J Nat Prod, 1991 Jul-Aug, 54(4), 1068 - 76 New cytotoxic beta-carboline alkaloids from the marine bryozoan, Cribricellina cribraria; Prinsep MR et al.; Bioactivity-directed separations led to the isolation of the new alkaloid, 1-vinyl-8-hydroxy-beta-carboline {1}, as the major cytotoxic component of the marine bryozoan Cribricellina cribraria . Another new beta-carboline alkaloid 2 with the novel sulfone structure was isolated, together with a number of known beta-carboline compounds . Cytotoxicity and antimicrobial effects are reported for these compounds and for other synthesized beta-carbolines. Steroids, 1991 Jul, 56(7), 395 - 8 Antimicrobial activity of basic cholane derivatives . X . Synthesis of 3 alpha- and 3 beta-amino-5 beta-cholan-24-oic acids; Bellini AM et al.; A simple and convenient route to 3 alpha- and 3 beta-amino-5 beta-cholan-24-oic acids was developed via Leuckart-Wallach amination reduction and subsequent acid hydrolysis . Two epimeric formylamino derivatives were produced (alpha and beta), approximately in a 1:1 ratio, as determined by 13C nuclear magnetic resonance spectroscopy . The two isomers were separated by making use of their different solubilities in ethyl ether . The absolute configuration of the two amino acids was assigned by comparison with authentic reference samples. J Antimicrob Chemother, 1991 Jul, 28(1), 79 - 86 The penetration of cefpirome into the potential sites of pulmonary infection; Baldwin DR et al.; The concentrations of cefpirome, a new semi-synthetic cephalosporin, in the bronchial mucosa and serum were assessed after a single 1 g intravenous dose in 37 patients . Bronchoalveolar lavage allowed epithelial lining fluid (ELF) concentrations to be measured in eight subjects . The mean concentration for serum was 34.5 mg/L (S.E.M . 3.3), for bronchial mucosa 19.3 mg/kg (S.E.M . 1.9) and for ELF 7.2 mg/L (S.E.M . 1.1) . The progressive reduction in cefpirome concentration in serum compared to that in bronchial mucosa and ELF is consistent with the permeability characteristics of beta-lactam antimicrobials and the barriers to movement of antimicrobial agents present in the lung. Mikrobiyol Bul, 1991 Jul, 25(3), 277 - 84 {Urogenital Chlamydia trachomatis infections}; Dereli D et al.; Urogenital Chlamydia trachomatis infections are the most common sexually transmitted diseases which have shown a significant increase in the last few years . This organism presents a major health problem in many countries . It is recognized as the cause of both complicated and uncomplicated infections in men, women and infants passing through an infected birth canal . Tissue culture is accepted as the gold standard in the diagnosis of chlamydial infections . But, since this technique is expensive and cumbersome, antigen detection tests such as DFA and EIA are more widely used . Tetracyclines and erythromycins are the first-choice antimicrobials in the treatment of chlamydial infections. Vnitr Lek, 1991 Jul-Aug, 37(7-8), 695 - 702 {Antibiotics and antimycotics in oncology}; Krcmery V; The submitted review gives an account of therapeutic and prophylactic indications in oncology, in aimed, not aimed (empirical) treatment of febrile neutropenic patients, prophylaxis of infection during neutropenic episodes and selective decontamination before and during transplantation of bone marrow, focused on new antimicrobial and antimycotic agents. Arzneimittelforschung, 1991 Jul, 41(7), 744 - 6 Synthesis of {carbonyl-14C}sparfloxacin; Kagemoto A et al.; A new antimicrobial quinolone, sparfloxacin (5-amino-1-cyclopropyl-7- (cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline -3- carboxylic acid, AT-4140; CAS 110871-86-8), was labeled by 14C for studies of disposition and metabolism . Ethyl pentafluoro{carbonyl-14C}benzoylacetate (I) was reacted with ethyl orthoformate, cyclopropylamine and then potassium tert-butoxide to give a quinolone intermediate (IV) . A benzylamino derivative (V) obtained by condensation of IV and benzylamine was subject to catalytic hydrogenolysis and hydrolyzed to give the carboxyl derivative (VII), which was condensed with cis-2,6-dimethylpiperazine to form {carbonyl-14C}sparfloxacin . The average yield of 3 preparations was 41.5% and specific activities were 310.8-366.3 MBq (8.4-9.9 mCi)/mmol . Both chemical and radiochemical purities were greater than 99%. Orthop Clin North Am, 1991 Jul, 22(3), 379 - 88 Bacterial resistance; Gentry LO; Pathogenic bacteria remain adaptable to an increasingly hostile environment and a wider variety of more potent antibiotics . Organisms not intrinsically prepared for defense have been able to acquire resistance to newer antimicrobial agents . Chromosomal mutations alone cannot account for the rapid emergence and spread of antibiotic resistance . It has been established that plasmids and transposons are particularly important in the evolution of antibiotic-resistant bacteria . Plasmid- or transposon-mediated resistance provides the bacteria with pre-evolved genes refined to express high-level resistance . In particular, transposons can transfer these resistance determinants in diverse bacterial species, and nature provides in humans and animals large intestinal reservoirs in which such communications are facilitated . Antibiotic therapy exerts selection pressures on bacteria . Eradication or marked reduction in the populations of susceptible organisms promotes the overgrowth of intrinsically resistant strains and favors those resistant as a result of favorable chromosomal mutations or via plasmids or transposons . In our hospitals, where antibiotic consumption continues to increase, the nosocomial flora consists of many resistant bacteria, and infections acquired in the nosocomial setting are now far more severe than their community-acquired counterparts . There is convincing evidence that infection control measures must take into further consideration the contribution of the hospital worker as carrier and mediator of antibiotic resistance. J Immunol, 1991 Jun 15, 146(12), 4295 - 300 Stimulus-induced maturation of probactenecins, precursors of neutrophil antimicrobial polypeptides; Zanetti M et al.; The antimicrobial polypeptides Bac7 and Bac5 (bactenecins) are stored in the large granules of bovine neutrophils as precursor forms, or probactenecins . Maturation of probactenecins has been investigated by studying the effects of stimulus-induced degranulation on this process . Stimulation of neutrophils with PMA, which is a secretagogue for specific and large granules but not for azurophils, induces a substantial discharge of uncleaved probactenecins in the extracellular medium, as revealed by Western blot analysis . When neutrophils are exposed to opsonized bacteria in the presence of cytochalasin B, resulting in exocytosis of the content of azurophils in addition to that of specific and large granules, probactenecins are secreted and rapidly converted into the corresponding mature antimicrobial peptides . Such a conversion is prevented if serine proteases, stored in the azurophils, are inhibited by pretreatment of neutrophils with PMSF . Phagocytosis, while causing a rapid discharge of the contents of azurophil and of the large granules into phagocytic vacuoles, as indicated by immunogold electron microscopy, also induces cleavage of probactenecins into mature peptides, as revealed by Western blot analysis . We conclude that the final processing of the storage forms of bactenecins arises from their interaction with the serine protease(s) of azurophils during bacteria-induced degranulation of neutrophils. J Immunol, 1991 Jun 15, 146(12), 4338 - 43 Macrophage cytostatic effect on Trypanosoma musculi involves an L-arginine-dependent mechanism; Vincendeau P et al.; Peritoneal macrophages from mice infected with an extracellular parasite, Trypanosoma musculi were effective in inhibiting parasite proliferation in vitro . This trypanostatic activity could be suppressed by NG monomethyl-L-arginine (NGMMA), a specific inhibitor of a biochemical pathway synthesizing L-citrulline and inorganic nitrogen oxides from L-arginine . Macrophages exerted this in vitro antiproliferative effect from the 10th day of infection on and this activity was maximum around 14th day of infection . Nitrite production paralleled development of macrophage trypanostatic activity . Macrophages collected from BCG-infected mice or treated with IFN-gamma in vitro also exerted a trypanostatic activity which was suppressed by NGMMA . A trypanostatic activity suppressed by NGMMA was also exerted by splenic macrophages from T . musculi-infected mice . Trypanostatic activity of IFN-gamma-treated macrophages was reduced by addition of anti-TNF-alpha showing the participation of TNF-alpha in IFN-gamma-mediated macrophage trypanostatic activity . Nitric oxide (NO) gas inhibited T . musculi proliferation . Addition of excess iron reversed the trypanostatic effect of both macrophages and NO gas . All these data showed that, as reported for a broad spectrum of microorganisms, activated macrophages displayed an antimicrobial effect on trypanosomes through the L-arginine: NO pathway that could participate in controlling infection in T . musculi-infected mice before appearance of antibody-dependent mechanisms . NO production by activated macrophages could trigger iron loss from critical target enzymes in trypanosomes. Biochim Biophys Acta, 1991 Jun 5, 1096(4), 338 - 44 Lysozyme is an ozone-sensitive component of alveolar type II cell lamellar bodies; Shelley SA et al.; Exposure of rats to 3 ppm ozone for up to 8 h results in significant changes in lamellar bodies, the surfactant storing organelles of type II cells . We have previously shown that a 14 kDa lamellar body protein is decreased as early as 4 h after the onset of ozone exposure . We have isolated this ozone-sensitive protein from rat lung lamellar bodies and identified it as lysozyme by immunochemical methods, as well as by its amino acid composition, N-terminal amino acid sequence and bacteriolytic activity . Reduced lysozyme activity in isolated lamellar bodies is detected as early as 4 h after the start of ozone exposure . Following an 8 h ozone exposure, the activity does not return to control levels for at least 48 h . Lamellar body lysozyme is expected to be secreted with surfactant phospholipids, thereby contributing to the antimicrobial defense of the alveolar lining layer . The acute lysozyme deficiency seen in ozone-induced oxidant injury may reduce the resistance of the lung to infection. Oral Surg Oral Med Oral Pathol, 1991 Jun, 71(6), 684 - 8 Penetration of erythromycin into periapical lesions after repeated doses of erythromycin acistrate and erythromycin stearate: a pilot study; Tuominen RK et al.; In 26 patients who had undergone apicectomy and extirpation of granulomas (n = 9) or radicular cysts (n = 17), concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms were determined with a novel chemical method in plasma and periapical lesions after at least 2 days of treatment with erythromycin acistrate (EA) (400 mg three times daily, n = 11) or erythromycin stearate (ES) (500 mg three times daily, n = 15) . Oral surgery was performed 2 1/2 to 3 hours after the last dose . Blood samples were collected at the time of operation, and immediately before antibiotic treatment, and 1, 2, and 6 hours after treatment . At all time points EA produced at least twice the total antibiotic (2'-acetyl erythromycin plus erythromycin) concentrations in plasma as ES . Erythromycin levels in plasma were at least as high after EA treatment as after ES . In periapical lesions erythromycin concentration after EA was three times higher (1.34 +/- 0.28 micrograms/gm) than after ES treatment (0.40 +/- 0.17 micrograms/gm) . Although the total drug concentration in periapical lesions was about the same after EA (2.64 micrograms/ml) and ES (3.41 micrograms/ml), most of the drug recovered after ES was antimicrobially inactive anhydroerythromycin (3.01 micrograms/gm) . The concentration of anhydroerythromycin in plasma was approximately the same as that of erythromycin after ES throughout the dose interval . After EA treatment both plasma and the periapical lesion samples contained hardly detectable amounts of anhydroerythromycin . Hence EA has a good bioavailability essential for treatment and prophylaxis of bacterial infections in dentistry. J Trauma, 1991 Jun, 31(6), 775 - 82; discussion 782-4 The cytotoxic effects of commonly used topical antimicrobial agents on human fibroblasts and keratinocytes; Cooper ML et al.; This study evaluated the cytotoxicity of commonly used topical agents to human dermal fibroblasts and epidermal keratinocytes, which play a prominent role in wound healing . The effects of these topical agents were assessed using two separate assays for the fibroblasts--tritiated thymidine incorporation and the uptake of a vital dye (neutral red) . Keratinocytes were evaluated with the neutral red assay . Serial dilutions of each of 10 commonly used topical agents produced decreases in both the uptake of neutral red and the incorporation of thymidine at clinically relevant doses . Only Neosporin G.U . irrigant showed no significant difference compared with controls in the assays for both the fibroblasts and the keratinocytes . Careful attention must be paid to which agent is used in the clinical setting, since many of these can have profound effects on cells that influence wound healing. Am J