Antimicrobials

Rev Saude Publica, 1993 Aug, 27(4), 291 - 9
{Information level and pharmacotherapeutic practice of dentists, 1990}; Battellino LJ et al.; Results of an investigation carried out into a population of 285 dentists in Cordoba City (Cordoba, Argentine) with a view to evaluating their pharmacological knowledge, prescriptive behaviour and proposals for the improvement of drug usage, are described . This study showed that 58.3% of the dentists surveyed get most of their pharmacological and therapeutic information through published material issued by pharmacochemical labs . At the same time, about one-third of the individuals surveyed either did not answer or gave incorrect answers to questions related to the pharmacotherapeutic effects the antimicrobial or anti-inflammatory analgesics of their preference . Although 63.5% of the dentists said that they had taken the essential drug model reference list issued by the social security system into account, many of the drugs selected as preferences were not to be found on it . Regarding anti-microbial or anti-inflammatory analgesic drugs, the brands most frequently prescribed were the more expensive ones, strong 66.5% of the dentists surveyed stated the contrary . Finally, this investigation revealed that five manufacturers together held a concentration of the anti-microbial and anti-inflammatory analgesics prescribed by 83.7% and 82.4% of the dentists consulted respectively.

Arch Fam Med, 1993 Aug, 2(8), 837 - 40
Multicenter comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis; Calhoun KH et al.; PURPOSE: To compare the safety and efficacy of orally administered clarithromycin, a new macrolide antimicrobial, and amoxicillin in the treatment of patients with acute maxillary sinusitis . PATIENTS AND METHODS: One hundred forty-two consecutive outpatients treated at four primary care centers for acute maxillary sinusitis were randomly assigned to receive oral clarithromycin (500 mg twice daily) or oral amoxicillin (500 mg three times daily) for 7 to 14 days . Clinical and roentgenographic responses to the antibiotic therapy were determined within 48 hours after the last dose and 6 weeks later . RESULTS: The success rates of clarithromycin and amoxicillin were comparable . A clinical success rate of 91% and a roentgenographic success rate of 78% were achieved in the clarithromycin group at the final visit; comparable results for the amoxicillin group were 89% and 92%, respectively . Differences between the two groups were not statistically significant (P = .766 and .064, respectively) . No serious adverse events were reported, although both drugs caused mild gastrointestinal distress . Dropout rates were low in both groups: 3% for clarithromycin and 4% for amoxicillin . No clinically significant changes in laboratory studies were observed in either group . CONCLUSION: Clarithromycin twice daily is effective and well tolerated in patients with acute maxillary sinusitis.

APMIS, 1993 Aug, 101(8), 575 - 81
Are antibiotics of any use in reactive arthritis?
Leirisalo-Repo M.
In the pathogenesis of reactive arthritis, infection through the mucosal route and genetic susceptibility (HLA-B27) are the most important contributing factors . With regard to non-specific urethritis, most probably caused by Chlamydia trachomatis infection, the use of early antimicrobial therapy has been shown to be effective in preventing arthritic recurrences . When the arthritis has been initiated, short-term conventional antimicrobial therapy seems unable to modify the course of the ongoing disease . In patients with acute reactive arthritis, a prolonged (3-month) treatment with tetracycline shortens the duration of arthritis when triggered by Chlamydia trachomatis, while such treatment has not proved effective in enteroarthritis . In patients with chronic reactive enteroarthritis, a prolonged course of quinolones, such as ciprofloxacin, might be of benefit . Sulfasalazine, which has an effect in the acute exacerbations of ankylosing spondylitis, is probably also effective in chronic reactive arthritis . An antimicrobial effect can be one of the mechanisms by which sulfasalazine exerts its therapeutic effect . Follow-up studies are necessary to assess the influence of antibiotic therapy on the late prognosis of patients with reactive arthritis.

Lett Appl Microbiol, 1993 Aug, 17(2), 78 - 81
Methods to demonstrate the bactericidal activity of bacteriocins; Benkerroum N et al.; Two simple techniques were developed to demonstrate bactericidal activity of bacteriocins . Both were based on allowing a lawn of indicator strain to grow first, then exposing the lawn to bacteriocin-containing cell-free supernatants in a well cut in the seeded agar lawn or by inoculating the bacteriocin-producing strain onto the indicator lawn . Lysis of cells of the indicator strain resulted in a clear zone . These techniques may be adapted to test antimicrobial substances other than bacteriocins and to help to determine their modes of action.

Diagn Microbiol Infect Dis, 1993 Aug-Sep, 17(2), 111 - 7
Characterization of Mycobacterium fortuitum isolates from sternotomy wounds by antimicrobial susceptibilities, plasmid profiles, and ribosomal ribonucleic acid gene restriction patterns; Yew WW et al.; An outbreak of sternotomy infections due to Mycobacterium fortuitum in patients who had received cardiovascular surgery occurred in a cardiothoracic hospital in Hong Kong, and 21 such isolates from different patients had antimicrobial susceptibility studies against 14 drugs in vitro . These isolates were also studied for plasmid profiles and ribosomal ribonucleic acid gene restriction patterns . The latter method proved valuable in categorization of these isolates into two groups (comprising of nine and seven isolates, respectively) and five other sporadic strains . When the plasmid profiles and ribotyping are matched against the clinical and epidemiologic data, multisource contamination is suspected to be responsible for the outbreak . The organisms were probably derived from the environment rather than contaminated surgical equipments and materials.

Hematol Oncol Clin North Am, 1993 Aug, 7(4), 841 - 64
Biologicals and hematopoietic cytokines in prevention or treatment of infections in immunocompromised hosts; Roilides E et al.; The number of immunocompromised hosts has dramatically increased in recent years . The primary reason for this increase has been the intensification of antineoplastic therapy for the treatment of various malignancies and the explosive spread of human immunodeficiency virus infection . Although the treatment and prevention of many infections have been improved with the rational use of antimicrobial agents, ultimate success can be blunted by protracted impairment of essential host defenses or by the virulence of certain organisms.

J Immunol, 1993 Jul 15, 151(2), 929 - 38
Role and effect of IL-2 in experimental visceral leishmaniasis; Murray HW et al.; In experimental visceral leishmaniasis, acquired resistance is T cell-dependent, involves IFN-gamma-activated macrophages, and is expressed in the tissues by granuloma formation . Resistance also correlates with Ag-stimulated IL-2 secretion; therefore, Leishmania donovani-infected BALB/c mice were treated with anti-IL-2 mAb or rIL-2 to determine the host defense effect of IL-2 . In control mice, intracellular hepatic infection peaked at 2 wk and then declined coincident with granuloma development . In contrast, liver parasite burdens in anti-IL-2-treated mice continued to increase until after 4 wk, at which time mature granuloma formation was inhibited . Treatment of mice with continuously administered IL-2 reduced liver burdens by > 50% and led to marked accumulation of granuloma mononuclear cells . The IL-2-responsive mechanism was T cell-dependent and required both L3T4+ and Lyt-2+ cells . IL-2 enhanced IFN-gamma mRNA expression in vivo and was required for IFN-gamma secretion in vitro, and anti-IFN-gamma mAb administration abolished the antimicrobial effect of exogenous IL-2 . These results: 1) identify the activity of endogenous IL-2 in both antileishmanial resistance and granuloma formation; 2) demonstrate that exogenous IL-2 can enhance the granulomatous tissue reaction; and 3) indicate that IL-2 treatment stimulates intracellular antimicrobial activity largely via the induction of IFN-gamma.

Blood, 1993 Jul 15, 82(2), 641 - 50
Posttranslational processing and targeting of transgenic human defensin in murine granulocyte, macrophage, fibroblast, and pituitary adenoma cell lines; Ganz T et al.; Human defensins are 29 to 30 amino acid (aa) antimicrobial peptides that are among the principal constituents of the neutrophil's azurophil granules . To determine the tissue specificity of posttranslational processing and subcellular targeting of defensins, the cDNA for a 94 aa human preprodefensin was transduced into murine cell lines (NIH 3T3 embryonic fibroblasts, AtT-20 pituitary adenoma, J774.1 and RAW 264.7 macrophages, and 32D and 32D cl3 granulocytes) using retroviral vectors . All transduced cell types expressed and to a variable extent constitutively secreted a 75 aa prodefensin formed by the removal of the amino terminal signal sequence . In AtT-20 cells, the 75 aa form accumulated intracellularly in granules and was releasable by secretagogues . Proteolytic processing to mature defensins was seen only in myeloid cells (J774.1, RAW 264.7, 32D, and 32D cl3) . Newly formed mature defensin was rapidly degraded in J774.1 and RAW 264.7 macrophages, but accumulated stably in multivesicular bodies in 32D cells and in cytoplasmic granules of 32D cl3 cells . Our data suggest that the enzymatic and transport machinery required to process preprodefensin to mature defensin and to store it in cytoplasmic granules is a specialized feature of cells of granulocytic lineage.

Infect Immun, 1993 Jul, 61(7), 3081 - 3
Antimicrobial activity of two bactenecins against spirochetes; Scocchi M et al.; Bac5 and Bac7 are antimicrobial peptides of bovine neutrophils that act on enteric gram-negative bacteria . We report here that these two peptides immobilize and kill Leptospira interrogans and Leptospira biflexa with MBCs of 6 to 25 micrograms/ml . Conversely, although both peptides bind to Borrelia burgdorferi, the organism is resistant to their action.

Infect Immun, 1993 Jul, 61(7), 2991 - 4
Selective inhibition of microbial serine proteases by eNAP-2, an antimicrobial peptide from equine neutrophils; Couto MA et al.; Equine neutrophil antimicrobial peptide 2 (eNAP-2), a recently described antimicrobial peptide isolated from equine neutrophils, was found to selectively inactivate microbial serine proteases (subtilisin A and proteinase K) without inhibiting mammalian serine proteases (human neutrophil elastase, human cathepsin G, and bovine pancreatic trypsin) . Although the primary structure of eNAP-2 resembled that of several known antiproteases that belong to the 4-disulfide core peptide family, this pattern of selectivity is unique . eNAP-2 formed a noncovalent complex with native subtilisin A or proteinase K but did not associate with these enzymes if they had been treated with phenylmethylsulfonyl fluoride, a serine protease inhibitor . The eNAP-2-microbial protease complex was disrupted by boiling or by exposure to low pH . We suggest that eNAP-2 exerted selective antiproteinase activity by binding tightly but noncovalently to the active site of subtilisin A or proteinase K . Since microbial exoproteases may act as virulence factors, the combined antimicrobial and antiprotease activities of eNAP-2 could allow it to play an important role in neutrophil-mediated antimicrobial defenses.

Eur J Clin Microbiol Infect Dis, 1993 Jul, 12(7), 519 - 26
Effect of pathological changes of pH, pO2 and pCO2 on the activity of antimicrobial agents in vitro; Konig C et al.; Since standard susceptibility tests reflect the physiological rather than the pathological conditions prevailing within an infected abdomen, as recently documented, the effect of reduced pH and pO2 and increased pCO2 on the activity of antibiotics in vitro was studied . MICs were determined in vitro under standard culture conditions (MICstandard) and modified conditions (MICmodification) simulating the previously determined pathological values . Various classes of antibiotics were affected differently by the modified conditions . However, within an antibiotic class similar results were obtained for gram-negative and gram-positive pathogens . Median MICmodification/MICstandard ratios were 4 for aminoglycosides, 2 for quinolones and clindamycin, 1 for cephalosporins, and 0.5 for penicillins and vancomycin . Anaerobic conditions and a pH of 6.4 further increased the ratio of aminoglycosides to 8 . Ratios were similar within an antibiotic class at inocula of 10(5) or 10(7) cfu/ml . All MICs determined in tests with imipenem against gram-negative and gram-positive bacteria and with vancomycin against gram-positive organisms were below the susceptibility breakpoint, whatever conditions and inocula were employed . In contrast, the percentage of MICs in susceptibility range using high inocula and modified conditions decreased to 78% for penicillins, 73% for cephalosporins, 22% for aminoglycosides, 11% for quinolones and 0% for clindamycin . In conclusion, routine susceptibility testing may overestimate the activity of aminoglycosides and underestimate the activity of beta-lactams under the conditions prevailing during abdominal infection.

J Immunother, 1993 Jul, 14(1), 43 - 50
Immunomodulatory effects of recombinant interleukin-3 treatment on human alveolar macrophages and monocytes; Thomassen MJ et al.; The purpose of these studies was to examine the effects of in vivo and in vitro recombinant IL-3 treatment on alveolar macrophage and monocyte activities associated with antitumor and antimicrobial properties . Alveolar macrophages and blood monocytes from 6 patients receiving IL-3 (125-500 micrograms/m2/day) subcutaneously were isolated before therapy and at various times during the 15 days of therapy . Results indicated that tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) secretion were enhanced from monocytes of all patients and from alveolar macrophages of patients receiving 500 micrograms/m2/day IL-3 . Constitutive cytokine gene expression was present before therapy, but further enhancement was not detectable during therapy, suggesting a rapid time course of cytokine gene transcription and translation . Serum neopterin levels were elevated 2-5 fold in all patient compatible with the presence of augmented monocyte/macrophage activity . Peak levels of neopterin did not coincide with peak levels of cytokine secretion . In vitro studies of IL-3-treated normal alveolar macrophage and monocyte population demonstrated that IL-3 significantly augmented TNF and IL-6 secretion in monocytes, but not in alveolar macrophages . These differences in alveolar macrophage cytokine secretion observed after in vivo and in vitro IL-3 treatment may reflect the involvement of other cell populations in IL-3 modulation of alveolar macrophages in vivo . Monocytes, in contrast were comparably activated by IL-3 whether presented in vitro or in vivo.

Bone Marrow Transplant, 1993 Jul, 12(1), 57 - 63
Single-drug oral antibacterial prophylaxis with ofloxacin in BMT recipients; Schmeiser T et al.; We evaluated the efficacy and safety of a new oral fluoroquinolone, ofloxacin (200 mg twice daily), as antibacterial prophylaxis after BMT in a non-comparative prospective study of patients nursed in either LAF plastic isolators or HEPA filtered single rooms . Of the 101 evaluable patients who were neutropenic (< 500 x 10(6)/l) for a median duration of 20 days, 92 (91%) had febrile episodes of varying length and causes . Infections were documented in 34 patients, of whom 14 had proven bacterial infection (13 with bacteremia and one with pneumonia) . Mortality rate within 6 weeks after transplant was 6% . Only one patient died from bacterial infection . Univariate analysis using an array of potentially prognostic factors including the type of isolation was not helpful in identifying significant variables for predicting the development of documented infection . Tolerance was excellent . Oral ofloxacin was associated with a relatively low incidence of documented bacterial infection and related mortality, although it did not obviate the need for frequent empiric antimicrobial therapy due to a high incidence of febrile episodes.

Arzneimittelforschung, 1993 Jul, 43(7), 756 - 60
Synthesis and pharmacological evaluation of a novel series of alpha-picolinium hydrazone analogues with anticipated antidiabetic activity; Girges MM et al.; A new series of substituted alpha-picolinium p-dimethylaminobenzalhydrazine derivatives and their o-hydroxy analogues has been prepared for evaluation of their efficacy as potential hypoglycemic agents . The synthesis was achieved by condensation of N-amino-alpha-picolinium perchlorate derivatives with the corresponding aromatic aldehydes . The structure of the synthesized products was inferred from elemental and spectral data . The hypoglycemic effect, antimicrobial activity and toxicity of the hitherto and possibly new chemotherapeutic agents were evaluated . Based on screening data, a possible structure-activity relationship has been discussed.

Fundam Appl Toxicol, 1993 Jul, 21(1), 66 - 70
Quaternary silsesquioxane: a developmental toxicity study in rats; Siddiqui WH et al.; The developmental toxicity of an antimicrobial organosilicon quaternary ammonium chloride (Quaternary Silsesquioxane) was evaluated in rats . Groups of 25 pregnant CD rats were administered 100, 300, or 1000 mg/kg/day of test material by gavage as a single daily dose on Days 6 through 15 of gestation at a volume of 10 ml/kg . The control group received only corn oil as the vehicle . Cesarean examinations were performed on all females on Gestation Day 20 followed by evaluation of the fetuses for teratogenicity . Maternal effects included a slight but statistically significant increase in relative liver weights at the 1000 mg/kg/day dose level . Using these hepatic changes as an adverse effect, the maternal no observable adverse effect level for this study was identified at 300 mg/kg/day . The number of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, the fetal body weights, the crown-rump length, and the gravid uterine and corrected body weights were not affected by the administration of Quat-Silsesquioxane . The occurrence of external and internal soft tissue malformations and variations and the incidences of skeletal malformations and variations in the treated groups were not significantly different from those in the control group . These results demonstrated that oral administration of Quat-Silsesquioxane as high as 1000 mg/kg/day did not produce teratogenicity or other indications of developmental toxicity in the rat conceptus.

Ann Pharmacother, 1993 Jul-Aug, 27(7-8), 974 - 7
Prescription of antimicrobial drugs to hospitalized children; Kolar JV et al.; OBJECTIVE: To analyze with regard to age, gender, and diagnosis, the profile, frequency of prescribing, and cost of antimicrobial drugs (AMDs) in hospitalized children . DESIGN: Retrospective study of medical records of children hospitalized during 1987 and 1988 . SETTING: First Pediatric Clinic, Children's Teaching Hospital, Bratislava, Czechoslovakia (now Slovakia) . PATIENTS: One thousand randomly selected hospitalized children . MAIN OUTCOME MEASURES: Patterns of AMD prescribing . Consumption is expressed by the number of drugs and cost per child . RESULTS: AMDs were prescribed to 69.9 percent of the patients (average 1.91 per patient) . Ampicillin was the drug most frequently prescribed (20.0 percent), followed by oxacillin (12.8 percent) . The mean length of stay was 15.9 days . An average of 3.61 drugs from other pharmacotherapeutic categories were prescribed per patient . Most children who received AMD treatment were in the 1-year group (patients between six months and 1.5 years of age {88.6 percent}) . CONCLUSIONS: This study provides an overview of the prescribing of AMDs and other drugs in hospitalized children in Bratislava.

Ann Pharmacother, 1993 Jul-Aug, 27(7-8), 870 - 3
Intrathecal administration of amikacin for treatment of meningitis secondary to cephalosporin-resistant Escherichia coli; Preston SL et al.; OBJECTIVE: To report a case of gram-negative bacillary meningitis (GNBM) secondary to cephalosporin-resistant Escherichia coli that was treated with intrathecal and intravenous amikacin and intravenous imipenem/cilastatin (I/C) . CASE SUMMARY: A patient who had undergone two recent neurosurgical procedures developed GNBM and bacteremia . He was treated empirically with ceftazidime . Both bloodstream and cerebrospinal fluid isolates were identified as E . coli, resistant to third-generation cephalosporins, penicillins, tobramycin, and gentamicin . The patient was subsequently treated with intravenous and intrathecal amikacin plus intravenous I/C . He experienced subjective and objective improvement on days 2-4 of antimicrobial therapy; two generalized tonic-clonic seizures occurred on days 7 and 12 . Intrathecal amikacin was discontinued after 6 days, and intravenous amikacin and I/C were discontinued after 23 and 27 days, respectively . The patient's mental status did not completely return to premeningitis baseline . DISCUSSION: Third-generation cephalosporins are the treatment of choice for GNBM . In the case reported herein, bacterial resistance to these agents prompted the use of a therapy that has not been well studied and is also considered to be less safe and perhaps less efficacious . Treatment of GNBM with an intrathecally administered aminoglycoside or with intravenous I/C plus an aminoglycoside is reviewed . CONCLUSIONS: Patients with GNBM secondary to third-generation cephalosporin-resistant organisms may require therapies that may be less effective and more toxic . Further study of alternative agents is warranted.

Ann Pharmacother, 1993 Jul-Aug, 27(7-8), 856 - 61
Design, implementation, and use of a new antimicrobial order form: a descriptive report; Lipsy RJ et al.; OBJECTIVE: To describe the development, implementation, and use of an antimicrobial order form . The article provides the design of the form and the rationale for including key aspects, and a report of the authors' experiences with the form over a three-year period . An analysis of compliance with the form and its impact on selected prescribing practices is also presented . DESIGN: Three thousand five hundred antimicrobial orders in four discrete sets over a three-year period were analyzed to assess compliance and characterize prescribing patterns with respect to duration of therapy and dosing frequency . SETTING: The setting of the study was a 300-bed, university-affiliated, tertiary-care, teaching hospital . MAIN OUTCOME MEASURES: Analysis of the forms was organized into the following sections: (1) compliance with use of the form, (2) duration of therapy, and (3) impact on antimicrobial dosing intervals . RESULTS: Use of the form was essentially 100 percent . Seventy-eight percent of the forms had all required data elements completed in the period following implementation; this fell to 67 percent at the end of three years . Duration of surgical prophylaxis went beyond the recommended 24 hours in 10 percent of all cases in period 1, and in 18, 8, and 4 percent in periods 2, 3, and 4, respectively . Declines in inappropriate dosing frequency were seen with cefazolin (from 14 to 2.3 percent), ceftriaxone (from 23 to 4 percent), cefuroxime (from 21 to 0 percent), and clindamycin (from 43 to 7 percent) . CONCLUSIONS: Our experience with implementation and use of the form was very positive . Significant difficulties with compliance were not encountered . Benefits of the form included reductions in the duration of surgical prophylaxis and in the frequency of inappropriate dosing intervals.

Antimicrob Agents Chemother, 1993 Jul, 37(7), 1444 - 6
In vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents; Levin JM et al.; The in vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents was investigated . The antimicrobial agents evaluated included ceftizoxime, FK037, cefotaxime, dirithromycin, clarithromycin and its metabolite 14-hydroxy-clarithromycin, erythromycin, doxycycline, amoxicillin, ciprofloxacin, and ofloxacin . Isolates of B . burgdorferi tested included two reference strains (B31 and ATCC 53899), six isolates from the midwestern United States, and three from Europe . A broth macrodilution method was used to determine MICs and MBCs . B . burgdorferi was inhibited by < or = 0.5 micrograms of each of the agents except the quinolones per ml . The MBCs for 90% of strains tested of ceftizoxime, FK037, clarithromycin, 14-OH clarithromycin, and dirithromycin (< or = 1.0 microgram of each per ml) were superior to those of amoxicillin (2.0 micrograms/ml) and doxycycline (4.0 micrograms/ml) . Further in vivo studies are warranted to determine whether these agents may be efficacious in the treatment of Lyme borreliosis.

Antimicrob Agents Chemother, 1993 Jul, 37(7), 1436 - 43
Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis; Walzer PD et al.; We compared Ro 11-8958, an analog of trimethoprim (TMP) with improved antimicrobial and pharmacokinetic properties, other dihydrofolate reductase (DHFR) inhibitors, sulfamethoxazole (SMX), and dapsone (DAP) in the treatment of Pneumocystis carinii pneumonia in an immunosuppressed rat model . In contrast to previous reports, high dosages of the DHFR inhibitors were used in combination with fixed, low dosages of SMX (3 mg/kg of body weight per day) or DAP (25 mg/kg/day) . When administered alone at these dosages, SMX and DAP reduced the median P . carinii cyst count about 5- to 15-fold . Ro 11-8958, TMP, and diaveridine used at a dosage of 20 mg/kg/day with SMX were only slightly more effective than SMX used alone . However, administration of these DHFR inhibitors at a dosage of 100 mg/kg/day with SMX lowered the cyst count about 500- to 1,000-fold, indicating a synergistic effect . Little or no synergism was found when other DHFR inhibitors (pyrimethamine, cycloguanil, and tetroxoprim) were combined with SMX . Regimens of Ro 11-8958 at a dosage of 20 mg/kg/day with DAP and of TMP or diaveridine used at a dosage of 100 mg/kg/day with DAP showed comparable anti-P . carinii activity, lowering the cyst count 100- to 200-fold . By contrast, Ro 11-8958 administered at a dosage of 100 mg/kg/day with DAP reduced the cyst count > 1,000-fold . Thus, the experimental approach used here enables the rat model of pneumocystosis to be used to compare synergistic combinations of antifolate drugs . The favorable results achieved with Ro 11-8958 indicate that it should be considered for clinical trials.

Mikrobiyol Bul, 1993 Jul, 27(3), 185 - 90
{Comparison of latex agglutination and coagglutination methods for the determination of bacterial antigens in cerebrospinal fluid}; Ayaslioglu E et al.; The latex agglutination and coagglutination tests were used to demonstrate specific bacterial antigens in cerebrospinal fluid of patients with bacterial meningitis . Latex agglutination was more sensitive than coagglutination . It detected 90% (18/20) of culture positive CSF specimens, whereas coagglutination detected 60% (12/20) . Antigens were also detected by latex agglutination in seven of seven additional cerebrospinal fluid specimens after 32-48 hours of antimicrobial therapy, but four of seven by coagglutination.

Kekkaku, 1993 Jul, 68(7), 479 - 86
{Clinical studies on lung disease caused by atypical mycobacteria in our hospital--especially in relation to drug susceptibility}; Mineshita M et al.; From 1987 to 1991, 27 patients were diagnosed as atypical mycobacteriosis in our hospital . Some strains of M . avium complex were found to be M . avium and M . intracellulare by means of a DNA probe test . 1 . Total cases consisted of 14 males (the average age was 66.7 years) and 13 females (65.7 years) . 2 . M . avium complex was observed in 24 patients (9 cases of M . avium and 5 cases of M . intracellulare): M . kansasii and M . chelonae were found in 2 patients and 1 patient, respectively . 3 . The findings of sputum cultures became negative three months after the chemotherapy treatment in 3 out of 25 patients . Two male patients were operated on and cured . Three patients died, and all of them had respiratory infections . 4 . To determine the susceptibility of mycobacteria strains isolated from patients to various antimicrobial agents, an investigation was carried out . There were 88 strains of M . tuberculosis, 52 strains of M . avium complex (23 strains of M . avium and 17 strains of M . intracellulare), 3 strains of M . kansasii, 2 strains of M . gordonae and 2 strains of M . chelonae . 5 . Strains of M . tuberculosis, M . kansasii and M . gordonae were susceptible to various antituberculous agents and ciprofloxacin . Strains of M . chelonae were susceptible to ciprofloxacin, and one strain was susceptible to streptomycin and ethionamide . 6 . The M . avium strains were more susceptible to cycloserine and ciprofloxacin than were the M . intracellulare strains . Conversely, the M . intracellulare strains were more susceptible to ethambutol than were the M . avium strains.

J Biomed Mater Res, 1993 Jul, 27(7), 895 - 900
Gentamicin sulfate attachment and release from anodized Ti-6A1-4V orthopedic materials; Dunn DS et al.; A novel method has been developed to attach, retain, and release antibiotics from titanium based materials . This technique consists of forming porous surface coatings by anodizing and using the surface chemical properties of the oxide coatings to attach antibiotics . Coatings with pores in the size range 0.1-0.5 micron have been formed in acid solutions . The attachment and retainment of gentamicin sulfate, a cationic antibiotic, to the coatings has been investigated using microbiological methods . In vitro test results have shown that the duration of antimicrobial activity on the surface of anodized materials is dependent on the porosity and isoelectric point of the coatings . Using microporous oxide coatings formed in phosphoric acid solutions, it has been found that antimicrobial activity could be retained for more than 2 weeks.

J Antibiot (Tokyo), 1993 Jul, 46(7), 1156 - 62
Delaminomycins, novel extracellular matrix receptor antagonist . IV . Structure-activity relationships of delaminomycins and derivatives; Ueno M et al.; Delaminomycins A, B, C and their derivatives were prepared and investigated biological activities of them . Among these compounds, spiro compounds (A2, B2 and C2) showed stronger inhibitory activity than natural products (A1, B1 and C1) on B16 melanoma cells adhesion assay and Con A-induced proliferation of murine splenic lymphocytes assay . In MLCR and antimicrobial assay, however, A1, B1 and C1 showed more potent inhibitory activity than spiro compounds (A2, B2 and C2) . On the other hand, as to C-5' substituents of pyrrolidine ring, the order of inhibitory activity was R = OH > R = OCH3 > R = H on Con A-induced proliferation of murine splenic lymphocytes assay . In MLCR and antimicrobial assay, however, the order of inhibitory activities were R = H > R = OCH3 > R = OH . Inhibitory activities of A4 which was lacked pyrrolidine ring were reduced on B16 melanoma cells adhesion assay and on cytotoxicity against tumor cells in vitro in comparison with those of A1.

J Antibiot (Tokyo), 1993 Jul, 46(7), 1089 - 94
UK-1, a novel cytotoxic metabolite from Streptomyces sp . 517-02 . I . Taxonomy, fermentation, isolation, physico-chemical and biological properties; Ueki M et al.; A new benzoxazole, UK-1, was isolated from the mycelial cake of an actinomycete strain 517-02 . Based on morphological, cultural and physiological characteristics, strain 517-02 was seemed to be a close relative of Streptomyces morookaense . UK-1 showed potent cytotoxic activity against B16, HeLa and P388 cells and did not show any antimicrobial activity.

Clin Microbiol Rev, 1993 Jul, 6(3), 266 - 310
The Mycobacterium avium complex; Inderlied CB et al.; Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients . However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS . M . avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals . The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection . Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance . The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function . There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival . Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise . These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS . The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement . Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue . Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated . Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied.

Curr Opin Rheumatol, 1993 Jul, 5(4), 414 - 9
Infectious agents in reactive arthritis; Keat AC et al.; It is now clear that the deposition and persistence of bacterial antigens in the joint are significant features of reactive arthritis . It is possible that in some instances this represents persistence of live bacteria, and several studies point to the potential value of antimicrobial therapy . Searches for bacterial DNA and RNA have yielded conflicting data, however, so further developments in this area will be of great importance . It is likely that bacterial antigens interact in some way with class I major histocompatibility complex (MHC) antigens in the pathogenesis of reactive arthritis . However, with the increasing understanding of the structure and function of HLA molecules, some evidence of a classic antigen-class I MHC-CD8 T-lymphocyte interaction is now emerging . Thus far, the mechanisms that link HLA-B27 and bacterial antigens with reactive arthritis remain unclear.

Infect Control Hosp Epidemiol, 1993 Jul, 14(7), 376 - 82
Trends in antimicrobial utilization at a tertiary teaching hospital during a 15-year period (1978-1992); Pallares R et al.; BACKGROUND: Antimicrobials are a major part of hospital pharmacy budgets and must be considered in resource planning and spending projections . Logically, trends in antimicrobial usage should be linked to trends in resistant pathogens . OBJECTIVE: To examine long-term trends in antimicrobial use over a 15-year period (1978 to 1992) and contrast them with changes in pathogens causing nosocomial bacteremia . SETTING: A 900-bed, tertiary care teaching hospital . METHODS: Pharmacy records were reviewed to identify parenteral antimicrobial agents administered to adult inpatients . Results were expressed in average daily adult doses per 1,000 patient days . RESULTS: Chloramphenicol use decreased, while use of penicillin G, antistaphylococcal penicillins, first-generation cephalosporins, and aminoglycosides remained relatively stable . In contrast, there was a sharp increase in the use of second- and third-generation cephalosporins (7-fold and 6.5-fold increase, respectively), vancomycin (161-fold increase), metronidazole (32-fold increase) and amphotericin B (35-fold increase) . The proportion of nosocomial bacteremias due to methicillin-resistant gram-positive bacteria rose, but gentamicin resistance in gram-negatives remained at low levels . During the past 14 years, the percentage of patients receiving at least one parenteral antimicrobial rose from 23% to 44% . Among patients receiving antimicrobials, the average number of different agents used per patient increased from 1.8 to 2.1 . CONCLUSIONS: If newer agents were available, use of older agents usually declined . If newer alternatives were not available, use of older agents rose sharply . The increased use of antimicrobials in adults was related to the expanded proportion of patients receiving these agents.

Clin Infect Dis, 1993 Jul, 17(1), 98 - 103
Efficacy of antimicrobial prophylaxis in placement of cerebrospinal fluid shunts: meta-analysis; Langley JM et al.; The objective of this study was to determine if perioperative antimicrobial prophylaxis decreases the incidence of subsequent shunt infection in patients who require placement of internal CSF shunts . Data sources included a computerized search of two biomedical data bases, contact with colleagues, and a review of abstracts of meetings and of references of identified trials and reviews . Studies were chosen for detailed review if they involved human subjects who underwent CSF shunt placement, with random allocation of patients to groups receiving perioperative systemic antimicrobial agents or to a control group and an outcome measure of subsequent shunt infection . Twelve (32%) of 37 studies met selection criteria and were included . Features of trial design were extracted and trial quality was evaluated with use of a predetermined protocol by three independent investigators who were blinded to titles, authors, and institutions . Individually, only one of 12 trials achieved statistical significance favoring prophylaxis; in the aggregate, the use of prophylactic antibiotics was associated with a significant reduction in subsequent CSF shunt infection (Mantel-Haenszel weighted risk ratio: 0.52; 95% confidence interval: 0.37, 0.73; P = .0002; approximate risk reduction: 50%) . This systematic overview of 12 trials of 1,359 randomized patients demonstrates that perioperative use of antimicrobial agents in CSF shunt placement significantly reduces the risk of subsequent infection.

