MRSA (Mersa, Staph) Questions

Rifampin shows some promise but results inconclusive

Link: Arch Intern Med -- Abstract: Adjunctive Use of Rifampin for the Treatment of Staphylococcus aureus Infections: A Systematic Review of the Literature, April 28, 2008, Perlroth et al. 168 (8): 805.

Results  The methods of in vitro studies varied substantially among investigations. The effect of rifampin therapy was often inconsistent, it did not necessarily correlate with in vivo investigations, and findings seemed heavily dependent on the method used. In addition, the quality of data reporting in these investigations was often suboptimal. Animal studies tended to show a microbiologic benefit of adjunctive rifampin use, particularly in osteomyelitis and infected foreign body infection models; however, many studies failed to show a benefit of adjunctive therapy. Few human studies have addressed the role of adjunctive rifampin therapy. Adjunctive therapy seems most promising for the treatment of osteomyelitis and prosthetic device–related infections, although studies were typically underpowered and benefits were not always seen. Conclusions  In vitro results of interactions between rifampin and other antibiotics are method dependent and often do not correlate with in vivo findings. Adjunctive rifampin use seems promising in the treatment of clinical hardware infections or osteomyelitis, but more definitive data are lacking. Given the increasing incidence of S aureus infections, further adequately powered investigations are needed.

Daptomycin approved for Scotland

Link: Pioneering new drug to fight MRSA is given go-ahead in Scotland - Scotsman.com News.

A NEW drug to help treat patients struck down by MRSA has been approved for use on the NHS in Scotland. The Scottish Medicines Consortium recommended Cubicin (daptomycin) to treat severe infections caused by the superbug. The decision was welcomed by microbiologists, who said there was still a need for treatments for MRSA, which is resistant to most antibiotics. Cubicin is one of only two new classes of antibiotics to be developed in the past 20 years.

Tigecycline an MRSA antidote?

Link: Tigecycline for the treatment of patients with severe sepsis or septic shock: a drug use evaluation in a surgical intensive care unit -- Swoboda et al. 61 (3): 729 -- Journal of Antimicrobial Chemotherapy.

Results: The majority of patients had co-morbidities such as cancer (51%) or renal replacement therapy (57%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of patients at admission was 27. Intra-abdominal infection was most frequently diagnosed (50% of patients); intra-abdominal infection and pneumonia were diagnosed in 14%. Methicillin-resistant Staphylococcus aureus was found in 16% of patients (colonization; infection: 6%) and vancomycin-resistant enterococci in 27% (colonization; infection: 21%). The mean duration of tigecycline therapy was 9 ± 4 days; 76% of patients received tigecycline in combination, with 64% being treated second line. APACHE score and renal replacement were identified as predictive factors for mortality. SICU mortality was 30%. Conclusions: Tigecycline treatment of critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality. Tigecycline may be an important treatment option for septic patients with infections resistant to other available agents.

Ceftobiprole effective against MRSA

Link: In vitro activity profile of ceftobiprole, an anti-MRSA cephalosporin, against recent Gram-positive and Gram-negative isolates of European origin -- Pillar et al. 61 (3): 595 -- Journal of Antimicrobial Chemotherapy.

Ceftobiprole activity against MRSA (MIC90 2 mg/L) was 4-fold less than the activity against methicillin-susceptible S. aureus (MIC90 0.5 mg/L) and a similar trend was observed for methicillin-resistant CoNS (MIC90 2 mg/L) and methicillin-susceptible CoNS (MIC90 0.25 mg/L). Activity against S. pneumoniae (MIC90s: penicillin-susceptible, 0.015 mg/L; -intermediate, 0.25 mg/L; -resistant, 0.5 mg/L) was comparable to that of ceftriaxone. Ceftobiprole activity against Enterobacteriaceae (MIC90s: ceftazidime-susceptible, 0.12 mg/L; non-susceptible, >32 mg/L), P. aeruginosa (MIC90s: ceftazidime-susceptible, 8 mg/L, non-susceptible, >32 mg/L) and Acinetobacter spp. (MIC90: >32 mg/L for imipenem-susceptible and non-susceptible) was comparable to that of cefepime. As with cefepime, ceftobiprole activity was decreased among cephalosporin-resistant isolates of Gram-negative bacilli [extended-spectrum β-lactamase (ESBL) or non-ESBL mediated]. Conclusions: Ceftobiprole demonstrated potent in vitro activity against MRSA and showed activity against key Gram-negative bacilli comparable to that of cefepime. Given this broad spectrum of activity, ceftobiprole appears well suited for development and use in the treatment of a variety of healthcare-associated infections.

Antimicrobial Activity of Ceftaroline and ME1036

Link: Antimicrobial Activity of Ceftaroline and ME1036 Tested against Clinical Strains of Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA) -- Sader et al., 10.1128/AAC.01351-07 -- Antimicrobial Agents and Chemotherapy.

