Ampicillin-resistant enterococcal species in an acute-care hospital

The fibrin clot penetration and in vivo bactericidal activity of RP 59500, a new semisynthetic streptogramin, for two Staphylococcus aureus strains (one methicillin resistant and the other methicillin susceptible), two Staphylococcus epidermidis strains (one methicillin resistant and the other methicillin susceptible), and one Enterococcusfaecalis strain were evaluated. The clots, inserted subcutaneously, were infected with a mean of 108 CFU of the pathogen per g. For each strain, groups of four rabbits received a single intravenous injection of 50 mg of RP 59500 per kg of body weight over 30 min. The mean peak level of RP 59500 in serum in the infected rabbits was 61.9 + 6.3 ,ug/ml. The drug was detectable in serum at a level of 0.8 ,ug/ml up to 4 h after administration. The mean peak fibrin clot drug level at 1 h was 3.3 ± 0.1 ,ug/g. At 6 h, the level in clots was 1.2 + 0.1 ,ug/g. The mean half-life in serum in infected rabbits was 0.34 ± 0.01 h, while in clots the drug exhibited a longer half-life of 3.8 ± 0.4 h. In vivo, this new streptogramin sterilized the clots infected with the two S. aureus strains studied in less than 1 h and induced a marked reduction in colony counts of the two S. epidermidis strains studied for up to 24 h. The activity of the streptogramin against E. faecalis was limited.These results suggest that RP 59500 should be further evaluated for the treatment of infection with methicillin-resistant staphylococci.RP 59500 belongs to the streptogramin class of antibiotics. It is a mixture of two soluble semisynthetic derivatives of the purified natural pristinamycin produced by fermentation of the Streptomycespristinaespiralis compounds PI (RP 57669) and PII (RP 54476), which are present in a proportion of 30:70 (wt/wt), respectively (1, 7). The antibiotics of the streptogramin family are inhibitors of protein biosynthesis through their irreversible blocking action on the ribosome. RP 59500 is active against a range of gram-positive pathogenic bacteria. Included in this group are methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, erythromycin-resistant Streptococcus pneumoniae, other streptococci, and clostridia. It also has activity against Neisseria spp., Moraxella catarrhalis, Haemophilus influenzae, Legionella spp., Mycoplasma spp., and chlamydiae (7). As it is the first formulation of an injectable streptogramin, it may, if proven effective, have great clinical importance for the treatment of serious infections caused by gram-positive organisms.The present investigation was undertaken to study the efficacy and penetration of RP 59500 in fibrin clots. Fibrin is one of the main constituents of the inflammatory process, and bacteria located within the core of fibrin clots are protected from host defenses and the action of the antibiotics, as they often interact with and adhere to major constituents of clots. Moreover, penetration of antimicrobial agents within the clots is quite variable. New antibiotics that can penetrate fibrin and sterilize gram-...

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic interaction between RP 59500 and gram-positive bacteria infecting fibrin clots

Turcotte

Bergeron

1992

“…Clinical enterococcal isolates that are relatively resistant to beta-lactam antibiotics have been reported increasingly during recent years (1,(9)(10)(11). Whether these observations identify a trend toward increasing resistance to beta-lactams among this species or represent a greater awareness among investigators of antibiotic resistance in gram-positive organisms remains unclear.…”

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confidence: 99%

“…Whether these observations identify a trend toward increasing resistance to beta-lactams among this species or represent a greater awareness among investigators of antibiotic resistance in gram-positive organisms remains unclear. ; Enterococcusfaecium and Enterococcus raflinosus, which frequently possess intrinsic relative resistance to beta-lactams (3,7), have been notable in some reports (1,9,10). To identify any trend toward increasing antibiotic resistance among clinical isolates of E. faecium, we reviewed the susceptibilities of E. faecium strains that were isolated at one institution (Massachusetts General Hospital [MGH], Boston) and that were collected without bias to their antibiotic resistance during 1969 to 1990.…”