Anticancer Res, 1993 Jul-Aug, 13(4), 1019 - 25
Diverse biological activities displayed by phenothiazines, benzo{a}phenothiazines and benz{c}acridins (review); Molnar J et al.; This review summarizes our experiments which are investigating the relationship between the structure and activity of mainly phenothiazines, benzo{a}phenothiazines and benz{c}acridines . Phenothiazines had potent antiplasmid and antibacterial activities, but induced weak antimicrobial activity in vivo . Their antiplasmid activity seemed to be enhanced by Cl- or CF3- substitution at the 2C position of phenothiazines and modified by the side-chain length and hydrophobicity . Benzo{a}phenothiazines did not show any significant antiplasmid or antibacterial activity, but stimulated the differentiation of human myelogenous leukemic cell lines and natural killing activity of human peripheral blood mononuclear cells in vitro, and induced antimicrobial activity in vivo . Circuit current energy (CRE), circuit current (CC), bond current (BC), diatropic and paratropic properties of benzo{a}phenothiazines might be correlated with their biological activity . Benz{a}acridine showed both in vitro and in vivo antimicrobial activities, and carcinogenic activity for skin tumor . The carcinogenic benz{c}acridines showed out-of-phase in the L-region and their energy was accumulated in the K-region of the molecular orbitals . The results suggest the involvement of different molecular orbitals for the expression of various biological activities by phenothiazines, benzo{a}phenothiazines and benz{c}acridines.

Am J Trop Med Hyg, 1993 Jul, 49(1), 88 - 92
Mycoplasma pneumoniae and Chlamydia trachomatis in acute lower respiratory infections in Filipino children; Saikku P et al.; The role of Mycoplasma pneumoniae and Chlamydia trachomatis in acute lower respiratory infection (ALRI) was studied by serologic analysis of 216 Filipino children less than five years old living in periurban slums and middle-class neighborhoods . Diagnostic antibody responses to M . pneumoniae and C . trachomatis were observed in 18 (8.3%) and five (4.3%), respectively, of the cases with ALRI . These bacteria are not susceptible to the antimicrobial treatments currently recommended for the treatment of ALRI in developing countries.

Semin Nephrol, 1993 Jul, 13(4), 409 - 15
White blood cell response to burn injury; Griswold JA; Multiple sites of decreased immune response have been discovered, but the instigation of this diffuse immunosuppression remains a matter of much debate . Several investigators have observed immunosuppressive affects of low-molecular weight peptides found in the serum of burn and trauma patients . These substances have been termed suppressive active peptides (SAP) . Current research is also focusing on the intricate connection between stress hormones and neurotransmitters, in which there exist a complex information channel between the immune, endocrine, and central nervous systems . It is becoming clear that immune homeostasis may require regulatory influence via immunocompetent cells, along with influences from the central nervous system and a balanced endocrine environment . In fact, macrophages, lymphocytes, and neutrophils contain receptors for many hormones including corticosteroids, insulin, growth hormone, catecholamines, acetylcholine, and endorphins . The dramatic alteration in the hormonal milieu after injury may play a significant role in immunocompetence . Attempts to modulate specific defects in the immune system have been unsuccessful to date . Our goal, to decrease the risk of infection in burn patients, therefore, is meticulous supportive care . This includes not only reducing the risk of invading bacteria, but also increasing the patient's resistance to overall infection . The cornerstone of this support is to restore mechanical barrier function to as near normal as possible . Immediately after injury, vigorous wound management includes several daily debridements combined with wound protection using an appropriate topical antimicrobial substance.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Periodontol, 1993 Jul, 20(6), 395 - 401
Suppression of subgingival Actinobacillus actinomycetemcomitans in localized juvenile periodontitis by systemic tetracycline; Christersson LA et al.; The current study assessed the clinical and microbiological effects of systemic antimicrobial therapy alone in Actinobacillus actinomycetemcomitans-infected adolescents with periodontal disease . The study involved 6 localized juvenile periodontitis patients 13-18 years of age, who harbored high numbers of A . actinomycetemcomitans in subgingival plaque samples . The periodontal lesions were microbiologically monitored by selective culture, and clinically assessed for probing pocket depth and periodontal attachment level 3 months prior to baseline, and at 3, 6, 12, and 24 months posttreatment . Tetracycline-HCl (250 mg/QID) was prescribed until 1 week after subgingival A . actinomycetemcomitans was no longer detectable or for a maximum of 8 weeks . During 3 months prior to treatment, pocket depth was unchanged, and was then significantly reduced from an average of 7.1 mm to 5.1 mm 12 months after treatment (p = 0.02) . The mean change in clinical attachment level was a gain of 1.4 mm between baseline and 12 months (p = 0.02) . 3 of the 6 patients were still infected with A . actinomycetemcomitans after 8 weeks of antibiotic therapy and 4 subjects were infected at 12 months . Numbers of A . actinomycetemcomitans were still suppressed in most lesions . There was a strong association between mean numbers of A . actinomycetemcomitans in periodontal pockets and mean change in probing attachment level at any given time point . For 22 available comparisons, derived from all time points, there was a strong association (r = 0.68) between subgingival A . actinomycetemcomitans and change in probing attachment level.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1993 Jul, 31(7), 1932 - 5
Ramoplanin susceptibility testing criteria; Barry AL et al.; Ramoplanin and mupirocin are two antimicrobial agents that may be applied topically . They had similar potencies against susceptible gram-positive cocci, but they differed in their spectra of activity . In plastic microdilution trays, the in vitro activity of ramoplanin was slightly diminished but that activity was restored by the addition of bovine serum albumin (0.02%) . Susceptible strains were defined as those for which MICs of ramoplanin were < or = 2.0 micrograms/ml (without bovine serum albumin) and which had > or = 11-mm zones around 60-micrograms ramoplanin disks . Criteria for a resistant category cannot be defined at this time.

J Can Dent Assoc, 1993 Jul, 59(7), 619 - 22, 624
{Minocycline}; D'Aoust P et al.; Periodontal diseases are bacterial infections and antimicrobial agents appear to offer great potential in their treatment and prevention . One such chemotherapeutic agent is minocycline . The aim of this paper is to review the literature on this antibiotic concerning in vitro and in vivo studies, its pharmacokinetics and secondary effects.

J Trauma, 1993 Jul, 35(1), 8 - 19
Cytotoxic effects of topical antimicrobial and antiseptic agents on human keratinocytes in vitro; Teepe RG et al.; The cytotoxicity of commonly used antimicrobial and antiseptic agents to cultured human keratinocytes was investigated, combining a morphologic assay with a quantitative neutral red (NR) spectrophotometric assay . Main outcome criteria of response were the initial cytotoxicity (NR 90) and midpoint cytotoxicity (NR 50) and the highest tolerated dose (HTD), a concentration causing the first observed morphologic alterations . These values were compared with commonly administered clinical doses or calculated doses . Thirty-five agents were evaluated; five agents were also subjected to an assay for cell morphologic alterations, and HTD and percentage of cells taking up trypan blue and annihilation dose were assessed . These studies show that in clinical concentrations many, but not all, agents exert profound cytotoxic effects . The results suggest that under certain conditions cultured epithelial grafts may be exposed to clinical concentrations of neomycin, clindamycin, framycetin, erythromycin, gentamicin, and 0.1% solutions of povidone-iodine . Tetrachlorodecaoxygen anion complex (TCDO) should be further evaluated as a likely effective cleansing agent before culture grafting.

J Clin Epidemiol, 1993 Jul, 46(7), 671 - 3
Antimicrobial drug use in primary health care; Uppal R et al.; A survey was carried out to assess the extent and pattern of use of antimicrobials at two primary health care centres (PHCs) in northern India . At both PHCs 20-40% of all drugs prescribed were antimicrobials . The most prescribed antimicrobials at both PHCs were sulfa drugs (29%), followed by cotrimoxazole (15%) and penicillins (10%) . The pattern of infectious diseases was similar at both PHCs; with respiratory tract infections heading the list (12%), followed by skin infections (10%), enteritis (7%), injuries (4%), unknown pyrexias (3%) and worm infestations (2%).

Clin Plast Surg, 1993 Jul, 20(3), 507 - 16
Management of xerostomia in the irradiated patient; Jacob RF; Symptomatic management of xerostomia in the head and neck radiation patient often is a palliative process at best . There are secondary clinical effects, however, that require definitive management . Use of fluorides, antimicrobial rinses, saliva substitutes, and sialagogues is discussed.

South Med J, 1993 Jul, 86(7), 773 - 6
Hyperpyrexia among patients in a large community hospital: causes, features, and outcomes; Sioson PB et al.; Hyperpyrexia, defined as temperature elevation of at least 106 degrees F, is generally thought to be infrequently associated with infection . In a 3-year retrospective analysis of 39 episodes of hyperpyrexia in adults, 94% of cases were associated with infection . In 35 patients (90%) the causes were potentially treatable, and the majority were associated with common bacteria or fungi . Fourteen (36%) patients were bacteremic . Fifteen (43%) of those with treatable infections had additional noninfectious reasons for hyperpyrexia . Only three patients died in conjunction with hyperpyrexia, and none of these had treatable infection . Infection must be strongly considered by the clinician faced with a hyperpyrexic patient . Antimicrobial therapy is indicated in the majority of cases, and most patients will survive through hospital discharge.

Braz J Med Biol Res, 1993 Jul, 26(7), 699 - 702
Comparison of the urease test and of direct smear examination in the control of treatment of Helicobacter pylori-induced infection; Resende LM et al.; The sensitivity and specificity of the preformed urease test and of carbolfuchsin-stained smears for the diagnosis of the presence of Helicobacter pylori in gastric mucosa were evaluated before and after antimicrobial treatment . The results obtained by culture were used as the reference point . We studied 41 patients with endoscopically diagnosed duodenal ulcer . Twenty-five of these were treated with furazolidone (100 mg t.i.d.), amoxicillin (500 mg t.i.d.) and metronidazole (250 mg t.i.d.) for 5 days and then with only furazolidone (100 mg t.i.d.) for an additional 25 days . The 16 control patients were treated with cimetidine (800 mg, 4 times a day) . The sensitivity of the urease test and of direct smear examination was 100% before treatment and 84.6% and 92.3%, respectively, after treatment . We conclude that the urease test and carbolfuchsin-stained smears, which are highly sensitive for H . pylori diagnosis, present reduced sensitivity when they are employed for the follow-up of patients treated with antimicrobials.

Ann Vasc Surg, 1993 Jul, 7(4), 325 - 9
Vascular access surgery as an outpatient procedure; Wilson SE et al.; Construction of a vascular access site for hemodialysis has traditionally been done on an inpatient basis or more recently in a hospital operating room as a 1-day admission . Over 18 months we performed 49 vascular access procedures on 45 patients in a freestanding ambulatory surgical center . Four patients had an arteriovenous radiocephalic autogenous fistula constructed, 30 patients had a polytetrafluoroethylene (PTFE) prosthesis inserted as an arteriovenous bridge graft, 11 patients had a planned reconstruction of a previously placed graft, 1 patient had a false aneurysm corrected, 1 patient had a chronically infected graft removed, and 2 patients had a thrombectomy . All procedures were in the upper extremities except for one femorosaphenous PTFE graft and one excision of a false aneurysm in a thigh prosthesis . Only one patient, an 84-year-old woman, required hospitalization following the outpatient procedure because she was unable to care for herself . No postoperative infection had occurred at 1 month follow-up . A left upper extremity graft performed at another inpatient facility was removed because of infection . The protocol for outpatient vascular access surgery includes preoperative evaluation of the patient for determination of the access site within a week of operation; duplex scan of subclavian veins if central venous lines have been in place for more than 2 weeks; scheduling surgery for the afternoon or morning following routine hemodialysis; obtaining a hemoglobin level, serum/electrolyte study, and an ECG following the last hemodialysis; parenteral antimicrobial prophylaxis; local infiltration anesthesia with standby; a minimum of 1 hour of observation in the recovery room; and a repeat hematocrit study prior to discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathology, 1993 Jul, 25(3), 308 - 9
Osteomyelitis due to Mycobacterium haemophilum in a patient with AIDS; Sowden D et al.; A case of osteomyelitis resulting from infection with Mycobacterium haemophilum in a patient with the Acquired Immunodeficiency Syndrome (AIDS) and Hodgkin's disease is described . The clinical features and response to therapy are examined and compared to previous reported cases . Mycobacterium haemophilum infection in immunocompromised patients usually results in cutaneous lesions but osteomyelitis may be the presenting feature . Tissue samples should be obtained early for microbiological examination and treatment should consist of surgical debridement and appropriate antimicrobial therapy.

Surv Ophthalmol, 1993 Jul-Aug, 38 Suppl, 91 - 104
Differentiating conjunctivitis of diverse origins; Jackson WB; While symptoms can be very distressing, patients with conjunctivitis general maintain good vision and recover completely without permanent sequelae . The great majority of cases of conjunctivitis are infectious or allergic in origin . Seen with increasing frequency are external eye diseases related to contact lens wear or prolonged use of ophthalmic medications . The various forms of conjunctivitis are often not associated with pathognomonic features . A thorough history and ophthalmic examination often permit a presumptive diagnosis and initiation of empiric therapy . For example, a chronic bilateral conjunctivitis, characterized by itching and papillary hypertrophy, suggests an ocular allergy, most frequently the result of exposure to airborne allergens . However, a number of causes, including infections and hypersensitivity reactions, have the potential to threaten vision or produce marked conjunctival scarring which must be identified by the use of appropriate laboratory techniques, followed by specific therapy . Most bacterial and viral conjunctivitis are self-limited, but antimicrobial therapy for the former is advocated to shorten the course, improve patient comfort, prevent recurrence, avoid complications and limit spread to other individuals.

J Hepatol, 1993 Jul, 18(3), 290 - 4
Infectious sequelae after endoscopic sclerotherapy of oesophageal varices: role of antibiotic prophylaxis; Rolando N et al.; In order to determine the incidence of infection following sclerotherapy and the role of antimicrobial prophylaxis, a prospective randomized control study was performed comparing i.v . imipenem/cilastatin, with an infusion of dextrose-saline as a control group . One hundred patients with bleeding esophageal varices were included . All episodes of infection were documented during admission to the unit . Ninety-seven patients were evaluable . Post-sclerotherapy bacteremia developed in six (5.6%) of 107 sclerotherapy sessions in the control group and one (1.1%) of the 88 sclerotherapy sessions in the imipenem/cilastatin group (P < or = 0.1, NS): six of these seven post-sclerotherapy bacteremias occurred after emergency sclerotherapy . Infection within 7 days of the procedure was documented after 43 (22.1%) of the 195 sclerotherapy sessions, 18 (20.5%) in the imipenem/cilastatin group and 25 (23.4%) in the control group (P = NS) . These infections were significantly more common after emergency sclerotherapy, 40 (34.8%) of 115 sessions, than after elective sclerotherapy, three (3.8%) of 80 sessions (P < or = 0.0001) . A short prophylactic antibiotic regime does not reduce the risk of early bacteremia or the frequency of infection after sclerotherapy . The higher risk of infection after emergency sclerotherapy may be therefore related more to the gastrointestinal hemorrhage and its associated effects than to sclerotherapy.

J Antimicrob Chemother, 1993 Jul, 32(1), 153 - 61
Antibiotic guidelines and antibiotic utilization in Dutch hospitals; Stobberingh E et al.; In April-May 1991 the availability of antibiotic formularies in Dutch hospitals was analysed as well as data available on antibiotic susceptibility patterns . In addition data on the use of different groups of antimicrobial agents (aminoglycosides, beta-lactam compounds including aztreonam and imipenem, co-trimoxazole, vancomycin and fluoroquinolones) were collected by a questionnaire . Thirty-eight formularies were received which were used in 78 hospitals . No formulary was available from 31 hospitals: 15 hospitals did not intend to set up antibiotic guidelines, nine hospitals were using their first formulary and seven used a revised version of the existing one . Fifteen formularies dated from 1987 or earlier . The availability of antibiotic susceptibility patterns ranged from no data at all (n = 14) to extensive data per species, per agent and per ward (n = 5) . From 20 hospitals data on antibiotic usage as well as on antibiotic guidelines were obtained . Because several hospitals used the same formulary, 15 different formularies were analysed from 20 hospitals . Fluoroquinolones were used in all hospitals, but were only mentioned in the formularies of six hospitals . The data in the present study underscore the need for a collaborative approach of medical staff, hospital pharmacy and microbiologist in order to maintain a relatively low level of antibiotic resistance in Dutch hospitals.

Support Care Cancer, 1993 Jul, 1(4), 214 - 6
Fluconazol plus ofloxacin in prophylaxis of infections in patients with acute leukemia: a comparative study; Sajben P et al.; In a retrospective study the incidence of infections, number of afebrile days, duration of antimicrobial chemotherapy, and cost of antibacterials and antimycotics were compared in two groups of patients . One was a group of 57 patients who received no prophylaxis during induction remission therapy of acute leukemia treated in 1989-1990, the second was a group of 22 patients treated in 1991 where prophylaxis with fluconazol and ofloxacin was administered . For ethical reasons pertaining since 1991, when prophylaxis became mandatory, the study was not randomized . A decrease in the number of febrile days, the cost of antimicrobials and the duration of treatment with antibiotics and antimycotics was observed in the group receiving fluconazol and ofloxacin.

Mycoses, 1993 Jul-Aug, 36(7-8), 271 - 4
Dermatophytes on the feet of HIV-infected patients: frequency, species distribution, localization and antimicrobial susceptibility; Korting HC et al.; Skin scrapings from the toe clefts, soles and nail plates of 138 HIV-infected patients at various stages were examined for the presence of dermatophytes using both microscopy and culture . Dermatophytes, in particular Trichophyton rubrum, could be grown in 58 cases (42%) . Although cultures were more often positive in late stages of disease, there was no close correlation with the clinical stage or the T4/T8 ratio . Susceptibility to itraconazole, but not to other antimycotics, was correlated with the immune status (P < 0.05) . Pedal dermatophyte infection does not seem to be a major problem in HIV infection.

Br Heart J, 1993 Jul, 70(1), 79 - 83
Cost effectiveness of prophylaxis in dental practice to prevent infective endocarditis; Gould IM et al.; BACKGROUND--Although antimicrobial prophylaxis for infective endocarditis (IE) is common practice for many dental procedures, there is little information on whether it represents value for money . A study was performed to evaluate the effectiveness of prophylaxis for all at risk patients in routine dental practice with published data from the United Kingdom . METHODS--The risk of contracting infective endocarditis was calculated from published data to find (for high risk patients) both the annual number of deaths attributable to infective endocarditis and the number of high risk dental procedures performed without prophylaxis . Costs are estimated by examining the notes of 63 patients with proved IE during the decade 1980-90 . RESULTS--Such prophylaxis is highly cost effective before dental extractions, but its value for other invasive dental procedures is unproved . It was calculated that, for every 10,000 extractions in at risk patients, appropriate prophylaxis will prevent 5.7 deaths and a further 22.85 cases of non-fatal IE . This represents a saving in the costs of hospital care of 289,600 pounds for 10,000 extractions . CONCLUSION--Prophylaxis to prevent IE in at risk patients undergoing dental extraction is highly cost effective . Net savings each year throughout the United Kingdom, that might be achieved by improving the existing proportion of such patients given antibiotics from its present level of about 50% would amount to 2.5 million pounds and would prevent over 50 deaths.

J Antimicrob Chemother, 1993 Jul, 32 Suppl A, 91 - 7
Recombinant methionyl human granulocyte colony-stimulating factor for the prevention and treatment of non-neutropenic infectious diseases; Daifuku R et al.; Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, hereafter G-CSF) has been demonstrated in clinical trials to be effective in correcting iatrogenic neutropenia by stimulating the production of neutrophils . Not surprisingly, G-CSF has also been found to induce neutrophilia in non-neutropenic hosts . Experimental data suggest that G-CSF leads to the enhancement of neutrophil function . Endogenous G-CSF levels are elevated over a broad spectrum of serious infectious diseases, suggesting the clinical importance of G-CSF in these settings . These findings have stimulated research on the use of G-CSF alone or as an adjunct to conventional antimicrobial therapy in a number of non-neutropenic animal models of infections . In total these studies suggest that G-CSF may be useful in the prevention or therapy of infections in both non-neutropenic and neutropenic clinical settings.

Drugs, 1993 Jul, 46(1), 63 - 79
Treatment of Legionnaires' disease . Current recommendations; Roig J et al.; Legionnaires' disease is a relatively common cause of community-acquired pneumonia and of some outbreaks of hospital-acquired pneumonia . Moreover, Legionella pneumophila is frequently involved in the aetiology of the subset of pneumonias that is characterised by severe clinical course and high mortality . No sure clinical, radiographical or analytical features are useful in differentiating Legionella infection from other aetiologies of pneumonia . On the basis of these data, a rational initial therapeutic approach to community-acquired pneumonia, as well as to nosocomial pneumonia in certain circumstances, has to include an antimicrobial agent that is clinically effective against Legionella spp . Clinical studies have provided evidence that erythromycin is the first-line treatment . An intravenous dosage of 1g every 6 hours as initial therapy will be effective in most cases . Parenteral treatment may be switched to oral administration only after clinical response is observed . In vitro susceptibilities and preliminary experimental and clinical results suggest that clarithromycin will most likely become the preferred treatment once an intravenous preparation is available worldwide . However, orally administered clarithromycin at the dosage of 500 mg every 12 hours may be recommended in those developing countries in which health systems cannot afford the costs of intravenous therapy . In the case of clinically severe illness or in seriously immunosuppressed hosts with confirmed legionellosis, a combined therapeutic approach is warranted . Rifampicin 600 mg every 12 hours intravenously or orally has to be added to the usual dosage of erythromycin . Other alternative therapies, but with less distinct clinical efficacy, that can be combined with erythromycin are doxycycline 100 mg every 12 hours intravenously or orally, and intravenous ciprofloxacin 200 mg every 6 hours.

Am J Hosp Pharm, 1993 Jul, 50(7 Suppl 3), S19 - 26
Cost considerations in therapy with myeloid growth factors; Glaspy JA et al.; Costs of biologic response modifiers, specifically myeloid growth factors, are discussed relative to cost offsets they may produce in the total amount spent on health care in patients with certain disease states . Even though the biologic response modifiers granulocyte colony-stimulating factor (filgrastim) and granulocyte-macrophage colony-stimulating factor (sargramostim or molgramostim) are similar in name, they are chemically and biologically different . These differences result in different clinical applications . Administered after myelosuppressive antineoplastic therapy, filgrastim decreases the risk of infection . The growth factors may also be useful in patients undergoing bone marrow transplantation, in nonneutropenic patients with bacterial infections, and in patients with other disease states . Although the myeloid growth factors are somewhat expensive in terms of acquisition cost, their use is usually associated with a decrease in the risk of medical complications requiring health care expenditures, often for hospitalizations or antimicrobials . The precise cost of acquiring and administering myeloid growth factors depends on three interdependent variables: the factor used, the dosage of the drug, and the duration of therapy . Cost offsets may be more difficult to define, but they would include direct cost offsets, such as reduced episodes of febrile neutropenia and fewer, less-intense days of hospitalization or treatment . Sargramostim and molgramostim have demonstrated efficacy when given after bone marrow transplantation; filgrastim has been shown to lower infection rates by at least 50% after myelosuppressive antineoplastic therapy and in patients with severe chronic neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Hosp Pharm, 1993 Jul, 50(7 Suppl 3), S10 - 8
Clinical effects of biologic response modifiers; Louie SG et al.; The clinical use of the biologic response modifiers filgrastim, sargramostim, and regramostim is reviewed . All circulating blood cells are derived from totipotent hematopoietic stem cells . Various biologic response modifiers, including lymphokines and colony-stimulating factors, regulate and activate the lymphoid and myeloid cells of the blood . One of the more important types of blood cell for fighting infection is the neutrophil . Patients with low neutrophil concentrations are at high risk of developing neutropenic fevers and infections . The colony-stimulating factors filgrastim, sargramostim, and regramostim increase the production of circulating neutrophils, and this action is clinically useful in patients undergoing myelosuppressive antineoplastic therapy or bone marrow transplantation and in patients with the acquired immunodeficiency syndrome . Clinical studies of these agents in comparison with antimicrobial prophylaxis or placebo have shown a decreased rate of neutropenic-associated hospitalizations and infections . These agents are also under study for dose intensification of antineoplastics in patients with various solid tumors and for augmenting patient responses to antimicrobial therapy in situations where there is high risk of morbidity and mortality . Sargramostim and regramostim are both granulocyte-macrophage colony-stimulating factors that differ in their degree of glycosylation and source of production, and at high doses they can cause life-threatening adverse effects because they stimulate the production of a broad range of leukocytes . Filgrastim, which stimulates only the production of neutrophils, has been better tolerated, especially at higher doses . Biologic response modifiers hold much promise for improving therapy of certain clinical conditions by decreasing myelosuppressive complications and enhancing responses to other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Arch Intern Med, 1993 Jun 28, 153(12), 1496 - 8
Unrecognized coccidioidomycosis complicating Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus and treated with corticosteroids . A report of two cases; Mahaffey KW et al.; Coccidioidomycosis is becoming increasingly recognized as an opportunistic infection among patients infected with the human immunodeficiency virus . We treated two cases of concomitant coccidioidomycosis and Pneumocystis carinii pneumonia . In each case, the diagnosis of coccidioidomycosis was delayed despite appropriate examination of bronchoalveolar lavage fluid . Both patients were treated with antimicrobial therapy directed against P carinii and given adjuvant corticosteroid therapy . In both cases, this led to clinical worsening and was associated with the development of a reticulonodular pulmonary infiltrate on chest roentgenograms . When coccidioidomycosis and Pneumocystis pneumonia occur concomitantly in patients with human immunodeficiency virus infection, the diagnosis of coccidioidomycosis may be delayed or missed . In such cases, corticosteroids may lead to overwhelming coccidioidomycosis . Development of a reticulonodular pulmonary pattern on chest roentgenograms is suggestive of this complication.

Commun Dis Rep CDR Rev, 1993 Jun 18, 3(7), R91 - 6
Line-associated bacteraemias; Elliott TS; Sepsis associated with intravascular catheters is a significant cause of morbidity and mortality in England and Wales . Almost 4000 cases of line-associated bacteraemia were reported to the PHLS Communicable Disease Surveillance Centre in 1991 . The clinical and laboratory criteria used to diagnose these infections are reviewed and several approaches to the prevention of catheter-related sepsis are described, including the use of smooth antimicrobial polymers and electrical charge . The strict application of appropriate aseptic techniques is still, however, the most important factor in reducing the incidence of sepsis.

J Immunol, 1993 Jun 15, 150(12), 5529 - 34
IFN-gamma-mediated antimicrobial response . Indoleamine 2,3-dioxygenase-deficient mutant host cells no longer inhibit intracellular Chlamydia spp . or Toxoplasma growth; Thomas SM et al.; The role of indoleamine 2,3-dioxygenase (IDO) in IFN-gamma-mediated inhibition of intracellular parasite growth has been examined previously, although earlier work has been largely correlative . In this study, we defined more completely the role of IDO in the IFN-antimicrobial response . Two mutant cell lines, derived from ME180 cells and exhibiting reduced IDO activity (IR3B6A, IR3B6B) were characterized to determine if they retained the capacity to inhibit intracellular Chlamydia and Toxoplasma growth . Mutant cells treated with IFN-gamma exhibited reduced capacity to suppress pathogen growth . The expression of several IFN-regulated genes also was measured to confirm that the inability to inhibit pathogen growth was because of the lack of IDO . The expression of class II MHC, intracellular adhesion molecule-1, MxA, and P68 kinase genes was induced in the IFN-gamma-treated wild type ME180 cells, but was variable in the mutant cell lines, supporting the hypothesis that IFN-gamma-induced production of IDO is a key IFN-gamma-mediated antimicrobial mechanism.

J Am Vet Med Assoc, 1993 Jun 15, 202(12), 1959 - 62
Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma; Hall IA et al.; The effect of trimethoprim/sulfamethoxazole (T/SMX, 30 mg/kg, PO, q 12 h for 6 weeks) on thyroid function was evaluated in 21 dogs with pyoderma and normal baseline serum thyroxine concentrations . The population mean serum thyroxine concentration, but not the population mean serum triiodothyronine concentration, was significantly decreased at the end of treatment . After 6 weeks of treatment, the response in 3 dogs to thyrotropin administration was substantially reduced . Radionuclide thyroid imaging of 2 dogs after T/SMX treatment revealed higher-than-normal thyroid technetium 99m pertechnetate uptake, suggestive of an interference with iodide metabolism . Use of T/SMX may cause hypothyroidism, and inadequate thyroid function may be incorrectly diagnosed in dogs treated with this antimicrobial.

Neurosci Lett, 1993 Jun 11, 155(2), 208 - 11
Pentamidine, an inhibitor of spinal flexor reflexes in rats, is a potent N-methyl-D-aspartate (NMDA) antagonist in vivo; Block F et al.; The present study examined whether the antimicrobial agent pentamidine exerts an antagonistic action at the N-methyl-D-aspartate (NMDA) receptor as tested on spinal reflexes in rats in vivo . After intrathecal injection both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and pentamidine dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H-reflex . In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex . The depressant effect of pentamidine on the flexor reflex was prevented by coadministration with NMDA but not with the non-NMDA agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid . These data suggest that pentamidine exerts an antagonistic action at the NMDA receptor in vivo.

Clin Pharmacokinet, 1993 Jun, 24(6), 496 - 506
Optimisation of antibiotic therapy in cystic fibrosis patients . Pharmacokinetic considerations; Lindsay CA et al.; Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis . While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality . Much has been learned in the past 20 years about antibiotic use in this population . At the same time, new antimicrobial agents with the potential to treat this condition have become available for use . The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population . Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages . Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.

Clin Obstet Gynecol, 1993 Jun, 36(2), 433 - 44
Progress in the management of tuboovarian abscesses; Wiesenfeld HC et al.; The last 20 years have witnessed remarkable improvements in the treatment of tuboovarian abscesses . Gone are the days of significant mortality associated with ruptured and unruptured TOAs . Broad-spectrum antibiotics have enabled patients to be treated solely with medical therapy, avoiding the need for surgery . Operative intervention is still necessary in 25% of cases of unruptured TOAs, but the combination of conservative surgical procedures, such as unilateral salpingo-oophorectomy, and broad-spectrum antimicrobial agent therapy have reduced the need for total abdominal hysterectomy with bilateral salpingo-oophorectomy greatly . Although fertility after TOAs is compromised significantly, new advances in reproductive technology, including in vitro fertilization and donor egg transplantation, represent reproductive options for these women . Percutaneous drainage and laparoscopic treatment of TOAs are becoming popular treatment options, but prospective studies urgently are needed to assess their efficacy.

Burns, 1993 Jun, 19(3), 235 - 8
The cost of an extensive burn survival; Eldad A et al.; A 17-year-old male sustained 95 per cent body surface area burns (87 per cent full thickness skin loss) . He was hospitalized in the Department of Plastic Surgery that also treats burns . After 232 days he was discharged home when he was functionally independent . He had 16 surgical procedures for excision of burn eschar and skin grafting; received a total of 128 units of blood; 899 units of fresh frozen plasma and had enteral hyperalimentation for 175 days . About 1000 physician-hours, 3000 nurse-hours, 1000 physiotherapy and occupational therapy-hours and about 250 dietician-hours were needed for his treatment . More than 1850 laboratory tests and 120 X-rays were performed, and more than 600 kg of ointment and creams were used, as well as half a ton of topical antimicrobial solutions . Ten different antibiotics were used for a total of 85 treatment days . Some 8500 m of dressing were applied with more than 6000 pieces of petroleum jelly gauze dressing . Hospitalization costs were found to be US$141,750, only 37.5 per cent of which were salaries . An analysis of these costs is given.

Am J Occup Ther, 1993 Jun, 47(6), 523 - 8
Handwashing practices among occupational therapy personnel; Marcil WM; Handwashing is the most effective method of preventing the spread of nosocomial infection . Despite its simplicity, handwashing is frequently omitted by health care personnel . To date there have been no studies of the handwashing practices of occupational therapists . A telephone survey of 50 occupational therapy personnel indicated that the majority (60%) washed their hands with a liquid antimicrobial soap 9 or more times during the work day with a wash duration of 10 seconds or less . Analyses revealed no statistically significant differences between handwashing frequency and duration and age, years in practice, position, academic degree, or work setting . Overall, handwashing technique was found to be lacking . All respondents stated that handwashing was important to occupational therapy practice and most agreed that it was just as important for therapists as it was for physicians and nurses . Most agreed that hands should be washed both before and after each patient contact . However, few respondents actually did so regularly . Most respondents indicated that they received their knowledge of handwashing from inservice training at their place of employment . Their occupational therapy educational programs did not provide basic information on handwashing techniques.