Obstet Gynecol, 1991 Jun, 164(6 Pt 1), 1556 - 61; discussion 1561-2 Antibiotic treatment of tuboovarian abscess: comparison of broad-spectrum beta-lactam agents versus clindamycin-containing regimens; Reed SD et al.; One hundred nineteen patients with tuboovarian abscess were evaluated for response to antibiotics . Results were stratified into three groups by antimicrobial regimen . Group 1 consisted of 37 patients treated with a single-agent broad-spectrum intravenous antibiotic and oral doxycycline . Initial clinical response (defined as decreased pain, diminished white blood cell count, or defervescence) in group 1 was 31/37 (84%) . Group 2 consisted of 64 patients treated with clindamycin in combination with an aminoglycoside with or without a penicillin . There was an initial clinical response in 45 of 64 (70%) . Group 3 consisted of 18 patients from group 1 who were changed to a clindamycin-containing regimen after 2 to 3 days of initial treatment with a single-agent broad-spectrum antibiotic . The decision to switch antibiotics was not based on treatment failure but occurred when delayed ultrasonography confirmed the diagnosis of tuboovarian abscess . The switch reflected physician preference for clindamycin-containing regimens in the treatment of tuboovarian abscesses . The response rate in this subset of patients was 14 of 18 (78%) . Overall initial clinical response rate was 90 of 119 (75%) . There were no statistically significant demographic or clinical differences among the three groups . There was no statistical difference in the rate of early and late antibiotic failure rates among the groups . Our study demonstrates that extended-spectrum antibiotic coverage, including single-agent broad-spectrum antibiotics such as cefoxitin, in conjunction with doxycycline has efficacy that is equivalent to that of clindamycin-containing regimens . An overall medical treatment success rate of 75% suggests that conservative treatment of tuboovarian abscesses is warranted. Nurs Clin North Am, 1991 Jun, 26(2), 341 - 60 Update on antimicrobial agents; Walsh ML et al.; A variety of antimicrobial agents are currently in use to treat bacterial, fungal, and viral infections . Pharmacologic and microbiologic properties unique to the classes of drugs are reviewed in this article . Home parenteral antibiotics are an acceptable and efficacious way to treat certain infections and may lead to shorter hospitalizations . Knowledge of general drug characteristics, indications, and toxicities will help the nurse to manage effectively the patient receiving antimicrobial therapy. Arch Ophthalmol, 1991 Jun, 109(6), 869 - 72 An evaluation of saline irrigation and comparison of povidone-iodine and antibiotic in the surface decontamination of donor eyes; Nash RW et al.; We evaluated the effect of saline irrigation on 38 pairs of donor eyes and determined the relative efficacy of antibiotic rinse/storage (neomycin-polymyxin B-gramicidin) and povidone-iodine immersion . Microbial growth was found in 49 (64.5%) of 76 eyes from which cultures were taken before irrigation, and only four (8.2%) became culture negative after irrigation . Of 27 eyes culture negative before irrigation, 15 (55.6%) became positive after irrigation . One eye of each pair was then assigned randomly to antibiotic rinse/storage and the other eye to 3-minute immersion in 1% povidone-iodine . Both antimicrobial treatments decreased the numbers of positive cultures, with povidone-iodine showing an advantage that did not reach significance . These results demonstrate that saline irrigation of donor eyes in situ does not reduce surface contamination and that povidone-iodine immersion should be considered as an alternative for donor eye decontamination. Gastroenterology, 1991 Jun, 100(6), 1571 - 5 Helicobacter pylori-associated exaggerated gastrin release in duodenal ulcer patients . The effect of bombesin infusion and urea ingestion; Graham DY et al.; Recent studies have shown that the exaggerated meal-stimulated gastrin release in patients with duodenal ulcer abates after eradication of Helicobacter pylori infection . Bombesin-stimulated gastrin release was compared in 11 H . pylori-infected patients with chronic duodenal ulcer and 8 uninfected healthy volunteers both before and after therapy to eradicate H . pylori . Bombesin infusion significantly increased the gastrin release both in control subjects and in patients with duodenal ulcer . Antimicrobial therapy (bismuth, tetracycline, and metronidazole) to eradicate the H . pylori infection was associated with a significant reduction in bombesin-stimulated gastrin release in patients with duodenal ulcer (from 116.9 +/- 19 pg/mL to 69.5 +/- 7 pg/mL following 50 pmol.kg-1.h-1 bombesin; and from 158 +/- 29 to 83.4 +/- 10 following 200 pmol.kg-1.h-1 bombesin: P = 0.01 for each) . Antimicrobial therapy had no effect on gastrin release in uninfected volunteers, thus excluding a nonspecific effect of antimicrobial therapy on antral G-cell function . Serum gastrin was also not increased by feeding 500 mg of urea to 5 H . pylori-infected volunteers . This suggests that access of hydrogen ion to the pH-sensitive sites governing gastrin release by mucosal ammonia produced by H . pylori urease is not a critical factor . These data suggest that exaggerated gastrin release present in patients with duodenal ulcer disease is secondary to H . pylori infection. Obstet Gynecol Clin North Am, 1991 Jun, 18(2), 289 - 99 Respiratory insufficiency due to pneumonia in pregnancy; Maccato M; Respiratory insufficiency is a common complication of pneumonia in pregnancy . Respiratory insufficiency may progress to respiratory failure, requiring mechanical ventilation . Prompt diagnosis of the pneumonia and rapid institution of supportive care and effective antimicrobial therapy results in the best possible outcome for both mother and fetus . If the patient requires mechanical ventilation, resolution of the pneumonia usually allows for uneventful weaning from the respirator. Zentralbl Bakteriol, 1991 Jun, 275(2), 223 - 32 Modulation of antimicrobial effects of beta-lactams by amino acids in vitro; Gillissen G et al.; Glycine as well as 11 and 10, respectively, out of a total of 12 D-amino-acids tested increased the antimicrobial efficacy of imipenem (IMI) and of ampicillin (AMP) using the serosensitive strain E . coli ATCC 8739 . D-proline was ineffective in assays with IMI as well as D-proline and D-leucine in assays with AMP . - In contrast, L-amino-acids behaved differently: In assays with IMI, 9 out of 13 isomers were ineffective whereas 3 were antagonistic (L-phenylalanine, L-serine, L-tryptophan) . In combination with AMP, however, 10 L-amino acids had an antagonistic effect and 2 (L-leucine, L-methionine) were ineffective . L-alanine was an exception and showed a synergism with both antibiotics which was assumed to have been due to a racemase activity of cells . - Seroresistance of E . coli apparently reduced the synergistic effect of glycine and beta-lactams . - Glycine, alanine and tryptophan lost their typical synergistic or antagonistic effect with AMP when tested as di- or tri-amino-acid compounds . This was not the case with di-L-alanine - It is supposed that the synergistic effect of glycine or of D-amino-acids with beta-lactams can be explained mainly by an inhibition of carboxypeptidases. Ann Soc Belg Med Trop, 1991 Jun, 71(2), 81 - 113 {Epidemiology of sexually transmissible diseases in developing countries in the era of AIDS}; Goeman J et al.; Recent developments in the epidemiology of sexual transmitted diseases (STD) in developing countries are reviewed . STD are very frequent in the tropics, particularly in large urban areas . They put a heavy burden on public health because they affect the economically most important age groups and because their sequellae may be fatal . Pelvic inflammatory disease and its consequences, and morbidity during pregnancy and the neonatal period are among the most important causes of mother and child morbidity . STD favour sexual transmission of HIV and may therefore explain the explosive AIDS epidemics in many developing countries . Antimicrobial resistance has made treatment of gonorrhoea and chancroid more difficult and more expensive . STD and HIV infection may be responsible for up to 17% of productive years lost to disease in certain regions . Strategies to control STD should be developed and linked with the AIDS programs . Both should be integrated in the primary health care system. Antimicrob Agents Chemother, 1991 Jun, 35(6), 1232 - 4 In vitro activities of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae; Franzblau SG; The in vitro activities of a variety of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae were evaluated with the BACTEC 460 system . At 20 micrograms/ml, gentamicin, kanamycin, tobramycin, streptomycin, and amikacin were inactive . Lincomycin was active at 20 micrograms/ml, and clindamycin was active at 0.31 micrograms/ml . Rifamycin SV, rifabutin, and rifampin were active at 3.1, 3.1 to 12.5, and 200 ng/ml, respectively . The in vitro assay correlates well with the in vivo response of M . leprae to antimicrobial agents, with the exception of the aminoglycosides. Antimicrob Agents Chemother, 1991 Jun, 35(6), 1153 - 9 Beta-lactam antibiotics potentiate magainin 2 antimicrobial activity in vitro and in vivo; Darveau RP et al.; The ability of magainin 2 to augment antibiotic therapy was examined . Susceptibility to magainin 2 was determined on Escherichia coli incubated in the presence and absence of sublethal concentrations of antibiotics both in vitro and in vivo . Experiments in buffer and normal human serum revealed that E . coli exposed to sublethal amounts of cefepime, a beta-lactam antibiotic, was significantly more susceptible to the antimicrobial activity of magainin 2 . Bacteria incubated with subinhibitory concentrations of other beta-lactam type antibiotics, but not amikacin (an aminoglycoside) or ciprofloxacin (a quinolone), were also more susceptible to magainin 2 in normal human serum . Bacteria were less susceptible to magainin 2 when they were examined in heat-inactivated serum . Complement was shown to be required for magainin 2 activity in serum by using C8-deficient sera . The combination of magainin 2 and cefepime was shown to be more antimicrobial in normal human serum for a variety of bacterial strains . Magainin 2 was completely inactive as a therapeutic agent when it was administered alone (2 mg per mouse) but significantly increased the survival of mice when it was administered with a low level of cefepime. Eur J Clin Microbiol Infect Dis, 1991 Jun, 10(6), 509 - 11 Peritonitis with CDC group IVc-2 bacteria in a patient on continuous ambulatory peritoneal dialysis; Zapardiel J et al.; A case of CDC group IVc-2 peritonitis in a patient on continuous ambulatory peritoneal dialysis (CAPD) is described . To the authors' knowledge, this is the first case reported of CAPD peritonitis in which a member of this unusual group of bacteria was isolated as the sole microorganism . As this microorganism is usually resistant to most antibiotics commonly used to treat peritonitis in patients on CAPD, microbiological investigations with identification and antimicrobial susceptibility tests are mandatory. Biometrics, 1991 Jun, 47(2), 361 - 72 The 2 x 2 matched-pairs trial: exact unconditional design and analysis; Suissa S et al.; An exact unconditional method for the design and analysis of the 2 x 2 matched-pairs trial is presented . Unlike the exact conditional method, which is based on only the number of discordant pairs, the exact unconditional method uses the total number N of sampled pairs . This unconditional test, based on a simple Z statistic, yields sample sizes that are generally smaller than those produced by the exact conditional test for the cases tabulated herein, namely one-sided alpha = .01, .025, and .05 along with 80% and 90% power . Moreover, it is found to be uniformly more powerful than the latter for all the combinations of parameters considered in this paper, namely alpha = .01, .025, and .05, and N = 10(1)200 . The method is illustrated by assessing various design options of an in vitro study of the effectiveness of antimicrobial agents . Some numerical examples of matching efficiency are also given. Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Jun, 29(6), 698 - 702 {A clinical study of twelve cases of drug-induced pneumonitis}; Suzuki K et al.; Twelve cases of drug-induced pneumonitis were clinically investigated . Treatment of antimicrobial agents in 8 cases of drug-induced pneumonitis ranged from 7-21 days (mean 12 days) and that of other drugs in 4 cases from 18-150 days (mean 70 days) . The patients developed fever and dyspnea at a high rate of frequency . Abnormal laboratory findings included increased IgE (44%), eosinophilia (36%), and increased GOT and GPT in 33% . Chest X-ray films revealed a large reticulo-nodular or ground glass shadows in both lung fields . The results of lymphocyte stimulation tests were positive in 5 of 11 cases (45%) . Eight cases demonstrated a rapid improvement by discontinuation of the drug and corticosteroid was administered in 4 cases . The drug received by the patient and their known risk of pulmonary toxicity should be kept in mind in order to reach a diagnosis of drug-induced pneumonitis and grasp the clinical picture of this disease . A provocation test is potentially dangerous, therefore it should not be carried out lightly. Jpn J Antibiot, 1991 Jun, 44(6), 614 - 24 {Clinical study on fleroxacin in surgical infections}; Yura J et al.; We conducted clinical studies on fleroxacin (FLRX), a new pyridone carboxylic acid derivative, for the treatment of periproctal abscess, secondary infections (due to wounds, burns or surgical operations), mastitis or areolitis and others with once daily dose of 200 mg or 300 mg . We obtained the following results . Clinical efficacy was evaluated in total 27 cases including periproctal abscess 11, secondary infection 8, mastitis or areolitis 6, phlegmon 1 and infected atheroma 1 . Clinical efficacies were rated as excellent in 14, good in 9, fair in 4 cases . The overall efficacy rate was 85.2% . Bacteriological studies identified 14 strains of aerobic Gram-positive organisms, 12 of aerobic Gram-negative organisms and 6 of anaerobic organisms . The overall bacteriological efficacies were: eradicated in 26 strains, unchanged 2 and unidentified 4, hence the eradication rate was 92.9% . As for side effects, anorexia and nausea were observed in one of the 27 cases . In clinical laboratory tests, slight elevations of GPT and BUN were observed in 1 case each . We consider FLRX to be a useful antimicrobial agent at once daily dose for surgical infections. Curr Eye Res, 1991 Jun, 10(6), 557 - 63 Topical fluoroquinolones: antimicrobial activity and in vitro corneal epithelial toxicity; Cutarelli PE et al.; To assess the potential of fluoroquinolones as topical antimicrobial agents, we evaluated in vitro the antimicrobial activity of five fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, and temafloxacin), as well as gentamicin, tobramycin, and cefazolin against 96 isolates of common bacterial corneal pathogens . Ciprofloxacin and temafloxacin were the most active quinolones {minimal inhibitory concentration inhibiting 90% of stains (MIC90) of 1 microgram/ml}, followed by ofloxacin (MIC90 2 micrograms/ml), and norfloxacin and pefloxacin (MIC90s 4 micrograms/ml) . In contrast, gentamicin and tobramycin MIC90s were 32 and 64 micrograms/ml, respectively; cefazolin MIC90 was greater than 2048 micrograms/ml . The corneal epithelial cytotoxicity of the fluoroquinolones also was evaluated utilizing an in vitro assay of 3H-thymidine uptake of rabbit corneal epithelial cell cultures . The least to greatest toxicity of the fluoroquinolones were as follows: ciprofloxacin and temafloxacin less than norfloxacin less than ofloxacin less than pefloxacin . Our study suggests that the fluoroquinolones, especially ciprofloxacin and temafloxacin, possess excellent in vitro activity against common bacterial corneal pathogens and are less toxic to the corneal epithelium than the aminoglycosides. Jpn J Antibiot, 1991 Jun, 44(6), 635 - 42 {Dose calibration of aztreonam in pediatric patients by means of pharmacokinetic analysis}; Kawasaki H; One of the current pharmacological problems with antibiotics is possible overdose among children of 7 years of age and older, when their dose was calculated on a per kg basis . In order to evaluate the difficulties, a pharmacokinetic analysis of aztreonam (AZT), which is a monocyclic beta-lactam antimicrobial agent, was undertaken in 2 groups consisting of 5 children of ages 1-6 and 5 older children of 7-15 . Data from the younger children were fitted both to one- and two-compartment models while those from the older age group perfectly were fitted to a two-compartment model . Using these fitted curve, a simulation dose study was carried out in order to see if we can find a clue for a better dose calibration for the older group of children . The results suggested that the dose of AZT in per kg basis for the older children can be reduced to 60% levels of the younger, that is, 60 mg/kg for the older in contrast to 100 mg/kg for the younger. Ophthalmology, 1991 Jun, 98(6), 847 - 53 Use of corticosteroids in combination with antimicrobial drugs in the treatment of infectious corneal disease; Stern GA et al.; The use of corticosteroids in the management of infectious eye disease is controversial . In this study, the authors attempt to analyze the goals and risks of the use of corticosteroids in the treatment of various forms of infectious keratitis with reference to generally recognized principles for the treatment of infectious diseases . Existing clinical and research data are reviewed in this context to make appropriate recommendations for the use of corticosteroids in the treatment of bacterial, fungal, and acanthamoeba keratitis . The authors conclude that corticosteroids are definitely contraindicated in the treatment of fungal keratitis, and relatively contraindicated in the treatment of Acanthamoeba keratitis . Topical corticosteroid therapy may have a role in the treatment of bacterial keratitis if appropriate guidelines are followed. J Clin Microbiol, 1991 Jun, 29(6), 1249 - 51 Antimicrobial susceptibility testing of veterinary clinical isolates with the Sceptor System; Papp JR et al.; The Sceptor System (Becton Dickinson) was compared with an agar dilution method for antimicrobial susceptibility testing of veterinary clinical isolates . The results indicate that the Sceptor System may be used to test gram-positive and fastidious gram-negative bacteria. J Clin Microbiol, 1991 Jun, 29(6), 1157 - 61 Characterization of Gardnerella vaginalis and G . vaginalis-like organisms from the reproductive tract of the mare; Salmon SA et al.; Gardnerella vaginalis has been isolated from women with bacterial vaginosis, from the genital tracts of asymptomatic women, and from several other infected body sites in humans . However, until recently, it has not been isolated from any other animal species . Between June 1988 and October 1989, 31 isolates identified as G . vaginalis and 70 isolates identified as G . vaginalis-like organisms have been recovered from the genital tracts of 93 mares from Michigan and Ohio . Identification was based on biochemical reactions, hemolysis on media containing blood from various animal sources, and susceptibility to select antimicrobial agents . This report details the characterization of G . vaginalis and G . vaginalis-like organism isolates obtained from the reproductive tracts of these mares and compares the equine isolates with human isolates. Am J Hosp Pharm, 1991 Jun, 48(6), 1220 - 7 Use of antimicrobial drugs in adults before and after removal of a restriction policy; Himmelberg CJ et al.; The effects on the quantity and quality of antimicrobial drug use of removing an antimicrobial restriction policy are reported . Monthly totals for the number of courses of antimicrobial therapy and expenditures based on grams used were obtained from pharmacy records on adult inpatients for a portion (July-December 1987) of the restriction policy term and for the six months (July-December 1988) immediately after the policy ended . Data were obtained for nine restricted drugs and for three that were never restricted . Retrospective drug-use reviews were conducted for ceftazidime and imipenem-cilastatin . For the restricted agents, the total number of courses of therapy increased by 158% after the restriction policy was removed, and total expenditures increased by 103% . There were no significant changes in the number of courses of therapy or cost for the unrestricted antimicrobials . In the postrestriction period, ceftazidime and imipenem-cilastatin were used more often in patients who were less critically ill . Inappropriate use of imipenem-cilastatin occurred significantly more often after the restrictions were removed . Other factors potentially affecting the use of antimicrobials, such as patient age and the incidence of nosocomial infections, did not differ substantially between the two periods . The removal of an antimicrobial restriction policy resulted in increased use of and higher expenditures for previously restricted agents, as well as an increase in the inappropriate use of at least one agent. Semin Respir Infect, 1991 Jun, 6(2), 122 - 8 Sputum antimicrobial levels and clinical outcome in bronchitis; Hitt JA et al.; The role of antimicrobials in the treatment of bronchitis remains controversial . Antimicrobials are rarely indicated in acute bronchitis . Antimicrobials are indicated in a subset of patients with acute exacerbations of chronic bronchitis . The efficacy of an antimicrobial agent in bronchitis can be estimated by the ratio of the sputum concentration of the antimicrobial to its in vitro activity against common respiratory pathogens (S/M90) . These S/M90 rates are presented in tabular form . However, given the lack of solid data to support antimicrobial treatment for most episodes of bronchitis, use of the S/M90 to select antimicrobial therapy remains theoretical rather than of proven clinical benefit. Semin Respir Infect, 1991 Jun, 6(2), 112 - 21 Antimicrobial penetration into polymorphonuclear leukocytes and alveolar macrophages; Murdoch MB et al.; Infections caused by intracellular organisms often involve the lung and may be implicated in chronic disease . These intracellular bacteria may be protected from otherwise lethal concentrations of extracellular antimicrobials . Knowledge of the intracellular concentration of usual antimicrobials used to treat pneumonia may allow physicians to refine their initial choice of therapy . Lipid-insoluble antimicrobials, such as penicillin, cephalosporins, aminoglycosides, trimethoprim, and imipenem penetrate poorly into cells, if they penetrate at all . Isoniazid, tetracycline, and lincomycin have intermediate intracellular penetration, and chloramphenicol, rifampin, ethambutol, quinolones, and lincosamides, plus macrolides, are avidly concentrated . Nonetheless, to date it has been difficult to correlate intracellular concentrations of antimicrobials with cellular killing or clinical outcome . Information derived from a more standardized approach to the evaluation of antimicrobial agent intracellular penetration will be useful in improving the direct application of in vitro study results to the clinical care of patients with pneumonia. Arch Pharm (Weinheim), 1991 Jun, 324(6), 379 - 80 Antimicrobial activity of some isoquinoline alkaloids; Abbasoglu U et al.; The isoquinoline alkaloids are of great importance to humanity because of their medicinal value and different structure . During the last ten years, many isoquinoline alkaloids were isolated from Fumaria and Corydalis species growing in Turkey . There have been many researches on the antimicrobial activity of extracts of higher plants, but relatively few pure compounds have been investigated. Arch Pharm (Weinheim), 1991 Jun, 324(6), 355 - 7 Synthesis of new benzimidazole derivatives as potential antimicrobial agents; Badawey ES et al.; Barbiturates 3 as possible antimicrobial agents were obtained by reacting the N,N'-disubstituted urea 1a or the thiourea analogues 1b,c with the magic malonates 2a,b . On the other hand, reaction of 1a with ethoxycarbonyl isocyanate (4) yielded the substituted s-triazine-2,4,6(1H,3H,5H)-trione 5 . The reaction of 4 with 2-aminomethyl-benzimidazole (6) gave the allophanate 7 which upon treatment with Na2CO3 yielded N-(1H-benzimidazol-2-yl)urea 8. Boll Chim Farm, 1991 Jun, 130(6), 234 - 8 Evaluation of the interfacial properties of a new potent antimicrobial surfactant C31G; Unlu N et al.; The surface activity of a new potent antimicrobial mixture (C31G) of alkyl betaines and alkyl amine oxides were evaluated in order to determine the relationship between its antimicrobial effectiveness and physical properties . Therefore the surface tension measurements were performed at different temperatures using an interfacial tensiometer . Critical micelle concentrations, interfacial and thermodynamic parameters of C31G were obtained from the surface tension data. J Hosp Infect, 1991 Jun, 18 Suppl A, 473 - 80 Epidemiology, bacteriology and control of an outbreak of Nocardia asteroides infection on a liver unit; Sahathevan M et al.; An outbreak of Nocardia asteroides infection affecting seven patients is described . Over a 5-week period, five patients with liver disease admitted to a ward developed clinical and laboratory evidence of nocardiosis, and two further cases were diagnosed 3 and 5 months later . Three out of the five patients who received specific antimicrobial therapy responded to treatment; in three patients nocardia infection was considered to have contributed to death . In six out of the seven patients, nocardiosis followed immunosuppression . A common-source outbreak was considered to be responsible for infection in the first five patients . In two patients, presentation of infection 5 and 7 months after the first case may have been due to prolonged colonization or subclinical infection with Nocardia . Biotyping of the seven isolates using a fluorogenic biochemical method identified three distinct strains of N . asteroides . The most probable source of Nocardia was contaminated brick and plaster dust arising from building work in an area adjacent to the ward . However, samples of air, dust and water failed to yield N . asteroides . Infection control measures included ward closure followed by thorough cleaning, and formaldehyde fumigation. J Hosp Infect, 1991 Jun, 18 Suppl A, 424 - 31 The HELP system and its application to infection control; Burke JP et al.; The HELP system is a comprehensive hospital information