MRSA (Mersa) Questions

Linezolid rare reaction causes lesions

Link: HighWire Press -- Medline Abstract.

    In this case, there was a close temporal correlation between drug exposure and the onset of symptoms. When linezolid was discontinued, the skin lesions resolved quickly and the general condition of the patient improved. Furthermore, linezolid was the only drug added before the cutaneous lesions appeared. It is possible that the adverse reaction was associated with administration of amoxicillin/clavulanic acid. However, the patient had been treated with this antibiotic previously without appearance of any cutaneous reaction. An objective causality assessment revealed that an adverse effect was possible. CONCLUSION: Based on our observations, we conclude that linezolid was the most likely cause of the adverse reaction. Clinicians should be aware of this infrequent but severe reaction.

Good Clinical Outcomes but High Rates of Adverse Reactions during Linezolid Therapy

Link: Antimicrobial Agents and Chemotherapy.

     We assessed the toxicity and clinical outcomes associated with linezolid therapy (mean duration, 29 � 28 days; range, 8 to 185 days) in 44 patients with serious gram-positive infections. Although a clinical cure was achieved in 73% of the cases, 28/44 (64%) had adverse reactions (thrombocytopenia, n = 13; anemia, n = 7; gastrointestinal, n = 12; peripheral neuropathy, n = 1; serotonin syndrome, n = 1), such that a systematic monitoring protocol was developed.

Linezolid long term may cause damage

Link: Linezolid-associated toxic optic neuropathy

   The oxazolidinone antimicrobial linezolid is effective against gram-positive bacteria. Although maximal recommended therapy is 28 days, treatment durations greater than this are common. Linezolid may cause reversible optic neuropathy and irreversible peripheral neuropathy after months of treatment. Three cases of linezolid-induced optic and peripheral neuropathy are described, and previously reported cases of linezolid-induced optic neuropathy are reviewed. The mechanism of neural toxicity may be impairment of mitochondrial protein synthesis.

Does haemodialysis significantly affect serum linezolid concentrations in critically ill patients with renal failure?

Link: Does haemodialysis

Results. A total of 222 serum linezolid concentrations were available over 36 days of antibiotic therapy, during which patients underwent 31 HD sessions. Trough serum linezolid levels averaged 5.83 mg/l (range 1.48-15.84), exceeding 4.0 mg/l in 68.9% of the samples; however, the trough levels ‘with HD’ were lower than those ‘without HD’ (4.68 mg/l [range 1.48-9.07] vs 6.74 mg/l [range 2.04-15.84], P<0.001). Clearance and half-life were 6.0 l/h and 4.0 h, respectively, while patients were on-dialysis, and 4.4 l/h and 7.3 h, respectively, when they were off-dialysis.

Conclusions. HD can significantly reduce serum linezolid levels in critically ill patients with renal failure.

Is Linezolid still working? (Yes)

Link: Journal of Antimicrobial Chemotherapy

    Objectives: To investigate the activity of linezolid (an oxazolidinone), a potent choice for community- and hospital-acquired infections, via a worldwide surveillance network called the Zyvox� Annual Appraisal of Potency and Spectrum (ZAAPS) Program.  No linezolid resistance was detected in strains from 16 monitored countries in 2004. Results: Linezolid remained highly active against Streptococcus pneumoniae, viridans group and �-haemolytic streptococci (MIC90, 1 mg/L). Against Staphylococcus aureus, linezolid showed 99.5% of results at 0.5–2 mg/L with only one isolate at 4 mg/L. Oxacillin-resistant S. aureus rates varied between nations and ranged from 1.4% in Sweden to 29.5% in the UK to 65.2% in Mexico. Linezolid MIC values were generally one log2 dilution step lower for coagulase-negative staphylococci (CoNS) when compared with S. aureus. No CoNS strains produced a linezolid result at 4 mg/L. Compared with ZAAPS 2002 and 2003 results for enterococci where seven resistant strains were identified, the 2004 data revealed no resistance and 98.1% of linezolid MIC results were at 1 or 2 mg/L. Vancomycin-resistant enterococci (5.3% overall) varied markedly by country including a high of 47.2% in Korea.

Conclusions: Linezolid continues to be effective in vitro against Gram-positive pathogens from five continents and no oxazolidinone-resistant strains were identified among the 4098 systemically collected strains (2004) or among 20 158 non-United States isolates for the entire ZAAPS Program (2002–04).