Am J Med, 1993 Jun, 94(6), 583 - 8
Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture-documented Lyme borreliosis associated with erythema migrans: report of a prospective study; Nadelman RB et al.; BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment . A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment . METHODS: Skin biopsies were performed in patients with EM and cultured for B . burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C . Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy . RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria . Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001) . The only other identified factor associated with successful recovery of B . burgdorferi was shorter duration of EM . When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01) . B . burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy . Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart . CONCLUSIONS: After brief courses of antibiotics, B . burgdorferi appears to be rapidly eliminated from the skin at EM sites . The ability to recover B . burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Clin Immunol Immunopathol, 1993 Jun, 67(3 Pt 2), S2 - 15
Chronic granulomatous disease: the solving of a clinical riddle at the molecular level; Curnutte JT; Chronic granulomatous disease is an uncommon inherited disorder of phagocytes in which the defective production of microbicidal oxidants leads to an enhanced susceptibility to bacterial and fungal infections . Despite the near uniform absence of the respiratory burst in CGD phagocytes, there is a striking clinical and genetic heterogeneity in this disorder . The recent elucidation of the molecular basis of CGD now provides an explanation for this heterogeneity . CGD is caused by a defect in any one of four components of NADPH oxidase, the enzyme responsible for the generation of the antimicrobial oxidants . X-linked inheritance is seen in approximately 65% of patients and results from mutations in the gene encoding the gp91-phox subunit of the cytochrome b558 component of the oxidase . The remaining 35% of patients inherit CGD in an autosomal recessive manner due to mutations in the genes encoding the remaining three oxidase components: p22-phox (chromosome 16), p47-phox (chromosome 7), and p67-phox (chromosome 1) . Deletions, insertions, and point mutation leading to premature stop codons, amino acid substitutions, and splice site defects have all been identified . Most CGD patients have mutations unique to their families . The diversity of these mutations and the multiple genes affected provide an explanation for the clinical and genetic heterogeneity of CGD.

J Exp Med, 1993 Jun 1, 177(6), 1605 - 11
Histoplasma capsulatum modulates the acidification of phagolysosomes; Eissenberg LG et al.; The phagolysosome is perhaps the most effective antimicrobial site within macrophages due both to its acidity and to its variety of hydrolytic enzymes . Few species of pathogens survive and multiply in these vesicles . However, one strategy for microbial survival would be to induce a higher pH within these organelles, thus interfering with the activity of many lysosomal enzymes . Altering the intravesicular milieu might also profoundly influence antigen processing, antimicrobial drug delivery, and drug activity . Here we report the first example of an organism proliferating within phagolysosomes that maintain a relatively neutral pH for a sustained period of time . We inoculated P388D1 macrophages with fluorescein isothiocyanate (FITC)-labeled Histoplasma capsulatum or zymosan . Using the ratio of fluorescence excitations at 495 and 450 nm, we determined that vesicles containing either virulent or avirulent FITC-labeled H . capsulatum yeasts had a pH one to two units higher than vesicles containing either zymosan or methanol-killed H . capsulatum . The difference in pH remained stable for at least 5.5 h postinoculation . Longer-term studies using cells preincubated with acridine orange indicated that phagolysosomes containing live Histoplasma continued to maintain a relatively neutral pH for at least 30 h . Many agents raise the pH of multiple vesicles within the same cell . In contrast, H . capsulatum affects only the phagolysosome in which it is located; during coinoculation of cells with unlabeled Histoplasma and labeled zymosan, organelles containing zymosan still acidified normally . Similarly, unlabeled zymosan had no influence on the elevated pH of vesicles housing labeled Histoplasma . Thus, zymosan and Histoplasma were segregated into separate phagolysosomes that responded independently to their phagocytized contents . This localized effect might reflect an intrinsic difference between phagosomes housing the two particle types, active buffering by the microbe, or altered ion transport across the phagolysosomal membrane such that acidification is inhibited.

Cesk Farm, 1993 Jun, 42(3), 137 - 40
{Antimicrobial activity of diazole-(N-salicylidene-L-alpha- alaninato)-copper complexes}; Blahova M et al.; The antimicrobial activities of a group of copper(II) chelates with the composition {Cu(TSB)(L)} or {Cu(TSB)(L')} . (TSB = N-salicylidene-L-alpha-alaninate dianion, L = imidazole and its alkyl derivatives, L' = pyrazole and 3,5-dimethylpyrazole) were studied . Bis-diazole complexes with L' = pyrazole and 3,5-dimethylpyrazole were found to be the most active against S . aureus (MIC = 78 and 20 micrograms.cm-3), less effective against C . albicans (156 micrograms.cm-3), T . terrestre and M . gypseum (100 micrograms.cm-3) . The observed biological properties of complexes are discussed in relation to their proposed structures.

Antimicrob Agents Chemother, 1993 Jun, 37(6), 1259 - 63
Comparative antimycobacterial activities of the newly synthesized quinolone AM-1155, sparfloxacin, and ofloxacin; Tomioka H et al.; AM-1155 is a newly synthesized 6-fluoro-8-methoxy quinolone . We assessed its in vitro antimycobacterial activity using sparfloxacin (SPFX) and ofloxacin (OFLX) as comparison drugs . The MICs of these agents for various mycobacterial strains were determined by the agar dilution method with 7H11 medium . AM-1155 had lower MICs for 50 and 90% of tested strains of Mycobacterium kansasii, M . marinum, and M . fortuitum-M . chelonae complex than SPFX and OFLX, and the values for M . tuberculosis, M . scrofulaceum, and the M . avium-M . intracellulare complex were similar to those of SPFX and considerably lower than those of OFLX . In addition, the antimicrobial activity of AM-1155 against M . tuberculosis and M . intracellulare phagocytosed into murine peritoneal macrophages was compared with that of OFLX . AM-1155 (1 microgram/ml) inhibited the intracellular growth of both M . tuberculosis and M . intracellulare, whereas OFLX at the same concentration failed to show any such effect . Moreover, AM-1155 (10 micrograms/ml) exhibited a steady bactericidal action against M . tuberculosis, whereas OFLX at the same concentration had only a weak effect . AM-1155 (10 micrograms/ml) also inhibited the growth of M . intracellulare more effectively than OFLX.

J Clin Invest, 1993 Jun, 91(6), 2446 - 52
Evidence for antiviral effect of nitric oxide . Inhibition of herpes simplex virus type 1 replication; Croen KD; Nitric oxide (NO) has antimicrobial activity against a wide spectrum of infectious pathogens, but an antiviral effect has not been reported . The impact of NO, from endogenous and exogenous sources, on herpes simplex virus type 1 (HSV 1) replication was studied in vitro . HSV 1 replication in RAW 264.7 macrophages was reduced 1,806-fold in monolayers induced to make NO by activation with gamma IFN and LPS . A competitive and a noncompetitive inhibitor of nitric oxide synthetase substantially reduced the antiviral effect of activated RAW macrophages . S-nitroso-L-acetyl penicillamine (SNAP) is a donor of NO and was added to the media of infected monolayers to assess the antiviral properties of NO in the absence of gamma IFN and LPS . A single dose of S-nitroso-L-acetyl penicillamine 3 h after infection inhibited HSV 1 replication in Vero, HEp2, and RAW 264.7 cells in a dose-dependent manner . Neither virucidal nor cytocidal effects of NO were observed under conditions that inhibited HSV 1 replication . Nitric oxide had inhibitory effects, comparable to that of gamma IFN/LPS, on protein and DNA synthesis as well as on cell replication . This report demonstrates that, among its diverse properties, NO has an antiviral effect.

Farmaco, 1993 Jun, 48(6), 749 - 75
Synthesis and antimicrobial activity of arylazoenamines; Canu Boido C et al.; The possibility to obtain new arylazoenamines endowed with antifungal activity was examined by reacting with acids the arylhydrazones of several keto- and aldo-tert, amines as dimethyl-3-aminoacetone, 3-quinuclidinone, 1-methyl-3-piperidone and 2-formyl-1-methylpyrrolidine . The reaction was successful only in the last two cases . From each 1-methyl-3-piperidone arylhydrazone two isomeric arylazoenamines were formed, which were identical with those obtained from the analogous arylhydrazone of 2-formyl-1-methylpyrrolidine . The structure of these compounds was settled on the ground of UV, IR, NMR and mass spectra and confirmed by means of X-ray analysis . A mechanism is proposed for the formation of arylazoenamines through the contraction of piperidine ring and enlargement of the pyrrolidinic one . The prepared compounds {3-arylazo-1-methyl-delta 2-piperideines 17 and 1-methyl-2(arylazo)methylene pyrrolidines 18 exhibited only a very weak antibacterial activity, but were moderately active against several Candida species and other yeast-like fungi.

Baillieres Clin Gastroenterol, 1993 Jun, 7(2), 365 - 85
Travellers' diarrhoea; Arduino RC et al.; Although TD is usually a mild and self-limited illness, 30-50% of travellers from industrialized to less developed countries are affected . Enterotoxigenic E . coli (ETEC) remain the most frequent cause, being identified in 40-70% of cases . TD frequently occurs within the first 2 weeks of arrival in the foreign country . The clinical manifestation is variable, but watery diarrhoea is the most common clinical presentation . Chronic diarrhoea or remitting symptoms after empirical therapy in the returning traveller are indications for a stool culture and a careful search for stool parasites . Since the major precaution against TD is to avoid exposure to the infectious agents, careful selection of food and beverage is crucial . Bismuth subsalicylate has been proven to be safe and effective in the treatment and prophylaxis of TD . The tablet form has removed the inconvenience of previously required luggage space . Doxycycline, trimethoprim/sulphamethoxazole, trimethoprim and the quinolones have been shown to be effective for prevention of diarrhoea . However, side-effects, superinfection, development of antibiotic resistance and easy-to-treat illness may limit the use of these antimicrobial agents to those travellers with concomitant serious medical conditions that would be adversely affected by diarrhoea, or travellers with unaffordable temporary incapacity . A new oral-killed whole-cell and B-subunit cholera toxin vaccine was demonstrated to induce protection against severe ETEC-associated diarrhoea . This is a promising field under investigation . Finally, fluid replacement is the most important aspect of treatment . Patients with moderate to severe TD can be treated with one of the above-mentioned antimicrobial agents for 3-5 days . Selection of the antimicrobial agent is based on the pattern of resistance and the enteric organism prevalent in the geographical area . While TMP-SMX remains active against the strains prevalent in Mexico during summertime, the quinolones represent the choice for the therapy of diarrhoea acquired in the high-risk areas of South America, Africa and Asia.

J Antimicrob Chemother, 1993 Jun, 31(6), 901 - 8
Influence of methylprednisolone on the intracellular antimicrobial activity of erythromycin and clindamycin against Legionella pneumophila; Higa F et al.; We have investigated the effect of methylprednisolone on the intracellular activity of erythromycin and clindamycin in vitro . An assay system was developed for the determination of intracellular activity of antibiotics against Legionella pneumophila using guinea pig resident alveolar macrophages . Erythromycin at a concentration of 0.625 mg/L (5 x MIC) and clindamycin at a concentration of 8 mg/L (MIC) inhibited the growth of a single strain of L . pneumophila in macrophages, whilst ceftizoxime at a concentration of 0.625 mg/L (5 x MIC) did not . Methylprednisolone at therapeutic concentrations did not affect the intracellular antibacterial activity of either erythromycin or clindamycin against L . pneumophila . We found no direct effect of methylprednisolone on the intracellular antibacterial activity of either erythromycin or clindamycin.

Acta Neurol Scand, 1993 Jun, 87(6), 503 - 4
Idiopathic intracranial hypertension after ofloxacin treatment; Getenet JC et al.; We report the occurrence of idiopathic intracranial hypertension in a patient treated with ofloxacin, a fluoroquinolone antimicrobial agent, for 16 months . The withdrawal of ofloxacin and acetazolamide therapy were followed by a complete recovery of visual function.

Ann Pediatr (Paris), 1993 Jun, 40(6), 364 - 7
{Helicobacter pylori gastritis manifested by acute anemia}; Bruel H et al.; Helicobacter pylori gastritis usually manifests as recurrent abdominal pain but is sometimes discovered upon evaluation for digestive tract bleeding with severe anemia . An 11-year-old who was not under medication and had no history of pain was admitted for isolated regenerative anemia (5.6 g/dl) due to digestive tract bleeding . Laboratory tests showed only low serum iron and ferritin levels . Endoscopy disclosed hemorrhagic inflammation of the duodenal cap and antritis with a hillocky appearance . The diagnosis of H . pylori infection was established on the basis of the finding of curved Gram-negative rods on the smears and of a positive urea test . There was moderate interstitial antritis . The patient was given an H2 antagonist (ranitidine) and amoxicillin with tinidazole for six weeks . Serum IgG antibodies against H . pylori were found in the child's parents and siblings, with the exception of a 7 month old infant . A ten year old sister had been hospitalized two years earlier for hemorrhagic duodenitis ascribed at the time to use of acetylsalicylic acid . H . pylori has been reported in 40% to 95% of pediatric patients with primary gastritis . Physicians should be familiar with this frequent, often familial disease . Management rests on concomitant administration of two antimicrobials and an acid secretion inhibitor to the index patient and family members . Endoscopy is too invasive to be appropriate for monitoring the outcome . In practice, recovery is affirmed on the basis of resolution of clinical manifestations and decreased levels of anti-H . pylori antibodies.

J Nat Prod, 1993 Jun, 56(6), 907 - 14
The structures of aplysinamisines I, II, and III; new bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina cauliformis; Rodriguez AD et al.; Three new bromotyrosine-derived alkaloids, aplysinamisines I {4}, II {5}, and III {6}, were isolated from the sponge Aplysina cauliformis collected in Puerto Rico and their chemical structures elucidated on the basis of spectroscopic methods . Compounds 4-6 showed marginal antimicrobial activity, and aplysinamisines II {5} and III {6} displayed modest cytotoxicity.

Infect Dis Clin North Am, 1993 Jun, 7(2), 393 - 409
Antimicrobial susceptibility testing of bacteria that grow aerobically; Jorgensen JH; This article focuses on susceptibility testing methods for aerobic and fastidious bacteria that may be tested using standard dilution or agar diffusion methods . Also discussed are those bacteria that may be tested by use of an automated or nontraditional methodology.

J Antibiot (Tokyo), 1993 Jun, 46(6), 968 - 71
Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . II . Structural elucidation; Stadler M et al.; The structures of two new biologically active chlorinated metabolites isolated from submerged cultures of the ascomycete Lachnum papyraceum have been elucidated by NMR and mass spectroscopy . The compounds, lachnumon (1) and lachnumol A (2), which structurally are related with mycorrhizin A that also is produced by the fungus, contain an unusual chlorinated epoxide group.

J Antibiot (Tokyo), 1993 Jun, 46(6), 961 - 7
Lachnumon and lachnumol a, new metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . I . Producing organism, fermentation, isolation and biological activities; Stadler M et al.; Several chlorinated metabolites with nematicidal, antimicrobial, and cytotoxic activities were isolated from submerged cultures of the ascomycete Lachnum papyraceum . Three compounds were identified as (+)-mycorrhizin A (3), (+)-chloromycorrhizin A (4) and (+)-dechloromycorrhizin A (5) . The occurrence of 5 as a natural product is new . Two compounds, lachnumon (1) and lachnumol A (2), were found to be new fungal metabolites with cytotoxic, nematicidal and antimicrobial activities.

J Periodontol, 1993 Jun, 64(6), 566 - 70
Periodontal disease in three siblings with familial neutropenia; Kirstila V et al.; The periodontal status and treatment of three teenagers in a Finnish family with familial neutropenia is described . The mother was also diagnosed with neutropenia . At initial examination, the 15-year-old male and the 10-year-old female had severe periodontitis, whereas the 13-year-old male had oral ulcerations but no significant periodontal disease . The two siblings with periodontitis were treated and followed approximately 5 years . It was concluded that periodontal therapy including scaling, surgery, and use of antimicrobial agents can be successful in patients with familial neutropenia, and that such patients are not necessarily candidates for full mouth extraction . The role of granulocyte colony-stimulating factor in which was used in the treatment of these patients remains to be established.

J Clin Gastroenterol, 1993 Jun, 16(4), 292 - 4
Clarithromycin for the eradication of Helicobacter pylori; Graham DY et al.; Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate . Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0-15% . Clarithromycin has potential advantages over other macrolides to which H . pylori is susceptible because of its acid stability and solubility at low pH . We evaluated clarithromycin therapy (250 mg four times daily for 14 days) in 12 H . pylori-infected patients . The 13C-urea breath test was used to evaluate the effectiveness of therapy . Eradication was defined as a negative urea breath test 4-6 weeks after the end of treatment . Suppression of H . pylori was demonstrated in 11 of 12 patients (92%) by a negative urea breath test 2 days after start of treatment . H . pylori was eradicated in five (42%) of 12 patients . Adverse events were intermittent and mild . Clarithromycin is the first antimicrobial agent that appears to offer promise as monotherapy for the eradication of H . pylori.

Clin Infect Dis, 1993 Jun, 16(6), 756 - 60
Cutaneous Nocardia farcinica infection in a nonimmunocompromised patient: case report and review; Schiff TA et al.; Nocardia farcinica, the etiologic agent of bovine farcy, is microbiologically related to but distinct from Nocardia asteroides . N . farcinica is noted for its propensity to cause serious systemic infection in both normal and immunocompromised hosts and its marked degree of resistance to multiple antimicrobial agents . We present a case in which a nonimmunocompromised patient who sustained a contaminated facial laceration developed an abscess due to N . farcinica with underlying osteomyelitis . The severity of the infection necessitated surgical debridement followed by administration of intravenous amikacin therapy . The isolate was susceptible to amikacin and trimethoprim-sulfamethoxazole but resistant to erythromycin in vitro . Therapy with trimethoprim-sulfamethoxazole was started but was discontinued because of the patient's intolerance to the drug . Intramuscular amikacin was substituted, resulting in complete resolution of the infection . The history, epidemiology, and microbiological characteristics of this interesting and unusual microorganism are reviewed.

Antimicrob Agents Chemother, 1993 Jun, 37(6), 1313 - 7
Inactivation of rifampin by Nocardia brasiliensis; Yazawa K et al.; Rifampin was glycosylated by a pathogenic species of Nocardia, i.e., Nocardia brasiliensis . The structures of two glycosylated compounds (RIP-1 and RIP-2) isolated from the culture broth of the bacterium were determined to be 3-formyl-23-(O-{beta-D-glucopyranosyl})rifamycin SV and 23-(O-{beta-D-glucopyranosyl})rifampin, respectively . Both compounds lacked antimicrobial activity against other gram-positive bacteria as well as the Nocardia species.

Eur Heart J, 1993 Jun, 14(6), 812 - 8
Failure of provision of antibiotic prophylaxis for 'at risk' cardiac patients: impetus for improvement required from cardiologists; Forbat LN et al.; We conducted a survey by questionnaire to assess whether patients 'at risk' from infective endocarditis are aware of the need for good dental hygiene and antibiotic prophylaxis, and receive appropriate advice or treatment . Of 189 patients surveyed, half had told a dentist about their heart, 8% were aware of a dental problem, 12% had attended a dentist within one year, but 39% had not attended a dentist in 5 years . Only 21% accurately recalled instructions on prophylaxis and 44% recalled receiving antibiotics prior to treatment . Of replies from 262/480 general practitioners, half took a dental history but only 3% gave antibiotic advice in writing . Fifty-seven percent prescribed antibiotics recommended by the British Society for Antimicrobial Chemotherapy . Of the general practitioners and 72/240 dentists who replied, half were unaware of some of the cardiac conditions requiring prophylaxis, and did not receive adequate advice from their cardiac centre . We conclude most at-risk patients are unaware of the need for good dental hygiene and antibiotic prophylaxis . Communication needs to be improved to address these problems . A new 'endocarditis risk' card is proposed for patients to carry, with an identical 'sticker' to attach to medical notes.

Clin Infect Dis, 1993 Jun, 16 Suppl 4, S310 - 3
Tetracycline resistance in periodontal pathogens; Olsvik B et al.; Antimicrobial agents are used in combination with debridement to eliminate putative periodontal pathogens, including Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans, from diseased tissues . The most frequently used antimicrobial agents are the tetracyclines . However, these agents are not effective in some patients . This lack of efficacy may be due to antimicrobial resistance . As many as 75% of the bacteria in the subgingival flora may be resistant to tetracycline after long-term, low-dose treatment . Tetracycline resistance is mediated by the tet(M) determinant in some isolates of Veillonella species and Fusobacterium nucleatum, while a DNA probe to the tet(Q) determinant hybridizes to isolates of Prevotella denticola and P . intermedia . The mechanism of tetracycline resistance for most periodontal organisms, however, has yet to be determined . Before tetracycline is used as adjunctive therapy for refractory periodontitis, the subgingival bacterial flora should be tested for susceptibility.

Am J Vet Res, 1993 Jun, 54(6), 878 - 81
Linkage of serum resistance, aerobactin production, and resistance to antimicrobial agents on conjugal plasmids in some strains of Escherichia coli isolated from septic foals; Hirsh DC et al.; Fifteen isolates of Escherichia coli obtained from the blood and tissues of septic foals had plasmid DNA of size ranging from 2.5 to 93 megadaltons . These isolates grew in normal equine serum (serum resistant), a trait previously documented to be expressed by isolates obtained from blood and tissues of septic foals, but not by isolates obtained from the feces of clinically normal horses . Of these isolates, 3 contained conjugal plasmids that encoded resistance to multiple antimicrobial agents linked to serum resistance and, in 1 isolate, to production of aerobactin as well . Serum resistance and production of aerobactin are related to virulence of septicemic E coli from non-equine sources.

J Leukoc Biol, 1993 Jun, 53(6), 666 - 72
Stimulation of the bactericidal activity of polymorphonuclear leukocytes by manganese; Klebanoff SJ et al.; An antioxidant effect of manganese (Mn) complexes due to the scavenging of the superoxide anion (O2-.) or to the decomposition of hydrogen peroxide (H2O2) has been described . We report here that Mn also can exert a prooxidant effect under certain experimental conditions . Thus Mn2+ in phosphate buffer increased the bactericidal effect of phorbol myristate acetate-stimulated polymorphonuclear leukocytes (PMNs) on extracellular Escherichia coli . This effect was inhibited by azide, catalase, and a decrease in chloride concentration and was not observed when normal PMNs were replaced by those of patients with chronic granulomatous disease or myeloperoxidase (MPO) deficiency . Mn2+ could be replaced by Mn3+ or by superoxide dismutase (SOD) . These findings suggest that Mn (or SOD), by increasing the conversion of O2- . to H2O2, can increase the activity of the MPO-H2O2-chloride antimicrobial system released by stimulated PMNs.

Microb Releases, 1993 Jun, 2(1), 23 - 8
Synergistic toxicity of IFN-gamma-producing Escherichia coli K12 cells; Dijkmans R et al.; Genetically modified microorganisms (GMMs) are frequently used as producers of mammalian immunomodulatory proteins, e.g . interferons and interleukins . Here we have examined the question of whether such GMMs interact in a way different from that of their non-modified parent micro-organisms with mammalian antimicrobial defence systems . As a typical GMM host micro-organism we used Escherichia coli K12, and as a typical immunomodulatory protein produced by a GMM we used mouse interferon-gamma (MuIFN-gamma) . Two experimental systems are described in which synergistic "toxic" biological effects are induced by a combined treatment with E . coli and MuIFN-gamma but not, or less so, by the parental strain and the recombinant protein separately . First, it is shown that the IFN-gamma-producing GMM, or mixtures of E . coli cells and IFN-gamma, are cytolytic for mouse embryo fibroblastoid cells (MEF), whereas no cell killing occurs in MEF cultures treated with control E . coli cells or in those treated with bacteria-free recombinant IFN-gamma . Second, it is demonstrated that intraperitoneal injection in mice of high but not low numbers of control E . coli K12 cells induces a shock-like mortality, whereas co-injection with IFN-gamma induces killing at low numbers . IFN-gamma-producing E . coli cells cause a mortality rate that does not differ from that of control E . coli cells, probably because in these experimental conditions the level of recombinant MuIFN-gamma per cell is insufficiently high . Taken together, these data indicate that synergistic toxic effects induced by bacteria and their recombinant products can occur and may in certain situations enhance the intrinsic toxic capacity of the GMM . Synergistic toxic effects may thus be of relevance for identifying the safety level that should be employed when working with GMMs.

Oral Microbiol Immunol, 1993 Jun, 8(3), 172 - 6
In vitro antimicrobial susceptibility to combinations of drugs on bacteria from carious and endodontic lesions of human deciduous teeth; Sato T et al.; The purpose of this study was to clarify the antibacterial efficacy of mixed antibacterial drugs on bacteria of carious and endodontic lesions of human deciduous teeth in vitro . The antibacterial drugs used in this study were mixtures of ciprofloxacin, metronidazole, plus a third antibiotic: amoxicillin, cefaclor, cefroxadine, fosfomycin or rokitamycin . Samples taken from carious dentin (17 cases) and infected pulpal tissues (14 cases) were cultured on control plates and plates containing the mixed drugs . No bacteria were recovered in the presence of any combination of the mixture of the drugs (100 micrograms each/ml), and the bacterial growth occurred on control plates (10(1) to 10(7) colony-forming units), indicating that the mixed drugs inhibit the growth of bacteria in the samples . When carious and endodontic lesions on split surfaces of freshly extracted teeth were covered overnight with alpha-tricalcium phosphate cement containing a mixture of ciprofloxacin, metronidazole and cefaclor (1% each; 5 cases), no bacteria were recovered from the lesions . No bacteria were recovered from carious and endodontic lesions when these lesions were immersed in a solution of the mixture (200 micrograms each/ml; 5 cases) . These findings indicate that carious and endodontic lesions can be sterilized by the mixed drugs in situ.

Int J Paediatr Dent, 1993 Jun, 3(2), 63 - 70
The prevention of infective endocarditis-paedodontic considerations . British Society for Antimicrobial Chemotherapy; Longman LP et al.; This review of the literature considers the pathology and epidemiology of infective endocarditis (IE), dental procedures that may precipitate IE and prophylaxis against dentally induced IE . The most recent recommendations published in May 1992 by the British Society for Antimicrobial Chemotherapy are outlined and discussed.

Vet Microbiol, 1993 Jun, 35(3-4), 357 - 67
The proper use and benefits of veterinary antimicrobial agents in swine practice; Mackinnon JD; There are three main reasons for using antimicrobial agents in pig production: animal welfare, carcase quality and economics . The need to treat sick animals and to mitigate the effects of infection is of paramount humanitarian importance . The reduction of the pathological effects of infection is an essential aspect of carcase quality and of possible value in the control of potential zoonoses . It is beyond dispute that the judicious use of antimicrobial agents improves growth efficiency . In addition there are economic benefits to be gained from the control of infection in terms of improved carcase quality and reduced mortality . When antimicrobial agents are used, careful consideration must be given to their choice . An understanding of the disease complexes of pig herds, of pharmacokinetics and of methods of administration is necessary to achieve safe and cost-effective medication . Bacterial resistance to antimicrobial agents in pig production is of importance only in special circumstances where eradication of a disease is being attempted . Veterinarians specialising in pig production are concerned that there is a climate of restriction of use and availability of suitable agents which could jeopardize animal health and welfare.

Vet Microbiol, 1993 Jun, 35(3-4), 349 - 56
The proper use and benefits of veterinary antimicrobial agents in practice in cattle; Jackson ER; A rational basis for the therapeutic and prophylactic use of antimicrobials is discussed . Different approaches are needed to deal with the individual animal, group or herd disease problem . Improved antibiotic preparations are needed to enhance the efficacy of treatment and minimise suffering and lost production.

Vet Microbiol, 1993 Jun, 35(3-4), 289 - 301
Responsible use of antimicrobials in veterinary medicine: perspectives in France; Espinasse J; In France a survey of the use of antimicrobials in veterinary medicine was set up in connection with the Committee for the Marketing Authorization of Veterinary Medicinal Products . This survey has emphasized the importance of antimicrobials in veterinary medicine and the reality of antibiotic resistance in both man and animals . Certain epidemiological data tend to demonstrate that the use of antibiotics in animals increases the risk of antibiotic resistance in man, through selection in animals of resistant pathogenic bacteria or of a non-pathogenic resistant bacteria carrying resistance plasmids . Four proposals are put forward for the control of these different risks: reserve certain antibiotics (life-saving antibiotics) for human medicine, conform to a code of good practices for antibiotic use in animals, strengthen and connect up existing networks for the epidemiosurveillance of antibiotic resistance, provide for studies on the ecological impact of antibiotics in the registration dossiers for veterinary medicinal products . These evolutive measures, based on scientific progress in microbiology, epidemiology and clinical studies should respond satisfactorily to the expectations of all concerned.

Vet Microbiol, 1993 Jun, 35(3-4), 257 - 67
Evolution of resistance in microorganisms of human origin; Kayser FH; Resistance to antimicrobials in bacteria results from either evolution of "new" DNA or from variation in existing DNA . Evidence suggests that new DNA did not originate since the use of antibiotics in medicine, but evolved long ago in soil bacteria . This evidence is based on functional and structural homologies of resistance proteins in human pathogens, and resistance proteins or physiological proteins of soil bacteria . Variation in existing DNA has been shown to comprise variations in structural or regulatory genes of the normal chromosome or mutations in already existing plasmid-mediated resistance genes modifying the resistance phenotype . The success of R-determinants in human pathogens was due to their horizontal spread by transformation, transduction and conjugation . Furthermore, transposition has enabled bacteria to efficiently distribute R-determinants between independent DNA-molecules . Since the genetic processes involved in the development of resistance are rare events, the selective pressure exerted by antibiotics has significantly contributed to the overall evolutionary picture . With few exceptions, experimental data about the role of antibiotic usage outside human medicine with respect to the resistance problem in human pathogens are missing . Epidemiological data about the occurrence of resistance in human pathogens seem to indicate that the major contributing factor to the problem we face today was the extensive use of antibiotics in medicine itself.

Vet Microbiol, 1993 Jun, 35(3-4), 233 - 42
Mechanisms of antimicrobial resistance and implications for epidemiology; Smith JT et al.; The development of antibacterial agents has provided a means of treating bacterial diseases which were, previously, often fatal in both man and animal and thus represents one of the major advances of the 20th century . However, the efficacy of these agents is increasingly being compromised by the development of bacterial resistance to the drugs currently available for therapeutic use . Bacterial resistance can be combated in two ways . New drugs to which bacteria are susceptible can be developed and policies to contain the development and spread of resistance can be implemented . Both strategies require an understanding of the mechanisms of drug resistance, its epidemiology and the role of environmental factors in promoting resistance . Over the past thirty years our knowledge of bacterial resistance has increased dramatically mainly due to new technology that has become available . Bacteria are able to resist antibacterials by a variety of mechanisms: for example, altering the target to decrease susceptibility to the antibacterial, inactivating or destroying the drug, reducing drug transport into the cell or metabolic bypass . These drug resistance determinants are mediated via one of two distinct genetic mechanisms, a mutation in the bacterial chromosome or by a transmissible element; either a plasmid or a transposon . Significant differences exist between these two types of drug resistance as transmissible resistance, which is mainly plasmid-mediated, permits intraspecies and even interspecies transfer to occur . In contrast, chromosomal resistance can only be passed on to progeny . Transmissible antibacterial resistance is the major cause of concern as it can lead to the rapid spread of antibacterial resistance and has proven difficult, if not impossible, to eradicate . Furthermore, plasmids and transposons can code for multiple antibiotic resistance as well as virulence genes . Antibacterials for which transferable resistance has been identified include most commonly used antibacterials such as beta-lactams, aminoglycosides, macrolides, sulphonamides, tetracyclines, chloramphenicol and trimethoprim . One notable exception is the 4-quinolones for which plasmid-mediated resistance has yet to be identified.

Vet Microbiol, 1993 Jun, 35(3-4), 213 - 26
Allergy to antimicrobial residues in food: assessment of the risk to man; Dayan AD; Meat and other dietary products from food animals and farmed fish in the West may contain residues of many antibiotics and antibacterial agents, or haptenised macromolecules, e.g . penicilloylated proteins . General surveys have shown a low incidence of detectable residues in most products (up to 0.5-2%) . A notable proportion of the general population has true allergic sensitivity to these substances (up to 7-10% to "penicillin") due to prior medical treatment . However, cases of proven allergy to such substances in food are extremely rare, based on clinical and laboratory proof of an immunological reaction, whereas there are less well substantiated reports blaming antibiotics in up to 50% of cases of chronic urticaria . Consideration of nature of haptenisation by antimicrobial substances, of the inefficiency of the oral route for immunisation, and of the transient and unrepeatable nature of most examples of food-related reactions all suggest that allergy to antimicrobial residues in the diet is exceedingly rare.

