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 develo