as a tumour suppressor gene; Biggs PJ et al.; The human skin is a complex organ composed of the surface epidermis, the subjacent dermis (in which blood vessels, lymphatics and nerves are located) and the skin appendages . The latter include hair follicles, sebaceous glands (which secrete lipids that may serve as a permeability barrier, emollient or antimicrobial agent), apocrine glands (which secrete scents) and eccrine glands (which produce sweat for temperature control) . Hereditary cylindromatosis (MIM 123850) is a rare autosomal dominant disease characterised by the development of multiple neoplasms originating from the skin appendages . These neoplasms have been termed cylindromas due to their characteristic microscopic architecture and are believed to exhibit apocrine or eccrine differentiation . We have carried out a genome search using two families with this disease, which has provided strong evidence for linkage of cylindromatosis to loci on chromosome 16q12-q13 . Using markers close to the cylindromatosis gene, consistent loss of the wild-type allele was observed in 19 tumours from four individuals in the two families, indicating that the gene is likely to be a tumour suppressor gene.

J Ethnopharmacol, 1995 Nov 17, 49(1), 51 - 5
Some pharmacological studies on Artemisia herba-alba (Asso.) in rabbits and mice; Marrif HI et al.; The aqueous extract of Artemisia herba-alba Asso . (Compositae) produced an initial hyperglycaemia which was followed by hypoglycaemia in normoglycaemic and alloxan-treated rabbits and mice . The extract (0.39 g/kg) significantly increased gastrointestinal transit time and the reaction time to thermal stimuli but had no effect on the activity of alkaline phosphatase or concentrations of creatinine and urea in plasma . Histopathological examination indicated mild hydropic degeneration in hepatocytes and proximal convoluted tubules . The duodenum showed mild oedema of the substantia of the mucosal propria . The plant extract showed weak antimicrobial activity.

Lancet, 1995 Nov 11, 346(8985), 1271 - 9
Antimicrobial therapy in expectant management of preterm premature rupture of the membranes; Mercer BM et al.; We review the impact of antimicrobial treatment on maternal and fetal outcome during expectant management of preterm premature rupture of the membranes . Relevant studies were retrieved from Medline (1966 to August, 1994) with the search term fetal-membrane-premature-rupture and antibiotics or antimicrobial, Excerpta Medica (1972 to August, 1994) with the search term premature fetus, membrane rupture, and antibiotic or antimicrobial therapy, and the Cochrane database of systemic reviews with the criterion antibiotics and prelabour rupture of membranes . We also obtained unpublished data from a randomised clinical trial of ceftizoxime versus placebo . The selected studies were randomised controlled trials of systemic antimicrobial therapy for prolongation of gestation in non-labouring women after preterm premature rupture of the membranes . Data extraction was done by a single reviewer . Studies were evaluated for post-randomisation exclusion and other confounding variables that might introduce analytical bias . Analysis was done with SAS statistical software by a blinded investigator . Antimicrobial therapy after preterm premature rupture of the membranes is associated with a reduced number of women delivering within 1 week (62 vs 76%; OR 0.51, 95% CI 0.41-0.68), and reduced diagnosis of maternal morbidity including chorioamnionitis (12 vs 23%; 0.45, 0.33-0.60) and postpartum infection (8 vs 12%; 0.63, 0.41-0.97) . Fetal morbidity, including confirmed sepsis (5 vs 9%; 0.57, 0.36-0.88), pneumonia (1 vs 3%; 0.32, 0.11-0.96), and intraventricular haemorrhage (9 vs 14%; 0.65, 0.45-0.92) were less often diagnosed after antimicrobial therapy . Separate analysis of the six placebo-controlled trials revealed similar or improved odds of pregnancy prolongation, chorioamnionitis, neonatal sepsis, postpartum infection, positive infant blood cultures, and pneumonia . Antimicrobial therapy, when used in the expectant management of preterm premature rupture of the membranes is associated with prolongation of pregnancy and a reduction in the diagnosis of maternal and infant morbidity . Further study should be directed towards determination of optimal antimicrobial therapy, increasing pregnancy prolongation, and enhancement of corticosteroid therapy for induction of pulmonary maturity after preterm premature rupture of the membranes.