Vet Microbiol, 1993 Jun, 35(3-4), 193 - 7
The effect of antimicrobial agents on the ecology of the human intestinal microflora; Nord CE; The most common and significant cause of disturbances in the normal intestinal microflora is the administration of antimicrobial agents . The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent in the bile, or secretion from the intestinal mucosa . Administration of these agents may seriously disturb the balance of the normal intestinal microflora . This disturbance can cause bacterial overgrowth and emergence of resistant microorganisms which may lead to serious infections and also encourage transfer of resistance factors among bacteria . The ecological effects of penicillins, cephalosporins, monobactams, carbapenems, macrolides, clindamycin, tetracyclines, nitroimidazoles and quinolones on the human intestinal microflora are presented in this review article.

S Afr J Surg, 1993 Jun, 31(2), 65 - 70
Surgical management of retroperitoneal necrotising fasciitis by planned repeat laparotomy and debridement; Mokoena T et al.; Mortality remains high in patients with necrotising fasciitis despite use of modern powerful antimicrobial drug therapy and advances in the care of the critically ill . This is particularly so in patients with intra-abdominal retroperitoneal lesions . While necrotising fasciitis of the integument has been well described, its retroperitoneal (extraperitoneal) location has not been highlighted . Planned repeated laparotomies and debridement have been used in 10 recent patients with only 2 deaths . The initiating incident was caesarean section in 3 patients; perineal sepsis, trauma or intra-uterine death in 2 patients each; and uterine instrumentation to induce early abortion in the remaining patient . All patients received empirical antimicrobial therapy, which was changed when microbial isolates and their sensitivity indicated . Mechanical ventilation support was given to 60% of the patients early on during the illness . All received nutritional supplementation either parenterally or enterally throughout their inhospital treatment . This report focuses on intra-abdominal extraperitoneal necrotising fasciitis and the use of planned repeated laparotomy and debridement in the treatment of retroperitoneal (extraperitoneal) necrotising fasciitis per se and we recommend it as an essential part of the management of this condition.

Indian Pediatr, 1993 Jun, 30(6), 745 - 51
Adverse drug reactions in pediatrics with a study of in-hospital intensive surveillance; Dharnidharka VR et al.; A two-part prospective study of adverse drug reactions (ADRs) in Indian children was carried out at a teaching general hospital . Using an in-hospital intensive surveillance scheme (IISS) for the detection of ADRs, indoor patients of one of the two units in the pediatric ward were monitored daily for 6 months, with the other unit serving as a control group . A total of 347 patients were monitored, 2781 daily orders written and 24,474 doses of 96 different drugs given . Six patients suffered from ADRs (1.73%), and 1 reaction proved fatal (0.29%), while the control group reported only 1 ADR in the same time period . The frequency of ADRs (p < 0.001) and their resultant mortality in Indian children was less than that in a western prototype study . Though IISS showed a marked increase in ADR reporting, it was too cumbersome for routine use in our country . In the second part of the study, 40 cases of ADRs seen over 2 years were analyzed . Antimicrobials, especially sulphonamides, accounted for a high percentage of cases mostly as skin rashes and fairly severe reactions were common . Patients on anti-tuberculous and anti-convulsant drugs required prolonged supervision for late onset reactions.

Comp Biochem Physiol C, 1993 Jun, 105(2), 141 - 6
Antitumor and antimicrobial glycoproteins from sea hares; Yamazaki M; 1 . Novel antitumor and antimicrobial glycoproteins were found in the sea hares . These glycoproteins were purified to apparent homogeneity from Aplysia kurodai, Aplysia juliana and Dolabella auricularia, and designated as aplysianins, julianins and dolabellanins, respectively . 2 . The nine isolated glycoproteins lysed all the tumor cells tested but did not lyse normal white and red blood cells . 3 . The glycoproteins completely inhibited the synthesis of DNA and RNA by tumor cells within 2 hr and caused tumor lysis within 15 hr . 4 . Tumor lysis was inhibited by the presence of N-acetylneuraminic acid, suggesting that the recognition of the sugar moiety is a key step in the cytolysis by antitumor glycoproteins from sea hares . 5 . These antitumor glycoproteins, except dolabellanin P, also showed antimicrobial activities . 6 . The factors were active for Gram-positive and -negative bacteria and some fungi, and their action was not cytocidal but cytostatic . 7 . They exerted the antibacterial action by inhibiting nucleic acid synthesis, as does a DNA-inhibiting chemotherapeutic drug . 8 . The sequence of the N-terminal part of dolabellanin A was similar to other antibacterial peptides from arthropoda, amphibia and mammals, suggesting that dolabellanin-like antibacterial peptides are common throughout the animal kingdom.

J Vet Dent, 1993 Jun, 10(2), 6 - 9
The antimicrobial effectiveness of clindamycin in diseases of the oral cavity; Zetner K et al.; Veterinary dental ultrasonic equipment can cause bacteria to be aerosolized during prophy procedures . Preoperative treatment with clindamycin prior to removal of calculus using an ultrasonic scaler can reduce aerosolized bacteria . Reduction of plaque bacteria was assessed and was statistically significant in those patients receiving clindamycin . This article describes the evaluation and results of clindamycin application when given prior to dental prophy.

Antimicrob Agents Chemother, 1993 Jun, 37(6), 1253 - 8
Nucleotide and deduced protein sequences of the class D tetracycline resistance determinant: relationship to other antimicrobial transport proteins; Varela MF et al.; The nucleotide sequence of the plasmid pRA1 gene encoding the TetA(D) tetracycline/H+ antiporter was determined . The deduced amino acid sequence was compared with those of other antimicrobial and antiseptic transporters . The deduced product of tetA(D) is a 41.1-kDa protein consisting of 394 amino acids comprising 12 membrane-spanning domains . Three classes of amino acid motifs found in TetA(D) are highly conserved in other transporters, implying that they participate in structures necessary for substrate recognition, binding, or translocation . A common mechanism of transport is suggested, with subtle sequence variations accounting for varied substrate specificities, modes of transport, and directions of transport.

Curr Opin Biotechnol, 1993 Jun, 4(3), 275 - 9
Marine natural products as a source of novel pharmacological agents; Carte BK; Research into marine natural products is evolving from an empirical search for antimicrobial and cytotoxic compounds into a more mechanistic approach to the discovery of enzyme inhibitors and receptor antagonists with therapeutic potential . Several marine natural products have entered pharmaceutical development and others are making significant contributions to our understanding of cellular processes at the biochemical level.

Drugs, 1993 Jun, 45(6), 910 - 7
Travellers' diarrhoea . Which antimicrobial?
DuPont HL.
For those who venture from highly industrialised areas to developing tropical and semitropical areas, the chance of developing diarrhoea is about 40% . In most cases a bacterial pathogen is responsible for the illness . The antimicrobial agents with the greatest activity against these organisms are cotrimoxazole (trimethoprim/sulfamethoxazole) during the summer months in the interior of Mexico (a region where this agent has been studied extensively), and the fluoroquinolones for other places or other times, until data become available to indicate the appropriateness of cotrimoxazole here as well . Persons at risk should take along with them a drug to treat symptoms of travellers' diarrhoea, and an appropriate antimicrobial agent . At the passage of the third unformed stool, it is recommended that travellers treat themselves with fluids and salt (flavoured mineral water augmented with saltine crackers is sufficient in most cases), symptomatic treatment and antibacterial therapy . Of these, the antimicrobial is the most important component, which is given either as a single large dose or one or twice daily for 3 days . Perhaps optimal therapy for afebrile nondysenteric patients is loperamide in combination with the antibacterial drug . In the face of fever or dysentery, the antimicrobial should be used alone . In special situations where food and beverage restrictions cannot be followed and where the itinerary cannot tolerate even the slightest alterations because of illness, chemoprophylaxis can be considered . The most effective preventive medication in this case is the antimicrobial also used for therapy, taken in half the therapeutic dosage daily while in the area of risk . However, the majority of travellers should not use this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

FEMS Immunol Med Microbiol, 1993 Jun, 7(1), 15 - 22
Granulocyte colony-stimulating factor potentiates anti-Candida albicans growth inhibitory activity of polymorphonuclear cells; Yamamoto Y et al.; Granulocyte colony-stimulating factor (G-CSF) stimulates a subset of granulocyte colony forming cells and when administered to neutropenic individuals results in recovery of blood neutrophil numbers to normal levels . Therefore, G-CSF may be a useful therapeutic agent for infections in immunocompromised hosts . However, to date there has been only limited information that G-CSF activates the antimicrobial activity of neutrophils . In the present study, we found that recombinant G-CSF promotes the anti-Candida albicans activity of normal human blood polymorphonuclear (PMN) cells in vitro using both a 3H-glucose uptake procedure and a Candida colony counting assay . As little as 0.1 ng/ml G-CSF induced significant anti-Candida activity in the PMN cultures . G-CSF treatment also enhanced superoxide anion production by the PMNs in response to f-MLP as determined by the superoxide dismutase inhibitable cytochrome C reduction method . Such results show that G-CSF can promote the antimicrobial activity of peripheral blood PMNs against C . albicans.

J Infect Dis, 1993 Jun, 167(6), 1358 - 63
Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes; Schneemann M et al.; Nitric oxide synthase (NOS) has received immense interest as an antimicrobial and antitumoral effector system of mononuclear phagocytes from rodents . Because there is increasing doubt that an analogous system exists in human macrophages, NOS was reexamined in these cells . Under tightly controlled conditions, with murine macrophages as positive controls, human macrophages failed to secrete nitric oxide (< 0.1 mumol/10(6) cells/24 h), even after activation with endotoxin, interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, bacteria, or proliferating lymphocytes . The discrepancy between murine and human macrophages depended on neither the anatomic source (blood, peritoneum), the agent used for activation, nor the duration of activation . NOS activity was paralleled by metabolization of L-arginine to L-citrulline . Exogenous tetrahydrobiopterin, an essential cofactor of NOS not synthesized by human macrophages, did not support NOS activity in human macrophages . Also, no NOS activity was found in cellular subfractions of human macrophages . It appears that in humans, the inducible high-output NOS is not conserved as an antimicrobial system of macrophages.

Proc Natl Acad Sci U S A, 1993 May 15, 90(10), 4596 - 600
Airway epithelial cells are the site of expression of a mammalian antimicrobial peptide gene; Diamond G et al.; We previously reported the isolation and characterization of a broad-spectrum antimicrobial peptide from the bovine tracheal mucosa, which we called tracheal antimicrobial peptide (TAP) . We now show the TAP gene is expressed throughout the adult conducting airway, from nasal to bronchiolar tissue, but not in tissues other than airway mucosa, as determined by Northern blot analysis . In situ hybridization of airway sections localizes TAP mRNA to columnar cells of the pseudostratified epithelium . We report the structural organization of the TAP gene and show that TAP is a member of a large family of related sequences with high nucleotide identity in the 5' exon . The data support the hypothesis that antimicrobial peptides contribute to host defense of the respiratory tract.

J Med Chem, 1993 May 14, 36(10), 1356 - 63
Quinolone antimicrobial agents substituted with morpholines at the 7-position . Syntheses and structure-activity relationships; Araki K et al.; A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug . Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin . Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin . In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties . Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments . These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.

Science, 1993 May 14, 260(5110), 984 - 6
Sequestration from immune CD4+ T cells of mycobacteria growing in human macrophages; Pancholi P et al.; CD4+ helper T cells mediate resistance to tuberculosis, presumably by enhancing the antimicrobial activity of macrophages within which the Mycobacterium tuberculosis organism grows . A first step in resistance should be the presentation of mycobacterial antigens by macrophages to CD4+ T cells . However, when the antigenic stimulus is limited to organisms growing in human monocytes, the organisms become sequestered from immune CD4+ T cells . This block in presentation is selective for growing mycobacteria and not for other stimuli . Sequestration would allow replicating organisms to persist in infected individuals and may contribute to virulence.

Ugeskr Laeger, 1993 May 10, 155(19), 1436 - 41
{Daily single-dose aminoglycoside administration . Therapeutic and economic benefits}; Knudsen LM et al.; Aminoglycosides are among the most active antimicrobial agents against Gram-negative infections, but they also share the potential for oto- and nephrotoxicity . Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens . Pharmacokinetic and microbiological data support this finding . Clinical trials confirm that once-daily dosing is more efficient and less toxic than multiple daily dosing . The two most important risk factors for nephrotoxicity seem to be the duration of aminoglycoside treatment and high trough levels of aminoglycoside . Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens . Recommendations for once-daily dosing of netilmicin are given.

Med J Aust, 1993 May 3, 158(9), 631 - 2
Endocarditis caused by Brucella melitensis; Chan R et al.; OBJECTIVE: To describe the management of an uncommon but serious infection in Australia . CLINICAL FEATURES: A 25-year-old woman developed endocarditis after residence in Turkey and consumption of goat dairy products . Brucella melitensis was isolated from blood cultures . INTERVENTION AND OUTCOME: The valve remained infected after prolonged intravenous administration of trimethoprim-sulfamethoxazole, gentamicin and rifampicin . Uncontrolled sepsis and worsening haemodynamic function necessitated valve replacement . To date the patient remains well while taking trimethoprim-sulfamethoxazole and rifampicin . CONCLUSION: Endocarditis due to Brucella spp . is uncommon in Australia . This infection is difficult to cure with antimicrobial therapy alone and early surgical intervention is advisable.

J Gastroenterol Hepatol, 1993 May-Jun, 8(3), 259 - 66
Persistent childhood diarrhoea: patterns, pathogenesis and prevention; Gracey M; With improved management of acute episodes of infectious diarrhoea, increased attention is now being given to persistent diarrhoea and its nutritional consequences and associated mortality . Risk factors for the development of persistent diarrhoea include young age, malnutrition, impaired immune function, recent introduction of milk feedings, prior antimicrobial therapy and infection with pathogenic strains of Escherichia coli . Descriptive epidemiology indicates that 3-20% of episodes of acute diarrhoea in children in developing countries become persistent and cause about one-third to one-half of all deaths from diarrhoea . Environmental factors may be very important in causing persistent diarrhoea: these include undernutrition combined with the impact of living in highly contaminated environments and their effects on gastrointestinal microecology . Development of effective preventive strategies will depend on improved understanding of causes and pathogenesis of persistent diarrhoea.

Antimicrob Agents Chemother, 1993 May, 37(5), 1184 - 6
In vitro susceptibility of Helicobacter pylori to several antimicrobial combinations; Pavicic MJ et al.; Synergy between metronidazole and its hydroxymetabolite and between each compound and amoxicillin or tetracycline-HCl was determined against Helicobacter pylori . Metronidazole plus its hydroxymetabolite and either compound combined with amoxicillin showed synergism against all 10 strains of H . pylori tested . Metronidazole plus tetracycline-HCl or the hydroxymetabolite plus tetracycline-HCl acted synergistically against seven and six strains, respectively, acted additively against three strains, and had no additional effect against one strain . These results may help to explain the in vivo efficacies of metronidazole combinations in the treatment of H . pylori-associated gastritis.

Antimicrob Agents Chemother, 1993 May, 37(5), 1115 - 21
In vitro activity of vancomycin against the spirochete Borrelia burgdorferi; Dever LL et al.; Borrelia burgdorferi, a spirochete and the causative agent of Lyme disease, has been reported to be susceptible to a variety of antimicrobial agents . In this investigation, the action of vancomycin, a glycopeptide antibiotic not previously known to have activity against spirochetes, against borrelias was examined . The in vitro activity of vancomycin against a variety of strains of B . burgdorferi and one strain of Borrelia hermsii was determined by use of a microdilution MIC method (L.L . Dever, J.H . Jorgensen, and A.G . Barbour, J . Clin . Microbiol . 30:2692-2697, 1992) . MICs ranged from 0.5 to 2 micrograms/ml . MICs of the glycopeptides ristocetin and teicoplanin and the lipopeptide daptomycin against strain B31 of B . burgdorferi were all > or = 8 micrograms/ml . Subsurface plating, time-kill studies, synergy studies, and electron microscopy were used to investigate further the activity of vancomycin against B31 . The MBC of vancomycin was 2 micrograms/ml . Time-kill curves demonstrated > or = 3-log10-unit (99.9%) killing of the final inoculum after 72 h by vancomycin concentrations twice the MIC . Synergy between vancomycin and penicillin was demonstrated at concentrations one-fourth the MIC of each drug . In electron microscopy, B31 cells exposed to vancomycin showed a disruption of cellular integrity and were indistinguishable from those exposed to penicillin . These studies demonstrate another class of microorganisms susceptible in vitro to vancomycin.

J Antibiot (Tokyo), 1993 May, 46(5), 813 - 26
Synthetic studies of erythromycin derivatives . Synthesis and antimicrobial activities of 3''-EPI-erythromycin A and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11- oxoerythromycin A; Nakata M et al.; Two new derivatives, 3''-epi-erythromycin A (2) and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11-oxoerythromycin A (3), have been synthesized by using glycosylation with glycal (Ferrier rearrangement), bromomethoxylation and bis(tributyltin) oxide-bromine oxidation as the key steps . Their antimicrobial activities were compared with those of erythromycin A (1).

J Antibiot (Tokyo), 1993 May, 46(5), 803 - 12
Synthesis and antimicrobial activity of sperabillin derivatives; Hida T et al.; Modification of sperabillins was carried out . The 2-amidinoethylamino moiety was removed by brief acidic hydrolysis . The 2,4-hexadienoyl moiety was hydrogenated to the hexanoyl moiety and this was cleaved by an enzymatic reaction using the cells of Pseudomonas acidovorans IFO 13582 . The 2-amidinoethylamino and the 2,4-hexadienoyl moieties were replaced with other groups . The derivative which was prepared by condensation of two molar amounts of dehexadienoylsperabillin A with (E,E)-muconic acid showed better protective effects than sperabillin A against Gram-negative bacteria.

J Antibiot (Tokyo), 1993 May, 46(5), 728 - 34
Leptolstatin from Streptomyces sp . SAM1595, a new gap phase-specific inhibitor of the mammalian cell cycle . I . Screening, taxonomy, purification and biological activities; Abe K et al.; Leptolstatin, a new inhibitor of the progression of G1 and G2 phases of the mammalian cell cycle, was discovered through a unique screening system, in which effects of microbial metabolites on the cell cycle progression of the cultured rat fibroblasts were monitored by flow cytometry . The new inhibitor was extracted from the fermentation broth of Streptomyces sp . SAM1595 with ethyl acetate, and purified by silica gel column chromatography and HPLC . Leptolstatin showed a strong cytostatic effect on rat normal fibroblasts 3Y1 with an IC50 value of 0.4 ng/ml, but its antimicrobial activity was very weak . A 24-hour treatment of the fibroblast cells with 10 ng/ml of leptolstatin caused an arrest at G1 or G2 phase, as determined by flow cytometry . When the G2-arrested cells were freed from leptolstatin, those containing 4C DNA entered a new S phase without intervening M phase, resulting in the formation of proliferative tetraploid cells.

Sex Transm Dis, 1993 May-Jun, 20(3), 164 - 7
Granuloma inguinale (donovanosis) in women . An analysis of 61 cases from Durban, South Africa; Bassa AG et al.; BACKGROUND AND OBJECTIVES: Granuloma inguinale (GI) appears to be making a resurgence in South Africa . Local cases were reviewed in order to determine an increasing prevalence and whether differences appeared between pregnant and non-pregnant women . STUDY DESIGN: Retrospective analysis of clinical records of patients attending a large tertiary teaching hospital, serving an underprivileged population . RESULTS: Sixty-one women with GI were diagnosed over a 3-year period . The most common clinical presentation was genital ulceration in both pregnant (88.5%) and nonpregnant (45.7%) patients . The next most common presentation was genital tract bleeding (19.7%), which occurred mainly among nonpregnant women . The vulva was the most frequent anatomical site involved (54.1%), in both pregnant (88.5%) and nonpregnant (28.6%) women . Multiple sites of infection (vulva, vagina, cervix) occurred only among nonpregnant women . Fourteen of 33 (42.4%) patients whose syphilis serology results were available had reactive tests . Erythromycin and tetracycline were the most common single antimicrobial agents used for therapy and response varied according to site and size of lesion . CONCLUSIONS: This study confirms our clinical impression of the increasing prevalence of GI, especially among women in Durban, South Africa . The protean manifestations of the disease are demonstrated with sharp distinctions between pregnant and nonpregnant women and there was a high prevalence of concomitant syphilis.

Sex Transm Dis, 1993 May-Jun, 20(3), 121 - 5
Does addition of anti-inflammatory agents to antimicrobial therapy reduce infertility after murine chlamydial salpingitis?
Landers DV, Sung ML, Bottles K, Schachter J.
BACKGROUND AND OBJECTIVES: Infertility after murine chlamydial salpingitis can be prevented by tetracycline treatment given before or at the time of infection . This study evaluates the efficacy and timing of tetracycline treatment and anti-inflammatory agents in the prevention of inflammation and subsequent infertility . STUDY DESIGN: The left ovarian bursae and uterine horns were inoculated with the mouse pneumonitis strain of Chlamydia trachomatis . Mice were mated 54 days after inoculation . RESULTS: Infected mice treated with tetracycline beginning 2 days after infection showed mild inflammation and no significant reduction in fertility . However, when tetracycline treatment was delayed until 5 days after infection, a moderate degree of inflammation and a significant reduction in fertility (P < 0.01) was noted . Treatment with ibuprofen, prostaglandin E1 (PGE-1), or hydrocortisone beginning day 2 post-inoculation did not significantly alter the degree of inflammation or subsequent fertility . Mean anti-chlamydial IgG titers were significantly lower in mice treated with either PGE1 or hydrocortisone compared with infected, untreated mice . CONCLUSION: These results indicate that while early treatment of chlamydial salpingitis may prevent infertility, delay in treatment may result in significant inflammatory damage and infertility . There was no apparent benefit from the addition of anti-inflammatory agents.

Equine Vet J, 1993 May, 25(3), 214 - 9
A prospective study of septicaemia in colostrum-deprived foals; Robinson JA et al.; Fourteen mares and their foals were attended at parturition . After mare-foal bonding, 8 colostrum-deprived (CD) foals were removed from their dams, deprived of colostrum, and provided with an alternative milk source for the first 24 h of life . The mares were milked out every 2-4 h during this period to remove colostrum, after which the CD foals were returned to their mares and allowed to nurse . Six colostrum-fed (CF) foals were allowed to suck colostrum in the normal manner . Foal serum IgG concentration was determined by single radial immunodiffusion (means, CD = 0 mg/dl; CF = 1,508 mg/dl) . Accepted methods were used to minimise infections in the neonatal foals . Of the 8 CD foals, 7 demonstrated clinical signs of sepsis . Septicaemia was confirmed in 5 of the 7 septicaemic CD foals by ante-mortem blood culture or by culture of tissue at necropsy . Organisms isolated included: Actinobacillus equuli, Escherichia coli, undifferentiated coliforms, Pseudomonas spp., and Actinomyces pyogenes . Clinically ill foals were treated with antimicrobial drugs, intravenous fluid therapy, flunixin meglumine, and anti-endotoxin hyperimmune serum . Three septicaemic CD foals survived . Four of 7 septicaemic CD foals died or were destroyed . Post-mortem lesions included bacterial embolic pneumonia, glomerulonephritis/nephritis, lymphoid depletion/atrophy, splenic and lymphoid necrosis, hepatitis, septic arthritis, and systemic bacterial embolism . None of the CF foals became septicaemic . One CF foal had foal heat diarrhoea and 1 CF foal had a serum IgG concentration of 160 mg/dl (i.e . failure of passive transfer), but both foals were otherwise normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Nucl Med, 1993 May, 18(5), 417 - 22
Radionuclide hepatobiliary scanning in patients with AIDS-related sclerosing cholangitis; Quinn D et al.; Biliary disease, primarily manifesting as papillary stenosis or sclerosing cholangitis, is being increasingly recognized as a problem in the acquired immunodeficiency syndrome (AIDS) and may be amenable to specific treatment . Ultrasound, followed by endoscopic retrograde cholangiopancreatography (ERCP) for definitive diagnosis, is currently the prime mode of investigation of suspected hepatobiliary diseases in AIDS . There are few published reports of the use of radionuclide cholescintigraphy in the assessment of these patients . This report presents Tc-99m DISIDA cholescintigraphy data from three patients with AIDS-related hepatobiliary disease confirmed by ERCP . Radionuclide cholescintigraphy was abnormal in all three patients . In two of the subjects, there was focal duct dilation with strictures in the biliary tree . The third patient demonstrated diffuse hepatic parenchymal retention with marked delay in tracer washout . Two of the subjects, treated with specific anticryptosporidial therapy, subsequently underwent progress cholescintigraphy . In one of these patients with initial diffuse parenchymal retention, there was marked improvement in scan appearances . The second patient with initial duct dilation had no significant change in scan appearances, but quantitative analysis did demonstrate improvement in hepatobiliary tracer clearance rate . In conclusion, although ERCP remains the gold standard in the diagnosis of AIDS-related biliary disease, radionuclide cholescintigraphy may be a useful modality in these patients as a screening test before proceeding to more expensive and invasive techniques . In addition, quantitative analysis of cholescintigraphy may allow assessment of patient response to specific antimicrobial or surgical intervention.

Clin Infect Dis, 1993 May, 16(5), 671 - 6
Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis; Montejo JM et al.; This report describes the results of six antimicrobial regimens used for the treatment of brucellosis in an open, randomized study performed over two periods (1980-1983 and 1984-1987) . In the first period, rifampicin and doxycycline were used for 4 weeks, trimethoprim-sulfamethoxazole for 6 months, and doxycycline for 6 weeks . During the second period, we used streptomycin for 2 or 3 weeks together with doxycycline for 6 weeks and rifampicin with doxycycline for 6 weeks . Comparison of the results showed the following: (1) no statistically significant findings were revealed when the different regimens were compared and (2) the regimens containing streptomycin yielded statistically more favorable results than those consisting of rifampicin and monotherapy when the patients treated with rifampicin were compared with those taking streptomycin and those receiving single-agent therapy . No significant differences were observed between monotherapeutic regimens and those including rifampicin.

J Infect, 1993 May, 26(3), 305 - 8
Exogenous Nocardia asteroides endophthalmitis following cataract surgery; Atkinson PL et al.; We present a case of Nocardia asteroides endophthalmitis following cataract surgery . It is the second to be reported and the first in which vision has been preserved . Symptoms commenced 5 days after surgery and there followed a chronic relapsing anterior uveitis which lasted for 4 months . Nocardia asteroides was finally cultured from an aqueous aspirate and a combination of specific antimicrobial treatment and surgery resulted in a satisfactory visual outcome . Exogenous nocardial intraocular infection is rare and must be distinguished from fungal infection as the organism is resistant to antifungal agents.

Drug Saf, 1993 May, 8(5), 350 - 64
Overview of the tolerability profile of clarithromycin in preclinical and clinical trials; Guay DR et al.; Results of studies conducted to characterise local, systemic, reproductive, and mutagenic effects indicate that the new macrolide antimicrobial clarithromycin is well tolerated within reasonable multiples of the intended clinical dose . No adverse effects of clarithyromycin on male or female fertility, perinatal, or postnatal reproduction were indicated by data from rabbits, mice, rats and macaques . No evidence of mutagenic potential was revealed from various in vitro and in vivo study methodologies . Evidence of low potential for ototoxicity, oculotoxicity, hepatotoxicity and nephrotoxicity was provided in studies involving rats, dogs and primates . In agreement with studies with other macrolides, venous irritation potential for the intravenous lactobionate salt formulation was substantial in rabbit studies . In addition, the safety profile of this agent has been evaluated on the basis of adverse reactions and abnormal laboratory values seen in phase I, II and III international clinical trials conducted in adults . The most frequently reported adverse reactions occurring in 3768 patients receiving clarithromycin in phase II and III trials were nausea (3.8%), diarrhoea (3.0%), abdominal pain (1.9%) and headache (1.7%) . Adverse reactions were not serious and were usually rapidly reversible . The incidence of adverse reactions did not vary with gender, race or age . Adverse reaction rates were comparable to or less than those of comparator beta-lactams and macrolides . Overall, clarithromycin appears to be a safe and well-tolerated macrolide antimicrobial agent.

Poult Sci, 1993 May, 72(5), 979 - 83
Research note: pharmacokinetics of aditoprim in turkeys after intravenous and oral administration; Engeli J et al.; The pharmacokinetics of aditoprim, a not yet commercialized selective reversible inhibitor of dihydrofolate reductase, were determined in turkeys after intravenous (5 mg/kg BW) and oral (5.46 +/- .44 mg/kg BW) administration . The mean (+/- SD) total body clearance of 26.9 +/- 2.3 mL/min per kg BW was high when compared with that determined for other species, presumably a consequence of the higher metabolic rate of birds . Consequently, mean aditoprim elimination half-life was relatively short (3.3 +/- .2 h) . As determined in mammalian species, the apparent volume of distribution at steady state was large . Aditoprim in drinking water (100 and 300 mg/L water) provided plasma concentrations between .08 and .19 micrograms/mL . Circadian rhythms with highest concentrations in the late afternoon and lowest concentrations in the morning were observed . Despite its short elimination half-life, aditoprim may still be a valuable antimicrobial for use in avian medicine pending safety, efficacy, and residue depletion studies.

J Clin Periodontol, 1993 May, 20(5), 335 - 9
The effect of a mouthrinse based on nisin, a bacteriocin, on developing plaque and gingivitis in beagle dogs; Howell TH et al.; The aim of this study was to evaluate the effect of nisin, an antimicrobial peptide, on the development of plaque and gingivitis in beagle dogs when compared with 0.12% chlorhexidine and a placebo . 16 female beagle dogs 1 year of age were brought to optimum gingival health by scaling, root planing and polishing . At the conclusion of the pretreatment phase, the dogs were divided into 4 groups for the application of the test agents and were placed on a plaque promoting diet of Purina Dog Chow softened with water . Test agents included 100 micrograms/ml nisin and 300 micrograms/ml nisin formulated in a vehicle containing 1 mM NaEDTA; negative control comprised of exactly the same formulation but omitting nisin; and 0.12% chlorhexidine as Peridex . Throughout the treatment period, formulations were applied 2x daily to premolar teeth in each quadrant for 1 min using a Monojet syringe . The development of plaque and gingivitis was monitored at 15, 27, 39, 53, 74 and 88 days during the treatment phase using standard measurements of gingival index, plaque index, stain index and bleeding to probing . Throughout the treatment phase, plaque accumulation increased in all groups, but the rate of plaque build-up was less in groups treated with either nisin or chlorhexidine formulations compared with the placebo treated group . The gingival index of dogs in all groups increased throughout the study period . However, from day 27 onward, the groups receiving nisin had lower gingival index scores than did the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

J Allergy Clin Immunol, 1993 May, 91(5), 1015 - 23
Subacute sinusitis: are antimicrobials necessary?
Dohlman AW, Hemstreet MP, Odrezin GT, Bartolucci AA.
BACKGROUND: The need for antimicrobials in the treatment of subacute sinusitis was evaluated in 96 afebrile children who were prescribed antimicrobial (amoxicillin, amoxicillin clavulanate potassium, or trimethoprim-sulfamethoxazole) or no antimicrobial medication in addition to a decongestant and saline nasal spray for 3 weeks . METHODS: Response was determined by complete clearing of the initial radiologic abnormalities or in the case of mucosal thickening, by a significant decrease in thickness to < 6 mm within the maxillary sinuses associated with improvement of the clinical signs and symptoms of sinusitis . If there was evidence of partial clearing by radiograph, the same therapy was continued for another 3 weeks . Nonresponders demonstrated no change or worsening of clinical and radiologic findings . RESULTS: Sixty-seven of the 96 subjects (70%) responded: 58 (87%) in 3 weeks and 9 (13%) in 6 weeks . Fifty-five of the responders were in the antimicrobial treatment group, and 12 were prescribed no antimicrobial medication . Twenty-nine of the 96 subjects (30%) did not respond to treatment; 22 received an antimicrobial and seven received no antimicrobial medication . CONCLUSIONS: The number of responders and nonresponders was similar in the antimicrobial- and nonantimicrobial-treated groups (p = NS), and no single antimicrobial medication demonstrated greater treatment effectiveness.

AACN Clin Issues Crit Care Nurs, 1993 May, 4(2), 414 - 23
Improving survival: infection control and burns; Weber JM et al.; In the past, survival of the thermally injured patient was greatly hindered by invasive infection that originated in the burn wound . Current treatment modalities, including early excision of the burn wound and prompt wound closure, administration of systemic antibiotics and topical antimicrobial agents, and mechanical isolation, have improved survival . However, infection and the sequelae of infection continue to be the leading causes of morbidity and mortality for the thermally injured patient . In addition, the burn patient remains highly susceptible to other infectious processes . A thorough understanding of infection control and burns are essential to the successful treatment of burn injuries.