system that is linked to an allied financial data base . The clinical data base integrates information from areas such as admitting, pharmacy, radiology, surgery, pathology, nursing, respiratory therapy, and the clinical laboratories, including microbiology . This allows for the creation of an electronic medical record that contains all the clinical and financial data for each patient . The HELP system combines both communication and advice features through the use of data- and time-driven algorithms . We have used the HELP system to automate the surveillance and analysis of hospital-acquired infections and to identify patients at high risk for nosocomial infection . The expert system features have also been used to suggest alternatives for patients receiving inappropriate antimicrobial therapy, to improve the timing of antibiotic prophylaxis in surgery, and to curtail unnecessarily prolonged prophylaxis . Automated hospital information systems such as HELP can facilitate the investigation of a broad range of infection control, quality improvement, and cost-containment issues. J Hosp Infect, 1991 Jun, 18 Suppl A, 211 - 21 The future contribution of transposition to antimicrobial resistance; Bennett PM et al.; Antibiotic resistance is commonplace in clinical bacterial isolates . Many of the resistance genes are transposon-borne and have the potential for rapid dispersal throughout the bacterial kingdom . Resistance genes are constantly subject to mutation and reassortment . Given appropriate selection pressure, the new resistance determinants can emerge rapidly to pose significant treatment problems . It seems likely that in the future bacterial resistance will continue to be a problem, both with respect to current antibiotics and to new ones and that transposon-borne resistance genes will continue to figure prominently. J Hosp Infect, 1991 Jun, 18 Suppl B, 57 - 63 The influence of cosmetic additives on the acceptability of alcohol-based hand disinfectants; Rotter ML et al.; A prospective, randomized double-blind study with intra-individual comparison of the results was undertaken with 20 volunteers to assess the influence of cosmetic additives on the acceptability of a mixture of n-propanol (50% v/v) and isopropanol (30% v/v) for hand disinfection . Three to 5 ml of antiseptic was rubbed into the hands until dry 15 times a day, 5 days a week and for 2 weeks per preparation . For self-assessment the parameters 'appearance', 'intactness', 'turgor' and 'sensation' were evaluated weekly by visual analogue; for assessment by a dermatologist the same parameters except 'sensation' were used . Each score was compared before and after treatment . The antimicrobial efficacy of the alcoholic mixture was equivalent to or better than the standard (isopropanol 60% v/v, 1 min) . The frequent application of these antiseptic preparations caused a slight but significant deterioration of the skin condition as judged by both self-assessment and dermatologist; however, this was significantly less when the antiseptic contained cosmetic additives . It is concluded that the addition of suitable emollients can significantly increase the acceptability of alcoholic disinfectants. J Hosp Infect, 1991 Jun, 18 Suppl B, 13 - 22 Computerized image analysis of full-hand touch plates: a method for quantification of surface bacteria on hands and the effect of antimicrobial agents; Leyden JJ et al.; A method is described for quantification of the bacterial flora on the hand surface . Computer-assisted image analysis of bacterial growth of large full-hand touch plates provides a quantifiable measure of the bacterial flora on the hand surface . Image analysis pixel intensity values showed a significant correlation (P less than 0.0001) with colony forming unit values determined by the glove juice method . Image analysis of impressions from hands treated with various antimicrobial agents in detergent bases showed that 4% chlorhexidine gluconate produces a 96% reduction after a 30 s washing and 98% reduction after a 3 min washing while 7.5% povidone-iodine and 1% triclosan produce a 77% and 70% reduction after 3 min respectively, and 70% isopropanol produces a 98% reduction after a 30 s wash. Vestn Khir Im I I Grek, 1991 Jun, 146(6), 31 - 2 {The clinico-morphological characteristics of suppurative wound healing depending on the treatment method}; Nuzov BG et al.; Experimental and clinical investigations carried out in treatment of purulent wounds in 63 rabbits and in 80 patients have shown high curative efficiency of the local application of millet oil . It has a pronounced antiinflammatory, antimicrobial effect, stimulates reparative processes in the wounds in combination with a considerable reaction of cells responsible for immune defense. Clin Biochem, 1991 Jun, 24(3), 241 - 7 Regulation of cytoplasmic pH in phagocytic cell function and dysfunction; Grinstein S et al.; To ensure effective antimicrobial or tumouricidal function, phagocytic cells must maintain their cytoplasmic pH (pHi) at a level conductive to optimal intracellular enzyme activity . The mechanisms by which neutrophils and macrophages regulate their cytoplasmic pH include bicarbonate-independent ion transport systems, most notably the Na+/H+ exchanger, and bicarbonate-dependent ion transport systems, which can be subdivided into the cation-independent and Na(+)-dependent forms of chloride/bicarbonate exchange . In addition, macrophages have been shown to recover from intracellular acid loading by means of an ATP-dependent proton extrusion mechanism, which has the characteristics of a vacuolar-type H+ ATPase . In the microenvironment typically associated with abscesses, the low extracellular pH and the presence of short chain fatty acid by-products of bacterial metabolism tend to induce cytoplasmic acid loading . In this setting, the ability of the various pHi regulatory mechanisms to protect pHi may be overcome, leading to cytoplasmic acidification . Several investigators have shown that cytoplasmic acidification impairs the ability of neutrophils to migrate in response to chemotactic stimuli, and also impairs their ability to generate a respiratory burst, thus inhibiting the release of toxic oxygen radicals . This may result in the inability of phagocytes to effect complete abscess resolution. Am J Pathol, 1991 Jun, 138(6), 1405 - 11 Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult; Russler SK et al.; The authors report a case of pneumonitis in a young healthy man caused by coinfection with human herpesvirus 6 (HHV-6) and Legionella pneumophila . The patient's course was complicated by severe respiratory, renal, hepatic, and central nervous system dysfunctions, which were believed to be primarily the results of his Legionella infection . Aggressive antibiotic treatment produced no response, and Legionella remained isolatable from lung tissue throughout several weeks of antimicrobial therapy . Human herpesvirus 6 was isolated from a sample of peripheral blood during the acute stage of the patient's illness, and numerous HHV-6--infected macrophages and lymphocytes were detected by immunohistochemical staining of biopsy-derived lung tissue . Paradoxically treatment of the patient with high-dose corticosteroids resulted in dramatic improvement of his condition, including clearance of the Legionella infection . The demonstration that corticosteroids efficiently inhibit HHV-6 replication in vitro suggests that the virus may have contributed to the patient's pneumonitis by enhancing tissue inflammation, by compromising the function of pulmonary macrophages, and, perhaps, by destroying the patient's CD4+ T lymphocytes . Human herpesvirus 6 may be able to function as a synergistic cofactor in lung infections by Legionella and other pathogens. Am J Ophthalmol, 1991 May 15, 111(5), 601 - 10 Current practices in the management of ocular toxoplasmosis; Engstrom RE Jr et al.; To determine current practices in the management of ocular toxoplasmosis, 72 of 85 uveitis specialists (85%) in the American Uveitis Society completed a detailed questionnaire . Questions involved the indications for beginning treatment, choice of antiparasitic/antimicrobial agents, and experience with treatment of ocular toxoplasmosis in special situations including pregnancy, neonatal infections, and immunocompromised patients . Most of the respondents treat patients whose visual acuity had decreased to worse than 20/200, lesions located in the peripapillary, perifoveal, or maculopapillary bundle regions, and lesions associated with severe vitreous inflammation . Most would not treat patients who retained visual acuity of 20/20, lesions located in the far peripheral retina, or lesions associated with only trace to mild vitreous inflammation . Treatment of other combinations of factors remains controversial . Eight different antimicrobial drugs are used in various combinations for lesions threatening the macula or optic nerve head . Systemic corticosteroids are used by 59 of 62 respondents (95%) as part of their initial treatment regimen . The most commonly used regimens are pyrimethamine/sulfadiazine/corticosteroids (20 of 62 {32%}) and pyrimethamine/sulfadiazine/clindamycin/corticosteroids (17 of 62 {27%}) . Adjunctive therapies (photocoagulation, cryotherapy, or vitrectomy) have been used by 20 of 60 respondents (33%) . Most alter treatment during pregnancy, in newborn patients, and in patients with the acquired immunodeficiency syndrome. Blood, 1991 May 15, 77(10), 2109 - 17 Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine; Miles SA et al.; Twenty-two patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex and multilineage hematopoietic defects were treated with recombinant granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) in a phase I/II trial . All patients were neutropenic and anemic after withdrawal of all bone marrow-suppressive drugs . Daily, G-CSF was subcutaneously self-administered until an absolute neutrophil count (ANC) greater than 6,000/microL was achieved and maintained for 2 weeks . Subcutaneous EPO was added to the regimen and the dose increased until an increase of 15 g/L of hemoglobin was observed . Groups of patients were administered increasing doses of zidovudine to determine their tolerance . G-CSF and EPO therapy was continued with dose modification to maintain an ANC greater than 1,500/microL and hemoglobin greater than 100 g/L . The dose of zidovudine was not altered . All 22 patients responded to G-CSF with a mean 10-fold increase in neutrophils occurring in less than 2 weeks . Significant increases in CD4 and CD8 cell number, lymphocyte proliferative response, and bone marrow cellularity were seen . EPO therapy increased hemoglobin in all 20 evaluable patients within 8 weeks . Sixteen patients received 1,000 mg and four patients received 1,500 mg of zidovudine per day . The reinstitution of zidovudine resulted in a decline in reticulocytes and hemoglobin and the reappearance of transfusion requirements in eight of the 20 patients, six of whom had the study medications stopped . No patient had the study medications stopped because of neutropenia or thrombocytopenia . Toxicities were mild and did not require dose modifications . Limiting dilution plasma and lymphocyte co-cultures for HIV as well as serum p24 antigen levels did not change significantly during G-CSF or combined G-CSF and EPO therapy . HIV p24 antigen decreased significantly with zidovudine therapy . Opportunistic infections occurred in 14 patients but were successfully treated with myelosuppressive antimicrobial agents, including ganciclovir, without the development of neutropenia . These results suggest that combined therapy with G-CSF and EPO may improve the neutropenia and anemia of AIDS . Combined therapy may allow the resumption of full-dose zidovudine in most patients intolerant of the hematologic effects of zidovudine without apparent alteration of HIV expression or the efficacy of zidovudine. Biochemistry, 1991 May 14, 30(19), 4671 - 8 Hemolytic and antimicrobial activities of the twenty-four individual omission analogues of melittin; Blondelle SE et al.; Although melittin's hemolytic activity has been extensively studied, the orientation of membrane-bound melittin remains uncertain . We have investigated the effect of individually omitted amino acid residues on melittin's activity and related these results to the existing models of melittin-membrane interaction . The extent of hemolysis of the omission analogues closely followed the four known conformational regions of melittin: omission of any of the residues making up the two alpha-helical regions decreased the hemolytic activity relative to melittin, while omission of any of the residues making up the "hinge" or the C-terminal regions had little or no effect . Our results correlate best with a proposed model in which melittin initially forms "holes" in the membrane, resulting in an initial rapid loss of hemoglobin; the membrane-bound melittin is then internalized into the membrane, resulting in a later slow phase of hemoglobin loss . It was also found that induced structural effects caused by peptide-lipid interactions could be studied by using RP-HPLC, with an excellent correlation found between the retention times of the individual omission analogues and their hemolytic activities. N Z Med J, 1991 May 8, 104(911), 179 - 81 Pyogenic liver abscesses: a retrospective review of 24 cases; Burt MJ et