MRSA Infection

Other Drugs Spurring Vancomycin resistance

Rapid Depletion of Free Vancomycin in Medium in the Presence of {beta}-Lactam Antibiotics and Growth Restoration in Staphylococcus aureus Strains with {beta}-Lactam-Induced Vancomycin Resistance -- Yanagisawa et al. 53 (1): 63 -- Antimicrobial Agents and Chemotherapy.

A class of methicillin-resistant Staphylococcus aureus strains shows vancomycin resistance in the presence of β-lactam antibiotics (β-lactam-induced VAN-resistant methicillin-resistant S. aureus [BIVR]). Two possible explanations may be offered: (i) vancomycin in culture medium is depleted, and (ii) the D-Ala-D-Ala terminal of the peptidoglycan network is replaced with D-Ala-D-lactate. We tested these hypotheses by quantifying free vancomycin in the medium through the course of cell growth and by PCR amplification of the van genes. Growth of the BIVR cells to an absorption level of ~0.3 at 578 nm required about 24 h in the presence of vancomycin alone at the MIC (4.0 µg/ml). However, growth was achieved in only about 10 h when 1/1,000 to 1/2,000 the MIC of β-lactam antibiotic was added 2 h prior to the addition of vancomycin, suggesting that the β-lactams shortened the time to recovery from vancomycin-mediated growth inhibition. Free vancomycin in the culture medium decreased to 2.3 µg/ml in the first 8 h in the culture containing vancomycin alone, yet cell growth was undetectable. When the vancomycin concentration dropped below ~1.5 µg/ml at 24 h, the cells began to grow. In the culture supplemented with the β-lactam 2 h prior to the addition of vancomycin, the drug concentration continuously dropped from 4 to 0.5 µg/ml in the first 8 h, and the cells began to grow at a vancomycin concentration of ~1.7 µg/ml or at 4 h of incubation. The gene encoding the enzyme involved in D-Ala-D-lactate synthesis was undetectable. Based on these results, we concluded that BIVR is attributable mainly to a rapid depletion of vancomycin in the medium triggered or promoted by β-lactam antibiotics.

Vancomycin is failing as MRSA drug

HighWire Press -- Medline Abstract.

Glycopeptides have been the antimicrobials most commonly used for infections by Gram-positive organisms and methicillinresistant S. aureus (MRSA). In recent years, however, glycopeptide resistance and tolerance have become a serious problem. Thus, enterococci highly resistant to vancomycin, vancomycin-intermediate/ resistant S. aureus (VISA), and vancomycin tolerance in S. aureus are found, and increased therapeutic failure and mortality are clinically reported with vancomycin MIC for S. aureus >/= 1.5-2 mug/mL. When faced with these organisms, we therefore need potent bactericidal antimicrobials that may be empirically administered, effective against susceptible and resistant pathogens, easily dosed, with few adverse effects and no significant interaction with other drugs, and that can be administered in an outpatient setting. In bacteremia by methicillin-susceptible S. aureus, use of vancomycin is associated to a greater failure and mortality rate as compared to semisynthetic penicillins. New treatment options for MRSA infections include daptomycin, linezolid, tygecycline, and quinupristin/dalfopristin. New anti-MRSA drugs are also under development, including glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. This paper reviews the new antimicrobials against Gram-positive organisms.

Kidney problems for small percentage of Vancomycin users

Link: HighWire Press -- Medline Abstract.

The frequency of decreased renal function was compared between patients treated with brand and generic products of vancomycin injection (VCM) in a retrospective manner based on the clinical examination records archived in Okayama University Hospital. A total of 122 patients were found to have been solely treated with vancomycin injection for MRSA infection, and their examination records were analyzed. The renal function of those patients was evaluated based on the serum creatinine concentration (SCr), and patients whose SCr was maximally elevated above the defined upper limit of the normal range (1.20 mg/dl for males and 0.96 mg/dl for females) were considered to show decreased renal function. Although the amount of VCM administered to patients was larger in the case of generic rather than brand products, the percentage of patients whose renal function was decreased during VCM treatment was not significantly different between the VCM products, in which 2 among 62 patients receiving the brand product and 4 among 60 receiving the generic product were reported to show decreased renal function. It was additionally revealed that 3 of those 4 patients with a decreased renal function related to the generic product were not treated as instructed by the package insert, and their trough VCM concentration exceeded the recommended level of 10 mug/ml. With these findings, the brand and generic VCM products are considered to be similar regarding the adverse effect of decreasing renal function.