AACN Clin Issues Crit Care Nurs, 1993 May, 4(2), 378 - 87
Burn wound management; Walter PH; Management of a burn wound is interrelated with many patient care protocols . After the patient has received initial care, is in stable condition, and has been transported to the appropriate medical facility, the selection of burn wound treatment protocols is based on patient population . Hydrotherapy, debridement, topical antimicrobial agents, and dressings reduce bacterial colonization until the wound closes . Supportive care is essential to the preservation of viable tissue . Excision and autografting are the primary method of wound management . The practical application of cultured autograft and growth factors is under study.

Tijdschr Diergeneeskd, 1993 May 1, 118(9), 293 - 7
{Rapid detection of antimicrobial residues in slaughter animals via ATP determination}; Stekelenburg FK; A rapid antibiotic test was developed, based on ATP/bioluminescence, to detect antimicrobial residues in slaughter animals as early as possible . Several aspects that influence the assay were studied . For many samples of renal fluid the results of the test agreed very well with the inhibition zones obtained with the new Dutch agar diffusion test . The ATP/antibiotic test offers the possibility of detecting a wide range of antibiotics in renal fluid within 3.5 to 4 hours after receipt of the kidney samples . The detection level is comparable to that of existing agar diffusion tests.

J Fam Pract, 1993 May, 36(5), 507 - 12
Randomized placebo-controlled trials of antibiotics for acute bronchitis: a critical review of the literature; Orr PH et al.; BACKGROUND . Acute bronchitis is a common clinical problem that causes considerable morbidity and presents both diagnostic and treatment dilemmas for the physician . An evaluation of all published randomized controlled trials of antibiotics in the treatment of acute bronchitis was conducted to (1) quantitatively assess methodologic rigor, (2) determine if effectiveness of antimicrobial therapy is known, and (3) analyze strengths and weaknesses of randomized controlled trials in family practice settings . METHODS . A scoring system for the evaluation of randomized controlled trials was adapted for this study . Four raters, who were blinded to which journals published the studies and the type of antibiotic used in each study, assessed the six-randomized clinical trials for treatment of bronchitis identified through a literature search . The trials were rated according to criteria that measured internal validity . RESULTS . Scores for internal validity ranged from 65.5 to 102.5 points with a maximum possible score of 120 points (54.6% to 85.4%) . The two trials with the highest scores assessed doxycycline and showed no benefit from use of this antibiotic . Single trials that studied erythromycin and trimethoprim-sulfamethoxazole showed improvement in outcome from use of these drugs; however, of the six trials, these two studies ranked fourth and fifth for internal validity . Low scores resulted from small sample size, possible contamination with other treatment measures, and poor assessment of subjects' compliance with antibiotic regimen . CONCLUSIONS . An evaluation of the current literature does not support antibiotic treatment for acute bronchitis . Further studies of this common illness are indicated . It is hoped that this critical review of randomized control trials will prove useful in the planning of future studies, in placing greater emphasis on methodologic rigor, and in giving greater consideration to the practical constraints of research in the family practice setting.

J Cell Physiol, 1993 May, 155(2), 408 - 13
Defensins are mitogenic for epithelial cells and fibroblasts; Murphy CJ et al.; Defensins are a family of structurally homologous peptides contained within phagocytic cells . Although these peptides are best known for their broad spectrum antimicrobial properties, they also inhibit ACTH (corticotropin) stimulated corticosterone production, chemoattract monocytes, and lyse mammalian cells . We now report that these peptides are potent mitogens in vitro in the same concentration range that they display potent antimicrobial activity in vitro . These concentrations are in the same range as those expected to be present in vivo during the wound healing process . All defensins tested were stimulatory for epithelial cells and fibroblasts and acted synergistically with insulin . These are the first data to disclose the strong growth-promoting effects of this unique family of peptides and point to another basic mechanism whereby the macrophage and neutrophil may participate in a variety of trophic, physiologic, and pathologic processes.

J Exp Med, 1993 May 1, 177(5), 1309 - 16
Regulatory role of OX22high T cells in mercury-induced autoimmunity in the brown Norway rat; Mathieson PW et al.; The monoclonal antibody OX22 defines a functional split within CD4+ T cells in the rat, with OX22high cells mainly producing interleukin 2 (IL-2) and interferon gamma and responsible for delayed-type hypersensitivity responses, and OX22low cells mainly producing IL-4 and -5 and responsible for providing B cell help . There are reciprocal interactions between OX22high and OX22low cells, and it has been suggested that the OX22low subset has a role in the prevention of autoimmunity . We have used OX22 in vivo to define the role of these subsets in mercuric chloride-induced autoimmunity in the Brown Norway rat . In this model, there is polyclonal B cell activation and animals develop widespread tissue injury . Treatment of thymectomized animals with OX22 led to a profound reduction in the number of OX22high T cells in the peripheral blood . OX22-treated animals consistently developed more severe tissue injury than controls given an irrelevant antibody of the same isotype . Control animals pretreated with broad spectrum antimicrobial drugs showed milder tissue injury, but this protective effect of antimicrobials was lost in OX22-treated animals . Transfer of naive T cells to OX22-treated animals provided protection, but if T cells were depleted in vitro of OX22high cells before transfer, this effect was lost . These data provide evidence for a protective immunoregulatory role for OX22high T cells in mercuric chloride-induced autoimmunity.

Cell Signal, 1993 May, 5(3), 345 - 56
Evidence that generation of inositol 1,4,5-trisphosphate and hydrolysis of phosphatidylinositol 4,5-bisphosphate are rapid responses following addition of fungal elicitor which induces phytoalexin synthesis in lucerne (Medicago sativa) suspension culture cells; Walton TJ et al.; Treatment of lucerne suspension culture cells with glycoprotein elicitor from the phytopathogenic fungus Verticillium albo-atrum R & B triggers Ca(2+)-mediated induction of antimicrobial secondary metabolites termed phytoalexins . The present study investigated the possible role of polyphosphoinositide signal transduction in phytoalexin elicitation . Within 1 min of addition of elicitor to lucerne suspension culture cells we found a 100-160% (15-25 pmol/g fresh wt) increase in the level of compound with chromatographic and electrophoretic properties expected for an inositol trisphosphate (InsP3) and which was strongly bound by an inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-specific binding protein; after 3 min the level of this compound had fallen below that observed prior to elicitor challenge . In 32P-prelabelled cells, the relative proportion of radioactivity which cochromatographed with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was found to have decreased by 48% 1 min after elicitor addition and that rapid depletion of membrane lipid radioactivity was specific to this lipid fraction . The rapid, transient increase in level of Ins(1,4,5)P3 and concomitant fall in PtdIns(4,5)P2 suggests that Ins(1,4,5)P3 generated by hydrolysis of PtdIns(4,5)P2 may provide a Ca(2+)-mobilizing signal in phytoalexin elicitation in lucerne.

Res Vet Sci, 1993 May, 54(3), 329 - 34
In vitro activity of danofloxacin, tylosin and oxytetracycline against mycoplasmas of veterinary importance; Cooper AC et al.; The activities of danofloxacin, a novel fluoroquinolone, and two other antimicrobials were determined in vitro against field isolates of seven Mycoplasma species of veterinary importance isolated from cattle, swine and poultry in five European countries . The minimum inhibitory concentrations (MIC) of danofloxacin, tylosin and oxytetracycline were determined against a total of 68 isolates . Danofloxacin showed excellent activity against isolates of all Mycoplasma species (range 0.008 to 0.5 microgram ml-1), but in some isolates there was evidence of reduced sensitivity to tylosin (range 0.008 to 2.0 micrograms ml-1) and oxytetracycline (range 0.008 to over 16.0 micrograms ml-1) . Danofloxacin was more active than other antimicrobials against M hyopneumoniae, M dispar and M bovigenitalium, and showed activity similar to that of tylosin against M bovis and M gallisepticum . Tylosin was the most active against M synoviae and M hyosynoviae . Generally, oxytetracycline showed the poorest activity, but was superior to tylosin against M bovigenitalium . A second (final) MIC reading was taken for all isolates 14 or 21 days after the initial reading, and MIC values rose during that time . However, the increase seen in danofloxacin values (typically one to two dilutions) was less than that seen for tylosin and oxytetracycline . It is concluded that danofloxacin is highly active in vitro against all of the Mycoplasma species tested, and thus shows great potential for the treatment of respiratory and other infections caused by Mycoplasma species in cattle, pigs and poultry.

Nat Immun, 1993 May-Jun, 12(3), 128 - 35
Progesterone but not estrogen depolarizes natural killer cells; Mandler RN et al.; Natural killer (NK) cell tumoricidal and antimicrobial activities can be rapidly modulated by molecules that interact with membrane receptors . The discovery of NK cell depolarization induced by steroid-like Na+ channel agonists prompted a study of purified human NK cell excitability to a variety of steroids . Progesterone, but not estrogen, depolarized NK cells with concentration and time dependency . Excitability was measured by using flow cytometry and the anionic voltage-sensitive dye oxonol . Preincubation with the Na+ channel antagonist tetrodotoxin or removal of the extracellular Na+ blocked the response . Progesterone may rapidly change membrane potential, and eventually function, by acting on putative NK plasma membrane receptors coupled to Na+ conductances.

J Antibiot (Tokyo), 1993 May, 46(5), 719 - 27
Delaminomycins, novel nonpeptide extracellular matrix receptor antagonist and a new class of potent immunomodulator . I . Taxonomy, fermentation, isolation and biological activity; Ueno M et al.; In order to develop a new class of immunomodulator we have searched for a low molecular weight inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin (FN), laminin (LM) and collagen type IV (CL), and succeeded to find a group of novel antibiotics, named delaminomycins . Delaminomycins were isolated from the mycelium and cultured broth of Streptomyces albulus MJ202-72F3 . It was purified by use of centrifugal partition chromatography (CPC), preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder . Delaminomycins with inhibitory activity for cell adhesion to ECM components suppressed immune responses in vitro and in vivo and exhibited antimicrobial activity on Gram-positive bacteria.

Clin Exp Rheumatol, 1993 May-Jun, 11(3), 301 - 7
Effect of antimicrobial treatment on chronic reactive arthritis; Toivanen A et al.; In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated . At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group . We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.

Rinsho Byori, 1993 May, 41(5), 548 - 52
{Current state and problems in the microbiology laboratory--organizing the laboratory}; Machida K; The microbiological laboratory in the hospital has many roles including the rapid and precise identification of pathogenic bacteria in specimens, their antimicrobial susceptibility tests, microbial antigen detection using immunological methods and DNA hybridization methods, surveillance of bacterial milieu of the hospital environment, monitoring quality control of microbiological methods, to educate microbiological skills of staffs, the economical management of laboratory and so on . The last two issues are our major concerns . Improvement of the microbiological skills of the staff is most important in the laboratory, but is a time-consuming . From our experience, a technical expert, intermediately skilled technicians and beginners should always work in the laboratory, together . On the other hand, the economical management of the microbiological laboratory is also another concern . Although the mechanization of procedures comes to mind, it is hard to improve the economical conditions in the laboratory . Because of the control of the machines is not completely automatic and requires the knowledges and decisions of technical experts, the work force and running cost can not be reduced . As the technical expert can economize in the use of media or tests for identification of pathogens, good training of beginners into skillful successors, is important.

Chem Pharm Bull (Tokyo), 1993 May, 41(5), 978 - 80
Antimicrobial activity and conformation of tachyplesin I and its analogs; Tamamura H et al.; We investigated the structure-antimicrobial activity relationship of tachyplesin I (T-I) . Even when Lys1 and Trp2 were both deleted from the N-terminal end of T-I, the antimicrobial activity against gram-negative bacteria was not decreased . But as Lys1 and Trp2 were deleted one by one, the antimicrobial activity against gram-positive bacteria and antiviral activity were gradually decreased . Deletion of two disulfide bridges caused a significant decrease in all activities . The circular dichroism (CD) spectra revealed that the analogs containing the two disulfide bridges took a beta-sheet structure and that the analogs without the disulfide bridges took a random coil conformation . These results suggest that the beta-sheet structure maintained by two disulfide bridges plays an important role in the antimicrobial activity of T-I.

J Antimicrob Chemother, 1993 May, 31 Suppl D, 17 - 27
Pharmacokinetics of antibiotics in shallow and deep compartments; Barza M; This paper reviews the influence of the type of capillary bed, type of compartment, and the presence of active transport systems, on the pharmacokinetics of antimicrobial agents in tissues and fluids of the body . In the absence of active transport or local degradation, the mean concentration or 'area under the curve' of free (unbound) drug in ordinary extravascular sites over the dosing interval at equilibrium is equal to that in the serum . Because the latter is easily measured, there should be no need to measure tissue concentrations except in unusual circumstances . Among the factors that will alter the relationship described above are active transport, pH partition, and bulk flow . Antibiotics such as the macrolides, lincosamines and quinolones may accumulate in high concentrations in cells containing lysosomes . There is some evidence that the intracellular sites may serve as a reservoir from which these drugs may later be released into tissue fluids, a phenomenon not taken into account in the relationships described above . Although knowledge of the in-vitro activity and local concentrations of antibiotics is of use in predicting therapeutic activity, many factors which are difficult to quantify in a given instance make precise correlations impossible . The inability of antibiotics alone to sterilize abscesses is probably not due to a problem in antibiotic penetration but to insusceptibility of the organisms and inefficacy of the phagocytes in an abscess . Similar processes operate to reduce the efficacy of antibiotics when treatment is delayed.

J Antimicrob Chemother, 1993 May, 31 Suppl D, 167 - 75
Definitions of antibacterial interactions in animal infection models; Renneberg J; Combination of antibiotics in order to achieve antimicrobial synergy is often necessary in the treatment of infections due to resistant bacterial strains . Therefore, several in-vitro test systems have been developed with the purpose of predicting in-vivo action of antibiotics, and the fractional inhibitory concentration (FIC) index has been used to interpret results obtained in different test systems . Using these systems it seems that only antibiotic synergy in vitro is predictive of the results of treatment . It is therefore of interest to have an in-vivo test system that makes it possible to describe antibiotic interaction in detail . Animal infection models such as the foreign body model system enable the measurement of many parameters at the site of infection, such as bactericidal effect (BE) and antibiotic concentrations . A new calculation of drug interaction is suggested in which the measurements used are the BE and the time during which the MIC is exceeded, for the individual drugs and the combination . This calculation enables us to penetrate into observed antibiotic efficacy in vivo to find out whether an observed high BE is due to real synergy or simply to optimal pharmacokinetics of antibiotics at the site of infection.

J Antimicrob Chemother, 1993 May, 31(5), 627 - 35
Antimicrobial resistance spread in aquatic environments; Young HK; The increased use of antimicrobials in farming, together with the practice of raw sewage discharge into receiving waters, has resulted in a significant increase in the numbers of antibiotic resistant bacteria present in aquatic environments . The role of this environment to act, not only as a reservoir of clinical resistance genes, but also as a medium for the spread and evolution of resistance genes and their vectors, is discussed.

Kekkaku, 1993 May, 68(5), 367 - 70
{Antimicrobial activity of new quinolones against Mycobacterium avium and Mycobacterium intracellulare determined by the dilution methods using 7H11 agar and Ogawa egg media}; Tomioka H et al.; Various new quinolones were measured for their in vitro antimicrobial activities against Mycobacterium avium and M . intracellulare by the two-fold dilution methods using two types of media, 7H11 agar medium and 1% Ogawa egg medium . The MIC90s of test quinolones determined on 7H11 agar medium and Ogawa egg medium were as follows . M . avium (20 strains): ofloxacin (OFLX), 50 and 50 micrograms/ml; ciprofloxacin (CPFX), 12.5 and 25 micrograms/ml; sparfloxacin (SPFX), 6.25 and 12.5 micrograms/ml; fleroxacin (FLRX), 50 and 50 micrograms/ml; Y-26611, 100 and 100 micrograms/ml; OPC-17116, 12.5 and 50 micrograms/ml, for 7H11 agar and Ogawa egg medium, respectively . M . intracellulare (20 strains): OFLX, 50 and 50 micrograms/ml; CPFX, 25 and 25 micrograms/ml; SPFX, 12.5 and 12.5 micrograms/ml; FLRX, 50 and 50 micrograms/ml; Y-26611, > 100 and > 100 micrograms/ml; OPC-17116, 12.5 and > 100 micrograms/ml, for 7H11 agar and Ogawa egg medium, respectively . Thus, the MIC values determined by the 7H11 agar medium were comparable to those by the 1% Ogawa egg medium, except for OPC-17116 . Moreover, from the above MIC values, it can be regarded that the potencies of in vitro antimicrobial activity of test quinolones against M . avium are in the order of SPFX > CPFX > or = OPC-17116 > or = OFLX > or = FLRX > Y-26611 and those against M . intracellulare are in the order of SPFX > OPC-17116 not equal to CPFX > OFLX = FLRX > Y-26611 . There was found the tendency that M . avium has somewhat higher susceptibility to these quinolones as compared to M . intracellulare.

Unfallchirurg, 1993 May, 96(5), 248 - 52
Splenic function after splenic rupture treated with an absorbable mesh; Vanderschot P et al.; Overwhelming postsplenectomy sepsis remains a problem despite the introduction of a vaccine and antimicrobial prophylaxis . Removal of the spleen increases the risk of death from overwhelming sepsis to approximately 50 times that in healthy persons . The morbidity and mortality due to infection increase with the extent of associated injuries . Between 1987 and 1991, 24 patients were admitted at the Katholieke Universiteit Leuven for a splenic injury and treated with an absorbable vicryl mesh (woven polyglycolic acid mesh; Polyglactine 910) . The injuries to the spleen were classified according to Barrett . Three patients died of severe craniocerebral trauma . A splenectomy was performed in one polytraumatized patient because of rebleeding . The spleen was evaluated in 20 patients after a mean of 20 weeks using 99mTc-denaturated erythrocyte scintigraphy together with tomographies . A type IV injury is a contraindication . All abnormalities on scintigraphy are mainly seen in type III lesions and less in type II and type I lesions . In type IV injury splenectomy and autotransplantation are indicated . Except for type IV lesions, we conclude that a ruptured spleen can be safely treated with a vicryl mesh without great loss of function.

Jpn J Antibiot, 1993 May, 46(5), 404 - 10
{Prospective randomized study on effect of duration of antimicrobial prophylaxis for mastectomy}; Morimoto K et al.; A prospective randomized trial was done to study effects of the duration of ofloxacin (OFLX) administration for prophylaxis against mastectomy wound infections . One hundred and seventeen women who were hospitalized, during periods between June 1990 and September 1992 were considered for enrollment in this study . Selected patients were treated with 600 mg of OFLX daily in 3 divided doses starting the day before surgery . One group was treated for 5 days and the other was treated for 10 days . A hundred and ten patients were found eligible to complete the study and 58 patients were assigned to the 5-day group and 52 patients were assigned to the 10-day group by the random-envelope method . Nine episodes of infections occurred among the patients in the 5-day group and 12 episodes of infections occurred among those in the 10-day group . The mean time until onset of infection was not significantly different between the 2 groups (12 versus 8 days) . The number of strains isolated from the drainage tube when removed was highly correlated with occurrences of infections, and the number of strains isolated from infected wounds was also highly correlated with the need to use a different antibiotic . By multiple regression analysis, age was the only significant factor identified for wound infection . The duration of OFLX administration had no significant effect on the development of wound infections . Prolonged prophylactic use of this drug for mastectomy did not reduce the incidence of postoperative infections in this study.

Cancer Pract, 1993 May-Jun, 1(1), 72 - 6
Surveillance of surgical wound infections in cancer patients; Barber GR et al.; Despite the increasing number of therapeutic options available to cancer patients, surgery represents a mainstay of treatment . Surgical wound infections (SWIs) account for frequent patient morbidity, and the true incidence of these infections is probably underestimated . Little data exist that identify SWI rates among patients with cancer . Due to their disease, intensive treatment regimens, or both, profound immunosuppression is an all too frequent occurrence among cancer patients . Thus these patients may have a higher intrinsic risk for acquiring an SWI . Surveillance of SWIs coupled with reporting of wound infection rates has been shown to reduce these infectious complications . Surveillance of SWIs as well as other nosocomial infections is often accomplished through combined methodologies . Multidisciplinary communication is essential for accurate reporting . Additionally, proper use of antibiotics for prophylactic or therapeutic purposes must be maintained and periodically evaluated hospital-wide . Prescribing, dispensing, and administrating antimicrobials warrant the strong consideration of all healthcare professionals who are responsible for carrying out orders for these agents.

J Clin Pathol, 1993 May, 46(5), 403 - 7
Comparison of techniques for antimicrobial susceptibility testing of mycobacteria; Limb DI et al.; AIMS--To evaluate adenosine triphosphate (ATP) bioluminescence as a rapid technique for antimicrobial susceptibility testing of Mycobacterium spp by comparing it with conventional and radiometric methods, and to assess its potential for use in clinical microbiology laboratories . METHODS--115 clinical isolates from a wide range of mycobacterial species and four control organisms of known susceptibility were tested against six antimicrobial agents . Minimum inhibitory concentrations (MICs) were determined after 4-6 weeks' incubation on Middlebrook 7H10 agar . Susceptibility was also determined radiometrically using a Bactec 460, and by bioluminescent assay of ATP using a 1250 luminometer (LKB-Wallac) . RESULTS--Susceptibility results after 7 days showed excellent correlation with conventionally determined MICs . 714 susceptibility tests were performed by both techniques, with seven major discrepancies between the two systems . For pyrazinamide, agreement was 100%, but five strains of M tuberculosis, including one control, and 11 mycobacteria other than M tuberculosis (MOTT) failed to grow on Middlebrook agar at pH 5.5 . 606 tests were performed by radiometry, with four major discrepancies between this technique and ATP bioluminescence . No particular species of Mycobacterium gave aberrant results . Contamination was a problem; 12 of the 119 strains tested were contaminated at day 1 and had to be repeated before results were obtained . Contamination of individual tests increased significantly after 7 days of incubation . CONCLUSIONS--ATP bioluminescence can be used to monitor mycobacterial growth in fluid culture media; the technique has considerable potential for rapid susceptibility testing . Advantages include lower initial cost of analytical equipment, lower reagent cost per test, and the use of non-radioactive substrates.

J Fla Med Assoc, 1993 May, 80(5), 327 - 9
Human ehrlichiosis in Florida; Rathore MH et al.; Human ehrlichiosis has been relatively recently identified in the United States . We report a case of human ehrlichiosis recently diagnosed in Jacksonville . A high index of suspicion in an appropriate clinical setting is needed to make this diagnosis . This disease is most often confirmed by serologic tests . Patients benefit from antimicrobial therapy.

J Am Dent Assoc, 1993 May, 124(5), 56 - 8
Reducing bacteria in dental aerosols: pre-procedural use of an antiseptic mouthrinse; Fine DH et al.; This study, using a simulated office visit model, showed that the pre-procedural use of an antimicrobial mouthrinse produces a significant reduction in number of viable bacteria in a dental aerosol.

Rev Med Chil, 1993 May, 121(5), 553 - 6
{Multiple splenic abscesses . Report of 2 cases}; Gatica MA et al.; Splenic abscesses are infrequent and usually associated to sepsis and immunodepression . The diagnosis is commonly made in the necropsy . We report two cases of multiple splenic abscesses in type II diabetic patients that were diagnosed by ultrasound . Both patients were successfully managed with surgery (drainage of left subphrenic space in one and splenectomy in the other) and antimicrobial agents.

Trans R Soc Trop Med Hyg, 1993 May-Jun, 87(3), 296 - 8
Fatal arteritis due to Pythium insidiosum infection in patients with thalassaemia; Wanachiwanawin W et al.; Six thalassaemic patients had a distinct clinical syndrome characterized by progressive ischemia of the lower extremities, with ascending arteritis and thrombosis of the main arteries of the lower limbs . With periodic acid Schiff and Gomori's methenamine silver staining a large number of hyphae were revealed in the arterial wall and the outer part of the thrombus . Pythium insidiosum was isolated from 3 patients . The clinical course of the disease was progressive gangrene of the extremities and the patients invariably died when the infectious process reached the bifurcation of the aorta . There is no effective antimicrobial agent for the syndrome and radical amputation was the only method to ensure survival of the patients . P . insidiosum infection should be considered in thalassaemic patients with leg ulcers or arterial occlusion of the lower limbs.

New Horiz, 1993 May, 1(2), 194 - 201
Gut sterilization to prevent nosocomial infection; Koruda MJ; Nosocomial infections, particularly respiratory tract infections, are common complications that not only lengthen ICU stay but also increase mortality . Since it has been recognized that colonization of the oropharynx and proximal gastrointestinal tract by Gram-negative bacteria is predictive of subsequent pneumonia, attempts have been directed toward sterilizing the upper gastrointestinal tract of pathogenic organisms . Selective decontamination of the digestive tract (SDD) utilizes the administration of topical, nonabsorbable antimicrobials to the gastrointestinal tract and parenteral antibiotics to eradicate the carriage of pathogenic bacteria and, hopefully, improve outcome in critically ill patients . This review of 19 recently published studies indicates that SDD significantly reduces colonization with pathogenic bacteria and nosocomial respiratory tract infections . Reduction in mortality, however, is not a proven effect of SDD.

New Horiz, 1993 May, 1(2), 187 - 93
Quinolone therapy in intensive care unit settings; Beam TR Jr; Three fluoroquinolone antimicrobials (norfloxacin, ciprofloxacin, and ofloxacin) could be used to prevent or treat infections in intensive care unit patients . All of these fluoroquinolones are particularly active against Gram-negative, aerobic bacteria . However, the pharmacokinetic properties of each fluoroquinolone are unique . Furthermore, only ciprofloxacin and ofloxacin are available for intravenous administration . Based on current, available information: a) fluoroquinolones are not endorsed for inclusion in selective decontamination protocols; b) fluoroquinolones are endorsed for empiric therapy of suspected Gram-negative bacterial infections based on local microorganism susceptibility patterns; and c) fluoroquinolones are endorsed for treatment of microbiologically documented infections based on their distribution properties, low rate of toxicity, and rapid bactericidal effect.

Hinyokika Kiyo, 1993 May, 39(5), 445 - 9
Prostate-specific antigen levels in acute and chronic bacterial prostatitis; Yamamoto M et al.; Prostate-specific antigen (PSA) is now widely accepted as a useful tumor marker for the diagnosis and follow-up of prostatic cancer . An elevated level of PSA has been asserted to be highly specific for prostate cancer, although patients with large benign prostate glands and those with bacterial prostatitis may also have slightly elevated levels . We measured the serum PSA level in the patients with acute and chronic bacterial prostatitis and consecutively monitored the PSA level in 6 patients who had acute prostatitis and an elevated PSA level . The PSA level was found to be elevated during the acute phase of prostatic inflammation, and the elevated, PSA level in the patients with acute prostatitis returned to the normal level within 14 days after initiation of antimicrobial therapy in all 6 patients . In one patient with chronic prostatitis the elevated PSA level persisted after antibiotic treatment . He was found to have adenocarcinoma by transrectal ultrasonography and biopsy . A markedly elevated serum PSA level in bacterial prostatitis can cause confusion in the diagnosis of prostatic carcinoma . Therefore, PSA determination should be obtained after complete clinical resolution of inflammation to exclude prostatic malignant involvement.

Drugs, 1993 May, 45(5), 788 - 856
Epirubicin . A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cancer chemotherapy; Plosker GL et al.; Epirubicin is the 4' epimer of the anthracycline antibiotic doxorubicin, and has been used alone or in combination with other cytotoxic agents in the treatment of a variety of malignancies . Comparative and noncomparative clinical trials have demonstrated that regimens containing conventional doses of epirubicin achieved equivalent objective response rates and overall median survival as similar doxorubicin-containing regimens in the treatment of advanced and early breast cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), non-Hodgkin's lymphoma, ovarian cancer, gastric cancer and nonresectable primary hepatocellular carcinoma . Recently, dose-intensive regimens of epirubicin have achieved high response rates in a number of malignancies including early and advanced breast cancer and lung cancer . The major acute dose-limiting toxicity of anthracyclines is myelosuppression . In vitro and clinical studies have shown that, at equimolar doses, epirubicin is less myelotoxic than doxorubicin . The lower haematological toxicity of epirubicin, as well as the recent introduction of supportive measures such as colony-stimulating factors, has allowed dose-intensification of epirubicin-containing regimens, which is particularly significant because of the definite dose-response relationship of anthracyclines . Cardiotoxicity, which is manifested clinically as irreversible congestive heart failure and/or cardiomyopathy, is the most important chronic cumulative dose-limiting toxicity of anthracyclines . Epirubicin has a lower propensity to produce cardiotoxic effects than doxorubicin, and its recommended maximum cumulative dose is almost double that of doxorubicin, thus allowing for more treatment cycles and/or higher doses of epirubicin . In summary, dose-intensive epirubicin-containing regimens, which are feasible due to its lower myelosuppression and cardiotoxicity, have produced high response rates in early breast cancer, a potentially curable malignancy, as well as advanced breast, and lung cancers . Furthermore, there is evidence to suggest that improved response rates can improve quality of life in some clinical settings, but whether this leads to prolonged survival has not yet been determined . Recently implemented supportive measures such as colony-stimulating factors, prophylactic antimicrobials and peripheral blood stem cell support may help achieve other potential advantages of dose-intensive epirubicin-containing regimens such as reductions in morbidity and length of hospital admissions.

N Engl J Med, 1993 Apr 22, 328(16), 1137 - 44
Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection; Small PM et al.; BACKGROUND . In the United States there have been recent outbreaks of multidrug-resistant tuberculosis . These outbreaks have primarily involved persons infected with the human immunodeficiency virus (HIV) . METHODS . We collected clinical information on 17 patients seen at a New York City hospital who had repeatedly positive cultures for Mycobacterium tuberculosis . Analysis of restriction-fragment--length polymorphisms (RFLPs) was performed on serial isolates of M . tuberculosis obtained from these patients . RESULTS . Six patients had isolates that remained drug-susceptible, and the RFLP patterns of these isolates did not change over time . Eleven patients had isolates that became resistant to antimicrobial agents . The RFLP patterns of the isolates from six of these patients remained essentially unchanged (two strains showed one additional band) despite the development of drug resistance . In five other patients, however, the RFLP patterns of the isolates changed dramatically at the time that drug resistance was detected . The change in the RFLP pattern of the isolate from one patient appeared to be the result of contamination during processing in the laboratory . In the remaining four patients, all of whom had advanced HIV disease, the clinical and microbiologic evidence was consistent with the presence of active tuberculosis caused by a new strain of M . tuberculosis . CONCLUSIONS . Resistance to antituberculous drugs can develop not only in the strain that caused the initial disease, but also as a result of reinfection with a new strain of M . tuberculosis that is drug-resistant . Exogenous reinfection with multidrug-resistant M . tuberculosis can occur either during therapy for the original infection or after therapy has been completed.

Biochim Biophys Acta, 1993 Apr 8, 1147(1), 42 - 9
Antimicrobial specificity and hemolytic activity of cyclized basic amphiphilic beta-structural model peptides and their interactions with phospholipid bilayers; Ando S et al.; We synthesized a series of cyclic antiparallel beta-sheet model peptides with various ring sizes, which were designed on the basis of a cyclic beta-structural antibiotic, gramicidin S (GS); cyclo(Val-Orn-Leu-D-Phe-Pro)2, and investigated in terms of their antimicrobial activity and specificity against Gram-positive and Gram-negative bacteria and lytic activity for human erythrocytes . In our planning, in order to compare the peptides with GS, D-Phe-Pro sequence forming beta-turn in GS molecule remained unaltered and repeating sequences of alternately hydrophobic (Leu)-hydrophilic (Orn) residue were introduced into the beta-structural parts . CD study in acidic liposomes as well as leakage study of carboxyfluorescein encapsulated in phospholipid vesicles indicated that the peptides strongly interacted with lipid bilayers by taking an amphiphilic beta-structure . Antimicrobial study showed that although GS is active only against Gram-positive bacteria, the antimicrobial spectra of the model peptides transformed gradually to be active against Gram-negative ones and finally only against Gram-negative bacteria whose repeating sequences increased . It should be noted that the designed cyclic model peptides show antibacterial activity but accompany no hemolysis . This indicates that an appropriate hydrophobicity together with a proper orientation of hydrophilic (cationic) and hydrophobic groups in cyclic beta-structural molecules can hold antimicrobial activity against both types of bacteria without damaging eukaryotic cells.

J Biol Chem, 1993 Apr 5, 268(10), 7044 - 54
Functional and chemical characterization of Hymenoptaecin, an antibacterial polypeptide that is infection-inducible in the honeybee (Apis mellifera); Casteels P et al.; As part of our ongoing search for novel antimicrobial agents and their use in singular or combined drug therapy, we have isolated a series of polypeptides from the lymph fluid of honeybees . These polypeptides are synthesized de novo, following experimental infection of the insect with live Escherichia coli cells, and confer a broad-spectrum antibacterial defense to the host . We have dissected this humoral "immune" system into its constituent components . In addition to the previously characterized apidaecins and abaecin, we also isolated a member of the defensin family of peptide antibiotics and, now, a novel 93-amino acid long, cationic polypeptide, termed hymenoptaecin . Detailed analysis established the complete chemical structure, including a 2-pyrrolidone-5-carboxylic acid at the N terminus, and indicated major differences with all known antibacterial polypeptides . Under physiological conditions, it inhibits viability of Gram-negative and Gram-positive bacteria, including several human pathogens . Lethal effects against E . coli are secondary to sequential permeabilization of outer and inner membrane . In combination, the six-constituent "peptide antibiotics" of bee lymph provide wide-spectrum antibacterial protection in vitro by virtue of complementarity rather than synergism.

