Medium-Dependent Variation in Bactericidal Activity of Antibiotics Against Susceptible Staphylococcus aureus (original) (raw)
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Clinical Microbiology and Infection, 2008
Decreased susceptibility of Staphylococcus aureus to antistaphylococcal agents may be associated with inability to eradicate intracellular forms, which could explain therapeutic failures. This hypothesis was tested using clinical isolates obtained from a patient with persistent staphylococcal bacteraemia under therapy. Four isogenic isolates (three from tissue, one from blood) with increased MICs for vancomycin (1-4 mg ⁄ L) and for daptomycin (1-4 mg ⁄ L) were collected after an initial 16-day treatment with vancomycin-rifampicin-gentamicin, followed by 13-20 days of treatment with daptomycin-rifampicingentamicin. Isolates were tested for MICs and for: (i) vancomycin (BODIPY-FL-vancomycin) and daptomycin binding; (ii) cell wall turnover (loss of N-acetyl-D D-[1-14 C]glucosamine in 30 min after 1 h of labelling); and (iii) Triton X-100-induced autolysis. Extracellular (broth) and intracellular (THP-1 macrophages) activities of rifampicin, linezolid and fusidic acid at C max , and of vancomycin, daptomycin, quinupristin-dalfopristin and oritavancin over a wide range of extracellular concentrations (with pharmacological modelling to determine E max ), were measured at 24 h. Increases in vancomycin MICs correlated with increased drug binding, and decreased cell wall turnover and detergent-induced autolysis. Increases in daptomycin MICs correlated with decreased daptomycin binding. Intracellular activity was weak (E max <1 log 10 CFU decrease) for vancomycin against all isolates, and for daptomycin against isolates with MICs >1 mg ⁄ L. Among all antibiotics tested, only quinupristin-dalfopristin and oritavancin provided close to bactericidal intracellular activities (1.6-2.5 log 10 CFU decreases at C max ). Determination of the intracellular susceptibility of S. aureus, combined with improved methods of diagnosis, could be useful when dealing with persistent staphylococcal infections and could improve therapy.
Enfermedades Infecciosas y Microbiología Clínica, 2015
Bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. Optimization of treatment is fundamental in the prognosis of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and-resistant isolates have led to research on novel therapeutic schemes. The interest in the new antimicrobials with activity against methicillin-resistant staphylococci has been extended to susceptible strains, which still carry the most important burden of infection. New combinations of antimicrobials have been investigated in experimental and clinical studies, but their role is still being debated. Also, the appropriateness of the initial empirical therapy has acquired relevance in recent years. The aim of this guideline is to update the 2009 guidelines and to provide an ensemble of recommendations in order to improve the treatment of staphylococcal bacteremia and infective endocarditis, in accordance with the latest published evidence.
Management of Staphylococcus aureus infections
American Family Physician, 2006
A pproximately 20 percent of healthy persons are persistent carriers of Staphylococcus aureus, and 60 percent are intermittent carriers. Colonization rates are increased in hemodialysis patients, illicit injection drug users, surgical patients, and patients with insulin-dependent or poorly controlled diabetes. 1 The National Nosocomial Infections Surveillance System 2 found that 60 percent of hospital-acquired S. aureus isolates in 2003 were methicillinresistant S. aureus (MRSA). Hospitalized patients with S. aureus infection have five times the risk of in-hospital mortality compared with inpatients without this infection. 3 Community-acquired MRSA infections, which usually cause skin and soft-tissue infections, have become more common. 4,5 Occurrence of these infections has increased in athletes, military recruits, children, Pacific Islanders, Alaskan Natives, Native Americans, men who have sex with men, and prison inmates. 6 These isolates often are associated with the Panton-Valentine leukocidin and type IV staphylococcal cassette chromosome, which are not typical of hospital-acquired MRSA. Post-influenza pneumonias, 7 necrotizing fasciitis, pyomyositis, 8 and Waterhouse-Friderichsen syndrome 9 caused by communityacquired MRSA also have been observed. Antimicrobial Therapy Table 1 lists the costs of antibiotic therapy for S. aureus infections. Antimicrobial therapy should be guided by the susceptibility profile of the organism. 6 Beta-lactamaseproducing strains of methicillin-susceptible S. aureus (MSSA) preferably are treated with a semi-synthetic penicillin (e.g., intravenous nafcillin, oxacillin [Bactocill], oral dicloxacillin [Dynapen]) in patients not allergic to penicillin. First-generation cephalosporins (e.g., oral cephalexin [Keflex], intravenous cefazolin [Ancef]) are an alternative. Vancomycin (Vancocin) should only be used for the treatment of MSSA in patients allergic to penicillins because of overuse and development of resistant organisms, and because clearance of bacteremia may be slow. 10 Vancomycin is preferred for treatment in severe MRSA infections and is used only Because of high incidence, morbidity, and antimicrobial resistance, Staphylococcus aureus infections are a growing concern for family physicians. Strains of S. aureus that are resistant to vancomycin are now recognized. Increasing incidence of unrecognized communityacquired methicillin-resistant S. aureus infections pose a high risk for morbidity and mortality. Although the incidence of complex S. aureus infections is rising, new antimicrobial agents, including daptomycin and linezolid, are available as treatment. S. aureus is a common pathogen in skin, soft-tissue, catheter-related, bone, joint, pulmonary, and central nervous system infections. S. aureus bacteremias are particularly problematic because of the high incidence of associated complicated infections, including infective endocarditis.
