Gentamicin Treatment of Staphylococcal Infections

Staphylococcus epidermidis is a major pathogen in early prosthetic valve endocarditis and cerebrospinal fluid shunt infections. Approximately 10 to 15% of hospital isolates are methicillin resistant. Ten clinically significant isolates of the latter were collected for antibiotic studies in vitro and in an experimental infection in animals. Time-kill studies of five strains showed gentamicin to be the single most effective antibiotic; however, dwarf colony variants emerged as survivors with two of these strains when challenged with gentamicin alone. The addition of a second antibiotic to gentamicin did not significantly improve the bactericidal rate but prevented the emergence of variant strains. A blood culture isolate of methicillin-resistant S. epidermidis combined with 5% hog gastric mucin was used to establish an experimental intraperitoneal infection in mice. Neither methicillin nor nafcillin treatment reduced mortality below that of untreated animals. Cephalothin treatment delayed early mortality but did not diminish overall mortality. Gentamicin was the most effective single antibiotic, and gentamicin in combination with vancomycin was the most effective regimen overall. The combination of rifampin plus vancomycin was as effective as gentamicin alone. The combinations of cephalothin or nafcillin with gentamicin and cephalothin with vancomycin demonstrated antagonism. The antagonism was not due to multiple injections or drug-drug inactivation.Staphylococcus epidermidis, in addition to being a common blood culture contaminant, may be an important cause of life-threatening infections. It is the predominant pathogen in meningitis associated with intraventricular shunts (30, 31) and early prosthetic valve endocarditis (14, 32) and accounts for 2 to 5% of reported cases of subacute bacterial endocarditis (9,18,21). Despite this clinical importance, appropriate antimicrobial therapy for S. epidermidis infections remains uncertain. Approximately 10 to 15% of S. epidermidis isolates are methicillin resistant (15,25). Susceptibilities of hospital isolates of this organism to other antibiotics are variable (1, 10), but routine antibiotic susceptibility studies usually suggest that strains of methicillin-resistant S. epidermnidis (MRSE) are susceptible to gentamicin, cephalothin, vancomycin, and rifampin (1, 10, 28

Section: Discussionmentioning

confidence: 99%

Antibiotic activity in vitro against methicillin-resistant Staphylococcus epidermidis and therapy of an experimental infection

Lowy¹,

Walsh²,

Mayers³

et al. 1979

“…A number of authors now accept the use of carbenicillin and an aminoglycoside alone for initial empirical management of febrile episodes in the compromised host (3,7,15), assuming that the aminoglycoside will provide initial antistaphylococcal coverage (11). The presence of GRS in an institution may require the addition of an appropriate anti-staphylococcal antibiotic for the initial management of febrile episodes in the compromised host.…”

Section: Discussionmentioning

confidence: 99%

Investigations of the Occurrence of Gentamicin-Resistant Staphylococcus aureus

Buckwold

Albritton

Ronald

et al. 1979

patients became colonized or infected with gentamicin-resistant Staphylococcus aureus (GRS). Of 63 adults, 56 had hospital-acquired GRS, whereas only 9 of 27 children had hospital-acquired GRS (P < 0.001). The other 7 adults and 18 children had GRS present on admission. More than half of those who acquired GRS in the hospital had received prior aminoglycoside therapy. Attack rates were higher in adults than in children and significantly higher on the plastic surgery service than on any other adult service. Phage typing revealed a single-strain outbreak on the plastic surgery ward involving 11 patients, whereas other isolates were of several phage types. Community-acquired GRS occurred more frequently in rural native communities (P < 0.02) and may be related to the use of topical gentamicin. Of 17 native children, 10 were from the same area but there was no common phage type. Agar dilution minimal inhibitory concentration (MIC) testing confirmed that all isolates were gentamicin resistant (MIC 2 8 ,ug/ml) and almost all were tobramycin resistant (MIC 2 8 ,ug/ml). Although the MIC distribution between gentamicin disk-susceptible and -resistant strains was significantly different, MIC's for 90% of gentamicin disk-resistant strains were c8 ,ug of amikacin per ml, and MIC's for 92% of the strains were c4 ,ug of netilmicin per ml.

“…Gentamicin has also been useful as an antistaphylococcal agent (5), but it has been used primarily for treating serious infections caused by gram-negative aerobic and facultative enteric bacilli (1). Because these two antibiotics have complimentary spectrums of activity which together include many bacterial species, they might be used in combination to treat certain types of serious infections of unknown or mixed etiology.…”

mentioning

confidence: 99%

Interaction of Clindamycin and Gentamicin In Vitro

Fass

Rotilie

Prior

1974

The minimal inhibitory concentrations of clindamycin and gentamicin alone and in combinations were determined by a microdilution method for 163 aerobic, facultative, and anaerobic clinical isolates. All 77 strains of Staphylococcus aureus, Diplococcus pneumoniae, Streptococcus pyogenes, and anaerobic bacteria (except for three strains of Clostridium) were inhibited by 1.6,ug or less of clindamycin per ml. Gentamicin did not interfere with the activity of clindamycin within the range of concentrations tested (0.1 to 100 Mg/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of Enterobacteriaceae and Pseudomonas aeruginosa were inhibited by 6.2 ,g or less of gentamicin per ml. Combinations of clindamycin and gentamicin were indifferent for 29 strains and synergistic for 33 strains. All 20 strains of enterococcus, three strains of Clostridium, three strains of Escherichia coli, and one stiain of Proteus rettgeri were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 ,g/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 ,g/ml). Combinations of clindamycin and gentamicin were indifferent for 16 and synergistic for 11 of the resistant strains. Except for clindamycin-sensitive isolates, synergy was usually observed only at concentrations of one or both drugs which are not readily obtainable in vivo. Antagonism was never observed.