Jpn J Antibiot, 1993 Apr, 46(4), 318 - 22
{Lactoferrin in cervical mucus of patients with chorioamnionitis}; Chimura T et al.; The antimicrobial activity of cervical mucus is regarded as a local defense mechanism against ascending infections by the vaginal bacterial flora . In this study, the content of lactoferrin in cervical mucus of patients with chorioamnionitis (CAM) and its correlation with other indicators of infection were determined . The results obtained are summarized as follows: 1 . The lactoferrin content in cervical mucous was higher in pregnant than in non-pregnant women . It was significantly lower in CAM(+) patients than in CAM(-) patients (P < 0.001) in preterm labor and was lower in preterm labor than in full-term control (P < 0.002) . Elastase contents in cervical mucus of CAM(+) patients were significantly higher than full-term control levels (P < 0.001), and showed a negative correlation with lactoferrin contents . 2 . With regard to other indicators of infection, CRP, ESR, and WBC were higher in CAM(+) patients and fibronectin was detected (> 50 ng/ml) in the cervical mucus of all CAM(+) patients.

Clin Infect Dis, 1993 Apr, 16(4), 481 - 5
Primary actinomycotic endocarditis: case report and review; Lam S et al.; Endocarditis due to Actinomyces species for which a portal of entry cannot be identified is extremely rare . We present a case of primary endocarditis due to Actinomyces israelii with an unknown portal of entry and review seven similar cases reported in the literature since 1939 . The disease predominantly affects males . Clinical features are similar to those of bacterial endocarditis due to other organisms . Penicillin remains the drug of choice for treatment of this condition . The optimal duration of treatment has not yet been determined; however, with early diagnosis and appropriate antimicrobial therapy, the prognosis is good.

Clin Infect Dis, 1993 Apr, 16(4), 463 - 71
Disseminated infection with rapidly growing mycobacteria; Ingram CW et al.; Disseminated infection with the rapidly growing mycobacteria Mycobacterium chelonae and Mycobacterium fortuitum is uncommon . Only eight cases were diagnosed at Duke University Medical Center (Durham, NC) over the last 14 years . We identified 46 other cases by review of the medical literature since 1960 . We categorized these 54 cases into three groups according to underlying disease and outcome . Group 1 comprised patients with no identified immune defect, a kidney transplant, collagen vascular disease, or chronic renal failure; these patients usually presented with skin involvement and responded well to antimicrobial therapy (survival rate, 90%) . Group 2 comprised patients with cell-mediated immune deficiency, lymphoma, or leukemia; they presented with widespread, multiorgan involvement and severe illness . The survival rate in this group was only 10% . Patients in group 3 (who had other underlying diseases) had intermediately severe illnesses and intermediate responses to therapy . These groups provide the basis for an understanding of disseminated infection secondary to rapidly growing mycobacteria and of the profound effect that unresolved immunosuppression has on survival.

Enferm Infecc Microbiol Clin, 1993 Apr, 11(4), 206 - 9
{Capnocytophaga spp . bacteremia in compromised patients}; Ramos JM et al.; BACKGROUND: To analyze the clinical characteristics of three patients with Capnocytophaga spp . bacteremia . METHODS: We have review the clinical charts of three patients with Capnocytophaga spp . bacteremia, two patients with acute leukemia and one epileptic patient with chronic alcoholism . RESULTS: All the patients had oral cavity troubles and were treated with different antimicrobial agents . The three patients recovered, one of them requiring changing of the antimicrobial therapy in one of them . CONCLUSIONS: We should be aware of the importance of Capnocytophaga spp . especially in immunosuppressed patients or in other patients with poor dental hygiene and fever.

Eur J Radiol, 1993 Apr, 16(3), 217 - 20
Chest radiographic findings in childhood lipoid pneumonia following aspiration of animal fat; Annobil SH et al.; The pulmonary radiological manifestations of lipoid pneumonia following a cultural practice of forced feeding of rendered animal fat (ghee) in 24 Saudi children are described . The age range is 15 days to 11 years with 68% of cases being in infancy . The chest radiographic appearances encountered could be grouped into four broad patterns, viz, bilateral multilobar consolidations (BMLC) in 50% (12 cases), bilateral perihilar infiltrates (BPHI) with or without associated lobar consolidation in 21% (five cases), right perihilar infiltrates (RPHI) in 21% (five cases) and unilateral right multilobar consolidation (RMLC) 8% (two cases) . The pneumoniae were non-resolving acute or chronic lung consolidations despite the usual antimicrobial chemotherapy . Associated nodular dense opacities (granulomas) were seen in the lower lobes of four of the 12 cases in the first group . Complications, seen also in this first group, included chronic collapse consolidation, fibrosis and death in three cases . In communities where the traditional practice of infant feeding with ghee exists, these pulmonary radiological patterns, although in some cases indistinguishable from those of bacterial pneumoniae, should raise the suspicion of ghee administration with consequent early diagnosis and energetic management to avert prolonged morbidity and potential death.

Kekkaku, 1993 Apr, 68(4), 293 - 9
{In vitro antimycobacterial activity of clarithromycin and its therapeutic efficacy against Mycobacterium intracellulare infection induced in mice}; Tomioka H et al.; A new macrolide, clarithromycin (CAM), with increased acid-stability and thus having a markedly improved absorption efficiency from gastrointestinal tract, was evaluated for its in vitro antimicrobial activity against various mycobacterial species . CAM had nearly the same level of anti-mycobacterial activity as that of sparfloxacin (SPFX) and slightly higher activity than rifampicin (RFP), except that its anti-M . tuberculosis activity was much lower than those of SPFX and RFP . Anti-M . avium complex activity of CAM (MIC90 values against M . avium and M . intracellulare were 12.5 and 6.25 micrograms/ml, respectively) was in similar level as SPFX and RFP . However, MIC distribution pattern revealed that anti-M . avium activity was in the order of SPFX > CAM > RFP, while anti-M . intracellulare activities of them were almost the same with each other . Moreover, CAM showed bactericidal action against M . intracellulare growing in 7H9 medium . Furthermore, we investigated the therapeutic efficacy of CAM against M . intracellulare infection induced in mice and also determined its combined effect with other antimicrobials including KRM-1648, SPFX and ethambutol (EB) . When CAM suspended in 5% gum arabic-saline was given s.c . to mice infected i.v . with M . intracellulare (8 x 10(6) CFU) at 0.2 to 2 mg/mouse/day, once daily six times per week from day 1 for 8 weeks, CAM exhibited a potent therapeutic efficacy, in terms of reduction in the incidence of gross lung lesions and reduction of bacterial loads in the visceral organs (reduction of bacterial CFU by 0.9-3.4 log units in the lung and by 0.4-4.6 log units in the spleen during week 4 to 8, depending on its administration dose).(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Pathol, 1993 Apr, 46(4), 372 - 3
Antibacterial action of the urease inhibitor acetohydroxamic acid on Helicobacter pylori; Phillips K et al.; The urease inhibitor acetohydroxamic acid (AHA) was assessed for its bacteriostatic and bactericidal effects on Helicobacter pylori . For eight isolates of H pylori, the minimum inhibitory concentration (MIC) was either 200 mg/l or 400 mg/l . Interactions between AHA and antimicrobial drugs used to treat H pylori were also determined . For most isolates AHA reduced the MIC for colloidal bismuth subcitrate (CBS), tetracycline, metronidazole, and amoxicillin . In a few isolates, however, AHA increased the minimum bactericidal concentration (MBC) for these antimicrobial treatments . In vitro AHA is active against H pylori and it interacts with other agents directed against H pylori.

Arch Pharm (Weinheim), 1993 Apr, 326(4), 237 - 40
{Iminium compounds against bacteria and fungi . 29 . 3-Alkoxymethyl-1-ethyl-, 3-alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1-butylbenzimidazolium chloride}; Pernak J et al.; Syntheses and antimicrobial activity of 3-alkoxymethyl-1-ethyl-, 3-alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1-butylbenzimidazolium chlorides are described . The compounds were obtained by reaction of 1-ethyl- or 1-butylbenzimidazole with chloromethylalkyl ethers or chloromethylalkyl sulfide . Antibacterial properties were tested on 13 strains of bacteria and fungi . 3-Dodecylthio-methyl-1-ethyl-benzimidazolium chloride exhibited the highest antibacterial activity.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 908 - 10
In vitro activity of RP 74501-RP 74502, a novel streptogramin antimicrobial mixture, against clinical isolates of Legionella species; Edelstein PH et al.; Agar and broth microdilution MICs of RP 74501-RP 74502, a mixture of streptogramin antimicrobial agents that inhibited 90% of 22 Legionella strains tested, were 0.64 and 0.08 microgram/ml, respectively; respective erythromycin values were 1.0 and 0.12 microgram/ml . RP 74501-RP 74502 at 1 microgram/ml was more active than the same erythromycin concentration in a macrophage system for both L . pneumophila strains studied but at a lower concentration (0.25 microgram/ml) was much less active than erythromycin.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 882 - 4
In vitro antimicrobial susceptibilities of Nocardia species; Khardori N et al.; The in vitro activities of various quinolones, two new aminoglycosides, a new cephamycin analog (cefmetazole) and a new spectinomycin analog (trospectomycin), imipenem, and trimethoprim-sulfamethoxazole against 26 isolates of Nocardia asteroides, 7 isolates of N . brasiliensis, and 6 isolates of N . caviae were determined by a broth microdilution method . The three new quinolones, PD 117558, PD 117596 and PD 112739, inhibited 90% of N . asteroides at 1 to 2 micrograms/ml, and two new aminoglycosides, SCH 21420 and SCH 22591, inhibited 90% of N . asteroides at 2 to 4 micrograms/ml . Among the beta-lactams, cefmetazole was more active than imipenem . N . brasiliensis and N . caviae isolates were also very susceptible to the three quinolones (MICs for 50% of the isolates, 0.25 to 1 microgram/ml) and the two aminoglycosides (MICs for 50% of the isolates, 1 to 2 micrograms/ml) . Cefmetazole was moderately active against N . brasiliensis, whereas imipenem showed poor activity against both of these species.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 846 - 50
Comparative efficacies of ofloxacin, cefotaxime, and doxycycline for treatment of experimental epididymitis due to Escherichia coli in rats; Vieler E et al.; The in vivo efficacy of ofloxacin was compared with those of cefotaxime and doxycycline in a rat model of epididymitis due to Escherichia coli . Treatment was started 24 h after infection and was continued for 7 days . Ofloxacin reduced the numbers of E . coli organisms in the epididymides significantly more than the other therapeutic regimens and cured the infection more frequently . Histopathological changes in the epididymides of ofloxacin-treated animals were significantly less severe than those observed in untreated animals . Doxycycline was less effective than ofloxacin but significantly reduced the titers of organisms in rat epididymides . In contrast, despite excellent in vitro activity, cefotaxime failed to reduce the magnitude of infection . The results of this study suggest that ofloxacin may be a very effective antimicrobial agent for the treatment of epididymitis due to E . coli.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 801 - 3
In vitro and in vivo antichlamydial activities of newly developed quinolone antimicrobial agents; Kimura M et al.; The in vitro and in vivo activities of three newly developed quinolone antimicrobial agents (sparfloxacin, tosufloxacin, and OPC-17116) were investigated . All three agents showed potent in vitro activities against Chlamydia psittaci, C . trachomatis, and C . pneumoniae with MICs that ranged from 0.031 to 0.125 micrograms/ml . These values were higher than those of minocycline (0.0075 to 0.015 micrograms/ml) but lower than those of erythromycin (0.25 to 0.5 micrograms/ml) and ofloxacin and ciprofloxacin (0.5 to 1.0 micrograms/ml) . Mice were challenged with 10(5) inclusion-forming units of C . psittaci each by nasal instillation . All untreated control animals died within 7 days . The survival rates of mice treated with 40 mg of sparfloxacin, OPC-17116, or tosufloxacin per kg of body weight every 12 h for 7 days were 73, 73, and 60%, respectively, 7 days after the challenge . The survival rate of mice treated with ofloxacin at the same dosage was 53% . On the basis of the above results, we concluded that these three new quinolones might be useful in the treatment of chlamydial respiratory infections.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 652 - 61
Activities of fluoroquinolone, macrolide, and aminoglycoside drugs combined with inhibitors of glycosylation and fatty acid and peptide biosynthesis against Mycobacterium avium; Barrow WW et al.; Smooth- and rough-colony variants of Mycobacterium avium serovar 4 were treated with three classes of drugs . The drugs were chosen for their potential inhibitory effects on the biosynthesis of the cell envelope-associated serovar-specific glycopeptidolipid antigens . Growth was monitored radiometrically with a BACTEC 460-TB instrument, and MICs were determined for each drug . Both variants were then treated with inhibitory drugs in combination with antimicrobial agents that have demonstrated effectiveness against M . avium . No growth inhibition was observed with 6-fluoro-6-deoxy-D-glucose or avidin . Inhibitors of glycosylation, i.e., 2-deoxy-D-glucose, bacitracin, and ethambutol, were inhibitory to smooth- and rough-colony variants, whereas drugs that inhibit peptide synthesis, i.e., N-carbamyl-L-isoleucine and m-fluoro-phenylalanine, were more inhibitory for the rough-colony variant . Cerulenin, which affects fatty acid synthesis, was inhibitory for both variants, but it appeared to be more effective at inhibiting the growth of the smooth-colony variant at equivalent concentrations . Generally, when inhibitors of glycosylation were used with sparfloxacin and amikacin, a synergistic effect was observed for only the smooth variant . When drugs that affect peptide synthesis were used in combination with amikacin, a synergistic effect was observed for the rough variant, and when cerulenin was used in combination with sparfloxacin or amikacin, a synergistic effect was observed for both variants . Lipid analysis revealed that although the rough variant lacks the serovar-specific glycopeptidolipid antigens, it does possess a group of phenylalanine-isoleucine-containing lipopeptides that may explain its different susceptibility patterns to m-fluoro-phenylalanine and N-carbamyl-L-isoleucine . The significance of these results is discussed with reference to various components in the cell envelope and their importance in cell wall permeability.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 619 - 24
Antimicrobial strategies in the care of organ transplant recipients; Rubin RH et al.; Since the early days of transplantation, infection has been a major consequence of antirejection immunosuppressive therapy . Increasingly effective prophylactic and preemptive strategies are being developed to prevent the infectious consequences of immunosuppressive therapy . Although the data base is incomplete and there remains a compelling need for well-designed, randomized, comparative trials, the potential for controlling life-threatening viral, bacterial, fungal, and protozoal infections exists . The cornerstone of this effort is the recognition that effective immunosuppressive strategies require an antimicrobial program to make them safe and that such an antimicrobial program needs to be individualized in order to be appropriately matched with the needs of the antirejection program . Thus, escalation and de-escalation of the antimicrobial program should be carried out to match the immunosuppressive program . Infection and rejection remain closely intertwined, linked by the immunosuppressive program that is prescribed.

Oncology (Huntingt), 1993 Apr, 7(4), 80 - 3
What's new in the management of infectious diseases; Trowbridge JF; The 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held late last year in Anaheim, California . Sponsored by the American Society for Microbiology, the conference is designed to encourage the exchange of new information among microbiologists, clinicians, pharmacologists, pathologists, and members of related disciplines . The following highlights include those that may be of particular clinical interest to physicians in the oncology specialties.

Am J Vet Res, 1993 Apr, 54(4), 546 - 50
In vitro susceptibility of Actinobacillus pleuropneumoniae strains to 42 antimicrobial agents; Gutierrez CB et al.; Minimal inhibitory concentration of 42 antimicrobial agents was determined against 57 field strains of Actinobacillus pleuropneumoniae isolated from pigs in Spain . Penicillins, aminoglycosides, and tetracyclines had irregular activity; ticarcillin, tobramycin, and doxycycline were the most active of each group, respectively . Macrolides, vancomycin, dapsone, and tiamulin, to which strains had high rate of resistance, were almost ineffective . Thiamphenicol, colistin, rifampin, fosfomycin, mupirocin, and metronidazole had good activity, with resistance ranging between 0 and 8.8% . Finally, cephalosporins (except cephalexin) and quinolones (especially ciprofloxacin, enrofloxacin, and sparfloxacin) were the most active antibiotics against A pleuropneumoniae.

Ophthalmology, 1993 Apr, 100(4), 534 - 41
Results of therapeutic penetrating keratoplasty; Killingsworth DW et al.; PURPOSE: To determine the anatomic and visual results of therapeutic penetrating keratoplasty (PK) and its role in the management of corneal disease . METHODS: The authors reviewed the records of all of their patients who had undergone therapeutic PK over the past 9 years and evaluated each for the following criteria: cure of disease, graft clarity, and visual acuity . Patients were divided into seven categories: (1 and 2) bacterial and fungal keratitis, (3 and 4) herpetic keratitis, with and without inflammation, (5) acanthamoebic keratitis, (6) perforations due to keratoconjunctivitis sicca, and (7) other causes of perforation . RESULTS: In microbial keratitis, therapeutic PK eradicated the disease in all cases . Seventy-three percent of grafts for bacterial keratitis and 60% for fungal keratitis remained clear . A higher percentage of clarity was achieved when grafts were 9.0 mm or less . Seven patients with secondary endophthalmitis were cured with a surgical approach including therapeutic PK . In herpetic keratitis with active inflammation, only 36% of grafts remained clear, and inflammation recurred in 36% . All perforations due to post-herpetic persistent epithelial defects in "quiet" eyes were grafted successfully . In patients with severe keratoconjunctivitis sicca, eyes were anatomically stabilized in 83%, but all grafts failed because of complications from ocular surface disease . CONCLUSIONS: Therapeutic PK is valuable in the management of microbial keratitis that does not respond to antimicrobial therapy . Results are poorer for patients with herpetic keratitis, although selected patients respond to therapeutic PK when other methods of management have failed . Patients with perforations due to keratoconjunctivitis sicca have a uniformly poor prognosis for graft clarity.

Clin Microbiol Rev, 1993 Apr, 6(2), 118 - 36
Pathogenesis and pathophysiology of bacterial meningitis; Tunkel AR et al.; Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy . Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis . Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia . Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity . Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown . By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space . There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure . Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials . Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

Am Rev Respir Dis, 1993 Apr, 147(4), 946 - 51
Clinical significance of borderline quantitative protected brush specimen culture results; Dreyfuss D et al.; In patients with clinical suspicion of pneumonia, quantitative cultures of protected brushing specimens (PBS) yielding > or = 10(3) CFU/ml of at least one microorganism have been found useful for differentiating airway colonization and lung infection, especially in mechanically ventilated patients . The amount of secretions collected by protected catheter brushing is small and difficult to determine accurately . Thus, the clinical significance of PBS cultures yielding organisms in concentrations > or = 10(2) but < 10(3) CFU/ml, in the absence of active antimicrobial treatment, is unknown . The 34 consecutive results of PBS cultures yielding organisms in concentrations > or = 10(2) but < 10(3) CFU/ml in 30 patients under mechanical ventilation or weaned for < or = 4 days were prospectively studied . No patients were receiving agents active on the organism recovered . In 5 cases, the diagnosis of pneumonia was ruled out by recovery without treatment (n = 4) or negative postmortem lung cultures (n = 1) . A second PBS was cultured in 29 episodes (2.7 +/- 1.8 days after the first PBS) . In 12 instances (Group 1), cultures of the second PBS yielded > or = 10(3) CFU/ml of the same organism as that found in the first PBS (S . pneumoniae, 1; S . aureus, 1; H . influenzae, 1; E . coli, 1; P . aeruginosa, 4; and A . baumannii, 4), and these patients were therefore treated with appropriate antibiotics . A total of 17 patients had a negative repeat PBS culture (no growth or trivial concentrations) and were considered free of pneumonia and given no antibiotic treatment for this episode.(ABSTRACT TRUNCATED AT 250 WORDS)

J Pediatr, 1993 Apr, 122(4), 591 - 3
Long-term outcome of Lyme disease in children given early treatment; Salazar JC et al.; Sixty-three patients treated with appropriate antimicrobial therapy between 1985 and 1990 for physician-documented erythema migrans were identified . A telephone interview program 1 to 6 years after the initial episode of Lyme disease revealed that none of the patients had evidence of carditis, arthritis, or neurologic complications attributable to Lyme disease . A new episode of erythema migrans was reported in 7 (11%) of the patients 1 to 4 years after the initial episode.

Gastroenterology, 1993 Apr, 104(4), 1133 - 8
Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with ascites; Andreu M et al.; BACKGROUND: This study was performed to investigate the risk factors for a first episode of spontaneous bacterial peritonitis in cirrhotic patients . METHODS: One hundred ten cirrhotics with sterile ascites, without previous spontaneous bacterial peritonitis (SBP), were included from March 1988 to October 1989 and followed up until October 1990 (follow-up, 46 +/- 3.5 weeks; range, 4-120 weeks) . RESULTS: Twenty-eight patients (25.45%) suffered SBP . In multivariate analysis (Cox's regression model) including only variables commonly used in clinical practice, ascitic fluid protein concentration and serum bilirubin level independently correlated with first SBP development . Using these two variables the relative risk of a first SBP episode was calculated for each patient . According to the median relative risk coefficient (1.2), a low-risk group (relative risk, < 1.2) and a high-risk group (relative risk, > 1.2) were established . Kaplan-Meier estimates of patients free of SBP were significantly higher in the low-risk group . CONCLUSIONS: The probability of a first SBP episode is significantly influenced by the antimicrobial capacity of ascitic fluid and hepatic function.

J Immunol, 1993 Apr 1, 150(7), 2892 - 900
TNF-alpha response of human monocyte-derived macrophages to Mycobacterium avium, serovar 4, is of brief duration and protein kinase C dependent; Gan H et al.; Human monocyte-derived macrophages (M phi) from the majority of normal donors respond to inoculation with Mycobacterium avium, serotype 4, (MAI) by elaboration of the inflammatory monokines TNF-alpha, IL-1 beta, and IL-6, which are of central importance for the protection against bacterial and parasitic infections . Peak TNF-alpha mRNA levels were of brief duration, being maximal at 1.5 h, and were only slightly higher than background levels at 4 h . Increases of IL-1 beta and IL-6 mRNA levels, on the other hand, persisted for 48 to 72 h . In contrast to LPS, MAI induced the production of only small amounts of TNF-alpha protein in the first 12 h and of large amounts of IL-1 beta and IL-6 protein between 3 and 72 h . MAI-induced TNF-alpha transcripts, in contrast to LPS induced TNF-alpha transcripts, were highly unstable . Their accumulation was blocked and their t 1/2 significantly decreased by the protein kinase C inhibitor staurosporine . In contrast, LPS-induced increases of TNF-alpha mRNA levels and MAI-induced increases of IL-1 beta and IL-6 mRNA levels were PKC independent . The cAMP- and cGMP-dependent protein kinase inhibitors, KT5720 and KT5823, respectively, and the tyrosine kinase inhibitors herbimycin and erbstatin had no effect on the MAI-dependent mRNA accumulation of TNF-alpha, IL-1 beta, and IL-6 . W7, a calmodulin-dependent protein kinase inhibitor, was inhibitory in all cases . Thus, MAI-induced TNF-alpha mRNA accumulation is of short duration and PKC dependent . MAI-induced TNF-alpha protein production is low, possibly resulting in a mitigated antimicrobial effect.

Infect Immun, 1993 Apr, 61(4), 1330 - 3
Effector role of blood monocytes in experimental visceral leishmaniasis; Cervia JS et al.; In BALB/c mice, liver granulomas provoked by visceral infection with intracellular Leishmania donovani are rapidly populated by influxing blood monocytes . To determine the host defense effector role of these mononuclear phagocytes, we treated three populations of infected animals with 5C6, an anti-type 3 complement receptor monoclonal antibody (MAb), which inhibits monocyte recruitment into inflamed tissues . In naive BALB/c mice, injections of 5C6 impaired the initial acquisition of antileishmanial resistance and arrested the development of mature liver granulomas . In sensitized mice with established immunity, both resistance to rechallenge and accelerated granuloma formation were similarly inhibited by MAb administration . Finally, in naive mice, 5C6 MAb also abolished the antileishmanial activity induced by treatment with the macrophage-activating lymphokine gamma interferon . Together, these results suggest a key effector role for the influxing blood monocyte in both initial and established antileishmanial defense and granuloma assembly and in the infected liver as the mononuclear phagocyte target for the antimicrobial effects of gamma interferon.

Ann Intern Med, 1993 Apr 1, 118(7), 557 - 61
Resistance to antimicrobial drugs--a worldwide calamity; Kunin CM; The introduction of penicillin 50 years ago was followed by an extraordinary period of discovery, exuberant use, and predictable obsolescence . Resistant bacterial strains have emerged and have spread throughout the world because of the remarkable genetic plasticity of the microorganisms, heavy selective pressures of use, and the mobility of the world population . New and more expensive drugs have appeared almost in the nick of time, but it is doubtful that they will keep pace . The problem of resistance to antimicrobial drugs is particularly troublesome in developing countries . The underlying problems are largely economic and societal, and no ready solutions are available . An urgent need exists for more appropriate selection and use of antimicrobial drugs in the developed as well as in developing countries . The focus in developing countries should be on the availability of safe and effective drugs and on the enforcement of more responsible national drug policies . These issues must be addressed by the collective action of governments, the pharmaceutical industry, health care providers, and consumers . The developed countries have an important stake in the ways in which antibiotics are used in developing countries because resistant microorganisms do not recognize national boundaries.

Ginecol Obstet Mex, 1993 Apr, 61, 81 - 5
{Antibiotic use in pregnancy . II.}; Figueroa Damian R et al.; Tetracyclines are antimicrobial agents that must be avoided during pregnancy . Metronidazole has showed to be carcinogenic in animals like mouse, but in humans this effect has not been proved . In developing countries the tuberculosis has a high prevalence, so tuberculosis in pregnant women isn't a rare event, all of this patient must receive antituberculosis agents . Of the extensive group of antiviral agents only few has proved clinical efficiency, of this acyclovir can be used during pregnancy with caution . At his moment there aren't sufficient information about the utility of zidovudine in pregnant women.

Avian Dis, 1993 Apr-Jun, 37(2), 515 - 22
A comparison of danofloxacin and tylosin in the control of induced Mycoplasma gallisepticum infection in broiler chicks; Tanner AC et al.; Experimental mycoplasmosis was induced in 1-day-old chicks by intrapulmonary inoculation of Mycoplasma gallisepticum (MG) . This method of infection proved to be useful for evaluating the efficacy of antimicrobial medication, by measuring mortality, weight gain, pathological responses, frequency of reisolation of MG, and seroconversion . Using this model, the efficacies of danofloxacin (a novel fluoroquinolone) and tylosin were compared for two MG isolates, a reference isolate (the R-strain) and a field isolate from California . Danofloxacin administered in the water at 50 ppm for 3 days was equivalent to tylosin at 500 ppm for 3 days in the degree of control of mortality and maintenance of weight gain . Danofloxacin was superior to tylosin in preventing air-sac lesions, reducing the frequency of reisolation of MG, and preventing seroconversion in surviving birds.

J Autoimmun, 1993 Apr, 6(2), 171 - 84
'Classic' anti-neutrophil cytoplasmic autoantibodies (cANCA), 'Wegener's autoantigen' and their immunopathogenic role in Wegener's granulomatosis; Gross WL et al.; Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG) . WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7 . Like other lysosomal proteins, WA/PR3 displays enzymatic activity, differentiation factor activity for myeloid precursor cells, and antimicrobial functions . Neutrophilic polymorphonuclear leukocytes (PMN) and a subpopulation of monocytes contain high levels of WA/PR3 in their myeloperoxidase-positive granules . The autoantibodies from WG sera produce a finely granular, centrally accentuated fluorescence pattern on PMN and monocytes and have been designated 'classic' pattern antineutrophil cytoplasmic autoantibodies (cANCA) . However, PMN/monocyte activation (in vitro/ex vivo) is associated with the translocation of WA/PR3 on the cytoplasm membrane . WA/PR3 is accessible to the WG-associated autoantibody: cANCA stimulate cytokine-preactivated PMN to produce oxygen radicals and to degranulate . Furthermore, cANCA interfere with the biological functions of WA/PR3 (e.g . inhibition of elastinolytic activity) . Hence, cANCA represents not only the best seromarker for WG so far available, but several lines of evidence indicate that the autoantibodies against WA/PR3 play a major role in the pathogenesis of this enigmatic disease.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 901 - 2
Antimicrobial effects of a new carboxyquinolone drug, Q-35, on five serogroups of Leptospira interrogans; Takashima I et al.; New carboxyquinolone drugs, including the recently developed Q-35, were evaluated for their in vitro potency against five serogroups of Leptospira interrogans . Q-35, ofloxacin, ciprofloxacin, and tosufloxacin showed MICs (0.05 to 0.20 microgram/ml) comparable to those of tetracycline . However, MBCs of these drugs varied between 10- and 100-fold above the MIC for most strains tested . Q-35 was shown to be active against L . interrogans in vitro as judged by the MICs obtained.

Free Radic Biol Med, 1993 Apr, 14(4), 351 - 60
Reactive nitrogen intermediates and antimicrobial activity: role of nitrite; Klebanoff SJ; The reactive nitrogen intermediate (RNI) nitric oxide (NO.) is formed from L-arginine by an NO . synthase and, following secondary reactions yielding additional toxic intermediates, nitrite (NO2-) and nitrate are formed . Nitrite, however, also has toxic properties . At acid pH, nitrous acid (HNO2) is bactericidal to Escherichia coli, in association with the loss of HNO2/NO2- and the uptake of oxygen, an effect which is increased by H2O2 . Under conditions in which HNO2/NO2- +/- H2O2 were ineffective, the further addition of peroxidase (myeloperoxidase {MPO}, eosinophil peroxidase, lactoperoxidase) or catalase resulted in bactericidal activity and the disappearance of HNO2/NO2- . Paradoxically, HNO2/NO2- also inhibited the bactericidal activity of MPO by the formation of a complex with MPO with a shift in the absorption spectrum, and by reaction with hypochlorous acid (HOCl) (the product of the chloride-supplemented MPO-H2O2 system), with loss of the bactericidal activity of HOCl and the disappearance of both HOCl and HNO2/NO2- from the reaction mixture . Thus, HNO2/NO2-, rather than being solely an end product of RNI formation, may influence antimicrobial activity either by acting alone, with H2O2, or with H2O2 and peroxidase as a source of toxic agents, or by inhibiting the peroxidase-mediated antimicrobial systems.

Pathology, 1993 Apr, 25(2), 180 - 3
Susceptibility of Legionella species to antimicrobial agents; Chen SC et al.; Thirty-five clinical isolates of Legionella species were tested against 7 antimicrobial agents using an agar dilution technique . Results obtained on charcoal-supplemented (BCYE) and charcoal-free agar (BSYE) were compared . On BCYE, the most active agent was rifampicin; the minimal inhibitory concentration inhibiting 90% of the strains (MIC90) was 0.008 mg/L . Imipenem was the next most active in vitro (MIC90 0.06 mg/L) . The macrolide antibiotics and ciprofloxacin also inhibited the organisms at low concentrations (MIC90 < or = 2 mg/L) . In general, MIC's obtained on BCYE agar were at least twofold higher than on BSYE agar except for that of imipenem . BSYE agar is a suitable alternative medium for susceptibility testing of most Legionella species . Erythromycin and rifampicin continue to demonstrate good in vitro activity against legionellae in Australia . On the basis of in vitro susceptibility tests, the other macrolides and ciprofloxacin are likely to be suitable alternatives for the treatment of legionellosis.

Farmaco, 1993 Apr, 48(4), 515 - 28
Synthesis of 4-quinolylazide derivatives and evaluation of their antitumor and antimicrobial activity; Savini L et al.; Synthesis and pharmacological evaluation of a series of 4-quinolylazide derivatives are reported . These were screened against P388 lymphocitic leukemia in mice, but they resulted inactive . All the compounds were also tested for their antimicrobial activity against gram-positive, gram-negative strains and fungi; only three derivatives exhibited poor activity.

Farmaco, 1993 Apr, 48(4), 487 - 501
Synthesis and antimicrobial activity of some new indolo{2,1-b}quinazolin-6(12H)ones; Baiocchi L et al.; A series of indolo{2,1-b}quinazolin-6(12H)ones 4a-i was prepared and tested for the antimicrobial activity . The synthesis of the new compounds and the results of the antimicrobial screening are reported.