Which Drug Battles MRSA Pneumonia Best

Link: HON - News

The drug linezolid (brand name Zyvox) seems about 40 percent more effective in combating a deadly and increasingly common form of antibiotic-resistant bacteria than the drug vancomycin. That's according to research published online in the March issue of Intensive Care Medicine . This form of pneumonia -- ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) -- was once primarily found in intensive care unit patients. But it is now increasingly common in the general population, particularly among children. Linezolid is a relatively new drug. Vancomycin has been used to treat pneumonia for about a decade. In this current paper, a team led by researchers at Washington University School of Medicine in St. Louis combined and analyzed data of about 544 patients with ventilator-associated pneumonia who were part of two previous studies. They found linezolid was about 15 percent more effective in curing infection than vancomycin (49 percent vs. 34 percent). Overall survival rates were marginally better for patients taking linezolid compared with those taking vancomycin. When they analyzed a subset of patients with MRSA, the researchers found a 60 percent cure rate for patients taking linezolid, compared to a cure rate of 22 percent for those taking vancomycin. Survival rates were 84 percent for patients taking linezolid compared to 62 percent for those taking vancomycin.

Dalbavancin better than linezolid?

Link: Randomized

Dalbavancin and linezolid demonstrated comparable clinical efficacy in the clinically evaluable population at the test-of-cure visit (88.9% and 91.2% success, respectively). The rate of clinical success at the end of therapy was >90% in both arms. Less than 1.0% of patients in either treatment arm experienced relapse after the test-of-cure visit. Both treatments yielded successful microbiological response in excess of 85% among microbiologically evaluable patients at end of therapy and at the test-of-cure visit for all pathogens combined, for all S. aureus strains, and for MRSA. Gastrointestinal symptoms were among the most common adverse events in both arms. A higher proportion of patients in the linezolid arm reported adverse events that were judged by the investigator to be probably/possibly related to treatment (dalbavancin arm, 25.4% of subjects; linezolid arm, 32.2% of subjects). CONCLUSIONS: Two doses of dalbavancin (1000 mg given on day 1 followed by 500 mg given on day 8) were as well tolerated and as effective as linezolid given twice daily for 14 days for the treatment of patients with complicated SSSI, including those infected with MRSA.

Linezolid versus vancomycin

Link: Linezolid versus vancomycin .

Of 99 clinically evaluable patients, primary infection was cured in 28 (55%) of 51 linezolid recipients and 25 (52%) of 48 vancomycin recipients [odds ratio (OR) for cure with linezolid versus vancomycin, 1.12; 95% confidence interval (CI), 0.51-2.47]. There were no between-group differences in the meta-analysis (OR, 1.16; 95% CI, 0.5-2.65). Of 53 evaluable patients with methicillin-resistant S. aureus (MRSA) bacteraemia, clinical cure occurred in 14 (56%) of 25 linezolid recipients and 13 (46%) of 28 vancomycin recipients (OR, 1.47; 95% CI, 0.50-4.34). Microbiological success occurred in 41 (69%) of 59 linezolid recipients and 41 (73%) of 56 vancomycin recipients (OR, 0.83; 95% CI, 0.37-1.87). Fifty-five (74%) of 74 linezolid recipients survived versus 52 (74%) of 70 vancomycin recipients (OR, 1.00; 95% CI, 0.47-2.12). In the multivariate analysis, treatment group was not a significant predictor of clinical cure or survival. CONCLUSIONS: Linezolid was associated with outcomes that were not inferior to those of vancomycin in patients with secondary S. aureus bacteraemia.

MRSA Drug Maker Rapped

Link: Reuters.com.

U.S. regulators warned Pfizer Inc. (PFE.N: Quote, Profile, Research) about "misleading promotion" of its antibiotic drug Zyvox in a professional journal, according to a letter released on Tuesday. The advertisement does not include information about Zyvox's risks, implies it is superior without supporting evidence, and claims it can treat more infections than for which it was approved, the U.S. Food and Drug Administration letter said. The agency called on the drugmaker to halt the advertisement and take the extra step of sending out new, more accurate promotions.

Linezolid better, quicker, less invasive but expensive?

Link: Skin infections

Pfizer's antibiotic ZYVOX (linezolid injection, tablets, and for oral suspension) is more effective than vancomycin for the treatment of complicated skin and soft tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA), according to the largest MRSA cSSTIs study to date published in Antimicrobial Agents and Chemotherapy. Of the total study population, including those treated for methicillin-susceptible infections, the number of patients cured with ZYVOX was comparable to those cured with vancomycin. In addition, patients taking ZYVOX spent up to five fewer days on IV treatment because of its availability as a pill. Available in interchangeable IV and oral formulations, ZYVOX is the only oral medicine approved by the U.S. Food and Drug Administration for MRSA infections. This study involved 1,180 patients with cSSTIs, 361 of whom had confirmed MRSA infections. MRSA is a serious, multidrug-resistant infection, which is on the rise and can lead to prolonged hospitalization, along with increased morbidity, mortality and cost. Patients in the microbiologically evaluable MRSA subgroup treated with ZYVOX had better microbiologic cure rates: 88.6 percent for ZYVOX patients vs. 66.9 percent for vancomycin patients.

Click link above for more