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JM9 strains, a new type of group B streptococci from Japan.

JM9 strains isolated from human carriers and patients in several districts of Japan, represent a new serotype of group B streptococci (GBS, Streptococcus agalactiae). They were first detected in 1983 but are meanwhile prevailing among all other GBS serotypes in Japan. Outside of Japan, strains of this type have not been reported until now. In the present work, N-acetylneuraminic acid was detected in all strains investigated, by chemical analysis as well as by interaction with a sialic acid-binding lectin. This component is characteristic of all analyzed GBS type polysaccharides. In a chicken embryo model, all strains exhibited a very strong virulence. Examination of the antibiotic sensitivity revealed that all strains were susceptible to penicillin, cephalothin, clindamycin, mezlocillin, azlocillin, erythromycin, methicillin, chloramphenicol, tetracyclin, oxacillin and sulfamethoxazole/trimethoprim, whereas all strains were resistant against gentamicin, kanamycin and neomycin. Electron microscopic studies revealed for these strains relatively small capsules but unusually thick cell walls. By immunogold labelling, the type polysaccharide, the group polysaccharide, the lipoteichoic acid and in some strains, the protein R were localized.

Animals↗

Relapsing malignant otitis externa successfully treated with ciprofloxacin.

Two cases are presented, both patients with advanced relapsing malignant otitis externa. The antibiotic ciprofloxacin has strong anti-pseudomonal activity. It was given orally for six months to both patients, following administration of the traditional parenteral antibiotic courses, and in each case the disease has been extinguished. We therefore recommend that the management of patients shown to have malignant otitis externa should include strict diabetic control, regular local aural toilet, gentamicin ear drops and a six week course of parenteral antipseudomonal antibiotic agents (usually gentamicin and azlocillin) together with metronidazole to cover any anaerobic element in the infection. This regimen should be followed by a six month course of oral ciprofloxacin (750 mg b.d.). Indium scans should be used to monitor recovery. We believe that this regimen can significantly reduce the morbidity and mortality of patients suffering from malignant otitis externa with cranial nerve involvement.

Aged↗

Antibiotic resistance in intensive care unit areas.

The incidence of nosocomial infections and antimicrobial resistance rates of nosocomial pathogens vary considerably among countries and even among intensive care units (ICUs) within one hospital. Such differences might be partly due to the selection pressure exerted by certain antibiotics, since intensive care patients are given more antimicrobials than any other group of patients. We therefore compared resistance rates of four important nosocomial pathogens (Staphylococcus aureus, E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) isolated from patients in general wards and ICUs. There were few trends toward higher resistance of ICU isolates, and most differences were found with Klebsiella pneumoniae. We also tried to relate antibiotic use in ICUs and frequency of antibiotic resistance of five selected nosocomial pathogens. The ampicillin and cephalosporin resistance of E. coli and Klebsiella pneumoniae arose along with an increase in usage of both drugs. Decreasing prescription of cotrimoxazole was not reflected by decrease in resistance of Staphylococcus aureus and Staphylococcus epidermidis. Increasing prescriptions of tetracyclines were followed by an increasing resistance of E. coli, but not of Staphylococci. The oxacillin resistance of Staphylococcus epidermidis almost paralleled the consumption, the opposite was true for Staphylococcus aureus. There seemed to be a rather close relationship between the incidence of resistant Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa strains and the quantities of gentamicin, tobramycin and azlocillin prescribed. The increase or decrease of prescriptions of certain antimicrobials increased or decreased their resistance rate to the respective drugs of only certain bacterial strains in one ICU, but not in the other. The findings in our hospital cannot necessarily be applied to other hospitals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates.

1. Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an open-intestinal perfusion model and an intestinal loop model respectively. 2. In the presence of quinidine, verapamil and cyclosporin (substrates of the P-glycoprotein (P-gp)), plasma AUCs of ciprofloxacin were 1.5 - 2 fold increased, while biliary clearance (1.5 - 2 fold), intestinal overall and net clearances (2 - 4 fold and 1.5 - 8 fold respectively) decreased. The weak effect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct from the P-gp, as the OCT1 transporter which could be inhibited by quinidine. 3. With cephalexin and azlocillin, two beta-lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3 - 2 fold), suggesting the involvement of organic anion and/or cation transporters. 4. In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance of ciprofloxacin. In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased. 5. The specificity of ciprofloxacin intestinal transport appears to be different from P-gp as outlined by the lack of competition with sparfloxacin, a P-gp substrate. Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil.