Zentralbl Veterinarmed A, 1993 Apr, 40(3), 185 - 93
Efficiency of 5-hydroxytryptamine receptor blockade as therapeutic measure during acute respiratory distress syndrome in double-muscled cattle; Genicot B et al.; During this investigation, which involved 58 Belgian White and Blue double-muscled calves affected by a naturally occurring Acute Respiratory Distress Syndrome, the clinical efficiency of a 5-HT2 receptor blockade with metrenperone (group A) was compared to the efficiency of a non-steroidal (flunixine meglumine--group B) and a steroidal (prednisolone sodium succinate--group C) antiinflammatory drug . Each animal of this trial was treated with ceftiofur sodium as antimicrobial agent . A clinical score and a breathing score were calculated at each step of the investigation period, i.e . before (T0) and 1 hour (T1), 12 hours (H), 24 H, 48H and 168 H (T3) after the first treatment, the interval 12H-48H being considered as period T2 . Three clinical parameters were also taken into account separately: rectal and peripheral temperatures and heart rate . A significant improvement of the clinical score was registered at T2 in group A and at T3 in groups A and B, while this score did not significantly change in group C . In group A, the breathing score was significantly improved at T2 and T3, but not in groups B and C . Peripheral and rectal temperatures recorded at T1 were, in group A, significantly increased and decreased respectively, but not significantly changed in groups B and C . The proportions requiring change of treatment during the investigation period were significantly (P = 0.022) different in the three groups, being 5.6, 21.4 and 50.0% in groups A, B and C respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmazie, 1993 Apr, 48(4), 301 - 4
{Antibacterial activity of thymol, carvacrol and cinnamaldehyde alone or in combination}; Didry N et al.; The antimicrobial activity of thymol, carvacrol and cinnamaldehyde was tested by several methods on bacteria involved in upper respiratory tract infections . Their combinations were investigated too . The broad spectrum of activity and the synergistic effect observed with some combinations (specially thymol and carvacrol) could allowed the use of the three compounds alone or, like thymol an carvacrol, combined during the treatment of respiratory infections.

Pharmazie, 1993 Apr, 48(4), 295 - 301
{Descriptive modeling of the chemical structure-biological activity relations of a group of malonic polyethylenic acids as shown by different pharmacotoxicologic tests}; Valla A et al.; 48 new polyethylenic-malonic acids have been submitted to an antimicrobial and antifungal screening . After a suitable recording, the experimental results were analyzed according to two mathematical multivariate analysis using a computer process i.e . Correspondence Factorial Analysis and Cluster Analysis . These methods allowed an accurate study of the structure of the system and a thorough investigation of the structure-activity-specificity relationships . On the other side, magnitude and/or specificity of the observed biological effects were related to structural features . These results should be useful in order to elaborate synthetic strategies.

Postgrad Med J, 1993 Apr, 69(810), 291 - 5
Imprint cytology--a cheap, rapid and effective method for diagnosing Helicobacter pylori; Misra SP et al.; To compare the efficacy of imprint cytology, histology and CLO-test (for biopsy urease) in detecting Helicobacter pylori infection, antral biopsies were taken from 239 patients undergoing upper gastrointestinal endoscopy . Both imprint cytology and histology showed the presence of H . pylori in 215 (90%) patients . The sensitivity and specificity of imprint cytology vis-a-vis histology was noted to be 100% . The CLO-test was performed in 165 patients and was positive in 130 (79%) patients . The sensitivity and specificity of the CLO-test were 89% and 95%, respectively . The median time required for the CLO-test to become positive and for imprint was 60 minutes for each . The sensitivity of the CLO-test was reduced further in patients receiving colloidal bismuth subcitrate . Of the 27 patients receiving the drug the sensitivity of the CLO-test was only 9% after 4 weeks of therapy . However, the specificity was 100% . The sensitivity and specificity of imprint cytology were unaffected by the antimicrobial therapy and after 4 weeks of treatment were still 100% . It is concluded that the CLO-test has a lower sensitivity and specificity for diagnosing H . pylori infection compared to imprint cytology, which had a sensitivity and specificity equal to that of histology . Imprint cytology may be prepared as an adjunct to histology in patients in whom antral biopsies are taken as it offers a relatively quick diagnosis of H . pylori infection, is considerably cheaper than the CLO-test and does not require additional biopsy material.

J Cutan Pathol, 1993 Apr, 20(2), 177 - 9
Neutrophilic tuberculous panniculitis in a patient with polymyositis; Langenberg A et al.; The clinical spectrum of cutaneous M . tuberculosis infections is varied and atypical . Once a major cause of death, with the advent of antimicrobial drugs it had, until recently, been an uncommon consideration in the differential diagnosis of cutaneous disorders . Panniculitis can be caused by a variety of etiologic agents; however, only rarely has it been reported caused by tuberculosis . Herein, we describe a patient with an unusual case of neutrophilic panniculitis caused by M . tuberculosis that arose following corticosteroid therapy for presumptive polymyositis . This case illustrates the need to include mycobacterial infection in the differential diagnosis of panniculitis in immunocompromised patients, and the importance of early detection via microbiologic culture and histopathologic examination.

Int Dent J, 1993 Apr, 43(2), 143 - 8
Preventive aspects of root caries; Keltjens H et al.; Several factors are responsible for an increasing number of exposed root surfaces, resulting in a higher root caries risk . Assuming that the pathogenesis of root and enamel caries have strong similarities, the same preventive methods could be applied for root caries and for enamel caries . However, due to a higher critical pH for dentine/cement, the prevention for root caries should be more intensive . Several studies indicate that fluoride is the cornerstone of root caries prevention . In addition, antimicrobials, in particular chlorhexidine, can be helpful in inhibiting root caries development . This paper proposes the use of three different risk categories for root caries to help adjust the intensity of preventive measures to the needs of the individual patient.

Cryobiology, 1993 Apr, 30(2), 164 - 71
Effects of antibiotics on the endothelium of fresh and cryopreserved canine saphenous veins; Schmehl MK et al.; To determine if antibiotic solutions for potential use in antimicrobial treatment of tissues were detrimental to cell viability, canine saphenous veins were exposed to three different antibiotic solutions at 37 degrees C for 12 h . Viability was determined by tissue culture, utilizing a limiting dilution assay . The antibiotic series included two formulations currently used for the preservation of heart valves and a new formulation containing imipenem, a broad spectrum beta-lactam . Currently used antibiotic regimes and imipenem with gentamicin resulted in a decrease of 30 to 50% of the viable endothelial cells within 12 h . Exposure of the saphenous veins to imipenem or imipenem combined with amphotericin B had no adverse effects on the viability of the endothelial cells with 12 h exposure . However, veins exposed to amphotericin B were more susceptible to subsequent damage during freezing and thawing than veins frozen after incubation with either imipenem alone or imipenem combined with flucytosine . These studies indicate that imipenem combined with flucytosine is suitable for use with vein grafts.

Aust N Z J Surg, 1993 Apr, 63(4), 289 - 93
Inhibition of wound contraction by topical antimicrobials; Leitch IO et al.; Spontaneous wound healing occurs partly by wound contraction, a process that requires intact functioning fibroblasts, and collagen production . Disruption of fibroblasts by the topical antimicrobials, silver sulfadiazine and mafenide acetate has been demonstrated in vitro . An acute rat wound model was used to show that wound contraction in vivo is significantly impeded by silver sulfadiazine and mafenide acetate.

Bangladesh Med Res Counc Bull, 1993 Apr, 19(1), 1 - 7
Antibiotic in general surgery: selection, timing and duration of administration; Zaman MA et al.; A continuous surveillance of hospital acquired infection (HAI) was done in the Department of Surgery, Dhaka Medical College Hospital during the period of 1st February '90 to 31st March '90 . A new antibiogramme was prepared and applied in the same unit for chemotherapy and chemoprophylaxis of surgical cases in the subsequent six months from April '90 to September '90 . The result of this selection, timing of administration and the duration of antimicrobial use have been described in this report . The antibiotic policy adopted in this study has been found to improve the problem of infection in our surgical practice substantially . The incidence of HAI has been reduced to 0.5% from 3.9% which was seen in our previous study . The median post operative hospital stay has been reduced to 15.5 days from 18.5 days in case with HAI and to 8.5 days from 9 days without HAI . We conclude that a continuous surveillance of hospital acquired infection is necessary to develop an appropriate antibiogramme . The appropriate antibiotic should be started at the induction of anaesthesia and may be a part of the induction procedure.

Arch Fam Med, 1993 Apr, 2(4), 409 - 13
Liver function test abnormalities in early Lyme disease; Kazakoff MA et al.; OBJECTIVE: Lyme disease is a widespread, tick-borne, spirochetal infection with multiple organ system involvement Hepatic dysfunction has not been emphasized in the literature . We report clinical findings and laboratory abnormalities in 73 patients with the pathognomonic erythema migrans rash early in the course of the illness . DESIGN: Case series . SETTING: Offices of family physicians in private practice and the model offices of a family practice residency program in the lower Connecticut River valley, an area to which Lyme disease is endemic . PATIENTS: Thirty-seven female and 36 male patients with erythema migrans who had not yet been treated with antimicrobial agents . MAIN OUTCOME MEASURE: Liver function tests . RESULTS: Twenty patients (27%) had liver function abnormalities . Elevation of gamma-glutamyltransferase was the most common finding . Only seven patients (9%) had a positive titer in response to the enzyme-linked immunosorbent assay for Lyme disease . Other laboratory and clinical findings are described . CONCLUSION: Subclinical hepatitis is a common finding in early Lyme disease.

Biull Eksp Biol Med, 1993 Apr, 115(4), 427 - 9
{Inhibitory effect of antimicrobial antibodies on the generalization of wound infection}; Pal'tsyn AA et al.; The antibody titer in wound and burn patients has been subjected to agglutination test to reveal bacterial autostrains . The antibodies to blood--isolated autostrains were shown to be present in lower titer, but more often they weren't found at all . At the clinical manifestation of sepsis the pathogenic strain (uniformly present in wound and secondary focuses, agglutinated by patient's serum in higher titer) hasn't been detected in blood . The authors conclude that the bacterial invasion of blood and generalization of infection occurs in the very first days following the emergence of bacteria in primary focus, when the antibodies to these bacteria haven't arisen yet and these is no clinical evidence of sepsis due to the small amount of those bacteria in primary focus . At the clinical manifestation of sepsis there is scant likelihood that the pathogen might be isolated from blood, occasional strains with no antibodies, may, however, be encountered.

Antibiot Khimioter, 1993 Apr-May, 38(4-5), 6 - 9
{Correlation between crystalline structure and biological properties of sodium cefazolin}; Op'lchenova GG et al.; Antimicrobial activity and toxicity of four polymorphic forms of sodium cefazolin were studied in comparison to those of the initial cefazolin . The observed changes reflecting a broader antimicrobial spectrum and low toxicity of one of the forms as compared with those of the initial cefazolin could serve as a prerequisite to successful screening of more active crystalline forms of the antibiotic aimed at designing the drug with better therapeutic properties.

J Clin Microbiol, 1993 Apr, 31(4), 872 - 81
Rochalimaea elizabethae sp . nov . isolated from a patient with endocarditis; Daly JS et al.; A Rochalimaea-like organism (strain F9251) was isolated from a patient with endocarditis after blood drawn for culture before antimicrobial therapy was subcultured onto blood and chocolate agars and incubated for 2 weeks in 5% CO2 . The strain was phenotypically similar to known Rochalimaea species . The cellular fatty acid composition of strain F9251 was close to but distinct from those of the three known Rochalimaea species and was most similar to that of R . vinsonii . Labeled DNA from strain F9251 was 59 to 67% related to DNAs from type strains of the three described Rochalimaea species, and its 16S rRNA gene sequence was 98.9% or more homologous to their 16S rRNA gene sequences . These findings support classification of F9251 as a new Rochalimaea species, for which the name Rochalimaea elizabethae sp . nov . is proposed . The patient infected with the organism had large bacterial vegetations on his aortic valve and was cured with antibiotics and valve-replacement surgery . Recognition of the procedures required to identify this and other Rochalimaea species suggests that clinical laboratories should prolong the incubation times of cultures of blood and tissue from patients with suspected endocarditis, patients with fever of unknown origin, and immunocompromised patients with fever so that the full spectrum of disease caused by these organisms can be recognized.

Biochem Biophys Res Commun, 1993 Mar 31, 191(3), 983 - 90
Molecular cloning of a cDNA encoding the precursor of adenoregulin from frog skin . Relationships with the vertebrate defensive peptides, dermaseptins; Amiche M et al.; Adenoregulin has recently been isolated from Phyllomedusa skin as a 33 amino acid residues peptide which enhanced binding of agonists to the A1 adenosine receptor . In order to study the structure of the precursor of adenoregulin we constructed a cDNA library from mRNAs extracted from the skin of Phyllomedusa bicolor . We detected the complete nucleotide sequence of a cDNA encoding the adenoregulin biosynthetic precursor . The deduced sequence of the precursor is 81 amino acids long, exhibits a putative signal sequence at the NH2 terminus and contains a single copy of the biologically active peptide at the COOH terminus . Structural and conformational homologies that are observed between adenoregulin and the dermaseptins, antimicrobial peptides exhibiting strong membranolytic activities against various pathogenic agents, suggest that adenoregulin is an additional member of the growing family of cytotropic antimicrobial peptides that allow vertebrate animals to defend themselves against microorganisms . As such, the adenosine receptor regulating activity of adenoregulin could be due to its ability to interact with and disrupt membranes lipid bilayers.

J Biol Chem, 1993 Mar 25, 268(9), 6649 - 53
Characterization of the disulfide motif in BNBD-12, an antimicrobial beta-defensin peptide from bovine neutrophils; Tang YQ et al.; BNBD-12, a prototype beta-defensin peptide from bovine neutrophils, was chosen for determination of the disulfide motif in this family of tridisulfide antimicrobial peptides . Disulfide-containing fragments of BNBD-12 were generated by incubation with trypsin, and the amino acid composition of one tryptic fragment allowed for the assignment of one of the three disulfides . The remaining two disulfides, contained in a 16-residue tryptic oligopeptide, were characterized by amino acid analysis of fragments generated by a single round of Edman degradation which cleaved the Cys-Cys peptide bond present near the carboxyl terminus of BNBD-12 . Cleavage of this bond produced two disulfide-containing oligopeptides, the compositions of which provided unambiguous assignments of the disulfides involved . The cystine motif in BNBD-12 differs from that of classical defensins, and indicates that the beta-defensins and defensins must have differently folded chains, though they share several functional properties.

Am J Med, 1993 Mar 22, 94(3A), 166S - 173S
Systemic antimicrobial therapy for skin and skin structure infections: comparison of fleroxacin and ceftazidime; Parish LC et al.; Intravenous fleroxacin, 400 mg once a day, was compared with ceftazidime, 0.5-2 g three times a day or 1-2 g twice a day, for the treatment of skin and skin structure infections . Duration of treatment was 4-21 days . The study was a multicenter, unblinded comparison . Of the 316 patients enrolled, 212 were randomized to treatment with fleroxacin and 104 to ceftazidime (2:1 ratio); 92 fleroxacin-treated patients and 50 ceftazidime-treated patients were included in the standard analysis of efficacy . The most common diagnoses were wound infections and cellulitis, which affected 36% and 30% of the fleroxacin group, and 24% and 24% of the ceftazidime group, respectively . In the fleroxacin group, 82% of the infecting organisms were eradicated, and in the ceftazidime group, 79% . The overall rates of bacteriologic cure, by infection, were 79% for the fleroxacin group and 74% for the ceftazidime group, and those for clinical cure were 82% and 73%, respectively . It could not be concluded with 95% confidence that the two regimens resulted in equivalent cure rates because the range of between-group differences was outside the stipulated limits of +/- 15% . The percentage of patients with one or more adverse events was approximately twice as high (17% vs . 9%) in the fleroxacin group than in the ceftazidime group . The most frequent event in both groups was nausea . In this study, intravenous therapy with fleroxacin or ceftazidime produced similar bacteriologic and clinical cure rates, but the statistical requirements permitting a conclusion of equivalence at protocol levels were not met.

Science, 1993 Mar 19, 259(5102), 1739 - 42
Multiple defects of immune cell function in mice with disrupted interferon-gamma genes; Dalton DK et al.; Interferon-gamma (IFN-gamma) is a pleiotrophic cytokine with immunomodulatory effects on a variety of immune cells . Mice with a targeted disruption of the IFN-gamma gene were generated . These mice developed normally and were healthy in the absence of pathogens . However, mice deficient in IFN-gamma had impaired production of macrophage antimicrobial products and reduced expression of macrophage major histocompatibility complex class II antigens . IFN-gamma-deficient mice were killed by a sublethal dose of the intracellular pathogen Mycobacterium bovis . Splenocytes exhibited uncontrolled proliferation in response to mitogen and alloantigen . After a mixed lymphocyte reaction, T cell cytolytic activity was enhanced against allogeneic target cells . Resting splenic natural killer cell activity was reduced in IFN-gamma-deficient mice . Thus, IFN-gamma is essential for the function of several cell types of the murine immune system.

J Am Vet Med Assoc, 1993 Mar 15, 202(6), 973 - 5
Intermittent antimicrobial infusion for management of a septic distal interphalangeal joint in a horse; McClure SR et al.; A 13-month-old Quarter Horse colt sustained a puncture wound to the frog region of the foot, which penetrated the navicular bursa and distal interphalangeal joint, 7 days prior to examination . A street-nail procedure was performed to debride the tract and provide drainage of the navicular bursa and distal interphalangeal joint . An indwelling lavage system was placed through the dorsal aspect of the joint and antimicrobials were infused intermittently to supply a high local concentration of drug and to frequently lavage the distal interphalangeal joint and navicular bursa.

J Biol Chem, 1993 Mar 15, 268(8), 6058 - 63
Antibacterial 15-kDa protein isoforms (p15s) are members of a novel family of leukocyte proteins; Levy O et al.; We have previously described the isolation and initial characterization of functionally distinct 15-kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind with high affinity to Escherichia coli and modulate the antibacterial actions of other leukocyte proteins on this Gram-negative bacterium . We now report the cloning and sequencing of two distinct cDNAs from a rabbit bone marrow library that encode p15s differing at only 2 residues (His-3, Arg-88 versus Arg-3, Trp-88) . Tryptophan-directed chemical cleavage of two isoforms purified from a single rabbit confirms the existence of multiple isoforms with distinct function and primary structure in a single rabbit . The p15 cDNAs encode putative signal sequences and studies of cellular and subcellular localization indicate that the p15s are granule-associated proteins of PMN . Both purified isoforms bind avidly to lipopolysaccharide (LPS), the major component of the Gram-negative bacterial outer membrane . Analysis of the deduced primary structures of the p15s reveals homology to three other leukocyte proteins: CAP-18, an 18-kDa LPS-binding protein from rabbit PMN, pro-indolicidin, a 16-kDa precursor of an antibacterial peptide of bovine PMN, and cathelin, an 11-kDa cysteine protease inhibitor from porcine leukocytes, suggesting the existence of a novel family of leukocyte proteins with LPS-binding, antimicrobial, and protease-inhibitory activities.

Am J Ophthalmol, 1993 Mar 15, 115(3), 293 - 8
Treatment of microsporidial keratoconjunctivitis with topical fumagillin; Diesenhouse MC et al.; Encephalitozoon hellem is a newly described cause of microsporidial keratoconjunctivitis, occurring chiefly in patients with significantly diminished CD4+ T-lymphocyte levels . This disorder is symptomatically disabling and generally recalcitrant to topical antimicrobial therapy . Two homosexual men with E . hellem keratoconjunctivitis diagnosed by Gram stain, transmission electron microscopy, and specific indirect immunofluorescent assay were treated with topical fumagillin (Fumidil B) . Both patients had marked symptomatic improvement with reduction of clinical findings . Symptoms and signs recurred with temporary discontinuation of the drug . Both patients, however, remained symptom-free on maintenance levels of topical fumagillin with no evidence of toxic side effects.

Proc Natl Acad Sci U S A, 1993 Mar 15, 90(6), 2517 - 21
Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages; De Nichilo MO et al.; The colony-stimulating factors (CSFs) greatly influence mature macrophage function in vitro: macrophage (M)-CSF induces maturation of monocytes and enhances differentiated cell function; granulocyte-macrophage (GM)-CSF stimulates a variety of antimicrobial functions . In vivo M-CSF is thought to promote differentiation, and GM-CSF is thought to potentiate the inflammatory response . One mechanism by which these differential effects may be achieved is through the receptor-mediated interaction of macrophages with their extracellular matrix . Here we show that M-CSF induces specifically the expression of the alpha v beta 5 integrin receptor, whereas GM-CSF rapidly induces mRNA and surface expression of the alpha v beta 3 integrin . The M-CSF-treated cells acquire a flattened epitheloid phenotype, and on vitronectin the alpha v beta 5 is located in adhesion plaques . These cells do not bind collagen or laminin . In contrast, cells treated with GM-CSF adopt an elongated phenotype on a number of substrates, including collagen and laminin, and express alpha v beta 3 at the leading edge of cells on vitronectin . These results suggest that a primary means by which the CSFs exert their individual effects on mature cells may be through regulating integrin expression.

Dent Update, 1993 Mar, 20(2), 65, 67 - 8, 70-1
Pulsed oral irrigation in the management of inflammatory periodontal diseases; Walsh TF; While subgingival scaling and root planing are effective at removing plaque, the use of periodic subgingival irrigation with a antimicrobial solution could be a useful adjunct . This paper initially discusses the management of inflammatory periodontal diseases in general, covering current mechanical therapy and chemical antimicrobials, before describing pulsed oral irrigation in more detail.

J Ethnopharmacol, 1993 Mar, 38(2-3), 209 - 14
Recent trends in research into African medicinal plants; Sofowora A; Recent trends in research into African medicinal plants show that while ethnobotanical surveys continue, there is an appreciable increase in research activity in the area of bioactivity of natural products . The biological areas most researched include antimicrobial, molluscicidal, toxicity tests and antitumour in decreasing order . The isolation and characterisation of natural products from African plants without biological testing has yielded several compounds of novel structure and constitutes the majority of all the recent publications on African medicinal plants.

Jpn J Antibiot, 1993 Mar, 46(3), 205 - 21
{In vitro MIC break point for appropriate clinical use of antibiotic}; Uete T et al.; In vitro antimicrobial susceptibility tests can play an essential role in clinical management of infectious diseases, and in vitro MIC break point is important in choice of antibiotic . Standardization of method for measuring MIC is necessary, if break points are to be fixed internationally . However, it is difficult to settle on uniform international break points, since standard doses of antibiotics and the preferred routes of administration differ in different parts of the world . With respect to in vitro MIC break points, the NCCLS system is used in the U.S.A., and in Japan, Showa disc system and the NCCLS system are both used . In Europe 6 different systems are utilized (BSAC, DIN, SFM, SIR, NCCLS, and WRG) . There is a certain degree of similarity between different concentration values used to define break points in these systems . In general, however, the BSAC and DIN systems recommend lower break points and the NCCLS and SFM systems higher break points . The MIC values of the break points, +3 and +2 categories of Showa 4 category classification system (+3, +2, +, -) used in Japan, are similar to those of the BSAC system . Higher ratio of positive responses to bactericidal antibiotic therapies have been reported when ratios of peak concentrations of drugs in plasma/in vitro MIC are increased, and maximum responses are obtained when the ratio reaches about 8 in cases with aminoglycosides and beta-lactams . In neutropenic compromised patients, drug concentrations with ratios higher than 8 to 10 may be required to treat infections . Drug availabilities are different depending on drugs and sites of infections . Susceptibility patterns to antibiotics are also quite different with different organisms . From the evidence presented above, a multiple (at least 2, low and high) sensitivity MIC break point system appears to be more appropriate than a single sensitivity MIC break point system to cope with various infections . Multiplicity of break points should depend on types of organisms, antibiotic availabilities at sites of infections, and specific factors in patients . Pharmacokinetic data on antibiotics must be more precisely taken into account with respect to the diversity of dosages, and especially effective antibiotic concentrations at sites of infections.

J Burn Care Rehabil, 1993 Mar-Apr, 14(2 Pt 1), 132 - 40
Cytotoxicity to human leukocytes by topical antimicrobial agents used for burn care; Zapata-Sirvent RL et al.; We tested two topical antimicrobial agents (TAAs), silver sulfadiazine and mafenide acetate, to determine their cytotoxic effects when human lymphocytes and neutrophils were incubated with the agents in vitro for 30 minutes . Dilute concentrations of both TAAs markedly inhibited neutrophil respiratory burst activity and mitogen-stimulated lymphocyte proliferation (p < 0.05) . The components of silver sulfadiazine (silver and sulfadiazine) were separately tested, and each component inhibited both neutrophil and lymphocyte functions . Mafenide acetate markedly decreased intracellular Ca+2 flux in lymphocytes . The effects of the TAAs were partially reversed when cells were washed and resuspended in medium after they were exposed in vitro to the TAAs . Commonly used TAAs may contribute to local immune dysfunction in the patient with burns . Because evidence suggests that T lymphocytes may participate in wound healing, prolonged treatment with TAAs may also effect certain aspects of wound healing.

Acta Paediatr, 1993 Mar, 82(3), 271 - 5
Fever and neutropenia in children with cancer: diagnostic parameters at presentation; Riikonen P et al.; We evaluated 91 episodes of fever in 46 profoundly neutropenic children with cancer, in a search for any symptom, sign or laboratory test that would serve to identify patients with septicemia and differentiate them from those in no immediate need of prompt antimicrobial therapy . Seventeen episodes (19%) were bacteremias, 59 (64%) were suspected septic infections, 9 (10%) were focal bacterial infections and 6 (7%) proved not to be bacterial infections . We were unable to detect any parameter, either on admission or after two days of antimicrobial therapy (except for blood culture findings), that would be helpful in differentiating bacteremia from an episode not of bacterial origin . We focused on serum levels of C reactive protein and found them unreliable on an individual level . Prompt institution of antimicrobial therapy at the occurrence of fever results in low mortality, but does not allow assignment of cases to different categories.

Cesk Epidemiol Mikrobiol Imunol, 1993 Mar, 42(1), 25 - 8
{Sorbitol-negative E . coli 016 in a 10-year-old child diagnosed with hemolytic-uremic syndrome and in his asymptomatic father}; Puzova H et al.; In Escherichia coli strains isolated from faeces and smears from the rectum in haemolytic-uraemic syndrome of a child and healthy relatives the authors assessed the biochemical activity, antigenic characteristic, sensitivity to twelve antimicrobial substances and factors of virulence . Sorbitol negative strains were isolated from the ill child and his father . The strains belonged into serogroup 016 . The remaining strains were sorbitol positive . They belonged into serogroups 02, 012 and 019 . Nineteen sorbitol negative strains of E . coli from the sick child caused mannose sensitive agglutination of chicken and guinea pig erythrocytes, they produced colicin V and aerobactin . Except for one strain they were serum resistant . Fourteen strains induced the oedema on the foot of mice and eleven produced a lethal effect in mice . Except for three ampicillin resistant strains the remaining were sensitive to the examined antibacterial substances . Two sorbitol negative strains of E . coli isolated from the asymptomatic father produced aerobactin and one strain was serum resistant.

Fam Pract Res J, 1993 Mar, 13(1), 53 - 61
Diabetic limb infections: identification of microorganisms and selection of treatment; Taylor AT; Polymicrobial lower limb infections are common complications among diabetic patients, yet their antimicrobial management remains mostly empiric . A retrospective study of the clinical circumstances of 74 patients accounting for 101 hospital admissions was performed . Risks for vascular disease, clinical and microbiologic evidence for infection, as well as antimicrobial drug selection in these patients, were compiled . Culture materials were obtained from either swab or incision and drainage techniques in 65 (64.4%) patients . Eighty-two (81.2%) patients received antimicrobial therapies . Of the 172 antimicrobial agents prescribed, cephalosporins were utilized 83 times . Twenty-nine (28.7%) patients received amputations . Average total hospital charges were $7,368 per hospital stay, $485 per day.

Ophthalmic Surg, 1993 Mar, 24(3), 203 - 5
Systemic herpetic infection diagnosed by retinal biopsy; Friedberg MA et al.; We describe a patient with systemic lupus erythematosus who developed myelopathy, optic neuropathy, retinopathy, and aseptic meningitis unresponsive to immunosuppressive and antimicrobial therapy . Although cultures and brain biopsy were unrevealing, a Herpes virus was suggested by retinal biopsy . The patient recovered dramatically after institution of acyclovir therapy and optic-nerve-sheath decompression . This case demonstrates that herpetic retinitis can occur in an iatrogenically suppressed host and underscores the value of tissue diagnosis.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 265 - 74
Formulary control of antimicrobial usage . What price freedom?
Dunagan WC, Medoff G.
Formulary controls are the most common and probably the most effective method for controlling abuse of antimicrobial agents in hospitalized patients . Such programs may include restriction of both the number of agents available and the way these agents may be used . These programs have been demonstrated to control pharmacy expenditures . Other potential advantages include reductions in the incidence of adverse drug reactions and the antimicrobial resistance among the hospital flora, and improvements in the overall quality of prescribing of antimicrobials . There are few data to document such benefits, however . Potential disadvantages are also poorly documented but include inconvenience for prescribing physicians, increased administrative costs, prescribing errors, and increased antimicrobial resistance . Antimicrobial control programs will likely remain common, but the availability of new information technologies should enable a transition to systems based on concurrent assessment of antimicrobial appropriateness with immediate feedback to the prescribing physician.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 255 - 64
Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory; Schentag JJ et al.; Rapid reporting of culture and susceptibility data is the first of several important steps in the successful management of infected patients . As has been said many times, rapidly reported data are of little value unless the patient directly benefits . Benefit requires better overall communication and an action plan linked to timely use of these results . In 1989 the Millard Fillmore Hospital Antibiotic Review Committee developed and implemented a prototype approach to hospital wide antimicrobial management . The formulary was revised and the drug use evaluation process modified to enhance effectiveness and to lower the cost of therapy and inventory . Clinical pharmacy antimicrobial agent management specialists were then recruited to individualize patient treatments to the isolated pathogens in conjunction with the Division of Infectious Diseases . To provide the clinical pharmacy specialists with rapid and clinically useful information, a real-time computer link was created between the pharmacy (antibiotic orders) and the microbiology laboratory (culture results) . Customized software was implemented to screen all patients automatically for mismatches between pathogens and drugs, or to screen for doses inappropriate to minimum inhibitory concentration or renal function . Special attention was paid to identification of opportunities to target a more appropriate narrow-spectrum regimen after culture results became available . Changes in antimicrobial regimen or dosage were made by contacting the prescribing physician . Over 90% of the recommended changes were made, and virtually all changed regimens had satisfactory clinical outcome . Real dollar expenditures for antimicrobial agents declined by > $200,000 per year . Prior to the institution of this computerized clinical management strategy, antimicrobial purchases were rising yearly at the rate of 12%-15% . The combined efforts of clinical pharmacy, microbiology, and infectious disease personnel successfully optimized antimicrobial therapy on a hospital wide basis . Antimicrobial agent optimization improved patient outcome, and the cost savings more than covered the costs of the program personnel and software.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 251 - 4
Effective reporting of susceptibility test results; Sharp SE; An overview of effective reporting of susceptibility test results is presented . Areas included in effective antimicrobial reporting are selective reporting of antimicrobials within drug families and by specific drug-organism combinations, automatic computer-delivered susceptibilities to patient-care areas, "flagged" results that are unusual and/or could seriously effect patient care, and the use of a coherent report format . Also included are areas that may significantly enhance antimicrobial result formats such as the reporting of cost information with susceptibility results, reporting "predictive sensitivities" based on institutional antibiograms, and reporting specific drugs for therapy based on gram's stain, and preliminary and final culture information.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 245 - 9
Selection of antimicrobial agents for routine testing in a clinical microbiology laboratory; Jorgensen JH; Each clinical microbiology laboratory must establish its own standard battery of antimicrobial agents to be tested routinely on clinical isolates of various organism groups . Some choices are based upon the intrinsic activities of antimicrobial agents for a particular group of organisms, for example, agents primarily active against either Gram-positive or Gram-negative bacteria . For final selection of limited batteries of agents for routine testing, however, it is necessary to use additional criteria based upon physician prescribing patterns and the availability of antimicrobial agents in a particular institution . A fundamental principle in the selection process should be routine testing and reporting of those antimicrobial agents that physicians actually use, that is, the institution's formulary agents . Testing of the most appropriate drugs for an institution may be complicated by lack of availability of some antimicrobial agents among the standard panels offered by automated instrument or commercial test system manufacturers . The laboratory should develop its final test batteries in consultation with the infectious disease and pharmacy services and the pharmacy and therapeutics and infection-control committees of the medical staff . These choices should not be made based upon the most convenient selection of drugs from the laboratory's perspective or based upon pharmaceutical industry promotional efforts.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 237 - 43
The impact of same-day tests versus traditional overnight testing; Granato PA; Within the last decade, major technologic advances have been made in clinical microbiology that have resulted in the availability of a wide variety of different methods for the rapid reporting of test results . Included among these technologies are rapid methods for producing antimicrobial susceptibility reports that many regard as the most important information generated by the microbiology laboratory . Ideally, the early availability of this important information should favorably affect patient care by enabling the more judicious use of alternative drug therapies that are equally efficacious yet less toxic and less costly to the patient . Clinicians appear to have been reluctant to modify initial empiric therapies, however, despite the availability of the rapid antimicrobial susceptibility report . This article addresses some of the issues responsible for this long-standing problem and discusses and explores various strategies that can be implemented for improving the use and for controlling the cost of antimicrobial agents within the hospital.