VISA case raises vancomycin concerns

Link: Methicillin-Resistant Staphylococcus aureus Infection With Intermediate Sensitivity to Vancomycin: A Case Report and Literature Review -- Schairer et al. 23 (5): 338 -- Journal of Intensive Care Medicine.

We report a case of 43-year-old woman with of MRSA bacteremia, who relapsed after initial, apparently successful vancomycin treatment and developed left-sided endocarditis and vertebral osteomyelitis. Two weeks into her second admission, the vancomycin minimal inhibitory concentration rose from ≤ 2 µg/mL (susceptible) to 4 µg/mL (intermediate). The antibiotic was changed to daptomycin. Subsequent blood cultures were negative and sepsis resolved.

Vancomycin resistance being passed on at birth?

Link: Vancomycin heteroresistance of Staphylococcus capitis bloodstream isolates -- D'mello et al., 10.1128/JCM.00592-08 -- Journal of Clinical Microbiology.

Nine Staphylococcus capitis from blood cultures of newborns were examined for resistance to vancomycin. Minimum inhibitory concentrations were within the susceptible range, but population profiling revealed a resistant sub-population. Only isolates with the largest subpopulation were identified as heteroresistant to vancomycin by E-test. This finding may have therapeutic implications.

Vancomycin Failure - What are the facts

Link: Relationship between Vancomycin MIC and Failure among Patients with MRSA Bacteremia Treated with Vancomycin -- Lodise et al., 10.1128/AAC.00113-08 -- Antimicrobial Agents and Chemotherapy.

There is a growing concern that vancomycin has diminished activity for MRSA with vancomycin MIC values at the high end of the CLSI susceptibility range. Despite this growing concern, there are limited clinical data to support this notion. To better elucidate this, a retrospective cohort study was conducted among patients with MRSA bloodstream infection who were treated with vancomycin between 01/2005 and 5/2007. The inclusion criteria were: age ≥ 18 years old, non-neutropenic, MRSA culture met CDC criteria for bloodstream infection, received vancomycin therapy within 48 hours of index blood culture, and survived > 24 hours after vancomycin administration. Failure was defined as 30-day mortality, bacteremia ≥ 10 days on vancomycin therapy, or recurrence of MRSA bacteremia within 60 days of vancomycin discontinuation. Classification and regression tree (CART) analysis identified the vancomycin MIC breakpoint associated with an increased probability of failure. During the study period, 92 patients met the inclusion criteria. The vancomycin MIC value breakpoint derived by CART analysis was ≥ 1.5 mg/L. The 66 patients with a vancomycin MIC value ≥ 1.5 mg/L had a 2.4-fold increase in failure compared to patients with an MIC value ≤ 1.0 mg/L (36.4% and 15.4%, respectively, p=0.049). In the poisson regression, vancomycin MIC value ≥ 1.5 mg/L was the independently associated with failure (Adjusted risk ratio 2.7, 95% CI: 1.3- 5.7, p=0.008). These data strongly suggest that patients with MRSA bloodstream infections with vancomycin MIC values ≥ 1.5 mg/L respond poorly to vancomycin. Alternative anti-MRSA therapies should be considered for these patients.

New ways to deliver Vancomycin trialled

Link: HighWire Press -- Medline Abstract.

