Hans O. Hallander

Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method.

Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of less than or equal to 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within +/- 0.2 for two-thirds of 40 repetitive assays and within +/- 0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 10(5) to 10(6) colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log 10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides.

Identification of Cephalosporin-Resistant Staphylococcus aureus with the Disc Diffusion Method

Methicillin-resistant strains of Staphylococcus aureus, in total 84, representing 16 laboratories in 8 different countries were all resistant to 32 μg of cephalothin per ml with the same typical heteroresistant pattern. With the disc diffusion method, they were easily detected when cephalexin discs were used. With cephalothin discs, on the other hand, 26 to 49% would have been falsely categorized as Group I or II after 24 hr. It is recommended that susceptibility testing of S. aureus to cephalosporins by using the paper disc method be performed with 30-μg cephalexin discs on Mueller-Hinton agar without blood. With an inoculum of 106 bacteria/ml, an incubation temperature of 30 C, and an incubation time of 24 hr, a zone of less than 10 mm indicates presumptive heteroresistance. This corresponds to the international recommendation with a minimal inhibitory concentration of 32 μg/ml as the upper limit of Group II.

Collection and transport of specimens for anaerobic culture

SummaryBy comparative studies of sampling methods it was shown that specimens should be obtained preferably by aspiration in order to avoid contamination by anaerobic flora. Anaerobic transport systems are recommended, though some anaerobic strains tolerate exposure to air surprisingly well. A gassed-out tube or vial is the method of choice for transporting fluid specimens for anaerobic culture.ZusammenfassungDurch Vergleichsuntersuchungen von Entnahmetechniken wurde gezeigt, daß Proben zur Vermeidung von Kontamination mit Anaerobierflora vorzugsweise durch Aspiration gewonnen werden sollten. Anaerobe Transportsysteme werden empfohlen, obwohl einige Anaerobierstämme Luftexposition erstaunlich gut vertragen. Ein von atmosphärischer Luft befreites Röhrchen oder Gefäß ist die Methode der Wahl für den Transport von flüssigen Untersuchungsproben für die anaerobe Kultur.

Pharmacological and Clinical Study of Bacampicillin in Acute Peritonsillitis–a Comparison with Ampicillin

The pharmacological and clinical properties of bacampicillin in three dosage groups were studied in 66 hospitalized patients with unilateral acute peritonsillitis in a comparison with ampicillin. Bacampicillin is a new semisynthetic aminopenicillin which is rapidly converted to ampicillin but is better absorbed. Both drugs were given orally. The mean individual peak serum levels achieved with 200, 400, and 800 mg of bacampicillin in the first morning dose were 4.9, 6.8, and 11.9 mg/liter, respectively, with an almost linear dose response. The peak level of 800 mg of bacampicillin was significantly higher than the 6.8 mg/liter noted after a nearly equimolar dose of 500 mg of ampicillin. A linear relationship was also seen between dose and area under the serum concentration-time curve. Preliminary antibiotic concentration studies in five patients indicated therapeutic levels in peritonsillar pus. Beta-streptococci alone or in combination with anaerobes were isolated from about half of the abscesses, whereas anaerobes were isolated from the other half. Treatment was supplemented by surgical procedures in the majority of cases. The clinical effect was good in all treatment groups, with only one relapse. All beta-streptococci were eliminated during therapy. The total number of gastrointestinal side effects was significantly lower in patients treated with bacampicillin, although the difference in frequency of diarrhea alone was not significant.