Animals↗

Evaluation of culture media for the recovery of Mycobacterium avium subsp. paratuberculosis from Cheddar cheese.

AIMS: The study evaluated the efficacy of four Mycobacterium avium subsp. paratuberculosis (MAP) culture media in suppressing commonly used starter cultures and typical nonstarter microflora present during the manufacture and ripening of Cheddar cheese, with a view to identify a suitable medium for the enumeration of MAP during laboratory-scale Cheddar production. METHODS AND RESULTS: Four Cheddar starter cultures and Cheddar cheese manufactured with these starters were inoculated onto Herrold's egg yolk medium (HEYM); HEYM supplemented with vancomycin, amphotericin B and nalidixic acid (HEYM/VAN); Middlebrook 7H10 agar containing polymyxin, amphotericin B, nalidixic acid, trimethoprim and azlocillin (PANTA) antibiotic supplement; and BACTEC 12B radiometric medium with and without a preliminary decontamination step (0.75% w/v hexadecylpyridinium chloride (HPC), 5 h). The inclusion of a decontamination step inhibited all Cheddar cheese starter and nonstarter micro-organisms. The medium 7H10/PANTA and to a lesser extent HEYM/VAN were effective inhibitors of cheese microflora when no decontamination step was employed. CONCLUSIONS: Middlebrook 7H10 medium, supplemented with PANTA antibiotics, suppressed all micro-organisms associated with ripening Cheddar cheese manufactured with pasteurized milk. SIGNIFICANCE AND IMPACT OF THE STUDY: A MAP culture medium has been identified, which may be used to enumerate this bacterium during the laboratory manufacture and ripening of Cheddar cheese and hence facilitate further research into the persistence of this pathogen in the product.

Animals↗

[Mycobacterium genavense infection in AIDS].

Fever, loss of weight, anaemia, hepatosplenomegaly and lymphadenopathy developed in two HIV-infected patients. At first malignant lymphoma with septicaemia was thought to be the cause. In both patients Salmonella enteritidis was isolated by blood culture and found to be sensitive against the antibiotics that were given (5 g azlocillin and 2 g cefotaxime, three times daily each; additionally in case 2, metronidazole, 500 mg three times daily). Because bone-marrow biopsy demonstrated acid-fast rods, antimycobacterial treatment was started (isoniazid 300 mg/d, rifampicin 600 mg/d, ethambutol 1,200 mg/d and pyrazinamide 2 g/d). Despite this the patients died of septic shock. Histological examination revealed massive amounts of acid-fast rods in spleen, liver, gut and bone marrow. Polymerase chain reaction and sequencing identified the structure as that of the recently discovered M. genavense.

AIDS-Related Opportunistic Infections↗

In-vitro activity of ciprofloxacin and other beta-lactam antibiotics against gentamicin- and carbenicillin-resistant isolates of Pseudomonas aeruginosa.

The susceptibilities of gentamicin- and carbenicillin-resistant clinical isolates of Pseudomonas aeruginosa to newer beta-lactams, netilmicin and ciprofloxacin were studied by a broth microdilution technique. Imipenem, aztreonam and ceftazidime were active against most of the P. aeruginosa strains with minimum inhibitory concentration (MIC) for 90% of the isolates at clinically achievable levels. Piperacillin, azlocillin, cefotaxime, ceftriaxone, cefsulodin, cefoperazone and netilmicin showed poor activity against these organisms, ciprofloxacin exhibited poor activity, inhibiting only 30% of these strains.

Anti-Bacterial Agents↗

Effect of temperature on antimicrobial susceptibilities of Pseudomonas species isolated from drinking water.

The susceptibility of 20 strains of Pseudomonas species isolated from drinking waters (4 P. aeruginosa, 7 P. fluorescens, 5 P. stutzeri, 1 P. maltophilia, 1 P. cepacia, 1 P. putida and 1 P. pickettii) to a variety of antibiotics (gentamicin, amikacin, azlocillin, cefotaxime, chloramphenicol and polymyxin B) were determined by Stoke's method at 20 degrees C, 30 degrees C, 37 degrees C and 42 degrees C. Minimum inhibitory concentrations (MIC) were determined for aminoglycosides on Mueller-Hinton agar at the above temperatures. There was a significant difference in susceptibility between 20 degrees C or 30 degrees C (most resistant), 37 degrees C (more susceptible) and 42 degrees C (most susceptible) to gentamicin and to a lesser degree to amikacin for P. maltophilia, P. cepacia and most strains of P. fluorescens. The P. aeruginosa, P. stutzeri, P. putida and P. pickettii strains showed no difference in susceptibility at 20 degrees C, 30 degrees C, 37 degrees C and 42 degrees C. The need for standardized conditions with special regard to temperature when antibiotic susceptibility tests are performed for P. maltophilia, P. cepacia and P. fluorescens strains is stressed.

Amikacin↗

Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses.

A total of 2,793 courses of treatment with seven beta-lactam antibiotics were administered to 121 cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, and the patients were evaluated with respect to clinical hypersensitivity reactions. Seventy-five patients (62%) experienced 125 reactions, for an overall frequency (based on the number of courses) of 4.5%. Immediate reactions occurred in 34 patients (28.1%) during 53 courses (1.9%). The highest rate of reactions involved piperacillin (50.9% of patients), and the lowest rate involved imipenem and aztreonam (4.0% and 6.5% of patients, respectively); intermediate reaction rates were noted for carbenicillin (23.6% of patients), azlocillin (20.8%), cefsulodin (17.1%), and ceftazidime (13.0%). Cross-reactivity did not appear to be a major problem. Reactions to aztreonam seemed to be restricted to a small group of patients with a high propensity for beta-lactam hypersensitivity.

Anti-Bacterial Agents↗

In vitro susceptibilities of nonfermentative gram-negative bacilli other than Pseudomonas aeruginosa to 32 antimicrobial agents.

The animal inhibitory concentrations of 32 antimicrobial agents for 322 strains of non-fermentative gram-negative bacilli, representing 30 species and unnamed groups other than Pseudomonas aeruginosa, were determined in cation-supplemented Mueller-Hinton broth with use of a microdilution method. The activities of beta-lactam antibiotics varied, but azlocillin, mezlocillin, piperacillin, cefotaxime, and moxalactam consistently were more active than were available penicillins and cephalosporins; the penicillin-like antibiotic mecillinam was less active. The activities of the aminoglycoside antibiotics were similar to each other although streptomycin and sometimes kanamycin were less active than the other aminoglycosides. Although minocycline and doxycycline usually were more active than tetracycline, the percentages of strains susceptible to the first two drugs at concentrations achievable in vivo were only occasionally higher than the percentage of strains susceptible to tetracycline. The activity of trimethoprim-sulfamethoxazole was variable. Chloramphenicol, erythromycin, clindamycin, and vancomycin were relatively inactive against most of the organisms tested, but the high degrees of activity of these drugs against specific species or strains, particularly those that were resistant to many drugs, indicated potential clinical usefulness of these agents.

Alcaligenes↗

Current problems in the treatment of infective endocarditis due to Pseudomonas aeruginosa.

Mortality from pseudomonas infective endocarditis remains high despite optimal use of available antibacterial agents. Infection of the tricuspid valve is subacute, but involvement of the mitral or aortic valve precipitates more serious disease. Most valvular infections are due to a single pseudomonad immunotype, but 20% of cases are mixed infections. Antimicrobial susceptibility tests and tests of synergy by beta-lactam and aminoglycoside antibiotics in combination were performed on 30 isolates of Pseudomonas aeruginosa. Azlocillin was the most effective beta-lactam in combination with an aminoglycoside; MKO 787 was least effective. Among the aminoglycosides tested, netilmicin was the most effective. Medical treatment combined with valvulectomy (without valve replacement) is now standard treatment for refractory right-sided endocarditis at this medical center. A high dose of aminoglycoside in combination with a beta-lactam has proved efficacious. For left-sided infection, immediate valve replacement accompanied by a six-week course of the high dose-combined drug regimen is recommended. Newer beta-lactam antibiotics, such as piperacillin, may be limited in usefulness due to beta-lactamase inactivation.