New smart surface-modified polypropylene (PP) was prepared for improving the loading and the sustained delivery of vancomycin and, thus, reducing the risk of biofilm formation when used as component of biomedical devices. Isothermal titration calorimetry (ITC) served for screening the most suitable monomers for grafting; the drug preferentially bonding to ionized acrylic acid (AAc). A net-PP-g-PNIPAAm-inter-net-PAAc was synthesized by first grafting and cross-linking of N-isopropylacrylamide onto PP films and then interpenetrating a second network by redox polymerization and cross-linking of AAc. PP-g-PAAc slabs were prepared by grafting AAc and, optionally, cross-linking. The amount and composition of grafted polymer (FTIR-ATR), morphology (SEM), temperature- and pH-responsiveness (swelling measurements), thermal behavior (DSC), friction coefficient (rheometry), drug loading and release rate, and effect against methicillin-resistant Staphylococcus aureus (MRSA) biofilms (modified robbins device) were evaluated. Grafting of AAc notably decreased the friction coefficient from 0.28+/-0.03 to 0.05+/-0.02 and enhanced the vancomycin loading (up to 2.5mg/cm(2)). Drug-loaded films showed a pH-dependent release rate, sustaining the release in pH 7.4 aqueous media at 37 degrees C for several hours. All drug-loaded films reduced biofilm formation by MRSA; the anti-biofilm effect being statistically significant (91.7% reduction, alpha<0.05) for PP-g-PAAc with the thinnest grafting layer.

Vancomycin alone not working?

Link: Community hospitals often fail to treat MRSA adequately.

About 40% of patients with bloodstream infection or a deep surgical site infection due to methicillin-resistant Staphylococcus aureus who were treated at community hospitals in Virginia and North Carolina did not receive appropriate antimicrobial treatment, according to researchers from Duke University. The researchers conducted a cohort study at one tertiary care hospital and eight community hospitals in Virginia and North Carolina from 1994 to 2003. Included were 129 patients with surgical site infection and 564 with bloodstream infection. The average age of patients in the cohort was 63.1 years. Patients were eligible if they had one or more MRSA cultures positively identified. [bar] Treatments Health care providers administered vancomycin to 44.2% of the patients with surgical site infection on the date of diagnosis. Other treatments administered included ciprofloxacin, linezolid, aminoglycoside, macrolide, sulfamethoxazole and carbapenem. By day seven following diagnosis, 73.6% patients with surgical site infection had received an agent active against MRSA. Within 90 days of surgery, 95 patients with surgical site infection were readmitted to the hospital. There was a 22% mortality rate within one year after infection in the surgical site infection cohort.

Are their drugs for when Vancomycin fails

Link: HighWire Press -- Medline Abstract.

Bis, tris and tetra(dihydrocaffeoyl)polyamine conjugates were synthesized using solid phase synthesis technique. These compounds were screened for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Bis, tris and tetra(dihydrocaffeoyl)polyamine analogues showed antibacterial activity against VRSA which were better than the reference drugs, vancomycin. Tetra(dihydrocaffeoyl) polyamine conjugate exhibited the highest activity. These compounds showed no cytotoxicity against vero cells.

Assessment of vancomycin use in chronic haemodialysis patients

Link: Assessment of vancomycin use in chronic haemodialysis patients: room for improvement -- Zvonar et al., 10.1093/ndt/gfn343 -- Nephrology Dialysis Transplantation.

Background. Vancomycin is frequently prescribed for the management of infections in haemodialysis patients. We evaluated the appropriateness of vancomycin use in our chronic haemodialysis population. Methods. Charts of all chronic haemodialysis patients who received vancomycin between 1 March 2003 and 1 March 2004 were retrospectively reviewed. Indication was assessed according to the modified Hospital Infection Control Practices Advisory Committee guidelines for vancomycin prescription. The prescribed dosing regimens were evaluated. Results. A total of 163 courses of vancomycin in 105 patients were assessed. Of all courses, 88% were considered to be initially appropriate, but this decreased to 63% once culture and sensitivity results were available. Use of vancomycin for the management of beta-lactam-sensitive organisms accounted for the majority of inappropriate use. The most common vancomycin-dosing regimen prescribed was 500 mg intravenously at each haemodialysis session (51%); however, considerable variability was observed. Conclusions. Although the initial indication for vancomycin use was generally appropriate, inappropriate continuation of this antibiotic, failure to obtain proper cultures to guide therapy and potentially subtherapeutic dosing regimens were some of the challenges identified. Centres providing chronic haemodialysis should take steps to optimize vancomycin prescription to improve clinical outcomes and reduce the risk of antimicrobial resistance.

