Antimicrobial therapy of multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus.
ABSTRACT Antibiotic resistance among pneumococci, enterococci, and staphylococci has become increasingly important in recent decades. Clinicians should be familiar with the nuances of antibiotic susceptibility testing and interpretation in selecting antibiotics for these infections. The clinical significance of penicillin-resistant Streptococcus pneumoniae, macrolide-resistant S pneumoniae, and multidrug-resistant S pneumoniae is discussed. The clinical spectrum and therapeutic approach to Enterococcus faecalis (i.e., vancomycin-sensitive enterococci) and E faecium (i.e., vancomycin-resistant enterococci) are discussed. Differences in therapeutic approach between methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus (MRSA) infections are reviewed. Differences between in vitro susceptibility testing and in vivo effectiveness of antibiotics for hospital-acquired MRSA (HA-MRSA) are described. Finally, the clinical features of infection and therapy of HA-MRSA and community-acquired MRSA (CA-MRSA) infections are compared.
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ABSTRACT: Gram-positive bacteria cause a broad spectrum of disease in immunocompetent and immunocompromised hosts. Despite increasing knowledge about resistance transmission patterns and new antibiotics, these organisms continue to cause significant morbidity and mortality, especially in the health care setting. Methicillin-resistant Staphylococcus aureus poses major problems worldwide as a cause of nosocomial infection and has emerged as a cause of community-acquired infections. This change in epidemiology affects choices of empirical antibiotics for skin and skin-structure infections and community-acquired pneumonia in many settings. Throughout the world, the treatment of community-acquired pneumonia and other respiratory tract infections caused by penicillin-resistant Streptococcus pneumoniae has been complicated by resistance to β-lactam and macrolide antibacterial drugs. Vancomycin-resistant enterococci are a major cause of infection in the hospital setting and remain resistant to treatment with most standard antibiotics. Treatment of diseases caused by resistant gram-positive bacteria requires appropriate use of available antibiotics and stewardship to prolong their effectiveness. In addition, appropriate and aggressive infection control efforts are vital to help prevent the spread of resistant pathogens.Mayo Clinic Proceedings 12/2011; 86(12):1230-43. DOI:10.4065/mcp.2011.0514 · 5.79 Impact Factor
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ABSTRACT: Reduced bactericidal efficacy at high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IE of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6-9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 10(4.5-5.7) CFU/thigh (low inoculum, LI) in one thigh and 10(6.4-7.2) cfu/thigh (high inoculum, HI) in the opposite thigh when treated for 24 hrs with 12-hr subcutaneous (sc) doses of DAP at 0.024-100 mg/kg and LZD at 0.313-320 mg/kg, and 6-hr sc doses of CFB at 0.003-160 mg/kg and VAN at 0.049-800 mg/kg. Dose-response data were analyzed by an E(max) model using non-linear regression. Static doses (SD) for each drug and at each inoculum were calculated and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7-4.6) for CFB, 4.1 (2.6-9.3) for DAP, 4.6 (1.7-7.1) for LZD, and 10.1 (6.3-20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3-3.3) for CFB, 2.0 (1.6-2.8) for DAP, 1.9 (1.7-2.2) for LZD, and 1.5 (0.8-3.2) for VAN; these values were similar for all drugs. In S. aureus, IE was much larger with VAN compared to CFB, DAM, and LZD (P < 0.05). In vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold higher doses at HI than at LI despite similar initial growth of controls.Antimicrobial Agents and Chemotherapy 01/2013; DOI:10.1128/AAC.00362-12 · 4.57 Impact Factor