al.; OBJECTS: to review our experience of pyogenic liver abscess with attention to the value of ultrasound and computerised tomography, and the duration of antimicrobial therapy . METHOD: retrospective review of all pyogenic liver abscesses in Christchurch hospitals between 1972 and 1989 . RESULTS: twenty-four cases were identified . The presentation of these cases was typical of those described in other series . Ultrasound scanning was positive in 69% of cases, and computerised tomography in 94% . Enteric organisms were isolated from blood or abscess cavities in all but two cases . Two patients died soon after admission and three were treated with antimicrobial therapy alone . The remainder underwent either a percutaneous or surgical drainage procedure, and received antimicrobial therapy . The antimicrobial therapy was clearly inappropriate in two patients . Eight patients (67%) with single abscesses received less than 10 days of antimicrobial therapy . Four patients (50%) with multiple abscesses received less than 18 days therapy . No patient relapsed . CONCLUSIONS: ultrasound is a convenient initial imaging technique, but may give false negative results . Computerised tomography should be done promptly if clinical suspicion of a liver abscess persists . Both surgical and percutaneous drainage techniques gave good results in combination with antimicrobial therapy . It is probably unnecessary to give prolonged courses of antimicrobial therapy following drainage of single liver abscess, provided there is rapid resolution . Multiple abscesses, or those which are not drained, may require longer courses of antimicrobial therapy. Rinsho Byori, 1991 May, 39(5), 474 - 7 {Present status and problems of clinical bacteriology}; Yokota T et al.; This symposium was made to clear the problems of clinical microbiology and discussed on the accurate identification of an etiological agent from a clinical specimen, proper specimen collection, susceptibility testing and the mechanism of antimicrobial resistance of bacteria . Some difficulties arise in the entire process of making use of a clinical microbiology laboratory, ranging from specimen collection to interpretation of results . One of the major limitations in the accurate identification of an etiological agent is imposed by poor communication between clinician and laboratory personnel . A number of problems in the entire process, from specimen collection to the interpretation of results, have remained unresolved . It came to the conclusion that important things are the information required to make a clinical decision, clear guidelines for specimen collection, rapid specimen transport, rapid transmission of the results and the establishment of a dialogue between clinician and microbiologist. Drug Saf, 1991 May-Jun, 6(3), 171 - 82 Adverse reactions in children . Special considerations in prevention and management; Leary PM; Adverse reactions occur in only 2 to 5% of children for whom drugs are prescribed . Most of those which do occur are mild and transient in nature . Practitioners who treat children should be familiar with the adverse effects of every drug they use and be certain that every drug prescribed is strictly necessary . Antimicrobials and antipyretic/analgesics are the drugs most commonly prescribed for children . Serious adverse reactions such as aplastic anaemia (with chloramphenicol) are fortunately rare . Erythromycin prescribed for intercurrent infection may precipitate signs of toxicity in children receiving carbamazepine or theophylline . Anticonvulsants impair cognitive function and thereby affect school performance . Phenothiazines and metoclopramide prescribed as antiemetics may cause spectacular dystonic posturings, although this adverse reaction is rapidly reversed with intravenous biperiden . The duration of drug therapy in paediatric practice should be limited to the minimum time compatible with full recovery . The management of adverse reactions in childhood hinges on early recognition and prompt withholding of the offending drug . Urgent resuscitation is essential when anaphylactic collapse occurs, but in most instances of adverse reaction symptomatic treatment of discomfort is all that is necessary . It is important that parents of a child who has suffered an adverse reaction be aware of this and know the name of the drug responsible . Practitioners who encounter an unreported adverse reaction have an obligation to notify the appropriate drug monitoring authority. J Antibiot (Tokyo), 1991 May, 44(5), 479 - 85 Tetrazomine, a new antibiotic produced by an actinomycete strain . Taxonomy, fermentation, isolation and characterization; Suzuki K et al.; A new antibacterial antibiotic tetrazomine was found from the fermentation broth of an actinomycete strain which was isolated from beach sand collected at Chichijima, Ogasawara Islands, Tokyo, Japan . The strain Y-09194L, was identified as Saccharothrix mutabilis subsp . chichijimaensis subsp . nov . The antibiotic exhibited broad antimicrobial activity against Gram-positive and Gram-negative bacteria in vitro . It also exhibited strong cytotoxic activity against P388 leukemia cells and showed antitumor activity against P388 leukemia . The apparent molecular formula of tetrazomine was determined as C24H34N4O5 . It has a rare structure which consists of six rings including piperidine, piperadine, oxazole, and pyrrolidine. J Antibiot (Tokyo), 1991 May, 44(5), 472 - 8 Kedarcidin, a new chromoprotein antitumor antibiotic . I . Taxonomy of producing organism, fermentation and biological activity; Lam KS et al.; Strain L585-6 (ATCC 53650) is an actinomycete isolated from a soil sample collected in Maharastra State, India . It produces a new chromoprotein antitumor antibiotic, designated kedarcidin . Taxonomic studies demonstrated that strain L585-6 is an unidentified and unknown actinomycete . Kedarcidin shows potent antitumor activity against implanted P388 leukemia (3.3 micrograms/ml/kg) and B16 melanoma (2 micrograms/kg) in mice . Kedarcidin also shows potent antimicrobial activity against Gram-positive bacteria but no activity against Gram-negative bacteria. Am J Obstet Gynecol, 1991 May, 164(5 Pt 2), 1377 - 80 Patient costs for prophylaxis and treatment of obstetric and gynecologic surgical infections; Stein GE; The use of newer broad-spectrum antimicrobials for prophylaxis and treatment in obstetric and gynecologic surgery can reduce patient morbidity and hospital costs . For prophylaxis, a single dose of a cephalosporin with a long elimination half-life can be as effective as a more prolonged course . Single-dose prophylaxis reduces not only toxicity and cost to the patient but also the likelihood of colonization of the vagina by resistant organisms . Treatment regimens for postoperative pelvic infections should have broad-spectrum coverage against aerobic and anaerobic pathogens to ensure high cure rates and prevent subsequent abscess formation . With the introduction of newer cephalosporins and penicillin combinations that include a beta-lactamase inhibitor, it is now possible to treat these polymicrobial infections effectively with monotherapy . Compared with traditional antibiotic combinations, these drugs can reduce side effects and the costs of drug administration as well as the need for therapeutic monitoring . The use of oral antibiotics to complete a course of treatment can also help decrease the high costs of parenteral antibiotic therapy and hospitalization. Mutat Res, 1991 May, 248(1), 145 - 53 Induction of chromosomal aberrations and SCE by chloramphenicol; Sbrana I et al.; The induction of chromosomal aberrations and sister-chromatid exchanges (SCE) was studied in human lymphocyte cultures treated with chloramphenicol (CAP), an antimicrobial agent acting by inhibiting protein synthesis . Moreover chromosomal aberrations and sister-chromatid exchanges were studied in bone marrow cells of treated mice and in Chinese hamster cell cultures (V79) respectively . While no aberrations were induced by short treatments in human lymphocytes exposed in G1 and G2 phases, high frequencies of aberrations, exclusively of the chromatid type, were induced when the drug was administered during a whole cell cycle . Aberrant metaphases were detected only at the end and a few hours after the end of treatment; at later times aberrant cells reached control values . Doses producing aberrations only slightly increased SCE both in human lymphocytes and in V79 cells . In mouse bone marrow cells CAP induced a high mitotic delay and few structural aberrations; intrachromosomal vacuoles were observed. Arch Intern Med, 1991 May, 151(5), 886 - 95 Mechanisms of bacterial resistance to antibiotics; Dever LA et al.; The three fundamental mechanisms of antimicrobial resistance are (1) enzymatic degradation of antibacterial drugs, (2) alteration of bacterial proteins that are antimicrobial targets, and (3) changes in membrane permeability to antibiotics . Antibiotic resistance can be either plasmid mediated or maintained on the bacterial chromosome . The most important mechanism of resistance to the penicillins and cephalosporins is antibiotic hydrolysis mediated by the bacterial enzyme beta-lactamase . The expression of chromosomal beta-lactamase can either be induced or stably depressed by exposure to beta-lactam drugs . Methods to overcome resistance to beta-lactam antibiotics include the development of new antibiotics that are stable to beta-lactamase attack and the coadministration of beta-lactamase inhibitors with beta-lactam drugs . Resistance to methicillin, which is stable to gram-positive beta-lactamase, occurs through the alteration of an antibiotic target protein, penicillin-binding protein 2 . Production of antibiotic-modifying enzymes and synthesis of antibiotic-insensitive bacterial targets are the primary resistance mechanisms for the other classes of antibiotics, including trimethoprim, the sulfonamides, the aminoglycosides, chloramphenicol, and the quinolone drugs . Reduced antibiotic penetration is also a resistance mechanism for several classes of antibiotics, including the beta-lactam drugs, the aminoglycosides, chloramphenicol, and the quinolones. J Clin Invest, 1991 May, 87(5), 1585 - 93 In vitro killing of oral Capnocytophaga by granule fractions of human neutrophils is associated with cathepsin G activity; Miyasaki KT et al.; The Capnocytophaga are inhabitants of the hypoxic human gingival crevice that are normally prevented by neutrophils from causing periodontal and systemic infection . To identify potential nonoxidative bactericidal mechanisms against Capnocytophaga within human neutrophils, gel filtration chromatography was used to fractionate neutrophil granule extracts . Seven granule fractions, designated A through G, were obtained . The Capnocytophaga were most sensitive to killing by fraction D . Fraction D exhibited substantial bactericidal activity under aerobic and anaerobic conditions . The bactericidal activity associated with ion-exchange subfractions D8-D11, which contained primarily cathepsin G as assessed by enzymatic activity, amino acid composition, and NH2-terminal sequence . Heat-inactivation, diisopropylfluorophosphate, PMSF, and N-benzyloxycarbonylglycylleucylphenylalanyl-chloromethyl ketone inhibited bactericidal activity against Capnocytophaga sputigena but not Escherichia coli . We conclude that (a) human neutrophil cathepsin G is an important antimicrobial system against the Capnocytophaga, (b) the bactericidal activity of cathepsin G against Capnocytophaga is oxygen independent, and (c) an intact enzyme active site is involved in the killing of C . sputigena but not E . coli . We suggest that human neutrophil cathepsin G is an important antimicrobial system against certain oral bacteria and that cathepsin G kills bacteria by two distinct mechanisms. Arch Pathol Lab Med, 1991 May, 115(5), 464 - 6 In vitro antimicrobial susceptibility testing for the newly identified AIDS-associated Mycoplasma . Mycoplasma fermentans (incognitus strain); Hayes MM et al.; Mycoplasma fermentans (incognitus strain) has recently been recognized as a possible infectious pathogen in humans . This mycoplasma is associated with an acute fatal disease in previously healthy patients who do not have the acquired immunodeficiency syndrome . Many patients with the acquired immunodeficiency syndrome suffer a systemic infection with this microbe . Quantitative assay of antimicrobial susceptibility for M fermentans (incognitus strain) in cultures to representative antibiotics has revealed that the microbe is not sensitive to erythromycin, the most commonly used antibiotic for human mycoplasma infections . The testing shows that M fermentans (incognitus strain) is sensitive in vitro to the antibiotics tetracycline, doxycycline, chloramphenicol, clindamycin, lincomycin, and ciprofloxacin. J Infect Dis, 1991 May, 163(5), 951 - 8 Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients . European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group; Isolation and characterization of two antimicrobial agents from mace (Myristica fragrans); Department of Pharmacognosy and Medicinal, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaThe two antimicrobial resorcinols malabaricone B {1} and malabaricone C {2} were isolated from mace, the dried seed covers of Myristica fragrans . Both compounds exhibited strong antifungal and antibacterial activities . Structure modifications