Vancomycin resistance related to heavy use

Link: Vancomycin MICs did not creep in Staphylococcus aureus isolates from 2002 to 2006 in a setting with low vancomycin usage -- Alós et al., 10.1093/jac/dkn246 -- Journal of Antimicrobial Chemotherapy.

Objectives: The aim of this study was to evaluate MIC trends for clinical isolates of Staphylococcus aureus to vancomycin over a 5 year period (2002–06) in a hospital in Spain. Methods: All clinical isolates of S. aureus (one per patient) from clinical samples of patients at Hospital Universitario de Getafe from January 2002 to December 2006 were used. MICs of vancomycin were determined by the CLSI broth microdilution procedure. For analysis of MIC trends over the 5 years, we grouped the isolates into those with MIC ≤1 mg/L [2428 methicillin-susceptible S. aureus (MSSA) and 518 methicillin-resistant S. aureus (MRSA)] and those with MIC ≥2 mg/L (MIC = 2 mg/L: 141 MSSA and 47 MRSA; MIC = 4 mg/L: 5 MSSA and 1 MRSA). MICs for the different groups in the different years were compared with the linear-trend {chi}2 test. Results: A total of 3141 strains of S. aureus collected over the 5 year period was included in this analysis. Of these, 2574 (82%) strains were MSSA and 566 (18%) strains were MRSA. One of the 566 MRSA strains (0.18%) and 5 of the 2574 MSSA strains (0.19%) were vancomycin-intermediate (not significant). The rest were susceptible. The overall percentage of MRSA isolates with a vancomycin MIC of ≥2 mg/L was much higher than that of MSSA during the 5 year period [8.5% (48/566) versus 5.7% (146/2574); P = 0.012]. No statistically significant change in the percentage of isolates with a vancomycin MIC of ≥2 mg/L was observed over the years for MRSA ({chi}2 = 0.01; P = 0.91) or MSSA ({chi}2 = 0.08; P = 0.78). Annual consumption of parenteral vancomycin in our hospital in daily defined doses/100 stays was: 2002 (1.91), 2003 (1.63), 2004 (1.74), 2005 (2.06) and 2006 (1.64). Conclusions: In a setting of low consumption of vancomycin and with a large collection of S. aureus clinical isolates, we have demonstrated the stability of vancomycin MICs over time.

Company aims to resore usefulness of Vancomycin

Link: Funding For Superbug Spin-Out.

Procarta Biosystems, the company spun-out of the John Innes Centre in 2007 to develop a technology designed to defeat antibiotic-resistant superbugs, has received significant seed funding. The Rainbow Seed Fund and the Iceni Seedcorn Fund will enable Procarta to further develop its DNA decoy technique, which aims to restore antibiotic efficacy against resistant superbugs, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Procarta's pioneering approach to combating the threat of superbugs is based on injectable DNA therapies, called Transcription Factor Decoys (TFDs). TFDs are short pieces of DNA which inactivate the resistance genes the bacteria need to counter antibiotics. This new funding will initially allow Procarta to develop TFDs that prevent resistance to vancomycin, the so-called antibiotic of last resort.

