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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.
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.
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.
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).
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.
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.
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.
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.
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.
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BACKGROUND: Resistant bacteria often complicate the management of skin and soft tissue infections of the lower extremities. This open-label study compared oral linezolid and intravenous vancomycin for management of complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Patients aged 18 years or older with proven MRSA-related complicated skin and soft-tissue infections requiring surgical intervention were randomized to receive oral linezolid (n = 30) or intravenous vancomycin (n = 30) for 7 to 21 days. Clinical and microbiological outcomes, duration of hospitalization and drug treatment, and outpatient charges were determined. RESULTS: Linezolid was associated with greater rates of clinical cure and improvement (P = .015), a 3-day shorter median length of stay (P = .003), and reduced outpatient charges (P < .001). Vancomycin therapy was associated with more treatment failures and subsequent lower-extremity amputations (P = .011). CONCLUSIONS: Clinical outcomes were significantly better with linezolid than with vancomycin. Additionally, linezolid was associated with reduced length of stay and outpatient charges.
Link: The Annals of Pharmacotherapy.
CASE SUMMARIES: Case 1. A 38-year-old white female with cystic fibrosis treated with venlafaxine 300 mg/day for one year was prescribed linezolid 600 mg intravenously every 12 hours for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pulmonary infection. She displayed symptoms of ST 8 days after the introduction of linezolid. The venlafaxine dosage was decreased to 150 mg/day, and symptoms gradually abated over 36 hours. Case 2. A 37-year-old male with multiple myeloma received citalopram 40 mg/day and trazodone 150 mg/day for anxiety-related disorders. Linezolid treatment with 600 mg orally twice daily was instituted for MRSA cellulitis. The following day, the patient developed anxiety, panic attacks, tremors, tachycardia, and hypertension that persisted throughout linezolid treatment. Symptoms finally waned 5 days after linezolid treatment was stopped. DISCUSSION: The symptoms observed in our patients were consistent with Sternbach's criteria for ST. A review of published case reports showed a short time to onset of symptoms following the introduction of linezolid, generally within 1-3 days. Also of note is the use of relatively high dosages of serotonergic drugs. Use of the Naranjo probability scale indicated a possible relationship between the use of linezolid and the occurrence of ST in both cases. CONCLUSIONS: Clinicians should pay special attention to patients treated with serotonergic drugs, especially those receiving dosages in the higher end of the normal range who are prescribed linezolid, and consider tapering or reducing the dosage of serotonergic drugs for the duration of antibiotic therapy.
Link: Journal of Antimicrobial Chemotherapy.
Between May 1999 and September 2003, 20 patients with prosthetic joint infection were treated with linezolid. Pathogens isolated were: methicillin-resistant Staphylococcus aureus (MRSA), 14 strains; methicillin-resistant coagulase-negative staphylococci, five strains; and Enterococcus spp., one strain. The overall duration of treatment was 7.2 � 2 weeks (range 6-10 weeks). Patients were given intravenous therapy for 3-7 days as inpatients, then were changed as outpatients to oral therapy under weekly laboratory testing. At long-term follow-up (1 year), we observed four cases of failure due to relapsing infections. The other 16 patients treated with linezolid did not need further surgical substitution of prosthesis or surgical joint revision. Linezolid was well tolerated, and no drug-related events leading to discontinuation of treatment were recorded. Conclusions: Our data indicate that linezolid may be an effective alternative therapy for orthopaedic infections caused by Gram-positive resistant pathogens and that a prospective and comparative evaluation of linezolid in this setting is necessary.
A short introduction from Dave Roberts
This 12 minute introduction will help you grasp the key facts and the key issues surrounding drug resistant staph aureus (mersa, mursa)