by methylation or reduction resulted in diminished activity. J Nat Prod, 1991 May-Jun, 54(3), 774 - 84 Biologically active metabolites from Xenorhabdus spp., Part 1 . Dithiolopyrrolone derivatives with antibiotic activity; McInerney BV et al.; Five related antibiotic compounds, named xenorhabdins, were isolated from cultures of Xenorhabdus spp., bacteria symbiotically associated with insect-pathogenic nematodes . Their chemical structures were elucidated by X-ray crystallography, nmr, and mass spectral analyses to be N-acyl derivatives of either 6-amino-4,5-dihydro-5-oxo-1,2-dithiolo {4,3-b} pyrrole (compounds 1-3) or 6-amino-4,5-dihydro-4-methyl-5-oxo-1,2-dithiolo{4,3-b} pyrrole (compounds 4 and 5) . They are previously unreported members of the pyrrothine family of antibiotics . Antimicrobial and insectidical activities were found . These metabolites are specific to phase one Xenorhabdus. Farmaco, 1991 May, 46(5), 677 - 83 Synthesis and biological evaluation of N-salicyloyl-N-benzyl thiourea and 2,2-dimethyl-4-oxo-6-methoxy benzo-1,3-dioxin; Rashan LJ et al.; The synthesis of N-salicyloyl-N-benzyl-thiourea and 2,2-dimethyl-4-oxo-6-methoxy-benzo-1,3-dioxin are described . They were studied for their antiviral, antiproliferative and antimicrobial activities in vitro . N-salicyloyl-N-benzyl-thiourea exhibited significant activity against Gram-positive bacteria and against influenza viruses types A/Philippine/H3N2, A/Chilli/H1N1 and B/Paraha, as well as against K562 cell proliferation . By contrast, no such activity was demonstrated by 2,2-dimethyl-4-oxo-6-methoxy-benzo-1,3-dioxin. Farmaco, 1991 May, 46(5), 669 - 76 Synthesis and antimicrobial activity of hydroxy-isophthalaldehyde acid derivatives; Piscopo E et al.; 4-hydroxy-isophthalaldehyde acid (1), its alkyl esters (methyl, ethyl, propyl and butyl) and alkyl ethers (propyl, butyl, pentyl and esyl), as well as 6-hydroxy-isophthalaldehyde acid (2) ita alkyl esters (methyl and ethyl), 4-hydroxy-5-iodo-isophthalaldehyde acid (3) and its methyl ester were synthesized and characterized . Antimicrobial and antifungal activity was tested and the LD50 of the most active compound 4 was determined. Antibiot Khimioter, 1991 May, 36(5), 12 - 4 {Quantitative relationships of structure and antimicrobial activity in azole-containing chemotherapeutics}; Prodanchuk NG et al.; Several novel azole-containing compounds belonging to condensed heterocycles were studied in vitro within the program of screening antimicrobial substances . Changes in the activity of the compounds against 8 representatives of the microbial genera dependent on the chemical structure were followed up . The changes in the structure referred to the radicals at positions 1 and 3. J Ethnopharmacol, 1991 May-Jun, 33(1-2), 51 - 5 Isolation and identification of the antibacterial compounds from Helichrysum stoechas; Rios JL et al.; Fractionation of the dicholoromethane extract of the aerial parts of Helichrysum stoechas yielded seven isolates (1-7), which exhibited varying antimicrobial activity against Gram-positive bacteria . Pure compounds 1-3 have been previously reported in the same species and 4 and 5 were identified as italipyrone and plicatipyrone, previously isolated from H . italicum and H . plicatum . The two other isolates are helipyrone (6) and homoarenol (7) mixed with related substances . Compound 6c (4,4'-dihydroxy-5,6,5',6'-tetramethyl-3,3'-methylen-di-pyr-2-one) and 6b helipyrone with one methyl substitution, have not been previously reported in other species. Pathol Biol (Paris), 1991 May, 39(5), 539 - 42 {Determination of antibacterial activity of antiseptic biotextiles in vitro after standard washings}; Lehmann B et al.; A method in vitro is developed for evaluating antibacterial activity of antiseptic "biotextiles" . The latter are particular in that they possess remanent antimicrobial properties, given their ability to carry antiseptic molecules . The method has to detect and measure a potential activity, but also point out it's stability . The biotextile and an appropriated control were repeatedly washed, put in contact with reference bacterial strains and subsequently incubated . The survival bacteria are then plated and counted by method of successive dilution . Compared with the controls, all the washed biotextiles presented a significant activity. Chin Med J (Engl), 1991 May, 104(5), 402 - 8 Survey on use of antimicrobial agents and bacterial resistance in Huashan Hospital; Tung HH et al.; A cross-section study was carried out to assess the general patterns in use of antimicrobial agents and the trends of bacterial resistance in Huashan Hospital . Of 2,400 patients whose charts were reviewed, 61% were given such drugs . 3,596 antibiotic courses were prescribed . Gentamicin was most frequently used . Results of the susceptibility test of 320 bacterial strains showed a high percentage of resistance against gentamicin, ampicillin, and chloramphenicol . Our findings suggest that antibiotic policies in the hospital need reappraising. Rev Infect Dis, 1991 May-Jun, 13 Suppl 6, S486 - 91 Nutritional effects on response of children in developing countries to respiratory tract pathogens: implications for vaccine development; Keusch GT; Malnutrition and respiratory disease commonly occur together, and the immunologic defects caused by malnutrition may affect clinical responses and the impact of vaccines . These defects include impaired maturation and function of T lymphocytes, diminished secretory immune responses, poor humoral antibody responses to polysaccharide antigens, deficient complement activity (especially the alternative pathway), and impaired antimicrobial mechanisms by phagocytic cells . In addition, protein-energy malnutrition often leads to very high serum levels of IgE as a result of altered T cell regulation of IgE production and may contribute to IgE-mediated pathologic responses to respiratory syncytial virus or parainfluenza virus infection . Correction of these deficits may improve host response to infection and enhance vaccine-related protection . Both vitamin A and iron deficiency states have been epidemiologically associated with increased morbidity due to respiratory infection . The impact of preventive therapy with either vitamin A or iron is still uncertain, but such therapy has the potential for diminishing the incidence of respiratory infections and their consequences. J Infect Dis, 1991 May, 163(5), 1145 - 8 Immune cell activation in melioidosis: increased serum levels of interferon-gamma and soluble interleukin-2 receptors without change in soluble CD8 protein; Brown AE et al.; To evaluate immune cell activation in patients with melioidosis, serum samples were assayed for interferon-gamma (IFN-gamma), soluble interleukin-2 receptors (sIL-2R), and soluble CD8 protein (sCD8) . Forty patients with sepsis (23 fatal cases, 17 survivors) and 13 with localized disease were studied during acute illness; 12 additional patients were studied after discharge while on maintenance antimicrobial therapy . Serum concentrations of IFN-gamma and sIL-2R were greatly elevated, but sCD8 concentrations were not . These levels increased with disease severity and were associated with fatal outcomes . Macrophage activation by high concentrations of the cytokine IFN-gamma may contribute to pathophysiology and death in septicemic patients . Both IFN-gamma and sIL-2R seem to be predictive of outcome in patients with severe melioidosis and may prove useful in detection of relapse. Infect Immun, 1991 May, 59(5), 1633 - 8 Gamma interferon suppresses acute and chronic Trypanosoma cruzi infection in cyclosporin-treated mice; McCabe R et al.; To determine if exogenous gamma interferon is effective in immunosuppressed mice infected with Trypanosoma cruzi, recombinant murine gamma interferon was administered to cyclosporin-treated mice with either acute or chronic T . cruzi infection . Gamma interferon significantly decreased parasitemia and prevented death in acutely infected mice . Parasitemias and mortality of mice treated with both gamma interferon and cyclosporin were similar to those of immunocompetent controls . In chronically infected mice, cyclosporin treatment produced significantly more organ explant cultures positive for T . cruzi . Fewer positive cultures, particularly for spleen and heart, were obtained from cyclosporin-treated mice when they also received gamma interferon . Ketoconazole treatment of mice resulted in no positive cultures . Cyclosporin treatment did not prevent activation of peritoneal macrophages by parenteral gamma interferon, nor did it have a consistent effect on serum titers of alpha/beta or gamma interferon in response to a second challenge inoculum of T . cruzi . These data indicate that exogenous gamma interferon suppresses acute and chronic T . cruzi infection in cyclosporin-treated mice but that gamma interferon is not as effective as the relatively specific antimicrobial ketoconazole . Gamma interferon activates macrophages despite cyclosporin treatment, and its effects appear to be tissue specific. Pathol Biol (Paris), 1991 May, 39(5), 451 - 4 {Importance of the antimicrobial mode of action of antibiotics for their combined effect with glycine in subinhibitory concentrations on microbial growth}; Gillissen G et al.; Following previous observations of an increase in microbial sensitivity to the bactericidal beta-lactams ampicillin and imipenem in the presence of glycine, the aim of the presented study was to examine if such an effect is due to the antimicrobial mode of action of an antibiotic and/or to its bactericidal or bacteriostatic capacity . Using growth curves as an experimental parameter the same synergistic glycine effect could be shown if tested concomitantly with a number of other antibiotics acting equally on bacterial cell wall formation as cefaclor, cefadroxil, or fosfomycin . This glycine effect is, therefore, associated with the antibiotic mode of action, but is independent of wether the antibiotics are beta-lactams or not (fosfomycin) . In contrast, glycine had no particular effect in combination with antibiotics inhibiting protein synthesis (sisomicin, kanamycin, chloramphenicol, oxy-tetracycline) or nucleic acid polymerase activity (ciprofloxacin, cinoxacin; rifampicin being a certain exception) as well as with those acting on cytoplasmic and external membrane as polymyxin B . The synergistic effect of glycine and cell wall active antibiotics was interpreted predominantly by an action on carboxypeptidases. Jpn J Antibiot, 1991 May, 44(5), 506 - 14 {Clinical studies on ciprofloxacin in chronic respiratory tract infection}; Yoshida M et al.; Ciprofloxacin (CPFX), a new pyridone carboxylic acid, was administered orally to the patients with chronic respiratory tract infection and its clinical efficacy and safety were studied in a multicenter open trial . The results and summarized as follows . 1 . The efficacy rate for the patients with acute exacerbation as 52.5% (21/40) in 2 week-treatment, and 75.0% (24/32) in 4 week-treatment . 2 . The efficacy rate for the patients with chronic phase was 23.1% (6/26) in 2 week-treatment, and 26.9% (7/26) in 4 week-treatment, but acute exacerbation was not observed in any of the patients . 3 . CPFX was administered to 6 patients over 60 days for the prophylaxis of acute exacerbation . Only 2 patients had acute exacerbation in 2 and 3 months after the start of the therapy, respectively . 4 . Bacteriological eradication rate was high except P . aeruginosa, for which the eradication rate was about 20% . 