vancomycin not enough for many patients

Link: HighWire Press -- Medline Abstract.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) infections can be difficult to treat. We evaluated the rate of clinical failure in appropriately-treated patients and determined risk factors for failure. METHODS: We retrospectively studied a cohort of patients with invasive MRSA infections who completed recommended therapy at one hospital over a 7year period. RESULTS: Two-hundred and fifteen cases were included. Vancomycin monotherapy was given in 73%. Failure rates by infection site were as follows: osteomyelitis 37/81 (46%), epidural abscess five/18 (28%), surgical wound four/15 (27%), pneumonia eight/45 (18%), endocarditis five/32 (16%), bloodstream five/42 (12%), joint one/23 (4%), and meningitis zero/one (0%). In multivariate analysis, only a diagnosis of osteomyelitis was independently associated with relapse (p<0.001). CONCLUSIONS: We found a high rate of treatment failure in an urban population among patients who completed recommended therapy, largely with vancomycin alone. Failure in osteomyelitis was particularly common. High quality comparative studies of antibiotic regimens for MRSA infections, particularly osteomyelitis, are needed.

Vancomycin Resistance Growing

Link: FDA Lowers Vancomycin Breakpoints for Staph Infections.

The Food and Drug Administration (FDA) has lowered the breakpoints for vancomycin in the treatment of Staphylococcus aureus to reflect growing rates of resistance, and in response to urging from IDSA and others. According to a recently updated package insert for Baxter Healthcare Corporation’s vancomycin injection in GALAXY plastic containers, the susceptibility test interpretive criteria for S. aureus have been changed as follows: Minimum Inhibitory Concentration (MIC) (µg/mL) Susceptible (S) Intermediate (I) Resistant (R) Updated ≤2 4-8 ≥16 Previous ≤4 8-16 ≥32

A review of vancomycin therapeutic drug monitoring recommendations in Scotland

Link: A review of vancomycin therapeutic drug monitoring recommendations in Scotland -- Helgason et al. 61 (6): 1398 -- Journal of Antimicrobial Chemotherapy.

Confusion continues regarding the therapeutic monitoring of vancomycin. Most clinicians would agree that the analysis of peak concentrations is of limited value due to both the pharmacodynamic (time-dependency) and pharmacokinetic (multiexponential decline) properties of vancomycin.1 However, there is still a lack of uniformity with respect to trough concentrations. The historical recommendation of 5–10 mg/L was based on efficacy data from in vitro experiments, protein-binding information and early concerns about nephrotoxicity. However, recent evidence suggests that nephrotoxicity is rare with vancomycin monotherapy

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.

Vancomycin resistance emerging

Link: HighWire Press -- Medline Abstract.

One hundred and twenty methicillin resistant Staphylococcus aureus (MRSA) strains were checked for minimum inhibitory concenteration (MIC) of vancomycin. The results showed that 98 strains (81.7 %) had MIC 32microg/mL) values points towards possible emergence of low level vancomycin resistance in the organisms and may explain the reasons of delayed therapeutic success of vancomycin in S.aureus bacteraemia in some situations.

Vancomycin not always the best

Link: I Antimicrobial Agents and Chemotherapy.

This study compares beta-lactam vs. vancomycin among intravenous drug users (IVDUs) with methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE). Patients who received vancomycin had higher infection-related mortality even if they were switched to beta-lactam once culture results were available; this relationship persisted after logistic regression analysis controlled for clinical characteristics.

Vancomycin - effective doses getting bigger

Link: Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant S. aureus (MRSA) blood isolates from 2001-05 -- Steinkraus et al., 10.1093/jac/dkm258 -- Journal of Antimicrobial Chemotherapy.

Results: All isolates were susceptible to vancomycin, linezolid and daptomycin and resistant to oxacillin. MICs increased for vancomycin, linezolid and oxacillin (P < 0.0001); however, daptomycin MICs decreased slightly (P = 0.0386). For vancomycin, linezolid and oxacillin, there were significant increases (P < 0.0001) in the percentage of isolates with MICs that were higher than the respective 2001 median MIC, but not for daptomycin (P = 0.1361). Oxacillin MICs were associated with MICs of linezolid (r = 0.364, P < 0.0001), vancomycin (r = 0.353, P < 0.0001) and daptomycin (r = 0.106, P = 0.0063). Conclusions: Oxacillin, vancomycin and linezolid MICs increased over time. For vancomycin and linezolid, these MIC increases were not reliably detected by percentage susceptibility as they occurred below the susceptibility breakpoint. Although the MICs of all agents appeared to be associated with increasing oxacillin MICs, the strongest associations were noted for vancomycin and linezolid.

