Methicillin susceptible

It is important to determine (1) whether the isolate is methicillin-susceptible or methicillin-resistant and (2) whether the patient has a prosthetic valve. For patients with no prosthetic material, methicillin-susceptible staphylococci treatment should consist of a penicillinase-resistant penicillin (e.g., nafcillin or oxacillin) with or without gentamicin, and for methicillin-resistant strains, therapy should consist of vancomycin (see Table 71-4). Combination therapy with aminoglycosides, when used in these patients, typically is given only during the first 3 to 5 days of therapy. In the absence of prosthetic material, some treatment guidelines do not recommend combination therapy against MRSA. However, many clinicians may combine either gentamicin or rifampin with vancomycin if the patient is unresponsive to monotherapy. 

Goodacre, R. Rooney, P. I Kell, D. B. Discrimination between methicillin-resistant and methicillin-susceptible Staphylococcus aureus using pyrolysis mass spectrometry and artificial neural networks. J. Antimicrob. Chemother. 1998, 41, 27-34. 

Streptococcus pneumoniae Penicillin susceptible Penicillin intermediate Penicillin resistant Group B Streptococcus Staphylococcus aureus Methicillin susceptible Methicillin resistant Staphylococcus epidermidis Listeria monocytogenes... 

Compiicated skin and skin structure infections Caused by Staphyiococcus aureus (methicillin-susceptible strains only). Streptococcus pyogenes, E. coii, or Peptostreptococcus sp. 

Community-acquired pneumonia For the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible strains only), including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible strains only). 

Complicated skin and skin structure infections (SSSIs) For the treatment of complicated SSSIs caused by S. aureus (methicillin-susceptible and -resistant strains). Streptococcus pyogenes, or Streptococcus agalactiae. It has not been studied in the treatment of diabetic foot and decubitus ulcers. 

Levofloxacin (1), the levo-isomer or the (5)-enantiomer of ofloxacin, received FDA approval in 1996 (Fish, 2003 Hurst et al., 2002 Mascaretti, 2003 Norrby, 1999 North et al., 1998). The initial approval covered community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, uncomplicated skin and skin structure infections, acute pyelonephritis, and complicated urinary tract infections (North et al., 1998). Four years later, the levofloxacin indication list grew to include community-acquired pneumonia caused by penicillin-resistant Streptococcus pneumoniae. In addition, in 2002, nosocomial (hospital-acquired) pneumonia caused by methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Kliebsella pneumoniae, and Escherichia coli was added (Hurst et al., 2002). Finally in 2004, LVX was approved as a post-exposure treatment for individuals exposed to Bacillus anthracis, the microbe that causes anthrax, via inhalation (FDA, 2004). 

These semisynthetic penicillins are indicated for infection by 3-lactamase-producing staphylococci, although penicillin-susceptible strains of streptococci and pneumococci are also susceptible. Listeria, enterococci, and methicillin-resistant strains of staphylococci are resistant. In recent years the empirical use of these drugs has decreased substantially given increasing rates of methicillin-resistance in staphylococci. However, for infections caused by methicillin-susceptible strains of staphylococci these are considered the drugs of choice. 

A combination of trimethoprim-sulfamethoxazole is effective treatment for a wide variety of infections including P jiroveci pneumonia, shigellosis, systemic salmonella infections, urinary tract infections, prostatitis, and some nontuberculous mycobacterial infections. It is active against most Staphylococcus aureus strains, both methicillin-susceptible and methicillin-resistant, and against respiratory tract pathogens such as the pneumococcus, Haemophilus sp, Moraxella catarrhalis, and Klebsiella pneumoniae (but not Mycoplasma pneumoniae). However, the increasing prevalence of strains of E coli (up to 30% or more) and pneumococci that are resistant to trimethoprim-sulfamethoxazole must be considered before using this combination for empirical therapy of upper urinary tract infections or pneumonia. 

Interestingly, the undifferentiated antibacterial activity against both methicillin-susceptible and -resistant strains of Staphylococcus aureus was suggestive of an alternative mechanism of action compared to that of typical (3-lactams. The molecular modeling approach allowed the identification of interactions through oxygenated functions such as phenolic OH, which are valuable for the antibacterial activity [294]. 

Mason, B.W., Howard, A.J., and Magee, J.T., Fusidic acid resistance in community isolates of methicilline-susceptible Staphylococcus aureus and fusidic acid prescribing. J. Antimicrob. Chemother. 51, 1033-1036, 2003. 

Methicillin-susceptible staphylococci, penicillin-susceptible strains of streptococci and pneumococci. 

Regimen for Methicillin-Susceptible Staphylococci Nafcillin sodium or oxacillin 2 g IV every 4 h >6 therapy. First-generation cephalosporins or vancomycin... 

Shore AC, Rossney AS, O Connell B, Herra CM, Sullivan DJ, Humphreys H, Coleman DC (2008) Detection of staphylococcal cassette chromosome mec-associated DNA segments in multire-sistant methicillin-susceptible Staphylococcus aureus (MSSA) and identification of Staphylococcus epidermidis ccrAB4 in both methicilhn-resistant S. aureus and MSSA. Antimicrob Agents Chemother 52 4407-4419... 

Daptomycin is indicated in treatment of complicated skin and skin-structure infections caused by methicillin-susceptible and methicillin-resistant strains of S. aureus, hemolytic stteptococci, and vancomycin-susceptible E. faecalis. Its efficacy is comparable to that of vancomycin. Efficacy in more serious infections, such as endocarditis or complicated bacteremia, has not been demonsttated, although clinical ttials are under way. Daptomycin was inferior to comparators for treatment of community-acquired pneumonia and is not indicated for this infection. 

Linezolid is FDA approved for treatment of infections caused by vancomycin-resistant E. faecium nosocomial pneumonia caused by methicillin-susceptible and methicillin-resistant strains of S. aureus community-acquired pneumonia caused by penicillin-susceptible strains of S. pneumoniae complicated skin and skin-structure infections caused by streptococci and methicillin-susceptible and -resistant strains of S. aureus and uncomplicated skin and skin-structure infections. In noncomparative studies, linezolid (600 mg twice daily) has had clinical and miaobiological cure rates in the range of 85 to 90% in treatment of a variety of infections (soft tissue, urinary tract, and bacteremia) caused by vancomycin-resistant E. faecium. A 200-mg, twice-daily dose was less effective, with clinical and microbiological cure rates of approximately 75 and 59%, respectively. The 600-mg, twice-daily dose, therefore, should be used for treatment of infections caused by enterococci. A 400-mg, twice-daily dosage regimen is recommended only for treatment of uncomplicated skin and skin-structure infections. 

Quinupristin/dalfopristin is a streptogramin. Quinupristin inhibits the late phase of protein synthesis dalfopristin inhibits the early phase of protein synthesis. It is indicated in the treatment of serious or life-threatening infections associated with VREF treatment of complicated skin and skin-structure infections caused by Staphylococcus aureus (methicillin-susceptible) or Streptococcus pyogenes. 

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