5 . Side effects were observed in 3 patients, and abnormal findings of laboratory tests were observed in 5 patients, though they were not severe . These results show that CPFX is a useful antimicrobial agent for the treatment of chronic respiratory tract infections. J Pharm Sci, 1991 May, 80(5), 441 - 4 Relation between structure and antimicrobial activity of 2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates; Tsubone K et al.; A series of phosphobetaines {2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates}, having different alkyl chains and a methylene bridge separating the phosphate and ammonio group, was investigated in order to provide a new antimicrobial agent . Maximal activity was obtained with the compound having a hexadecyl group as a long-chained alkyl group, two methyl groups as short-chained alkyl groups, and a dimethylene bridge as an intercharge distance . In contrast, sodium 2-(N-hexadecyl-N-methylamino)ethyl hydrogen phosphate, 2-(N-hexadecyl-N,N-dimethylammonio)-1-hydroxyethyl iodide, and N-octadecyl-N,N-dimethylammonio acetate showed decreased activity, indicating that the presence of a phosphobetaine moiety was essential for activity . Thus, 2-(N-hexadecyl-N,N-dimethylammonio)ethyl hydrogen phosphate has been found to possess strong antimicrobial activity and a broad antimicrobial spectrum against nine kinds of bacteria (e.g., fungi, yeast, gram-negative and gram-positive bacteria), which are comparable with those of chlorhexidine digluconate. Dtsch Tierarztl Wochenschr, 1991 May, 98(5), 167 - 70 {The "protective acid coat" of the skin of our domestic animals}; Meyer W et al.; The study reviews and discusses functional aspects of the so-called "acid mantle" of the integumentum commune of domesticated mammals and birds . The problems referred to are closely related to the skin surface-pH and different factors influencing this phenomenon (chemical composition of the skin surface film, secretory activity of apocrine tubular glands, structure of the microflora, lack of skin glands in birds) . It becomes evident, that an "acid mantle" of the skin of domesticated animals cannot be verified, and that normal skin-pH (medium values weakly acid to alkaline) exerts no microbicidal effects . Integumental antimicrobial properties may rather be connected with free fatty acids as decomposition products of skin lipids. J Antimicrob Chemother, 1991 May, 27 Suppl C, 129 - 39 Empirical antimicrobial therapy with a single daily dose of ceftriaxone plus amikacin in febrile granulocytopenic patients: a pilot study; Meunier F et al.; The optimal management of fever in granulocytopenic patients remains controversial . This pilot study investigated the potential value of single daily doses of amikacin administered empirically with ceftriaxone in febrile granulocytopenic patients . None of the patients died as a result of infection or toxicity from the prescribed regimen . Serum concentrations failed to show drug accumulation . Modifications of empirical antimicrobial therapy were made at a similar rate to other conventional regimens . Vancomycin seemed to increase the incidence of nephrotoxicity . Overall, this pilot study suggests that empirical therapy with single daily doses of amikacin plus ceftriaxone is safe and effective and should be further investigated in a larger number of patients. Antimicrob Agents Chemother, 1991 May, 35(5), 995 - 7 In vitro susceptibilities of clinical isolates of cysteine-requiring Escherichia coli to 12 antimicrobial agents; McIver CJ et al.; The MICs of 12 antimicrobial agents for 42 cysteine-requiring strains of Escherichia coli showed a high concordance when determined on three different media, one of which was supplemented with cysteine . Differences in the MICs of several agents were detected between 18 prototrophic revertants and their parent auxotrophs . A total of 64.7% of the isolates were fully susceptible to all agents, and no particular resistance pattern was evident. Antimicrob Agents Chemother, 1991 May, 35(5), 873 - 8 Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors . The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group; Meunier F et al.; Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues . The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma . The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients {65%} versus 48 of 53 patients {91%}, P = 0.002) . Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin . Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin . This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients. Antimicrob Agents Chemother, 1991 May, 35(5), 869 - 72 Bactericidal effect of amoxicillin on Helicobacter pylori in an in vitro model using epithelial cells; Megraud F et al.; The treatment of Helicobacter pylori with antimicrobial agents has largely been ineffective, and susceptibility results are in disagreement with those obtained by standard in vitro testing . The bactericidal effect of amoxicillin was tested in an in vitro model by using sessile bacteria attached to HEp-2 cells; this bactericidal effect was compared with that against planktonic bacteria . Viable cell counts were performed by standard procedures after 1, 6, and 24 h of contact with the antibiotic at different concentrations . A bactericidal effect (99.9% killing) was observed against sessile bacteria after 24 h with concentrations of only 10, 1, and 0.1 mg/liter, while against planktonic bacteria it was also noted at concentrations of 0.01 and 0.001 mg/liter, and the effect was observed after 6 h with the three highest concentrations . When the results for five strains were studied by analysis of variance at 6 and 24 h, the main variable was the antibiotic concentration, followed by the culture conditions, e.g., planktonic or sessile bacteria, the strain tested, and the time of contact . A decreased pH of 5.4 did not affect the action of amoxicillin . The bactericidal effect of the combination of amoxicillin and metronidazole was additive against sessile H . pylori. Arch Surg, 1991 May, 126(5), 603 - 8 Effects of topical antimicrobial agents on the human neutrophil respiratory burst; Hansbrough JF et al.; The neutrophil oxidative burst plays an important role in killing intracellular microorganisms . We studied the effects of topical antimicrobial agents on the N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated oxidative burst of human peripheral blood neutrophils, using a flow cytometric assay . Mafenide acetate, sulfadiazine silver, gentamicin sulfate, neomycin sulfate-polymyxin B sulfate (Neosporin GU irrigant), acetic acid, amphotericin B, and povidone-iodine inhibited the neutrophil oxidative burst at or below clinical concentrations, while 0.25% modified diluted sodium hypochlorite (Dakin's) solution caused cell death . Bacitracin-polymyxin B sulfate (Polysporin) greatly augmented the respiratory burst; this effect was due to the bacitracin component . Diluted gentamicin and acetic acid also augmented intracellular hydrogen peroxide production, but to a lesser extent than Polysporin . Inhibition of the respiratory burst of neutrophils might be considered when these agents are used for topical wound care, although clinical correlates of these effects have not been determined. Infection, 1991 May-Jun, 19(3), 195 - 200 Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with beta-lactams and aminoglycosides; Fauser AA et al.; We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy . All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases . All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v . once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily) . All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy . The therapeutic regimen was well tolerated; only one adverse drug reaction was observed . We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy) . Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides. Int Endod J, 1991 May, 24(3), 119 - 25 The antimicrobial effect of calcium hydroxide as a short-term intracanal dressing; Sjogren U et al.; The antibacterial effect of calcium hydroxide as a short-term intracanal dressing was clinically evaluated by applying the medicament for 10 minutes or 7 days in root canals of teeth with periapical lesions . The results showed that the 7-day dressing efficiently eliminated bacteria which survived biomechanical instrumentation of the canal, while the 10-minute application was ineffective. Placenta, 1991 May-Jun, 12(3), 285 - 8 Antibacterial properties of human amniotic membranes; Talmi YP et al.; Amniotic membranes are widely used in a multitude of surgical applications and have been shown to reduce bacterial counts and promote healing in infected wounds . Antibacterial properties of amniotic fluid are well documented and the presence of many potentially antibacterial factors has been demonstrated . No such factors have yet been found in amniotic membranes . We have applied a direct disc-diffusion susceptibility test to try to establish the possible existence of such a factor . Amniotic membranes did not inhibit five bacterial species when tested at 3 X 10(6) and 3 X 10(8) colony forming units/ml . However, complete growth inhibition of all organisms was seen immediately under the amniotic membrane discs . These results support the hypothesis that the antimicrobial effect of amniotic membranes in vitro is due to their close adherence to the wound surface. Z Naturforsch {C}, 1991 May-Jun, 46(5-6), 442 - 50 Podoscyphic acid, a new inhibitor of avian myeloblastosis virus and Moloney murine leukemia virus reverse transcriptase from a Podoscypha species; Erkel G et al.; A novel enzyme inhibitor of RNA-directed DNA-polymerases of avian myeloblastosis and murine leukemia virus was isolated from fermentations of an tasmanian Podoscypha species . Its structure was elucidated by spectroscopic methods and oxidative degradation as (E)-4,5-dioxo-2-hexadecenoic acid (1) . The enzyme inhibitor, which was named podoscyphic acid, did not inhibit DNA and RNA synthesis in permeabilized L 1210 cells nor did it affect RNA synthesis in isolated nuclei of L 1210 cells . 1 inhibits protein synthesis in whole L 1210 cells and rabbit reticulocyte lysate and shows very weak antimicrobial and cytotoxic properties . The testing of ethyl (E)-4,5-dioxo-2-hexadecenoate (2) and (E)-4-oxo-2-tetradecenoic acid (11) revealed the importance of the free gamma-oxoacrylic acid unit for the biological activities of 1. Anticancer Res, 1991 May-Jun, 11(3), 1039 - 43 Effects of antimicrobial drugs on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin; Bergstrom P et al.; The effect of concomitant treatment with different antibiotics on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin was studied in vitro on fibroblasts (V79) and two cancer cell lines (colon cancer HT29 and lung cancer P31) . The cell lines were propagated under standard tissue culture conditions and evaluated as the number of surviving cell clones in comparison to untreated controls . Fifteen commonly used antibiotics were tested and thirteen of these were found to modify the cytotoxic effect in one or several of the combinations tested . One antibiotic agent could affect the toxicity of different cytostatics in opposite directions and there were marked differences between the cell lines tested . Only in one of the situations, the combination of bleomycin and ceftazidim, did the antibiotic cause opposite effects on the toxicity of a cytostatic when comparing fibroblasts and carcinoma cells . A most impressive observation was the pronounced increase in cisplatin-induced cytotoxicity by amphotericin B . In conclusion, the results suggest that antibiotics can interact with the cytotoxicity of antitumoral drugs but that the feature of this interaction is seemingly an erratic phenomenon . Further studies are certainly justified, especially regarding the effects of amphotericin B and its mechanisms in enhancing the cytotoxicity of cisplatin. Kansenshogaku Zasshi, 1991 Apr, 65(4), 457 - 64 {Study on Chlamydia trachomatis antigen detection by an EIA kit using a monoclonal antibody--comparison with a polyclonal EIA kit in urogenital infections}; Hayashi K et al.; We evaluated the clinical usefulness of a new EIA kit using a monoclonal antibody, IDEIA CHLAMYDIA (IDEIA, Novo Nordisk), for detection of C . trachomatis antigen from the genital tracts of male and female cases . The results were compared with those by Chlamydiazyme (Abbott) . 1 . C . trachomatis antigen detection by the IDEIA and Chlamydiazyme tests before treatment; IDEIA has a significantly higher detection rate (38.0%, 105/276) than Chlamydiazyme (29.8%, 80/276), for C . trachomatis antigen from urethral smears of 276 male patients with urethritis . In 646 female cases, including cervicitis and so on, IDEIA detected C . trachomatis antigen from cervical smears in 14.5% (94/648) of the total, while Chlamydiazyme did so in 11.9% (77/648) . When considering the different results using IDEIA and Chlamydiazyme, approximately 20% of the IDEIA-positive cases were Chlamydiazyme-negative . However, when IDEIA was negative, less than 1% showed Chlamydia-positive . 2 . C . trachomatis antigen detection during and after treatment; We studied the clinical courses of 14 male urethritis and 8 female cervicitis cases who had had positive results with both IDEIA and Chlamydiazyme before treatment . Two of the 14 urethritis cases showed positive results with IDEIA, but not with Chlamydiazyme after either 7 or 14 days treatment by an antimicrobial agent . These two also had symptoms indicating persistent urethritis . One of the 8 female cervicitis cases showed a positive result with IDEIA but not with Chlamydiazyme after 7 days treatment by an antimicrobial agent, and this case also had symptoms indicating persistent cervicitis . Thus, these clinical findings suggest that IDEIA can detect even a small quantity of antigen soon after treatment, but Chlamydiazyme can not . In conclusion, IDEIA has a higher sensitivity than Chlamydiazyme, in the detection of C . trachomatis antigen, suggesting that IDEIA is more useful. Antimicrob Agents Chemother, 1991 Apr, 35(4), 741 - 6 Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections; Widmer AF et al.; Antimicrobial therapy of device-related infections often fails, despite the in vitro susceptibility of the infecting strain . Therefore, alternative laboratory-based in vitro tests are required to predict the outcome . Fleroxacin, ciprofloxacin, aztreonam, and co-trimoxazole were tested against Escherichia coli ATCC 25922 in vitro and in the tissue-cage animal model . The importance of early treatment was evaluated by starting the drugs either 30 min before or 4, 12, and 24 h after bacterial challenge . Results were compared with the in vitro drug efficacy against nongrowing and adherent Escherichia coli ATCC 25922 . The alternative in vitro tests correlated highly with the outcome in the tissue-cage animal model . In the prophylaxis group (drug given 30 min before bacterial challenge), co-trimoxazole was less efficacious than the other three drugs (P less than 0.001) . In delayed treatment, ciprofloxacin showed the highest cure rate . It was also more potent than the other drugs against nongrowing and adherent E . coli ATCC 25922 . The efficacies of aztreonan, fleroxacin, and