Adolescent↗

Cefoperazone: a review of its antimicrobial spectrum, beta-lactamase stability, enzyme inhibition, and other in vitro characteristics.

The in vitro qualities of cefoperazone were reviewed on the basis of international medical literature and some new observations. Cefoperazone is highly active against the Enterobacteriaceae. Its activity against Staphylococcus aureus is comparable to that of the other newer cephem antibiotics. Cefoperazone is also active against all beta-hemolytic streptococci and Streptococcus pneumoniae and is relatively inactive against methicillin-resistant S. aureus and enterococci. Against Pseudomonas aeruginosa cefoperazone is at least fourfold more active than cefotaxime or moxalactam and is approximately as active as azlocillin or piperacillin. Haemophilus and Neisseria species, regardless of beta-lactamase production, are highly susceptible to cefoperazone. Against the Bacteroides fragilis group, cefoperazone is either very active or quite inactive because of endemic variations. The drug is slightly less stable to some beta-lactamases than are cefotaxime-like or 7-methoxy cephem drugs. Cefoperazone is a bactericidal beta-lactam, and its minimal inhibitory concentrations are influenced only by high inoculum concentrations of beta-lactamase-producing strains. Its ability to permeate bacterial cell membranes appears similar to that of cefotaxime. Synergy studies with cefoperazone plus beta-lactamase inhibitors or aminoglycosides against Enterobacteriaceae and P. aeruginosa show enhanced killing. Cefoperazone is 70%-94% protein bound and has high affinities for bacterial penicillin-binding proteins 3, 1a, 2, and 1 bs.

Anaerobiosis↗

Pneumonia caused by gram-negative bacilli: an overview.

Colonization of the oropharynx by Pseudomonas aeruginosa and enteric gram-negative bacilli in acutely ill or debilitated patients, alcoholics, diabetics, and persons with chronic bronchitis may lead to pneumonia. Although gram staining of sputum may provide immediate etiologic clues, the diagnosis is proven only by isolation of the pathogen from blood or pleural fluid or by various invasive techniques since expectorated specimens from highly susceptible patients are often contaminated with aerobic gram-negative bacilli colonizing the oropharynx. However, restricting the definition of cases to those involving empyema or bacteremia results in an underestimation of incidence. Combination therapy with a beta-lactam antibiotic plus an aminoglycoside is commonly recommended for gram-negative bacillary pneumonia because (1) the patients involved are usually debilitated and immunocompromised; (2) mortality is high; and (3) the spectrum of antibacterial activity is increased, emergence of resistance may be retarded, and synergistic activity may result. For example, a third-generation cephem antibiotic plus an aminoglycoside can be used for initial treatment of community-acquired gram-negative bacillary pneumonia, and piperacillin or azlocillin plus amikacin can be used for initial treatment of nosocomial infection in which P. aeruginosa or some other antibiotic-resistant gram-negative bacillus is more likely to be involved.

Acinetobacter Infections↗

A turbidimetric study of the responses of selected strains of Pseudomonas aeruginosa to eight antipseudomonal beta-lactam antibiotics.

Turbidimetric and morphologic responses to eight antipseudomonal beta-lactam antibiotics were compared for selected strains of Pseudomonas aeruginosa with different susceptibilities to carbenicillin. In conventional minimal inhibitory concentration tests, all of the newer antibiotics appeared more active than carbenicillin, and apalcillin and cefsulodin had the greatest overall activity. However, in turbidimetric tests the activity of apalcillin and three other N-acyl penicillins (azlocillin, mezlocillin, and piperacillin) was inferior to that of carbenicillin and the other agents. The N-acyl penicillins were also all susceptible to intrinsic pseudomonal beta-lactamase, so that dense bacterial populations inactivated these antibiotics in concentrations of greater 128 micrograms/ml during overnight incubation. Against carbenicillin-resistant strains, carbenicillin, ticarcillin, and sulbenicillin were the least active antibiotics, and cefsulodin had the best overall activity. Turbidimetric monitoring highlights the problems of interpreting the results of conventional minimal inhibitory concentration tests, particularly when large inocula are involved.

Ampicillin↗

Reduced sensitivity to beta-lactam antibiotics arising during ceftazidime treatment of Pseudomonas aeruginosa infections.

