Meeting Perspectives: Annual Meeting of the Infectious Diseases Society of America (IDSA) October, 2007

December 13, 2007

idsa.jpgCommentary by Neal Steigbigel MD, Professor of Medicine (Infectious Diseases/Immunology)

Methicillin resistant Staphylococcus aureus (MRSA) was a hot topic at this year’s IDSA meeting. The CA (community-acquired)-MRSA strains are spreading rapidly in the United States causing largely soft tissue infections, but also other infections such as serious necrotizing pneumonia. Clinicians can no longer rely on demographics in predicting which patient is at high risk for MRSA when an individual appears with a suspected staph infection. If the infection appears serious and is likely to be caused by S. aureus, treat them all as if they are MR and make antibiotic changes after culture and sensitivities are back. That means typically starting with intravenous vancomycin at the usual doses.

However, vancomycin therapy for MRSA infections has been shown in recent years to be too often associated with sub-optimal outcomes, especially when the in vitro MIC of the isolate is at 2ug/ml or above; the current MIC cut off for labeling the isolate as “sensitive” to vancomycin is 2ug/ml or below. Due to this observation, there is a new need for our microbiology laboratories to start including the vancomycin MIC’s in the sensitivity reports for S. aureus. However, there is no alternative antibiotic that is definitively better than vancomycin when the organism is in the sensitive MIC range (2 ug/ml)—only guesses based on pharmacokinetic (PK) data and expert opinion. If the MIC of the isolate is 2 ug/ml, population analysis done by in vitro research studies show that many of these strains are “heteroresistant” to vancomycin, meaning a given isolate has subpopulations that are clearly in the “resistant” MIC ranges (such as 4-8 ug/ml). So why not use higher doses (>2gm/24h) of vancomycin, which has been recently proposed, to achieve trough vancomycin levels of 15-20 ug/ml in patients, for which PK calculations suggest would lead to more effective results against strains of S. aureus that are “heteroresistant?”

There are at least two problems with this approach. First, at the IDSA meeting, George Drusano’s Albany group showed a retrospective study of patients divided into those who received high and usual (2g/24h) doses of vancomycin and found that the high dose group had a significantly higher likelihood of developing nephrotoxicity. Second, PK calculations indicate that to achieve trough levels of vancomycin in the 15-20ug/ml range, the needed dose for a S. aureus strain with an MIC of 2ug/ml or more would be unacceptably high—well over 4 gm per day.

What about alternative antibiotics such as daptomycin or lineziolid? Linezolid is expensive and can cause bone marrow suppression, especially when used for more than 10 days, and is poorly bacteristatic, a potential problem if the patient has endocarditis. Daptomycin is very bactericidal and has many other good characteristics, including a good clinical study showing at least non-inferiority to vancomycin in S. aureus infections, including right sided endocarditis. It can’t be used in bronchial pneumonia because it is inactivated by surfactant.

My opinion until potentially better agents are available (telavancin, dalbavancin, and ceftobiprole are undergoing study for a non-pneumonia patient with a serious MRSA infection who is not doing well on vancomycin and a MIC of at least 2ug/ml, is to switch to daptomycin at 6-8mg/kg daily, assuming normal renal function. For serious MSSA infections nafcillin or oxacillin are still the antibiotics of choice. For dialysis patients with MSSA bacteremia, cefazolin, 1gm/24h is more effective than vancomycin.

For patients with catheter related MSSA or MRSA bacteremia, the “expert” suggestion based on reasonable evidence is to rapidly remove the catheter, culture it, perform TEE in all patients (substantial incidence of vegetations) (not just TTE –too many false negatives) and if TEE negative, along with no other clinical evidence of other metastatic infection and with bacteremia and fever lasting less than 72h, continue the IV antibiotics for the S. aureus for 14 days (not just 10 days). If the patient does not meet that 14 day criteria, treat IV for 4 weeks. Recent studies indicate that catheters inserted properly in ICU’s (hand washing, sterile gloves, chlorhexidine skin prep, and other proper barriers) can lead to an eradication of catheter-related infections.

Newer data was presented that suggest that combinations of antibiotics for S. aureus infections are generally not indicated. The addition of rifampin prolongs S. aureus bacteremia, is associated with lower survival, promotes Rif resistance and is associated with drug interaction problems. Addition of gentamicin does not lead to lower mortality and is associated with increased nephrotoxicity.

Other highlights from this year’s IDSA conference included new evidence that anti-pseudomonal beta-lactam antibiotics were superior to non-beta-lcatam antibiotics. A promising report from Tom Quinn (Johns Hopkins and NIH) on progress against the African HIV pandemic highlighted the efficacy of efforts to reduce mother-to-child transmission with anti-retroviral medications, and male circumcision in reducing transmission from men to women.