Bactericidal synergy between penicillin or ampicillin and aminoglycosides against antibiotic-tolerant lactobacilli

Abstract

The bactericidal activities of penicillin G and ampicillin alone were compared with those of their combinations with streptomycin or gentamicin against 17 strains of lactobacilli classified as tolerant to various fl-lactam antibiotics. The penicillin G combinations with streptomycin and gentamicin were synergistic against 17 and 16 of these strains, respectively, whereas the corresponding ampicillin-aminoglycoside combinations were synergistic against 12 and 15 strains, respectively. Importantly, synergy was manifested at concentrations of these antibiotics that are attained in serum after their administration in conventional dose regimens. In no instances were combinations antagonistic. These in vitro observations provide a partial explanation for the favorable results obtained in preliminary clinical evaluations of the benefits of combination regimens in the treatment of lactobacillus infections refractory to single-drug therapy.Serious lactobacillus infections, particularly endocarditis, often result in therapeutic failure when treated with seemingly appropriate singledrug antibiotic regimens, despite readily achievable minimal inhibitory concentrations (MICs) (1,3,20). Our previous studies indicated that this disparity between in vitro susceptibility data and in vivo efficacy may be partially explicable on the basis of "antibiotic tolerance" exhibited by a number of Lactobacillus strains (3-5). The marked discrepancy between MICs and minimal bactericidal concentrations (MBCs) for individual Lactobacillus isolates (1, 3-5) and preliminary clinical evaluations suggesting efficacy of penicillin-aminoglycoside regimens in cases of refractory lactobacillus endocarditis (1,3,20) prompted the present study to Organisms were maintained in chopped meat-glucose broth (Scott Laboratories, Fiskeville, R.I.) and were transferred monthly into fresh media until the susceptibility testing was performed. In the week before testing, one additional transfer was done. All susceptibility studies were performed anaerobically.Antibiotic tolerance. These 17 isolates were confirmed as penicillin and ampicillin tolerant by the following criteria: (i) MBC/MIC ratios of 232:1 (18); and (ii) slow bactericidal effect on timed-kill analysis (<99.9% killing at 24 to 48 h).MBC/MIC ratios. MICs and MBCs were determined for penicillin G and ampicillin by a modified broth dilution technique as previously described (4), using prereduced Mueller-Hinton (MH) broth (BBL Microbiology Systems, Cockeysville, Md.) with 0.2% yeast extract and 0.05% L-cysteine. This medium has a maximal concentration of 0.5 mg per 100 ml of magnesium and 3.1 mg per 100 ml of calcium.Penicillin G and ampicillin were supplied by USP Standards, Rockville, Md. Stock solutions (8,000 ,ug/ ml) of each agent were prepared and stored at -20°C until the day of the study. Serial twofold dilutions were made of both antibiotics and added to broth under anaerobic conditions. A final inoculum of approximately 2 x 105 colony-forming units (CFU) per antibiotic-containing tube was use...

Lekoterapia zakażeń Lactobacillus sp. – przegląd piśmiennictwa

“…jest niejednorodną grupą mikrobiologiczną, kolonizującą błony śluzowe jamy ustnej, przewód pokarmowy oraz układ moczowo-płciowy człowieka [1,2]. W środowisku można je znaleźć na roślinach, materiałach pochodzenia roślinnego, w oborniku, w ściekach czy w fermentującej lub psującej się żywności [2].…”

“…Według różnych autorów Lactobacillus sp. najczęściej związany jest z zapaleniem wsierdzia [1,2,4,5]. Przyczyną bakteryjnego zapalenia wsierdzia, spowodowanego bakteriami kwasu mlekowego, w 47% są zabiegi dentystyczne [13].…”

“…nie przynosi efektu pomimo łatwo osiągal-nego MIC penicyliny i ampicyliny (Tabela 1) [1,2]. Przyczyną może być rozbieżność między MIC a minimalnym stęże-niem bakteriobójczym (ang.…”

“…minimal bactericidal concentration -MBC), różniącym się dla poszczególnych szczepów Lactobacillus sp. pochodzących z różnych źródeł [1].…”

“…Przedstawiono także ciekawą zależność: stężenie MBC penicyliny z ampicyliną było znacznie wyższe od stężenia MIC tych samych antybiotyków. Również Bayer udowodnił nieskuteczne działanie monoterapii [1]. Wszystkie badane przez niego izolaty były oporne na streptomycynę, z czego 14 wykazywało oporność na gentamycynę.…”