Pseudomonas aeruginosa isolated from two patients with empyema and one with bronchopneumonia became less sensitive after treatment with ceftazidime, while Ps. aeruginosa persisted in a patient with an infected compound fracture of the tibia treated with ceftazidime but did not become less sensitive. The reduction in sensitivity to ceftazidime, which was small, was accompanied by resistance to azlocillin but there are little reduction in sensitivity to carbenicillin. The resistant strains produced increased amounts of the chromosomally-mediated cephalosporinase produced by most isolates of Ps. aeruginosa. Variants with reduced sensitivity to ceftazidime, which resembled those that developed in vivo, were selected in vitro from each of the initial ceftazidime-sensitive isolates.

Adult↗

Comparison between the in-vitro activity of new agents on Pseudomonas aeruginosa isolates from cystic fibrosis patients and other chronic infections.

The in-vitro activities of the newer antipseudomonal agents cefsulodin, ceftazidime, U-63196, aztreonam and piperacillin were compared, together with azlocillin, carbenicillin, ticarcillin and tobramycin against 98 strains of Pseudomonas aeruginosa. On all of the 43 isolates from cystic fibrosis patients and the 55 strains from other chronically infected patients, ceftazidime (MIC90: 5.0 and 2.8 mg/l respectively) and cefsulodin (MIC90: 8.2 and 3.1 mg/l) were the most active cephalosporins, and U-63196 the least active (MIC90: 40.1 and 46.1 mg/l). A high incidence of resistance (23 of 55 strains) to tobramycin was found only in the non-cystic fibrosis isolates. The activity of the other agents was comparable in the cystic fibrosis and non-cystic fibrosis isolates. MIC90 for aztreonam were 15.8 and 13.6 mg/l. Piperacillin was the most active penicillin in both populations (MIC90: 25.8 and 21.8 mg/l). Cross resistance was demonstrated in both populations for the penicillin compounds.

Anti-Bacterial Agents↗

Specificity of beta-lactamase induction in Pseudomonas aeruginosa.

The in-vivo induction of the chromosomally determined class Id beta-lactamase of Pseudomonas aeruginosa was studied in the granuloma pouch model in rats. Treatment of animals with carbenicillin, ticarcillin, piperacillin, azlocillin (100 mg/kg bd) and cefsulodin (40 mg/kg bd) resulted in Id beta-lactamase induction. beta-Lactamase induction was not only observed in those animals receiving beta-lactamase therapy, but also in the untreated control group, thus suggesting 'non specific' beta-lactamase induction by body fluids (such as serum or exudate). These findings agree with the observation that commercially available complex media such as Mueller Hinton Broth, IsoS-ensitest Broth, Brain Heart Infusion and Diagnostic Sensitivity Test broth, respectively, also exhibited induction potency. Further experiments revealed that aromatic amino acids as well as histidine largely contributed to the phenomenon of 'non specific' induction of Id beta-lactamase in Ps. aeruginosa.

Amino Acids↗

Low frequency of bacterial resistance to enoxacin in vitro and in experimental pneumonia.

The tendency for bacteria to develop resistance to enoxacin (Cl-919, AT-2266), a new oxyquinolone derivative, was investigated in vitro and in vivo. The mutation frequencies of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella sp., and Haemophilus influenzae to enoxacin, norfloxacin, nalidixic acid, tobramycin, cephalexin, cefotaxime, ampicillin, azlocillin, oxacillin, and ticarcillin were determined by plating large numbers of organisms onto antibiotic-containing agar. Enoxacin resistance developed infrequently. For example, the mutation frequency of Ps. aeruginosa in the presence of enoxacin was 1 in 2.8 X 10(9) cells as compared to 1 in 1.1 X 10(6) for nalidixic acid. The increase in MIC after serial transfer through increasing concentrations of enoxacin ranged from 8-fold for Ps. aeruginosa and Staph. aureus to 256-fold for H. influenzae. Rats with chronic Ps. aeruginosa pneumonia were given subtherapeutic doses of enoxacin daily for ten weeks. Two rats were sacrificed weekly and the homogenized lungs were cultured on agar containing 5 mg/l of enoxacin and on antibiotic-free agar. No organisms resistant to 5 mg/l of enoxacin were recovered. No increase in the minimum inhibitory concentration of enoxacin for the infecting organism was seen.

Animals↗