Two investigational anti-methicillin-resistant Staphylococcus aureus (MRSA) {beta}-lactams, ceftaroline (cephalosporin) and ME1036 (carbapenem) were susceptibility tested by reference broth microdilution methods against 152 strains of community-acquired MRSA (CA-MRSA) from the United States (47 medical centers). Ceftaroline and ME1036 were 64- and >128-fold more potent that ceftriaxone, respectively. All isolates had the PVL genes and SCCmec type IV, while 67.8% of isolates showed PFGE clonal type USA300-0114.

One dozen drugs work against MRSA

Link: HighWire Press -- Medline Abstract.

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is characterized by variations (sometimes extreme) by country and geographic region. The conventional association of MRSA with healthcare settings has been upset by the emergence of community-associated MRSA infections in many areas. With this surge in MRSA comes a renewed interest in alternative agents to vancomycin for treatment of MRSA infections, including older drugs, such as clindamycin, doxycycline and trimethoprim- sulfamethoxazole. Newer agents, such as linezolid and daptomycin, are aiming to improve on the poor cure rates found with vancomycin in serious MRSA infections, but definitive studies showing superiority of these drugs are not yet available. Finally, the drug-development pipeline contains a number of agents for the treatment of MRSA infections, including enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA cephalosporins (ceftobiprole). As MRSA becomes the 'new normal' in many areas, clinicians will have to sort out the proper role of a dozen or more anti-MRSA drugs.

daptomycin helpful with catheter infections

Link: In vitro activity of daptomycin and vancomycin lock solutions on staphylococcal biofilms in a central venous catheter model -- LaPlante and Mermel 22 (8): 2239 -- Nephrology Dialysis Transplantation.

Conclusions. Our CVC model demonstrated that 72 h of exposure to 5 mg/ml lock solutions of daptomycin (plus calcium),  /– heparin or 5 mg/ml of vancomycin plus heparin demonstrate promise in treating catheter infections with biofilm-producing S. epidermidis. Similarly, 5 mg/ml of daptomycin (plus calcium) as a lock solution shows great promise in treating S. aureus catheter infections.

Which drugs for MRSA

Link: NEJM -- Methicillin-Resistant Staphylococcus aureus Infections.

In his review of skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Daum (July 26 issue)1 cites a study2 indicating that intravenous trimethoprim–sulfamethoxazole (TMP-SMX) is significantly less effective than vancomycin for the treatment of serious S. aureus infections. However, in this randomized, double-blind, comparative trial of TMP-SMX and vancomycin, therapeutic failures occurred only in patients with methicillin-susceptible S. aureus (MSSA) infections. TMP-SMX was successful in treating all MRSA infections, including tricuspid-valve endocarditis. Clinical failures commonly occurred with MSSA tricuspid-valve endocarditis; otherwise, the cure rates with TMP-SMX and with vancomycin were similar.

Efficacy of telavancin against MRSA

Link: Efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus -- Hegde et al., 10.1093/jac/dkm417 -- Journal of Antimicrobial Chemotherapy.

Results: At 48 h post-inoculation in the low and high pre-treatment titre groups, respectively, telavancin produced greater reductions (from pre-treatment values) in bacterial burden (–4.3 and –3.2 log10 cfu/g) than nafcillin (–1.3 and –1.8 log10 cfu/g), vancomycin (–2.9 and –2.2 log10 cfu/g) and linezolid (–0.4 and  0.3 log10 cfu/g). Conclusions: These findings support the potential clinical utility of telavancin in the treatment of MSSA pneumonia.

Dalbavancin - good but maybe not good for VRSA

Link: HighWire Press -- Medline Abstract.

The best-studied dosing schedule for dalbavancin involves the i.v. administration of 1 g of dalbavancin followed by 500 mg one week later. Phase III clinical trials comprising more than 1,500 patients evaluated once-weekly dalbavancin in Gram-positive skin and soft tissue infections (SSTIs). When compared to linezolid, cefazolin or vancomycin, dalbavancin met the primary endpoint of noninferiority at two weeks following therapy. The side-effect profile of dalbavancin is mild, with headache and pyrexia being the most common adverse effects. Dalbavancin is eliminated renally and hepatically, and does not need dose adjustments in patients with renal insufficiency. Once-weekly dosing with dalbavancin gives it another advantage when compared with vancomycin, and may alleviate the need for the continued presence of indwelling catheters in some patients with SSTIs and other infections requiring prolonged doses of antibiotics. While some in vitro evidence supports dalbavancin's effectiveness against vancomycin-resistant S. aureus, the preponderance of in vivo evidence does not demonstrate its effectiveness against vancomycin-resistant S. aureus. (c) 2007 Prous Science. All rights reserved. Publication Type: