MRSA, Staph, Staff, Mersa, Methicillin Resistant Staphylococcus Aureus Symptoms & Treatment

Main MRSA Drugs not Triggering More Infection?

Link: Nosocomial Infections Due to Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus: Relationships with Antibiotic Use and Cost Drivers (March) -- Mauldin et al., 10.1345/aph.1K501 -- The Annals of Pharmacotherapy.

Increased incidence of nosocomial infections due to methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) has been associated with the use of certain antibiotics and has resulted in increased morbidity, mortality, and costs of care. OBJECTIVE: To describe relationships between vancomycin and linezolid use and incidence of these nosocomial infections over time and to determine factors associated with the increased costs of care (cost drivers) associated with affected patients. METHODS: The association between institution-wide antibiotic use and the rate of nosocomial MRSA and VRE infections was assessed using segmented regression analysis for interrupted time series. The effect that patient characteristics and procedures, as well as certain antibiotic use, had on costs and length of stay of patients with MRSA or VRE nosocomial infection was also assessed and cost drivers for the 2 types of infections were compared. RESULTS: Our analysis included 206 patients who developed MRSA (n = 187) or VRE (n = 19) nosocomial infection. Although small numbers of VRE nosocomial infection may limit generalizations from our results, we found no significant relationship between vancomycin or linezolid use and the rate of either infection. While mean hospital costs were similar, cost drivers varied somewhat between infection types. CONCLUSIONS: The incidence of MRSA or VRE infections does not appear to be related to the use of vancomycin or linezolid. Costs of care are quite high in some affected patients and, while mean total hospital costs are similar, cost drivers appear to differ between the 2 infection types.

Vancomycin resistance emerging

Link: Relationships between vancomycin pharmacodynamics and the emergence of vancomycin-intermediate Staphylococcus aureus (VISA) from heterogeneous VISA in an in vitro pharmacodynamic model -- Rose et al., 10.1093/jac/dkn037 -- Journal of Antimicrobial Chemotherapy.

Results: The activity of vancomycin was highly dependent on the bacterial inoculum. At high inoculum, all vancomycin simulations displayed initial killing up to 24 h with no additional activity beyond this time point. Increased vancomycin doses had no impact on overall activity. Although bactericidal activity was achieved in all strains, regardless of the presence of hVISA, ~105cfu/mL of organisms remained after exposure. Doses as high as 5 g every 12 h (fAUC/MIC 799) had little influence on decreasing the hVISA bacterial load. More rapid bactericidal eradication was noted at lower inoculum in the non-hVISA isolate (T99 1.9 h versus 14.1 h and 15.3 h for Mu3 and 1629, respectively; P = 0.001). A 2- to 4-fold increase in vancomycin MIC was noted with both hVISA isolates compared with no increase in non-hVISA at high inoculum. Conclusions: Vancomycin doses ≥2500 mg and 2000 mg every 12 h (fAUC/MIC 374 and 271) suppressed the emergence of MIC increases in Mu3 and 1629, respectively. Our data suggest that at high inoculum, vancomycin has minimal to no activity against hVISA and leads to further reduced susceptibility.

Some MRSA strains need stronger Vancomycin dose

Link: HighWire Press -- Medline Abstract.

Episodes caused by strains with a vancomycin MIC of 2 microg/mL were independently associated with a lower risk of shock (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.15-0.75). Multivariate analysis selected receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (OR, 6.39; 95% CI, 1.68-24.3), receipt of inappropriate empirical therapy (OR, 3.62; 95% CI, 1.20-10.9), increasing age (OR, 1.02; 95% CI, 1.00-1.04), use of corticosteroids (OR, 1.85; 95% CI, 1.04-3.29), an ultimately (OR, 10.2; 95% CI, 2.85-36.8) or rapidly (OR, 1.81; 95% CI, 1.06-3.10) fatal underlying disease, high-risk (OR, 3.60; 95% CI, 1.89-6.88) and intermediate-risk (OR, 2.18; 95% CI, 1.17-4.04) sources of bacteremia, and shock (OR, 7.38; 95% CI, 4.11-13.3) as the best predictors of mortality. CONCLUSIONS: Mortality associated with MRSA bacteremia was significantly higher when the empirical antibiotic was inappropriate and when vancomycin was empirically used for treatment of infection with strains with a high vancomycin MIC (>1 microg/mL).

Vancomycin not so effective second time round

ink: Microbiological effects of prior vancomycin use in patients with methicillin-resistant Staphylococcus aureus bacteraemia -- Moise et al., 10.1093/jac/dkm445 -- Journal of Antimicrobial Chemotherapy.

Results: Vancomycin MICs were 0.5, 1.0 and 2.0 mg/L for 19, 55 and 7 isolates, respectively. Daptomycin MICs were 0.25, 0.5, 1.0 and 2.0 mg/L for 4, 50, 26 and 1 isolate, respectively. The agr-type distribution was agr group II (59%), group I (25%) and group III (16%); 90% harboured SCCmec II. The genetic background extrapolated by spa-typing showed that 58% of the isolates were of clonal complex 5. MRSA bloodstream isolates from patients who had received vancomycin within the preceding 30 days had a significantly decreased vancomycin killing at 24 h in vitro (median log10 decrease, 3.1 versus 2.2 cfu/mL; P = 0.021) and a significantly higher vancomycin MIC than isolates obtained from patients without that history (P = 0.002). Conclusions: MRSA bloodstream isolates from patients recently treated with vancomycin may demonstrate reduced susceptibility and increased tolerance to vancomycin in vitro. Given that such microbiological phenotypes have been associated with reduced vancomycin efficacy, consideration may be given to alternative Gram-positive antimicrobial therapy in patients who have recently been treated with vancomycin.

Vancomycin care needed with HIV patients

Link: An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR -- Barraclough et al. 22 (8): 2391 -- Nephrology Dialysis Transplantation.

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 – 42 µmol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points:

Daptomycin Use After Vancomycin Side Effects

Link: Daptomycin Use After Vancomycin-Induced Neutropenia in a Patient with Left-Sided Endocarditis -- Mergenhagen and Pasko 41 (9): 1531 -- The Annals of Pharmacotherapy.

CASE SUMMARY: A 55-year-old African American male was diagnosed with left-sided endocarditis, brain abscesses, and septic arthritis due to community-acquired MRSA. He began treatment with intravenous vancomycin to achieve a trough concentration of 15-20 �g/mL and oral rifampin 600 mg/day. A repair and resection of the mitral valve was completed on day 15 of hospitalization. Vancomycin was discontinued on day 36 secondary to drug-induced neutropenia (absolute neutrophil count nadir 162 cells/�L). Intravenous therapy with daptomycin 6 mg/kg every 24 hours was then initiated and the neutropenia resolved. The patient was discharged from the hospital on day 56. DISCUSSION: Upon discontinuation of vancomycin, treatment options were limited to a small number of alternatives. Documented clinical experience and relevant studies are limited regarding the use of quinupristin/dalfopristin (Q/D), linezolid, trimethoprim/sulfamethoxazole (TMP/SMX), and daptomycin for the treatment of MRSA left-sided endocarditis. Daptomycin was selected because of its bactericidal qualities and its recent approval for this indication. The prognostic outlook for use of daptomycin in this treatment was uncertain; however, Q/D, linezolid, and TMP/SMX posed greater risks of failure. CONCLUSIONS: Treatment of MRSA left-sided endocarditis in patients intolerant to vancomycin is challenging. The positive outcome in our patient is likely attributable to aggressive vancomycin dosing and extended duration of treatment prior to the initiation of daptomycin. The use of daptomycin in this case enabled successful management

Vancomycin not being dispensed properly?

Link: Vancomycin administration: the impact of multidisciplinary interventions -- Crowley et al. 60 (10): 1155 -- Journal of Clinical Pathology.

The clinical microbiology team observed that patients were not receiving all prescribed doses of vancomycin. Ward staff was confused about ordering and interpreting vancomycin therapeutic drug monitoring (TDM) levels. Aim: To audit the incidence of vancomycin dose omission. To implement a series of interventions to improve vancomycin dose administration, and to repeat the audit process to assess these interventions. Methods: Three prospective audits were conducted to assess the impact of vancomycin TDM on administration of vancomycin. After the first audit, a number of changes in the TDM process were undertaken. After review of the second audit, a senior pharmacist coordinated ward-based pharmacists in assisting staff to interpret levels, and TDM interpretative charts were designed for drug charts. Following the third audit, feedback to hospital management and a plan for ongoing education were undertaken. Results: There was a significant reduction in the number of vancomycin doses held inappropriately in the third (10% (78/782) of prescribed doses) when compared to the first audit (16% (161/1007) of doses) (p<0.01). Of doses that were held inappropriately, there was a significant decrease in doses held for no apparent reason in audit 3 (16% (27/170) of prescribed doses) when compared to audit 1 (25% (69/282) of doses) (p<0.05). Conclusions: The interventions resulted in a 37.5% reduction in inappropriately held vancomycin doses over a one-year period; 10% of doses are still being held inappropriately. This study highlights the difficulties in identifying barriers to change and changing healthcare worker behaviour.

Vancomycin not the best for MSSA

Link: Outcome of Vancomycin Treatment in Patients with Methicillin-susceptible Staphylococcus aureus Bacteremia -- Kim et al., 10.1128/AAC.00700-07 -- Antimicrobial Agents and Chemotherapy.

The cases for the case-control study were defined as patients who received vancomycin treatment for MSSA-B; the controls, who were patients that received beta-lactam treatment for MSSA-B, were selected with 1: 2 ratio according to the objective matching scoring system and the propensity score system. In the cohort study, SAB-related mortality in patients with vancomycin treatment (37%, 10/27) was significantly higher than that in those with beta-lactam treatment (18%, 47/267) (P = 0.02). In addition, multivariate analysis revealed that vancomycin treatment was associated with SAB-related mortality when independent predictors for SAB-related mortality and the propensity score were considered (adjusted OR 3.3, 95% CI 1.2-9.5). In the case-control study using the objective matching scoring system and the propensity score system, SAB-related mortality in case-patients was 37% (10/27) and in control-patients 11% (6/54), respectively (P < 0.01, respectively). Our data suggest that vancomycin is inferior to beta-lactam in the treatment of MSSA-B.

Vancomycin - side effects after prolonged use

Link: HighWire Press -- Medline Abstract.

CONCLUSIONS:: The results suggest that aggressive vancomycin dosing and prolonged vancomycin administration may be associated with greater risk for renal toxicity in patients with MRSA HCAP. However, this retrospective study cannot establish causation, and a prospective, randomized, double-blind trial is needed.

daptomycin may help long term vancomycin patients

Link: HighWire Press -- Medline Abstract.

Treatment of MRSA left-sided endocarditis in patients intolerant to vancomycin is challenging. The positive outcome in our patient is likely attributable to aggressive vancomycin dosing and extended duration of treatment prior to the initiation of daptomycin. The use of daptomycin in this case enabled successful management of left-sided endocarditis.