Journal of Infectious Diseases, 1989
Comparative Efficacy of Amoxicillin-Clavulanate, Cloxacillin, and Vancomycin Against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus Endocarditis in Rats Since the introduction of methicillin into clinical medicine in 1959 the prevalence of Staphylococcus aureus strains resistant to this antibiotic has reached epidemic proportions in certain geographic areas. The therapeutic options for treating such strains are largely limited to vancomycin. The ll-lactamase-resistant penicillins and cephalosporins have been controversial for the treatment of infections caused by these organisms [1]. Beta-lactamase inhibitors (e.g., clavulanic acid and sulbactam) have a weak intrinsic antibacterial activity but act synergistically with ll-lactamase-labile antibiotics against most ll-lactamase-producingorganisms such as methicillinsensitive S. aureus (MSSA). In the case of methicillinresistant S. aureus (MRSA), the resistance mechanisms are more complex and lesswellunderstood [1]. However,when the ll-lactamases of MRSA strains are inhibited by the addition of clavulanic acid, the minimal inhibitory concentrations (MICs) of amoxicillin and penicillin against these organisms are reduced by 2-4 dilutions to values of 4-16 ug/ml, for most of the strains tested [2-4]. While many authors consider this increase in in vitro activity to be of questionable significance, Washburn and Durack [5] showed with a rabbit model of S. aureus endocarditis that the combination of ampicillin and sulbactam was highly effective against endocarditis caused by two different nafcillin-resistant S. aureus strains and that the combination was superior to nafcillin alone. Because these in vitro and in vivo observations deserve further scrutiny, we designed this study: (1) to determine the MICs of amoxicillin and oxacillin, alone or in combination with clavulanic acid, for a large number of recent clinical isolates of MSSA and MRSA; and (2) to study the in vivo efficacy of the combination of amoxicillin with clavulanic acid against MSSA and MRSA strains in a rat model of S. aureus endocarditis and to compare it to that of cloxacillin and vancomycin. Materials and Methods In vitro study. (1) Microorganisms. A total of 167 strains of S. aureus originating in different locales (Eu
Using two strains of Staphylococcus aureus, one susceptible and one heterogeneously resistant to methicillin, for which MICs and MBCs of trimethoprim-sulfamethoxazole (TMP-SMX) were 0.06 and 0.06 g/ml and 0.06 and 0.25 g/ml, respectively (concentrations are those of TMP), we studied the efficacies of TMP-SMX and cloxacillin, teicoplanin, and vancomycin for treatment of experimental staphylococcal endocarditis. Rabbits were treated with dosages of TMP-SMX selected to achieve concentrations in serum equivalent to that obtained in humans treated for Pneumocystis carinii pneumonia. The overall mortality rate of rabbits treated with TMP-SMX was 84% at day 3, not different from that of the control groups (P > 0.1). No sterile vegetations were observed to be present in control groups or in animals treated with TMP-SMX. However, 26, 60, and 75% of rabbits treated with teicoplanin, cloxacillin, and vancomycin, respectively, showed sterile vegetations. For methicillin-susceptible S. aureus (MSSA), the mean vegetation counts were not significantly different between the control group and the group treated with TMP-SMX (P > 0.1). For methicillin-resistant S. aureus (MRSA), treatment with TMP-SMX was more effective than no therapy, decreasing the number of organisms in vegetations (P < 0.01). For both strains, therapy with cloxacillin and therapy with teicoplanin or vancomycin were significantly more effective than therapy with TMP-SMX. Despite high concentrations of teicoplanin in serum which exceeded MBCs for staphylococci more than 50 times at the peak and 10 times at the trough, therapy with cloxacillin or vancomycin was superior to therapy with teicoplanin against both MSSA and MRSA. These data do not support the use of TMP-SMX in treatment of endocarditis and other severe staphylococcal infections with high bacterial counts.