New Vancomycin type drugs on their way

Link: PharmaLive: New Drug Technology Being Developed by Wisconsin Start-Up Featured in Nature.

The study led by Centrose co-founder and UW-Madison Professor Jon Thorson was published last week in the Journal of the American Chemical Society. Nature reports that Centrose's technology allows for " ... an easier way to create vancomycin-like compounds that demonstrate more potency than their predecessor. The study highlights the simplicity of generating large libraries of such analogs [compounds modified using Centrose's unique technology] for optimizing antibiotics to target highly resistant pathogens." Centrose also plans to use its unique technology for methicillin-resistant Staphylococcus aureus, or MRSA, a bacterium responsible for more than 60% of hospital staph infections that can no longer be treated with methicillin, a penicillin-class antibiotic. A new national study released Monday by the Association for Professionals in Infection and Epidemiology (APIC) found that 46 out of every 1,000 hospital patients were either infected or colonized with MRSA. This rate is eight to 11 times greater than previous MRSA estimates

MRSA drifting towards Vancomycin resistance

Link: Journal of Clinical Microbiology.

      Staphylococcus aureus is one of the most commonly isolated organisms in nosocomial infections. While the prevalence of methicillin-resistant S. aureus (MRSA) continues to increase worldwide, there is concern about an increase in vancomycin MICs among S. aureus strains. The prevalence of MRSA and vancomycin MIC trends in S. aureus from patients in a university hospital were analyzed. Clinical Laboratory Standards Institute (CLSI, formerly NCCLS) reference broth microdilution MIC testing was performed on all clinically relevant S. aureus isolates from January 2000 through December 2004. A total of 6,003 S. aureus isolates were analyzed. No vancomycin-resistant S. aureus isolates were detected. One MRSA isolate had a vancomycin MIC of 8 �g/ml and was confirmed as vancomycin-intermediate S. aureus. Among the 6,002 remaining isolates, a shift in vancomycin MICs from ≤0.5 to 1.0 �g/ml was observed during the 5-year period. The percentage of S. aureus isolates with a vancomycin MIC of 1 �g/ml in 2004 was significantly higher than the percentage of isolates in 2000 (70.4% versus 19.9%; P < 0.01). This vancomycin MIC shift was more notable in methicillin-susceptible S. aureus. Our 5 years of routine testing of clinical isolates using the CLSI reference broth microdilution MIC method demonstrated a tendency toward decreasing susceptibility to vancomycin in S. aureus.

Aggressive Vancomycin Dosing Unlikely to Boost Survival in MRSA Pneumonia

Link: Aggressive Vancomycin Dosing Unlikely to Boost Survival in MRSA Pneumonia.

     For patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia acquired in the healthcare setting, aggressive dosing strategies for vancomycin may not offer any advantage over traditional dose targets, study findings suggest. Specifically, trough levels of vancomycin greater than 15 g/mL are unlikely to increase survival compared with dosing aimed at trough concentrations in the range of 5 to 15 g/mL, clinicians from St. Louis, Missouri report in the October issue of CHEST. Among 102 patients with MRSA healthcare-associated pneumonia identified at Barnes-Jewish Hospital, St. Louis, over a 6.5 year period, 32 (31.4%) died while in the hospital, Dr. Marin H. Kollef of Washington University, St. Louis and colleagues report. According to the investigators, the average vancomycin trough concentrations and AUC values did not differ between those that survived and those that died. Trough levels were 13.6 and 13.9 g/mL and AUC values were 351 and 354 g/h/mL, respectively. While time to apyrexia was shorter in patients with AUC values greater than 400, there was "no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome," the team notes in the report. "The main issue," Dr. Kollef told Reuters Health, "is that MRSA healthcare-associated pneumonia is becoming an increasingly important infection in terms of incidence and costs to society."