J Med Chem, 1995 Nov 10, 38(23), 4710 - 9
Synthesis and antimicrobial and toxicological studies of amino acid and peptide derivatives of kanamycin A and netilmicin; Kotretsou S et al.; Amino acid and peptide derivatives of aminoglycosides have been obtained by substitution of the 1-N or 6'-N amino functions of kanamycin A and netilmicin via the temporary complexation of vicinal and nonvicinal amino and hydroxy functions by copper ion {1-N kanamycin A derivatives: L-Ala (6a), D-Ala (6b), Gly (6c), L-Asp (6d), L-Ala-L-Ala (6e) . 6'-N kanamycin A derivatives: L-Ala (3a), D-Ala (3b), Gly (3c), L-Ala-L-Ala (3e), L-Leu (3f) . 6'-N netilmicin derivatives: L-Ala (9a), D-Ala (9b), Gly (9c), L-Asp (9d), L-Ala-L-Ala (9e)} . Characterization was made by FAB-MS, IR, 1H-NMR, and 13C-NMR . All derivatives were essentially inactive . The nephrotoxic potential of the derivatives obtained in sufficient quantities (3b,e and 9a-e) was assessed by measuring their inhibitory potential toward the activity of lysosomal phospholipase A1 acting on phosphatidylcholine embedded in negatively-charged membranes . One compound, 6'-N-L-Ala-netilmicin (9a), showed a 2-fold decrease of inhibitory potency compared to its parent drug . A conformational analysis revealed that it adopts two equally probable conformations and orientations when interacting with phosphatidylinositol . The first in which the drug lies parallel to the hydrophobic-hydrophilic interface, is similar to that of netilmicin . The second, in which the drug inserts itself in the bilayer across the hydrophilic/hydrophobic interface, is similar to that described for streptomycin, an almost non-nephrotoxic aminoglycoside.

Pharmacoeconomics, 1995 Dec, 8(6), 491 - 512
Formulary management of macrolide antibiotics; Guay DR; Selection of macrolide antibiotics for formulary addition can be a difficult task, with the increasing availability of new agents as well as the numerous differences in pharmacokinetic and pharmacodynamic properties of available agents . Nonetheless, appropriate evaluation of the important characteristics of macrolide antibiotics should allow selection of the most cost-effective agents for formulary addition . Most importantly, differences in antimicrobial activity and efficacy, product formulation, tolerability and cost should be carefully considered when making formulary decisions . Notably, evidence from in vitro studies and clinical trials indicate differences between the macrolide antibiotics, especially in the management of a variety of opportunistic infections in immunocompromised patients . For selected clinical situations, it may be important to select an effective agent available in both oral and intravenous formulations, especially in severe pneumonia caused by Legionella spp . In addition, the availability of generic formulations should be considered for its potential to reduce cost . Comparative drug costs, as well as costs associated with noncompliance, should also be evaluated carefully . Dosage regimens should also be considered, as shorter durations of therapy and less frequent dose administration may lead to increased compliance and thereby improved effectiveness and economic efficiency.

Physician Assist, 1995 Dec, 19(12), 73, 77 - 8, 80-1
The emerging infectious diseases; Pollard C; Emerging infectious diseases pose a significant but underappreciated threat to public health . In a world where international travellers, immigrants, and refugees can carry dangerous organisms almost anywhere, no region should be considered free from risk . Outbreaks of disease may be caused by newly recognized pathogens and drug-resistant organisms . These outbreaks demonstrate the need for improved worldwide surveillance and for improved compliance with guidelines for the use of antimicrobial agents.

Arzneimittelforschung, 1995 Nov, 45(11), 1222 - 4
In vitro activity of tylosin and its derivatives against Ureaplasma urealyticum; Zuzulova M et al.; Antimicrobial activity of tylosin (CAS 1401-69-0) and five other 16-membered macrolides biosynthesized by Streptomyces fradiae (lactenocin, desmycosin, macrosin (CAS 11049-15-3), relomycin (CAS 1404-48-4) and 5-O-mycaminosyl tylonolide) against Ureaplasma urealyticum was studied . The lowest minimum inhibitory concentrations (MIC) showed 5-O-mycaminosyl tylonolide, tylosin and descomysin . Absence of the aldehyde group in the structure of relomycin resulted in loss of the antimicrobial activity . Tylosin, desmycosin and macrocin proved better antimicrobial effect in the alkaline medium than in the acidic one.

Ann Acad Med Singapore, 1995 Nov, 24(6), 863 - 6
Two cases of lower respiratory tract infection due to Chlamydia pneumonia in Singapore; Tan YK et al.; Chlamydia pneumoniae, previously known as Chlamydia psittaci strain TWAR, causes both upper and lower respiratory tract infection . We report the first two cases of culture-positive Chlamydia pneumoniae lower respiratory infection in Singapore . Both patients had underlying fibrosing alveolitis and presented with a history of prolonged productive cough and fever . Chlamydia pneumoniae was isolated from the bronchoalveolar lavage fluid in the absence of other pathogens . The patients responded clinically to three weeks of oral doxycycline therapy . Infection due to Chlamydia pneumoniae should be considered when a patient with community-acquired pneumonia fails to respond to the usual standard antimicrobial therapyPublication Types:

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