In vitro activity of ceftriaxone combined with tazobactam against anaerobic bacteria.

The in vitro activity of ceftriaxone combined with tazobactam against 190 strains of anaerobic bacteria was compared with that of amoxicillin with clavulanic acid, ampicillin with sulbactam, piperacillin alone and with tazobactam, cefoxitin, and imipenem, i.e. beta-lactam antibiotics established in the treatment of anaerobic infections. All anaerobes tested were susceptible to < or = mg/l ceftriaxone when tazobactam was added at fixed ratios (ceftriaxone to tazobactam) of 2:1 and 8:1 and at constant concentrations of 2,4 and 8 mg/l, respectively. When 4 mg/l tazobactam was added, the MICs of ceftriaxone for 83 of 94 strains of the Bacteroides fragilis group were reduced by a factor of 8 to 512; for eight strains, this reduction was two to fourfold. Only the MICs of ceftriaxone for three Bacteroides fragilis strains were not influenced.

Penetration of clarithromycin into human saliva.

The concentrations of clarithromycin after a single oral dose of 500 mg were determined in serum and saliva of ten healthy adult volunteers. After 2 h, the levels were 4.04 +/- 1.14 (SD) mg/l in serum and 2.72 +/- 0.87 mg/l in saliva. After 7 h these values were 1.98 +/- 0.65 and 1.21 +/- 0.34 mg/l, respectively, and at the end of the dosing interval of 12 h, 0.95 +/- 0.38 and 0.73 +/- 0.35 mg/l, respectively. In comparison, amoxicillin (a 750-mg single dose) showed a much faster decline of serum levels and was virtually undetectable in saliva.

Comparison of the E test and a reference agar dilution method for susceptibility testing of anaerobic bacteria.

The susceptibility of 146 recent clinical isolates of gram-negative and gram-positive anaerobes was determined by the E test (AB Biodisk) on both Wilkins-Chalgren and PDM ASM II (AB Biodisk) agar. Results of the E test were compared with results obtained by the NCCLS agar dilution method using Wilkins-Chalgren agar. Incubation was for 20 hours and 44 hours in the E test and for 44 hours in the NCCLS method. In general, 44 hour results were more reliable; however, NCCLS readings were made only once after 44 hours. After two days of incubation, 91% of E test results on Wilkins-Chalgren agar were within one dilution and 98% within two dilutions of the corresponding NCCLS values; on PDM agar these values were 89% and 98%, respectively. Major and very major discrepancies combined were less than 1%.

Comparative in vitro activity of Ro 40-6890, Ro 41-3399, and other antimicrobial agents against anaerobic bacteria.

The in vitro activity of the ester Ro 41-3399 and its free active acid Ro 40-6890 was tested against 189 strains of anaerobic bacteria in comparison to other oral cephalosporins and to antimicrobial agents established in the treatment of anaerobic infections. Prevotella, Porphyromonas, Peptostreptococcus, Fusobacterium and Clostridium spp. were susceptible to Ro 40-6890, with few exceptions. Due to its lack of activity against the major pathogens of the Bacteriodes fragilis group, Ro 40-6890 does not promise to be of major use in the treatment of infections caused by anaerobes.

[The sensitivity of anaerobic bacteria to chemotherapeutic agents (Zurich, 1991)]. / Die Empfindlichkeit anaerober Bakterien gegen Chemotherapeutika (Zürich, 1991).

There have been numerous reports on resistance of anaerobic bacteria against antimicrobial agents. Therefore, to assess the situation in Zurich, 187 anaerobic strains of various bacterial genera, isolated from clinical specimens during winter 1990/91, were tested for their susceptibility to antimicrobial agents active against anaerobic bacteria. Besides the Bacteroides fragilis group, which is naturally resistant against penicillin, 30% of isolates of other Bacteroides species were also resistant against penicillin. In general, anaerobes have remained susceptible to cefoxitin, chloramphenicol, clindamycin, imipenem, the 5-nitroimidazoles (metronidazole, ornidazole) as well as combinations of beta-lactam antibiotics with beta-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam). Because rare strains resistant against cefoxitin, clindamycin and beta-lactams plus beta-lactamase inhibitors can be found, at least isolates from specific clinical situations should be tested for antimicrobial susceptibility. These are strains isolated from patients with brain abscess, endocarditis, osteomyelitis, arthritis, infected implants and prosthesis as well as those from persisting or recurrent bacteremia. Because the agar diffusion test yields unreliable results, minimal inhibitory concentration should be determined. Maybe the new 'E test' or the spiral gradient procedure can be used after evaluation.

Comparison of the Cobas-Bact five-hour susceptibility testing system with the NCCLS agar diffusion and dilution methods.

