Effects of subminimal inhibitory concentrations of Erythromycin, Clindamycin, and Pristinamycin on the penicillinase production of Staphlyococcus aureus

Abstract

The influence of subminimal inhibitory concentrations of erythromycin, clindamycin, and pristinamycin on the penicillinase production of Staphylococcus aureus was tested in 12 strains. Of the 36 experiments performed, 16 (44%) showed a lack of influence, 10 (28%) displayed an increase, and 10 revealed a decrease in penicillinase activity. The maximal effect produced was generally induced by concentrations ranging from ¼/ to 1/32 the minimal inhibitory concentration, irrespective of the susceptibility of the strain to the drug. In spite of the fact that the drugs are closely related, they sometimes produced opposite effects on the same strain.The problem of the effects of subminimal inhibitory concentrations (subMIC's) of antibacterial drugs has been investigated in the last few years and was recently discussed by Lorian (9) and Rolinson (15). Most of the available data concern the influence of various agents on bacterial growth (2,6,17) and the morphological changes induced by. the subMIC's of f,-lactam antibiotics (4,8,10,12). Only a few papers have dealt with the effects of the subMIC on bacterial enzymatic systems. Inducible enzymes were shown to be affected by the subMIC's of nitrofurans (7) and chloramphenicol (18). Gemmell has reported the influence of the subMIC's of antibiotics, especially .clindamycin, on the biosynthesis of some staphylococcal toxins and enzymes during experimental pyogenic infection (5). We have shown that the subMIC of chloramphenicol can inhibit ,8-lactamase production in gram-negative bacilli (13) and in Staphylococcus aureus (14) and that this inhibition sometimes leads to a synergistic bactericidal effect in vitro (13,14) and in vivo (16). More recently, Allen and Epp have shown that erythromycin can inhibit penicillinase induction in strains of S. aureus (1). To the best of our knowledge, a comparative study on the effect ofclosely related drugs on penicillinase production has not been reported in the literature. The purpose of the present paper was, therefore, to investigate the influence of subMIC's of erythromycin, clindamycin, and pristinamycin on the penicillinase production of strains of S. aureus. MATERIALS AND METHODSTwelve strains of penicillin G-resistant S. aureus were used. These were isolated in the diagnostic laboratory of the Department of Clinical Microbiology, Hadassah University Hospital, Mount Scopus, Jerusalem, from sputum, wound exudates, urine, and blood. Each was tested for ,B-lactamase production by the iodometric method, as described by Workman and Farrar (21). The minimal inhibitory concentrations (MICs) of erythromycin, clindamycin, and pristinamycin for these strains were determined by using a microdilution technique. Serial twofold dilutions of the antibiotic were made in tryptic soy broth (TSB; Difco Laboratories) in sterile Microtiter U-plates (Cook Engineering Co.). A suitable dilution of a 4-h culture of the bacteria in TSB at 37°C was prepared in TSB and added to the wells of the microtiter plates to give a final inoculum of 10' colony-forming ...

Influence of clindamycin on derepression of beta-lactamases in Enterobacter spp. and Pseudomonas aeruginosa

“…This synergy was due to the inhibition of A-lactamase synthesis by chloramphenicol and has been shown to be operative both in vitro and in vivo (15,18). In similar studies with Staphylococcus aureus, Michel et al demonstrated that clindamycin diminished penicillinase production by this organism (16). This effect, however, occurred only in tests with clindamycin-susceptible strains.…”

“…This derepression may occur via oneof two mechanisms: (i) spontaneous mutation of the wild type to a stably derepresaed -state or (ii) reversible derepression of the wild type by a 1-lactamase inducer (9,10,12,19). The former mechanism has been shown to be responsible for the, emergence of multiple ,B-lactam resistance during therapy with new cephalosporins (3,17,20),> whereas the latter mechanism has been shown to be responsible for the antagonism of 1-lactai drugs by cefo,.itin (8,, 11, '2, 27 First, it has been shown to inhibit synthesis of certain proteins in gram-positive bacteria without affecting others (5,6,16,23 possessing cefoxitin-inducible P-lactamases (10,17,20,22). The stable derepressed mutant of Enterobacter cloacae 55 was selected in the laboratory and has been described in detail previously (10 24,1983 suspended in broth (10' CFU/ml) containing the antibiotics and incubated at 37°C in air for 24 h. At various time points, samples were removed and the number of viable CFU per milliliter was determined by agar dilution plate counts performed in duplicate.…”

Lincomycin stimulates synthesis of TEM-2 beta-lactamase by Escherichia coli

“…have been shown to be derepressed by clindamycin (a lincomycin derivative) (29). It also inhibits penicillinase production by clindamycinsusceptible strains of Staphylococcus aureus (23). Effects of these antibiotics on P-lactamase synthesis seem to differ among types of 1-lactamases and bacterial strains.…”

Effects of Subminimal Inhibitory Concentrations of Aminoglycosides on the Penicillinase Production of <i>Staphylococcus aureus</i>

“…In a recent study on the influence of sub-MICs of erythromycin, clindamy cin and pristinamycin on the penicillinase production of S. aureus [9], we found an increase in the penicillinase activity in 28% and a decrease in 28% of the experi ments. These effects were irrespective of the susceptibility of the strain to the drug.…”

“…Of the 36 experiments performed, 16 (44%) dis played an increase and 9 (25%) produced a decrease in the penicillinase activity of the strains. These effects were observed at concentrations ranging from 1:2 to 1:2,048 of the respective minimal inhibitory concentration, irrespective of the susceptibility of the strain to the aminoglycoside drug.Effects of subminimal inhibitory con centrations (sub-MIC) of antibacterial drugs on various bacterial enzymatic sys tems have been reported [I,[4][5][6][7][8][9] II], In a previous report, we have shown that the sub-MIC of chloramphenicol can inhibit beta-lactamase production in gram-nega tive bacilli [7] and in Staphylococcus au reus [8], and that this inhibition sometimes leads to a synergistic bactericidal effect in vitro [7,8] …”