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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Article: Ceftaroline[Show abstract] [Hide abstract]
ABSTRACT: Cephalosporins are widely used antibiotics throughout the world. However, with the availability of multiple agents in this class with varying spectrum of activity and clinical use, selecting the most appropriate cephalosporin can become convoluted. Ceftaroline, a new-generation cephalosporin recently approved in the United States for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection may further complicate this dilemma. Ceftaroline is easily distinguishable compared to the other intravenous cephalosporins given its activity against methicillin-resistant Staphylococcus aureus (MRSA) including multidrug-resistant MRSA. Unfortunately, its Food and Drug Administration–approved indications offer little benefit for the antimicrobial, given cheaper, oral, and more experienced antimicrobials for these indications exist. Ceftaroline may be more appealing in the treatment of infections that require broad-spectrum intravenous antibiotics empirically (eg, endocarditis, meningitis, and osteomyelitis), especially if MRSA is a concern. However, future studies are needed to evaluate its efficacy for these indications. Until these are completed, ceftaroline should be considered as an alternative for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection at this time.Infectious Disease in Clinical Practice 01/2014; 22(1):8-17. DOI:10.1097/IPC.0b013e3182948d1c
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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 · 4.45 Impact Factor