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confidence: 99%

Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution

Grayson

Eliopoulos

Wennersten

et al. 1991

185

100

To identify any change in the antibiotic resistance of Enterococcus faecium, we examined the antibiotic susceptibilities of clinical strains (n = 84) isolated at one institution during the 22 years since 1968. A significant increase in resistance to penicillin was observed during the study period: the MICs of penicillin for 50 and 90% of isolates tested were 16 and 64 ,ug/ml, respectively, from 1969 to 1988 (n = 48; geometric mean MIC, 14 yLg/ml), whereas they were 256 and 512'Ig/ml, respectively, from 1989 to 1990 (n = 36; geometric mean MIC, 123 tig/ml) (P < 0.001). A comparable increase in resistance to ampicillin was also noted (P < 0.001). No straing produced detectable 3-lactamase. In contrast, susceptibilities to vancomycin, teicoplanin, and ciprofloxacin remained stable. High-level resistance to gentamicin was observed in none of 48 isolates from 1969 to 1988, but was present in 22 of 36 strains (61%) from 1989to 1990 (P < 0.001) and was significantly associated with resistance (MIC, .128 ,ug/ml) to penicillin (P < 0.001). 'To assess the potential evolution of antibiotic resistance in this species, clinical isolates (n = 24) were compared with strains isolated in 1968 from a human population in the Solomon Islands that was never exposed to antibiotics. Solomon Island isolates were significantly more susceptible than all clinical strains to penicillin, ampicillin, and vancomycin (P < 0.001 for each), but they exhibited no differences in susceptibility to teicoplanin or ciprofioxacin. The penicillip-binding affinit of penicillin-binding protein 5 (PBP 5) in penicillin-resistant clinical strains (MIC, 512 ILg/ml) was notably lower than that in strains with more typical susceptibilities, suggesting an alteration in this PBP as a possible mechanism for increased penicillin resistance. Solomon Island strains most susceptible to penicillin demonstrated a prominent PBP 5* and the absence of PBP 5. These changes in the antibiotic resistance of E. faecium emphasize the importance of identifying this species in patients with serious enterococcal infections and the necessity of assessing its susceptibility to both beta-lactams and aminoglycosides if effective therapy is to be identified.

“…The remaining four patients were admitted from nursing homes or long-term care facilities with decubitus or foot raffinosus from hospitalized patients have been published (3,28,34,36), only one other report has provided epidemiologic evidence of the nosocomial spread of this newly described Enterococcus species (3).…”

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confidence: 99%

Emergence and nosocomial transmission of ampicillin-resistant enterococci

Boyce

Opal

Potter-Bynoe

et al. 1992

102

Between 1986 and 1988, the incidence of ampicillin-resistant enterococci increased sevenfold at a universityaffiliated hospital. Forty-three patients acquired nosocomial infections with ampicillin-resistant enterococci, most of which were also resistant to mezlocillin, piperacillin, and imipenem. An analysis of plasmid and chromosomal DNAs of isolates revealed that the increase was due to an epidemic of 19 nosocomial infections that yielded closely related strains of Enterococcus faecium and to a significant increase in the incidence of nonepidemic, largely unrelated strains of ampicillin-resistant enterococci. The nonepidemic strains were identified as E.faecium, E. raffinosus, E. durans, and E. gallinarum. A logistic regression analysis revealed that patients with nonepidemic resistant strains were 16 times more likely than controls to have received preceding therapy with imipenem. In our institution, the increase in the incidence of ampicillin-resistant enterococci appears to be due to the selection of various strains of resistant enterococci by the use of imipenem and to the nosocomial transmission of E. faecium and E. raffinosus.Enterococci have become an increasingly important cause of nosocomial infections (10, 14-16, 18, 25, 38, 43). They are now the second most common cause of nosocomial urinary tract and surgical wound infections and are the third most common cause of nosocomial bacteremias (10). Most of these infections are caused by Enterococcus faecalis, a species that is usually susceptible to ampicillin, mezlocillin, piperacillin, and imipenem. A few strains of E. faecalis produce P-lactamase, rendering them resistant to ampicillin, mezlocillin, and piperacillin (17, 20-22, 24, 29-33), but nosocomial transmission of such strains has occurred infrequently (17,24,33).Other species of enterococci, such as E. faecium, may be resistant to imipenem as well as to penicillin, ampicillin, mezlocillin, and piperacillin (11). Such species do not produce P-lactamase and are resistant by virtue of their producing penicillin-binding proteins with a low affinity for betalactams (19,41). Infections caused by these species are much less common than those caused by E. faecalis.In 1987 and 1988, we noted an increase in the frequency of enterococci resistant to penicillin, ampicillin, mezlocillin, piperacillin, and imipenem among patients at a universityaffiliated hospital. The increase was due to an epidemic of closely related strains of E. faecium which was superimposed on an increasing incidence of nonepidemic, largely unrelated strains of E. faecium, E. raffinosus, E. gallinarum, and E. durans. The emergence of nonepidemic strains of ampicillin-resistant enterococci was associated with an increase in the use of imipenem. MATERIALS AND METHODSMicrobial identification and susceptibility tests. Isolates recovered from clinical specimens were identified as entero-* Corresponding author.