ciprofloxacin dropped significantly (P less than 0.01) when the time interval between bacterial challenge and the start of treatment was delayed to greater than 4 h . These data emphasize (i) the need for proper timing of prophylaxis in patients undergoing implant surgery, and (ii) the possibility of successful treatment of established device-related infections with drugs which kill not only growing but also nongrowing and adherent bacteria. Pediatr Infect Dis J, 1991 Apr, 10(4), 294 - 8 Concentration of cefuroxime in serum and middle ear effusion after single dose treatment with cefuroxime axetil; Haddad J Jr et al.; Antimicrobial agents play an important role in the treatment of patients with acute otitis media and otitis media with effusion (OME) . The study was undertaken to determine the concentrations of cefuroxime in the blood and middle ear effusions (MEE) of children between 6 and 12 years of age with acute otitis media and chronic OME after a single oral dose administration of cefuroxime axetil, the ester prodrug of cefuroxime . Cefuroxime axetil (250 mg) was administered 2 to 6 hours before either myringotomy for acute otitis media or myringotomy and tube insertion for chronic OME . Blood samples and middle ear aspirates were obtained from 31 children and the samples were analyzed by high performance liquid chromatography . Cefuroxime was recovered in measurable concentrations in all serum samples and in 15 (79%) of the 19 MEE specimens analyzed . No correlation was seen between cefuroxime MEE concentrations and effusion type, bacteriology or serum concentrations . This study shows that cefuroxime does penetrate into MEE when OME is present and that therapeutic concentrations can be achieved in some patients. Clin Podiatr Med Surg, 1991 Apr, 8(2), 341 - 57 A sensible approach to early postoperative foot infection in the otherwise healthy patient; Krantz JG; Many excellent articles published deal with the very important didactic minutiae of postoperative infection, including discussions about specific antimicrobial therapy, operatory sterility, surgical and aseptic technique, and other similar subjects . Very few discussions deal at great length with the more subjective aspects of the infected wound and its management, which is very much a learned art . Nonetheless, this article has been devoted to primarily three subjects: the patient, the wound, and the surgeon. Vet Clin North Am Equine Pract, 1991 Apr, 7(1), 53 - 61 Bacterial pneumonia; Traub-Dargatz JL; Bacterial pneumonia in the horse often occurs secondary to viral respiratory infection; however, primary infections can occur . A diagnosis of bacterial pneumonia is made on the basis of history, physical examination, and laboratory and radiographic findings . Treatment consists of appropriate antimicrobial therapy for at least 7 to 10 days; further therapy may be needed in more severe cases . Prevention of bacterial pneumonia includes attempting to prevent viral respiratory infections and appropriate management to prevent stress to the respiratory tract. Burns, 1991 Apr, 17(2), 155 - 8 The use of Omiderm as an interface for skin grafting; Eldad A et al.; Burn wounds which require skin grafts are often heavily contaminated . Conventional methods of skin grafting demand bulky dressings and immobilization for 3-5 days . During this period, we cannot treat the wound topically, but can only hope that the skin graft will win the battle against infection and survive on the wound . The concept of an interface that has emerged in the past few years allows us to treat the wound topically through a transparent, permeable membrane that covers the skin graft without disturbing it . Omiderm, a hydrophilic polyurethane film that was developed as a burn dressing, has been used as an interface on 10 patients . Skin grafts on problematical areas and heavily contaminated wounds were covered with 1:1.5 non-expanded meshed Omiderm . An external layer of dressing with a topical antimicrobial agent was changed 8-24 h postoperatively and then at regular intervals . About 75 per cent 'take' was achieved, which was better than expected with other dressings under similar conditions. Int J Oral Maxillofac Surg, 1991 Apr, 20(2), 65 - 8 Mediastinitis from odontogenic infection . Report of three cases and review of the literature; Garatea-Crelgo J et al.; Descending necrotizing mediastinitis secondary to dental infection occurs infrequently . The diagnosis of this condition is difficult and often a surgical approach is delayed due to initial clinical improvement after antimicrobial therapy . An incorrect evaluation of this apparent improvement may result in fatal mediastinitis and septic shock . We report 3 cases of mediastinitis of odontogenic origin . In one patient, a nonproductive cough was the first sign of thoracic involvement . A total of 25 similar cases of mediastinitis from odontogenic infection have been collected from the literature in the last 15 years . Some features have to be emphasized, such as the polymicrobial flora, the higher prevalence in males, and the high mortality rate of approximately 44%. Mol Gen Genet, 1991 Apr, 226(1-2), 214 - 23 Identification and chromosomal locations of a family of cytochrome P-450 genes for pisatin detoxification in the fungus Nectria haematococca; Miao VP et al.; The ability to detoxify the phytoalexin, pisatin, an antimicrobial compound produced by pea (Pisum sativum L.), is one requirement for pathogenicity of the fungus Nectria haematococca on this plant . Detoxification is mediated by a cytochrome P-450, pisatin demethylase, encoded by any one of six Pda genes, which differ with respect to the inducibility and level of pisatin demethylase activity they confer, and which are associated with different levels of virulence on pea . A previously cloned Pda gene (PdaT9) was used in this study to characterize further the known genes and to identify additional members of the Pda family in this fungus by Southern analysis . DNA from all isolates which demethylate pisatin (Pda+ isolates) hybridized to PdaT9, while only one Pda- isolate possessed DNA homologous to the probe . Hybridization intensity and, in some cases, restriction fragment size, were correlated with enzyme inducibility . XhoI/BamHI restricted DNA from reference strains with a single active Pda allele had only one fragment with homology to PdaT9; no homology attributable to alleles associated with the Pda- phenotype was found . Homology to this probe was also limited to one or two restriction fragments in most of the 31 field isolates examined . Some unusual progeny from laboratory crosses that failed to inherit demethylase activity also lost the single restriction fragment homologous to PdaT9 . At the chromosome level, N . haematococca is highly variable, each isolate having a unique electrophoretic karyotype . In most instances, PdaT9 hybridized to one or two chromosomes containing 1.6-2 million bases of DNA, while many Pda- isolates lacked chromosomes in this size class . The results from this study of the Pda family support the hypothesis that deletion of large amounts of genomic DNA is one mechanism that reduces the frequency of Pda genes in N . haematococca, while simultaneously increasing its karyotypic variation. Clin Pharm, 1991 Apr, 10(4), 280 - 91 Current and investigational therapies for AIDS-associated Mycobacterium avium complex disease; Rathbun RC et al.; The epidemiology, pathogenesis, clinical manifestations, and treatment of Mycobacterium avium complex (MAC) infection are reviewed . MAC infection is one of the most common infections in AIDS patients . Its pathogenesis is poorly understood, but it is believed to develop by gastrointestinal colonization followed by systemic invasion . The relatively poor response to treatment may be partly accounted for by the tremendous mycobacterial load present by the time patients develop systemic symptoms . Clinically, MAC infection is difficult to differentiate from the signs and symptoms of AIDS or from other opportunistic infections . Signs and symptoms include fever, malaise, anorexia, night sweats, and weight loss; diarrhea and abdominal pain may also be present . There is no established therapy for MAC infection, although combinations of three to five antimicrobial agents are typically used . There has been consistently poor correlation between in vitro results and in vivo outcomes in the treatment of MAC infection . Currently, the role of treatment is mainly to suppress the progression of infection and to relieve symptoms . Recent in vitro studies and animal studies have revealed possible alternative agents and combinations of agents (e.g., macrolide antibiotics, quinolones, amikacin, cytokines) that may influence therapy of MAC infection . No known therapy for MAC has been shown to prolong survival in AIDS patients, possibly because of the high organism load that exists once patients become symptomatic . Research is needed to find improved methods for earlier detection of MAC infection, determine optimal dosage regimens of current antimycobacterial agents, develop better antimycobacterial drug-delivery systems (e.g., liposomes), and discover new antimicrobials with better activity against MAC and methods of immune modulation that will overcome immune system defects. J Laryngol Otol, 1991 Apr, 105(4), 252 - 6 Biocompatible implantable antimicrobial release for necrotizing external otitis; Ostfeld EJ et al.; The efficacy of a biocompatible, surgically implantable, antimicrobial release system (IARS) as the exclusive antimicrobial therapy of necrotizing external otitis (NEO) was evaluated in six NEO patients . Gentamicin incorporated polymethyl-methacrylate beads were implanted, following surgical debridement and were removed two months later . Post-implantation alleviation of clinical symptoms: pain, periauricular tissue swelling, otorrhoea, eradication of pseudomonal infection (100 per cent) and substantially shortened hospitalization (4-15 days) were the salient results of this therapeutic modality . Three patients recovered . Two patients who died, one of sudden cardiac arrest and the other of paralytic ileus, 15 and 60 days post-operatively while the beads were still implanted, were symptomless . Recurrence was seen in one patient with early bead extrusion . Ipsilateral sensorineural hearing loss (one patient) and external meatal stenosis were the main complications . IARS appears to offer an effective alternative to long-term systemic antibiotic administration for the eradication of NEO-pseudomonal infection in patients who are sensitive, develop resistance, or when quinolone medical treatment has failed or is contra-indicated. Hematol Oncol Clin North Am, 1991 Apr, 5(2), 195 - 214 Hematologic abnormalities in AIDS; Aboulafia DM et al.; The hematologic manifestations of HIV infection include morphologic abnormalities of peripheral blood and bone marrow changes . Laboratory abnormalities, including measures of coagulation, serum vitamin B12 levels, and positive Coombs's test, are seen with HIV infection and may not carry the same clinical consequence as when noted in non-HIV infected populations . Antibodies to circulating red blood cells, platelets, and granulocytes may represent alterations in autoimmunity or nonspecific HIV-induced B-cell stimulation, but they do not necessarily correlate with development of peripheral blood cytopenias . The advent of commercially available hematopoietic growth factors has allowed greater insight into specific host-virus-drug interactions that may be important in regulating viral growth and expression . Novel clinical approaches using hematopoietins alone or in combination with antimicrobial, antiviral, and antitumor drugs represent exciting developments in the treatment of HIV infection. Am J Med, 1991 Apr, 90(4), 528 - 9 Acute psychoses associated with the use of ciprofloxacin and trimethoprim-sulfamethoxazole; McCue JD et al.; Although adverse drug reactions are a well-recognized cause of mental status changes in the elderly, antimicrobials are rarely implicated . Three patients with serious organic brain disease developed paranoid psychosis after therapy with trimethoprim-sulfamethoxazole or ciprofloxacin was begun . One of the patients was accidently rechallenged and again developed a psychotic reaction . The acute psychoses did not improve with moderate doses of major tranquilizers but resolved completely with drug discontinuation. Pediatrics, 1991 Apr, 87(4), 466 - 74 Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial; Kaleida PH et al.; A total of 536 infants and children with acute otitis media were randomly assigned to one of six consistent year-long regimens involving the treatment of nonsevere episodes with either amoxicillin or placebo, and severe episodes with either amoxicillin, amoxicillin and myringotomy, or, in children aged 2 years or older, placebo and myringotomy . Nonsevere episodes had more favorable outcomes in subjects assigned to treatment with amoxicillin than with placebo, as measured by the proportions that resulted in initial treatment failure (3.9% vs 7.7%, P = .009) and the proportions in which middle-ear effusion was present at 2 and 6 weeks after onset (46.9% vs 62.5%, P less than .001; and 45.9% vs 51.5%, P = .09, respectively) . In subjects whose entry episode was non-severe, those assigned to amoxicillin treatment had less average time with effusion during the succeeding year than t