The results of susceptibility tests performed by the Cobas-Bact system were compared with those of the NCCLS agar diffusion (Kirby-Bauer) and NCCLS agar dilution methods. A total of 998 clinical isolates were tested against 10 to 18 antimicrobial agents. Essential agreement (comprising full agreement and minor discrepancies) varied from 90.5% to 99.2% on comparison of Cobas-Bact with Kirby-Bauer results, depending on the bacterial group (mean for all 998 strains tested 95.7%). These figures ranged from 91% to 99.2% (mean 96.3%) for the Cobas-Bact/MIC comparison and from 95.2% to 99.7% (mean 98.7%) for the Kirby-Bauer/MIC comparison. The best results were found for Enterobacteriaceae and Staphylococcus aureus, whereas for enterococci and coagulase-negative staphylococci there was a lower rate of essential agreement in all three comparisons. In the case of Pseudomonas aeruginosa there was a good rate of essential agreement but many minor discrepancies, resulting in a disappointing rate of full agreement of between 67.5% and 78.9% in the three comparisons. The Cobas-Bact system would appear to provide satisfactory susceptibility test results in most cases, however there are still some major problems in the system which should be resolved.

Identification of contaminants during primary isolation of mycobacteria in the BACTEC system with the antimicrobial supplement PACT.

1500 sputum specimens and bronchial washings were cultured for mycobacteria. One half of the specimen was treated with N-acetyl-L-cysteine--sodium hydroxide (3%) (NALC) and the other with sodium dodecyl (lauryl) sulfate--sodium hydroxide (1%) (SDS). The different species of contaminants found with each pretreatment method with the BACTEC radiometric system were identified. Contamination occurred in 6% by using SDS and in 10% by using NALC. The SDS method was more effective against Bacillus ssp. and Streptomyces ssp., the major contaminants. However, the growth of Pseudomonas ssp. was a problem in both methods.

Studies on the resistance of Clostridium difficile to antimicrobial agents.

The susceptibility of C. difficile isolated at the Department of Medical Microbiology of the University of Zurich to a wide selection of antibacterial, antimycobacterial and antifungal agents was tested in vitro. Great differences in susceptibility were found against chloramphenicol, clindamycin, erythromycin, rifamycin, and tetracycline. Resistance to clindamycin and erythromycin could always be transferred jointly to a susceptible C. difficile strain by mixed culture on filters at low frequencies (1 X 10(-8) to 4 X 10(-8) per donor cell). Transfer of tetracycline resistance occurred at frequencies of 3 X 10(-7) to 5 X 10(-7). Chloramphenicol and rifamycin resistance could not be transferred in the system used (frequencies less than 10(-8)). Although a total of 38,000 colonies was screened by various methods known to affect plasmid replication, resistance to chloramphenicol, clindamycin, erythromycin, rifamycin, and tetracycline could not be eliminated. No connection between plasmid DNA and antimicrobial resistance could be established. Especially, no plasmid DNA was involved in the transfer of resistance determinants from resistant to susceptible strains.

[Sensitivity of anaerobic bacteria to therapeutic agents (Zurich 1984)]. / Die Empfindlichkeit anaerober Bakterien auf Chemotherapeutika (Zürich 1984).

There are several reports in the literature on resistance of anaerobic bacteria against antimicrobial agents. Therefore, 231 anaerobic strains of various bacterial genera, isolated from clinical specimens during fall 1984, were tested for susceptibility to antimicrobial agents active against anaerobic bacteria. Whereas 23% of the Bacteroides species not belonging to the B. fragilis group were resistant to penicillin, the anaerobic bacteria were still susceptible to chloramphenicol, clindamycin and the nitroimidazoles. The resistance rate against the various new beta-lactam antibiotics was comparable to results of other studies. Due to the increasing resistance it is recommended that the susceptibility of clinically important anaerobes be tested by appropriate techniques. The agar diffusion test must not be used due to unreliable results. Instead, the minimal inhibitory concentration should be determined or the "broth-disk" test performed.

Transferable resistance to clindamycin, erythromycin, and tetracycline in Clostridium difficile.

Resistance to clindamycin, erythromycin, and streptogramins in Clostridium difficile could be transferred to a susceptible strain by mixed culture at low frequencies (1 x 10(-8) to 4 - 10(-8) per donor cell). Transfer of tetracycline resistance occurred at frequencies of 3 x 10(-7) to 5 x 10(-7). No plasmid DNA involved in these transfers could be detected.

Investigation of an outbreak of antibiotic-associated colitis by various typing methods.

During an outbreak of diarrheal disease due to Clostridium difficile in a surgical ward, 16 C. difficile isolates were cultured from fecal samples of 15 patients. Agarose gel electrophoresis for the detection of plasmid DNA, crossed immunoelectrophoresis for the detection of extracellular antigens and toxins, polyacrylamide gel electrophoresis for analyses of soluble proteins, assays for cytotoxicity, and a comparison of susceptibility to antimicrobial agents were employed. At least 12 of the 16 isolates were shown to be phenotypically the same strain. These findings suggest that in a hospital setting, diarrhea and pseudomembranous colitis caused by C. difficile can be of nosocomial origin and that they can spread from patient to patient.