Diagn Microbiol Infect Dis, 1993 Mar-Apr, 16(3), 231 - 6
Qualitative susceptibility tests versus quantitative MIC tests; Craig WA; Qualitative susceptibility categories show reasonable, but incomplete, correlation with therapeutic outcome . Studies using quantitative MIC tests have demonstrated that treatment failures within the susceptible category are associated with higher minimum inhibitory concentrations (MICs) than with therapeutic successes . Other trials have exhibited enhanced response for increasing ratios of a pharmacokinetic parameter to MIC (for example, peak level to MIC ratio for aminoglycosides) . Dose-response studies in animal infection models also demonstrate an excellent correlation between the dose of drug required for a given response and the infecting organism MIC . These studies suggest that the use of quantitative MIC tests may enable more individualization of the therapeutic regimen, especially in regards to dose and dosing frequency, than provided by qualitative category susceptibility tests . However, there are only rare studies that have used MIC results or pharmacokinetic parameters to improve efficacy . Furthermore, these studies have not consistently documented enhanced clinical efficacy . MICs can also be used to reduce drug dosage and cost of antimicrobial therapy for very susceptible organisms . Additional studies are clearly needed to define the full potential of the quantitative MIC test result.

Can J Microbiol, 1993 Mar, 39(3), 318 - 28
Antifungal effect of bean endochitinase on Rhizoctonia solani: ultrastructural changes and cytochemical aspects of chitin breakdown; Benhamou N et al.; A chitinase, purified to homogeneity from ethylene-treated bean leaves, was applied to actively growing mycelial cells of Rhizoctonia solani to evaluate a potential antifungal activity . Light microscopic investigations at 30-min intervals following enzyme exposure revealed the induction of morphological changes such as swelling of hyphal tips and hyphal distortions . More precise information concerning fungal cell alteration was obtained by ultrastructural observation and cytochemical detection of chitin distribution in fungal cell walls . Chitin breakdown was found to be an early event preceding wall disruption and cytoplasm leakage . The large amounts of chitin present in the walls of control R . solani cells and the rapid chitin hydrolysis upon chitinase treatment lead us to suggest that this polysaccharide is one of the main components of this fungal cell wall and is readily accessible to chitinase, especially in the apical zone . By 60 min after enzyme treatment, labeled molecules were observed in the vicinity of some fungal cells, suggesting the release of chitin oligosaccharides from fungal cell walls . The antifungal activity of the bean chitinase on cells of R . solani grown in culture is discussed in relation to the potential of genetically modified transgenic plants to resist attack by R . solani through an antimicrobial activity in planta.

Pharmacotherapy, 1993 Mar-Apr, 13(2 Pt 2), 54S - 57S
Developing drug use evaluation criteria for parenteral fluoroquinolones; Guay DR et al.; The basic tenet of pharmaceutical care asserts that the delivery of optimal, cost-effective pharmacotherapy can be best achieved by identifying, resolving, and preventing drug-related problems . Drug use evaluation (DUE) is one of the primary tools used to achieve these ends . Fluoroquinolone antimicrobials meet Joint Commission criteria for targeting for DUE: the drugs are used in populations at high risk for adverse drug reactions, quality assurance or infection control committees target them for DUE, the drugs are costly, they may be suspected or known to be used inappropriately, and they are prescribed frequently . Outside this supplement, no published DUE criteria for parenteral fluoroquinolones currently exist . Suggested criteria include use in patients who would otherwise be candidates for oral fluoroquinolone therapy (for which published criteria exist) but who cannot use the oral route of administration due to gastrointestinal conditions predisposing to malabsorption or unavailability of the oral route; for severe infections due to gram-negative pathogens; as a replacement for aminoglycosides when ototoxicity or nephrotoxicity is a substantial risk; targeting to resistant pathogens (i.e., not as empiric therapy); and targeting to therapeutic use only (not for prophylaxis) . The DUE process is crucial for ensuring safe, effective, appropriate, and economical drug therapy . It is an effective mechanism for evaluating the use of new agents and as an educational tool for clinicians in the postmarketing period.

Pharmacotherapy, 1993 Mar-Apr, 13(2 Pt 2), 29S - 33S
Maximizing patient outcomes of antiinfective therapy; Dudley MN; Drug treatment of infectious disease requires consideration of both short- and long-term therapy . Although in most settings patients receive antimicrobials for acute events, long-term management of certain infections with drugs that delay progression of the disease adds a new facet to pharmacotherapy . In the past, broad questions regarding efficacy were posed: a drug was evaluated as either effective or not effective for a particular disorder . The actual question is, in whom is a given drug at a given dosage effective? Antibiotic control, restriction, and pharmacokinetic dosing programs have been useful, but they are reactive as opposed to proactive . The expensive products of biotechnology and the availability of oral drugs with activity exceeding that of parenteral antimicrobials require a more expanded scope of clinical pharmacy practice where patients are identified for these therapies prospectively using statistical models based on disease and other readily identified factors . Predictor variables for patient outcomes such as retreatment with other antibiotics, rehospitalization, toxicity, and mortality following the use of new drugs should be identified . Maximizing these outcome measurements will involve strategies that integrate epidemiology and statistical modeling techniques with principles of pharmaceutical care.

Pharmacotherapy, 1993 Mar-Apr, 13(2 Pt 2), 23S - 28S
Drug-drug interactions with fluoroquinolones; Marchbanks CR; Antimicrobials of the fluoroquinolone class are involved in a number of clinically important drug-drug interactions . Many of these interactions occur with all the available agents and exhibit little interpatient variability . In contrast, others occur only with specific fluoroquinolones and their extent varies markedly among subjects . The oral absorption of all fluoroquinolones is significantly impaired when coadministered with aluminum- and magnesium-containing antacids and sucralfate, as well as with other metal cations such as calcium and iron . Concomitant use of these agents, even when dosed several hours apart, should be avoided . Enoxacin and ciprofloxacin impair the hepatic metabolism of theophylline and caffeine, leading to significantly increased serum concentrations . Ofloxacin and lomefloxacin have only minimal effects on xanthine metabolism . Case reports suggest that concomitant administration of several fluoroquinolones and warfarin, a drug that is also highly metabolized by the liver, leads to increased hypoprothrombinemic effects; prospective studies, however, failed to confirm this interaction . Clinicians must be aware of these and other potential drug-drug interactions with fluoroquinolones for optimal use of the agents.

Int J Clin Pharmacol Ther Toxicol, 1993 Mar, 31(3), 130 - 6
The antimicrobial actions of taurolin and other preparations on the pathogenic spectrum in dentoalveolar infections; Zimmermann M et al.; Bacteriological specimens from a total of 64 patients with six common, highly relevant clinical indications were collected for an in vitro investigation . By means of standard microbiological methods, 149 species of organism were differentiated, and their relative sensitivity to Taurolin, a broad spectrum chemotherapeutic and antitoxin, as well as 5 conventional finished pharmaceuticals were tested in agar diffusion tests . Taurolin, which was tested in 3 different galenic formulations, produced practically identical, but considerably wider zones of inhibition than all other compared products . In contrast to other substances which exhibited a failure rate of up to 24.8%, no gaps in the activity spectrum in the form of the lack of inhibition zone formation were observed.

Infect Dis Clin North Am, 1993 Mar, 7(1), 135 - 52
Zoonotic endocarditis; Fernandez-Guerrero ML; The so-called zoonotic endocarditis is transmitted from animals to humans and is frequently found in some cattle-raising countries . Brucella endocarditis is a destructive process of the aortic valve with abscess formation that commonly leads to heart failure . Q fever endocarditis is a more indolent infection, but it is also capable of producing severe valvular damage and hemodynamic compromise . Treatment of zoonotic endocarditis includes the prolonged administration of doxycycline in combination with other antimicrobial agents and a judicious use of valve replacement . Mortality of Brucella endocarditis has been decreased significantly by a medical-surgical approach to treatment . On the basis of serologic and valve tissue culture results, no treatment is consistently able to cure Q fever endocarditis, and thus mortality of this infection remains high.

Antimicrob Agents Chemother, 1993 Mar, 37(3), 523 - 31
The fractional maximal effect method: a new way to characterize the effect of antibiotic combinations and other nonlinear pharmacodynamic interactions; Li RC et al.; The checkerboard technique leading to the fractional inhibitory concentration indexes and the killing curve method are currently the most widely used methods to study antibiotic combinations . For both methods, experimental conditions and interpretation criteria are somewhat arbitrary . The relevance of the fractional inhibitory concentration index computation, in the classic case of additivity {P = d1/(D1)p + d2/(D2)p, where d1 and d2 are the doses of drugs 1 and 2 in combination to produce an effect at a percent level (P) and (D1)p and (D2)p are the doses required for the two respective drugs alone to produce the same effect} relies on the assumption of a linear relationship between the MIC and the concentration of the test antibiotics . In addition, there is no consensus as to the definition of synergy in killing curve interpretation . The fractional maximal effect (FME) method is a new approach which was developed to handle the nonlinear pharmacodynamics exhibited by antibiotics and other drugs . This method relies on the mathematical linearization of the nonlinear concentration-effect scales and eventual construction of an isobologram-type data plot . The FME method was applied to study interactions between several antibiotic combinations: amoxicillin and tetracycline, ciprofloxacin and erythromycin, and ticarcillin and tobramycin . These combinations were selected because the pharmacologic basis for their interactions has been previously described . The FME method correctly identified antagonism for the first two combinations and synergism for the last combination . Conclusions were reproducible across the range of concentrations studied . Besides providing information on the nature of the interaction, the method can rapidly explore the effect of changing concentration ratios of two antimicrobial agents on the degrees of interaction . The FME method may be applied to interactions between drugs or agents with either a linear or nonlinear endpoint measurement . Methods frequently used for drug combination testing are also discussed in the paper.

EMBO J, 1993 Mar, 12(3), 1257 - 62
In vivo inhibition of duck hepatitis B virus replication and gene expression by phosphorothioate modified antisense oligodeoxynucleotides; Offensperger WB et al.; Antisense oligodeoxynucleotide strategies have been employed in a variety of eukaryotic systems both to understand normal gene function and to block gene expression . Pharmacologically, 'code blockers' are ideal agents for antitumour and antimicrobial treatments because of their specific mode of action . Here we report the inhibition of duck hepatitis B virus (DHBV) by antisense oligodeoxynucleotides in primary duck hepatocyte cultures in vitro as well as in DHBV-infected Pekin ducks in vivo . The most effective antisense oligodeoxynucleotide was directed against the 5' region of the pre-S gene and resulted in a complete inhibition of viral replication and gene expression in vitro and in vivo . These results demonstrate the application of antisense oligodeoxynucleotides in vivo and exemplify their potential as human antiviral therapeutics.

Ginecol Obstet Mex, 1993 Mar, 61, 53 - 9
{Use of antibiotics in pregnancy . I}; Figueroa Damian R et al.; The use of antibiotics during pregnancy have particularly risk, choosing an antibiotic requires consideration of the effects on both the mother and the unborn child . Some antimicrobial agents are safe for use throughout pregnancy, while other are completely contraindicated . Pregnant women need treatment for serious infections, in this cases antibiotics must be used nevertheless the adverse effects of the antimicrobial agent, we must choose the antibiotic with more antimicrobial activity and less risk for the mother and the fetus.

Clin Infect Dis, 1993 Mar, 16(3), 426 - 31
Environmental mycobacterial peritonitis complicating peritoneal dialysis: three cases and review; Hakim A et al.; Mycobacterial peritonitis is rare among patients undergoing peritoneal dialysis . It is usually caused by group IV environmental mycobacteria . We report three such cases and review the literature on this subject . Negative results in routine bacterial cultures and persistent peritonitis may be the only clues indicating the presence of mycobacterial infection . The lack of specific symptoms and signs as well as inadequate culture techniques may delay diagnosis . Multiple cultures of centrifuged dialysis fluid may be required for isolation of the organism . Peritoneal biopsy may yield additional diagnostic information . Management frequently entails removal of the dialysis catheter in addition to antimicrobial therapy . Significant morbidity may ensue if treatment is delayed . Amikacin--with or without another antibiotic--provides adequate coverage.

J Clin Periodontol, 1993 Mar, 20(3), 172 - 8
Comparison between mechanical cleaning and an antimicrobial rinse for the treatment and prevention of interdental gingivitis; Caton JG et al.; This study compared the efficacy of an antimicrobial mouthrinse (0.12% chlorhexidine gluconate) plus toothbrushing (mouthrinse group), mechanical interdental cleaning plus toothbrushing (mechanical group), and toothbrushing alone (control group), at reducing and preventing interdental gingival inflammation . 92 male subjects were examined for interdental inflammation using the Eastman interdental bleeding index at baseline, then monthly for 3 months after using one of the above oral hygiene regimens . The mechanical cleaning group had significant reductions in bleeding sites compared to baseline at 1 month (56.90% versus 13.17%) that persisted throughout the study (2 months = 6.65%, 3 months = 5.70%) . The other regimens showed no significant bleeding reduction at any time point in the study . The mechanical interdental cleaning group showed improvement over baseline at 1 month with the full benefit apparent after 2 months . The effect of location in the mouth on bleeding reduction was also assessed . The % of posterior sites which bled was always higher than anterior sites . Analysis of maxillary versus mandibular, and buccal versus lingual sites showed no significant differences . Additional observations of the data demonstrated that sites which bled at baseline were more likely to stop bleeding in the mechanical cleaning group . Also, sites which did not bleed at baseline were unlikely to bleed subsequently when mechanical cleaning was used . Neither of these observations were true for the other cleaning regimens . These data show that only mechanical interdental plaque removal combined with toothbrushing is effective at reducing or preventing interdental inflammation . This underscores the importance of instituting mechanical interdental cleaning to eliminate interdental inflammation.

Gastroenterol Clin North Am, 1993 Mar, 22(1), 183 - 98
Treatment strategies for Helicobacter pylori infection; Marshall BJ; Helicobacter pylori can be eradicated easily in most patients with a 14-day triple-therapy regimen . In patients in whom this treatment fails or who cannot take a full course, other antimicrobial combinations must be considered . This article discusses the various alternatives and explains why various agents should or should not be used . It also includes many new therapies developed in 1992 that allow the physician to treat virtually all H . pylori infections.

J Prosthet Dent, 1993 Mar, 69(3), 250 - 7
Effects of disinfecting irreversible hydrocolloid impressions on the resultant gypsum casts: Part I--Surface quality; Tan HK et al.; This study evaluated the effects of disinfection time (10, 30, and 60 minutes) on the surface quality of stone casts poured against an alginate impression material (Jeltrate) . Five antimicrobial agents were tested: Sporicidin spray, sodium hypochlorite, and iodophor for spray; and Sporicidin cold sterilization solution and Cidexplus glutaraldehyde solution for immersion . Impressions, flushed with water and stored for 0, 10, 30, and 60 minutes before pouring, served as untreated controls . On completion of the disinfection treatments, the impressions were rinsed and poured in Velmix stone . The effects on cast surface were evaluated under a stereomicroscope by three experienced raters . A 1-to-4 scoring system was developed to rate the surface quality in terms of smoothness and detail reproduction . Both immersion disinfectants proved to be unacceptable for treating alginate impressions . The mean scores of other disinfectant-time combinations were compared with the use of the Tukey-Kramer method with a 95% confidence interval . The results indicated that treatment time had statistically significant effects on the quality of cast surface in Sporicidin spray, sodium hypochlorite, and untreated control groups but not in the iodophor spray group.

Bol Med Hosp Infant Mex, 1993 Mar, 50(3), 145 - 50
{Antibiotic consumption in a community of Mexico City . II . Survey of purchases at pharmacies}; Calva JJ et al.; In developing countries, antibiotics are the most common sales of drugs and it has been suggested that their irrational use leads to the emergence of resistant bacteria . In order to assess the purchase of antimicrobials in a peri-urban community in Mexico City six local drug stores were randomly selected . A social worker made five visits to each pharmacy and she observed the events during the purchase of the drug and applied a structured questionnaire to the customer immediately after the transaction . Antibiotics were the majority (29%) of the drug sales . Of all purchasers of an antibiotic 43% did it without medical prescription and 72% answered that a physician had influenced on the purchase . Duration of the antibiotic therapy was specified in one out of three prescriptions that were examined and only in 28% of the sales the purchase was enough for a treatment duration of more than four days . More information, from similar surveys in drug stores in other settings, is needed to support the reinforcement of actions to control the sales of antibiotics in the community.

Am J Hosp Pharm, 1993 Mar, 50(3), 463 - 6
Justification of a pharmacy intravenous admixture service in an Australian hospital; Plumridge RJ et al.; The time and cost of i.v . admixture preparation by hospital pharmacy staff members in an established admixture unit was compared with that by nurses working on wards . The preparation time of antimicrobial admixtures was determined by using a stopwatch . The total cost of preparing an admixture by pharmacy and nursing staff was calculated by combining the respective labor costs (preparation time x average salary rates weighted for overtime) with the cost of disposable items . The mean +/- S.D . time for admixture preparation in the pharmacy was 3.38 +/- 0.38 minutes, whereas preparation by nurses required 14.37 +/- 1.55 minutes . The mean +/- S.D . total cost (in Australian dollars) of admixture preparation was $1.42 +/- 0.34 per dose, and $4.59 +/- 0.46 per dose, respectively . Centralization of admixture preparation would reduce the time required by 18.32 hours for every 100 admixtures prepared, equivalent to an annual cost avoidance of $112,420 for every 100 admixtures prepared each day . Centralizing the preparation of i.v . admixtures in a hospital pharmacy resulted in significant time savings and cost avoidance.

Med Clin North Am, 1993 Mar, 77(2), 427 - 41
Antimicrobial prophylaxis for surgery; Paluzzi RG; Infection of the surgical wound or deep structures violated during surgery account for a major portion of postoperative morbidity . The medical consultant should have an understanding of the principles of antimicrobial prophylaxis for postoperative infection in order to manage this complication in the postoperative period . This article assesses the risks for infection, patient preparation for surgery, and antibiotic usage in frequently performed surgeries.

Crit Care Med, 1993 Mar, 21(3), 318 - 27
Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis . The CB0006 Sepsis Syndrome Study Group; Fisher CJ Jr et al.; OBJECTIVES: To determine the safety, pharmacokinetics, and activity of an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody in severe sepsis . DESIGN: Open-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006) . SETTING: Twelve academic medical center intensive care units in the United States and Europe . PATIENTS: Eighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody . INTERVENTIONS: Patients were treated intravenously with one of four dosing regimens with CB0006: 0.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart . MEASUREMENTS AND MAIN RESULTS: The murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients . No survival benefit was found for the total study population, but patients with increased circulating TNF concentrations at study entry appeared to benefit by the high dose anti-TNF antibody treatment . Increased interleukin (IL)-6 levels predicted a fatal outcome (p = .003), but TNF levels were not found to be a prognostic indicator . TNF levels were higher (206.7 +/- 60.7 vs . 85.9 +/- 26.1 pg/mL; p < .001) and outcome was poor (41% vs . 71% survival; p = .007) in patients who were in shock at study entry when compared with septic patients not in shock . CONCLUSIONS: The murine anti-TNF-alpha monoclonal antibody CB0006 has proven to be safe in this clinical trial and may prove to be useful in septic patients with increased circulating TNF concentrations . Further studies are needed to determine efficacy and the ultimate clinical utility of this immunotherapeutic agent in sepsis.

Infect Immun, 1993 Mar, 61(3), 966 - 9
Characterization of bovine neutrophil antibacterial polypeptides which bind to Escherichia coli; Litteri L et al.; Bovine neutrophils contain several cationic polypeptides which exert potent microbicidal effects in vitro . To better characterize the repertoire of these polypeptides, we have incubated extracts of bovine neutrophils or neutrophil granules at pH 4 or 7 with either a smooth strain of Escherichia coli or a rough one . Only a few polypeptides interacted with the bacterial surface and were subsequently desorbed with 200 mM MgCl2, as revealed by gel electrophoresis and analysis of Western blots (immunoblots) with appropriate antibodies . Two of the main proteins appearing in Coomassie blue-stained gels have molecular masses of 53 and 15 kDa and correspond to the heavy and light chains of myeloperoxidase . Another prevailing protein band with a molecular mass of 31 kDa was purified and shown to be 87% identical to human azurocidin/CAP37 in its 22-amino-acid N-terminal sequence . Proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted to nitrocellulose did not react with an antiserum to human bactericidal/permeability-increasing protein . Conversely, immunoglobulin G against Bac7 or Bac5, two members of the antimicrobial proline- and arginine-rich polypeptide family, recognized in Western blots both the inactive precursor molecules, proBac7 and proBac5, and the mature polypeptides.

Ann Intern Med, 1993 Mar 1, 118(5), 331 - 6
Syndrome of Rochalimaea henselae adenitis suggesting cat scratch disease; Dolan MJ et al.; OBJECTIVE: To describe a clinical syndrome of cat scratch disease caused by Rochalimaea henselae, including methods for isolation of the organism from tissue and for identification . DESIGN: Case series . SETTING: U.S . Air Force referral hospital infectious diseases clinic . PATIENTS: Two previously healthy patients . MAIN MEASUREMENTS AND RESULTS: Two immunocompetent patients who had handled cats developed unilateral upper-extremity adenitis associated with a distal papular lesion and fever . The adenitis and distal lesions persisted and progressively worsened . Cultures of the involved lymph nodes from both patients grew R . henselae, a recently described organism associated with bacillary angiomatosis and peliosis hepatis in human immunodeficiency virus-infected patients and with bacteremia in immunocompromised and immunocompetent hosts . The organism was characterized as oxidase negative and X-factor dependent and had a characteristic pattern in analysis of whole-cell fatty acids differing from Afipia felis, a bacterium that has been associated with cat scratch disease . The identity of the isolate was confirmed by analysis of whole-cell fatty acids using gas chromatography and by amplification of the citrate synthetase gene sequence and analysis of the polymerase chain reaction-amplified product . The organisms were broadly susceptible to a variety of antimicrobials by broth microdilution; however in-vitro resistance to first-generation cephalosporins correlated with clinical failure of therapy . CONCLUSION: Rochalimaea henselae can be a cause of cat scratch disease in immunocompetent patients.

Pract Periodontics Aesthet Dent, 1993 Mar, 5(2), 59 - 65; quiz 66
Guided tissue regeneration (GTR) of nonsubmerged implants in immediate extraction sites; Schultz AJ; The learning objective of this article is the placement of nonsubmerged implants immediately after extraction, with membrane barriers, according to the principles of guided tissue regeneration (GTR) . Fixtures were immobilized by engaging bone beyond the apex and were exposed to the oral cavity during healing . The implants and cell-occlusive barriers were placed in 6 patients; all barriers were removed by week 10 . Three patients received freeze-dried bone allografts . A systemic antibiotic, an oral antimicrobial rinse, and reinforced plaque removal were employed . Radiographic and attachment level measurements at 3 and 6 months indicated that osseous regeneration had taken place and was still ongoing . All fixtures were restored after each implant reached 6-month maturity.

FEMS Immunol Med Microbiol, 1993 Mar, 6(2-3), 241 - 4
beta-Lactamase production and in vitro antimicrobial susceptibility of Porphyromonas gingivalis; Pajukanta R et al.; beta-Lactamase production by 98 Porphyromonas strains was investigated by the nitrocefin (chromogenic cephalosporin) test . Human isolates of P . gingivalis (91), P . endodontalis (2), and P . asaccharolytica (1) were tested, with four closely related Porphyromonas spp . of animal origin and four reference strains . The in vitro susceptibility of 64 P . gingivalis strains was investigated on Brucella blood agar by the E test . None of the human Porphyromonas isolates tested produced beta-lactamase, but one Porphyromonas strain of animal origin, most closely resembling P . endodontalis, produced beta-lactamase . P . gingivalis was susceptible to almost all of the drugs tested: benzylpenicillin, ampicillin, cefaclor, cefuroxime, erythromycin, clindamycin, tetracycline, doxycycline, metronidazole and ciprofloxacin; all strains were inhibited at 0.016 microgram/ml, 0.023 microgram/ml, 0.315 microgram/ml, 0.064 microgram/ml, 0.19 microgram/ml, 0.016 microgram/ml, 0.094 microgram/ml, 0.047 microgram/ml, 0.023 microgram/ml, and 0.75 microgram/ml of these drugs, respectively . Cotrimoxazole exhibited variable efficacy against P . gingivalis; the range of MICs was 0.1095-32.0 micrograms/ml . The results indicate that beta-lactamase production is currently not a problem amongst clinical isolates of P . gingivalis and strains are susceptible to most antimicrobial agents.

Arzneimittelforschung, 1993 Mar, 43(3), 384 - 6
In vitro synergistic activity between ofloxacin and ansamycins against Mycobacterium leprae; Dhople AM et al.; The antimicrobial effects of ofloxacin, alone and in combination with either rifampicin or rifabutin, were evaluated against M . leprae, using in vitro cell-free culture system . The minimum inhibitory concentration (MIC) of ofloxacin against M . leprae was 1.5 micrograms/ml, while MICs of rifampicin and rifabutin were 0.4 and 0.2 microgram/ml, respectively . Combination of 0.375 microgram/ml ofloxacin and 0.05 microgram/ml of rifabutin exhibited synergistic bactericidal activity while the effect of combination of 0.75 microgram/ml ofloxacin and 0.2 microgram/ml rifampicin was additive bactericidal . Thus, combination of ofloxacin and rifabutin deserves further attention in multi-drug therapy of leprosy.

J Dairy Sci, 1993 Mar, 76(3), 812 - 8
Effect of Aspergillus oryzae fermentation extract (Amaferm) on in vitro fiber degradation; Beharka AA et al.; The influence of Aspergillus oryzae fermentation extract (Amaferm) on in vitro fiber degradation was determined by incubating eight ground fibrous feed-stuffs with rumen fluid and buffer inoculum . Amaferm was added at 0, .4, .8, or 1.2 g/L of fermentation mixture . Both NDF and ADF degradabilities were determined after 96 h of incubation . Addition of extract had no effect on NDF or ADF degradability of pure cellulose, low endophyte fescue, wheat straw, corn silage, or prairie hay . Addition of Amaferm at .8 or 1.2 g/L increased NDF and ADF degradations of bromegrass hay and alfalfa hay; its addition at .4 or .8 g/L, but not at 1.2 g/L, increased NDF and ADF degradation of high endophyte fescue hay . In a second set of in vitro fermentations, selective antimicrobials (penicillin, streptomycin, and cycloheximide) were used to assess the influence of Amaferm on various microbial groups . The enhanced fiber degradation by Amaferm was attributed to its stimulation of bacterial activity because its addition to whole rumen fluid without or with cycloheximide increased fiber digestion . In contrast, addition of Amaferm to the whole rumen fluid plus penicillin and streptomycin treatment had no effect on fiber degradation, suggesting that fungal or protozoal activity was not affected by treatment . In conclusion, Amaferm increased fiber digestibility of certain feedstuffs, and the increase was mediated via stimulation of rumen bacterial, but not fungal or protozoal, activities.

Res Vet Sci, 1993 Mar, 54(2), 247 - 8
Comparison of an HPLC and bioassay method to determine antimicrobial concentrations after intravenous and oral administration of enrofloxacin in four dogs; Kung K et al.; Plasma samples of dogs given 5 mg kg-1 bodyweight of a broad spectrum antimicrobial with the active ingredient enrofloxacin were assayed by two different methods (bioassay: Escherichia coli 14 ICB 4004 on ISO sensitest agar; high performance liquid chromatography with a RP C18 column) . At concentrations up to 1000 ng ml-1 a linear correlation between values obtained by the two assay methods was found . At concentrations above 1000 ng ml-1 no correlation could be determined . The main metabolite of enrofloxacin, ciprofloxacin, is an important determinant of overall antimicrobial activity and hence influences bioassay results.

J Dent Res, 1993 Mar, 72(3), 630 - 3
Reduction of proteolytic degradation by chlorhexidine; Grenier D; The present investigation was designed to evaluate the effect of the antimicrobial agent chlorhexidine on proteolytic degradation . Chlorhexidine, at a final concentration of 0.01%, significantly (p = 0.05) affected the degradation of the general chromogenic substrate azocoll by both commercial proteases and cell-bound bacterial proteases . Reduction of proteolytic degradation was observed following pre-treatment of either azocoll or bacterial cells with chlorhexidine . Chlorhexidine was also found to prevent degradation of type I collagen by Porphyromonas gingivalis cells . The mechanism of inhibition of proteolytic degradation appears to be related to an electrostatic chlorhexidine-protein interaction.

Bratisl Lek Listy, 1993 Mar, 94(3), 162 - 6
{What are the costs of septic complications in surgery?}; Prochotsky A et al.; Infectious complications have remained the most frequent cause of morbidity in surgical patients, and that despite the constantly broadening range of up-to-date antimicrobial drugs administered prophylactically and therapeutically, the improved methods of cultivating microorganisms and of establishing sensitivity to antibiotics . Infections in surgical patients lead to prolonged hospitalization, prolonged working disability, and to increased cost of treatment . Considerable economic consequences of infections in surgical patients are demonstrated on the basis of the authors' clinical material and possibilities of preventing infections and of their treatment are also discussed . (Fig . 1, Tab . 2, Ref . 21.)

Rev Inst Med Trop Sao Paulo, 1993 Mar-Apr, 35(2), 129 - 39
Respiratory complications in Brazilian patients infected with human immunodeficiency virus; Weinberg A et al.; PURPOSE: To determine how often and by what means an indentifiable pulmonary pathogen can be recognized in human immunodeficiency virus (HIV) infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms and what impact specific therapy has on these agents . PATIENTS AND METHODS: Thirty-five HIV seropositive subjects with respiratory complaints were studied . All patients had a complete history, physical examination and blood counts . The pulmonary assessment included chest radiograms; sputum examination for bacterial and fungal pathogens; bronchoscopy with bronchoalveolar lavage and transbronchial biopsy . Patients with treatable complications received standard antimicrobial therapy . RESULTS: One or more microorganisms were found in 24 subjects and another 3 individuals showed nonspecific interstitial pneumonitis . The sputum examination identified the pulmonary pathogens in 7 cases . The bronchoalveolar lavage and the histopathologic examination were diagnostic in 14% and 83%, respectively, of the 28 individuals that were submitted to bronchoscopy . The most frequently identified microorganism was P . carinii (55%), followed by M . tuberculosis (41%) and cytomegalovirus (8%) . The clinical, laboratory and radiographic findings failed to distinguish the specific pulmonary pathogens . Twenty-three individuals with P . carinii pneumonitis and/or tuberculosis received specific therapy; among the evaluable patients the therapeutic response rates were 79% for PCP and 100% for TB . CONCLUSIONS: We have determined that tuberculosis, P . carinii and cytomegalovirus pneumonitis are the most common respiratory opportunistic diseases in Brazilian patients infected with HIV . The histologic evaluation was crucial in order to identify the pulmonary pathogens . Tuberculosis in AIDS individuals displayed clinical and radiographic findings atypical for reactivation disease . However, most of the features observed in HIV infected patients had been previously described in infection of the normal host . Furthermore, the AIDS subjects showed a good therapeutic response to anti-tuberculous drugsPIP: The authors conducted complete histories, physical examinations, blood counts, chest radiograms, sputum examinations for bacterial and fungal pathogens, and bronchoscopy with bronchoalveolar lavage and transbronchial biopsy on 35 HIV-seropositive individuals with respiratory complaints in a study to determine how often and by what means an identifiable pulmonary pathogen can be recognized in HIV-infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms, and what impact specific therapy has on the agents . One or more microorganisms were found in 24 subjects, while another three individuals showed nonspecific interstitial pneumonitis . Tuberculosis (TB) found in 41% of cases, P . carinii in 55%, and cytomegalovirus pneumonitis in 8% were the most common respiratory opportunistic diseases among the study subjects . Histologic evaluation was essential to identify the pulmonary pathogens, with clinical, laboratory, and radiographic findings failing to distinguish the specific pathogens . 23 individuals with P . carinii pneumonitis and/or TB received specific therapy; among the patients who could be evaluated, the therapeutic response rates were 79% for PCP and 100% for TB . TB in these individuals displayed clinical and radiographic findings atypical for reactivation disease . The authors note that most of the features observed in HIV-infected patients had been previously described in infection of the normal host .

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