Vancomycin evalauted

Link: HighWire Press -- Medline Abstract.

    CONCLUSIONS: Surgery within the previous 6 months and intensive care unit admission were identified as significant risk factors for patients with MRSA bacteremia with a vancomycin MIC 2 microg/mL undergoing hemodialysis. These patients experienced a longer mean hospital length of stay and increased hospital costs compared with patients with MRSA bacteremia with a vancomycin MIC < or =0.5 microg/mL and uninfected controls.

Bigger Doses of Vancomycin as MRSA grows more robust

Link: Journal of Clinical Microbiology.

      Staphylococcus aureus is one of the most commonly isolated organisms in nosocomial infections. While the prevalence of methicillin-resistant S. aureus (MRSA) continues to increase worldwide, there is concern about an increase in vancomycin minimal inhibitory concentrations (MICs) among S. aureus. The prevalence of MRSA and vancomycin MICs trends in S. aureus from patients in a university hospital was analyzed. Clinical Laboratory Standards Institute (CLSI) reference broth microdilution MIC testing was performed on all clinically relevant S. aureus isolated from January 2000 through December 2004. A total of 6,003 S. aureus were analyzed. No vancomycin-resistant S. aureus was detected. One MRSA isolate had a vancomycin MIC of 8 �g/ml and was confirmed as a vancomycin-intermediate S. aureus. Of the 6,002 remaining isolates, a shift in vancomycin MICs from ≤ 0.5 to 1.0 �g/ml was observed during the five year period. The percentage of S. aureus isolates with a vancomycin MIC of 1 �g/ml in 2004 was significantly higher than the percentage of isolates in 2000 (70.4% vs. 19.9%, P < 0.01). This vancomycin MIC shift was more notable in methicillin-susceptible S. aureus . Our five years of routine testing of clinical isolates using the CLSI reference broth microdilution MIC method demonstrated a tendency of decreasing susceptibility to vancomycin in S. aureus.

Physicians warm of overuse of vancomycin in treating hospital-acquired pneumonia - Formulary

Link: ICAAC 2006:

     Vancomycin may be overused for the treatment of hospital-acquired pneumonia, perhaps because of physicians' perceptions that patients are at high risk for methicillin-resistant Staphylococcus aureus (MRSA), according to a study by Robert H. Eng, MD, and colleagues at the Veterans Affairs New Jersey Health Care System in East Orange, NJ. The study was presented at the 45th ICAAC meeting in Washington, DC. The researchers sought to determine whether vancomycin was used appropriately or inappropriately for the treatment of pneumonia at their institution, in accordance with guidelines developed by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). To do so, they developed an electronic form at the point of antibiotic order to capture vancomycin prescribers' decisions and thoughts.

More at the link above

Helping prevent Vancomycin Side Effects

Link: Entrez PubMed.

       Vancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use. Two types of desensitization protocols have been reported, and these utilize different infusion intervals; rapid desensitization and slow desensitization. We herein report a case of vancomycin hypersensitivity with methicillin-resistant Staphylococcus aureus infection. A combination of the two desensitization protocols, rapid desensitization followed by slow desensitization, effectively inhibited the hypersensitivity reaction during vancomycin infusion, and methicillin-resistant Staphylococcus aureus was successfully eradicated.

Vancomycin weakened by long term use with other drugs

Link: Prevalence and Clinical Implications

       In addition to vancomycin-intermediate Staphylococcus aureus (VISA), S. aureus with a vancomycin MIC of 4 microg/ml has been reported to be the cause of therapeutic failure. This study was designed to determine the prevalence of methicillin-resistant S. aureus (MRSA) with a vancomycin MIC of 4 microg/ml and to clarify the clinical characteristics of infections caused by these isolates. During the 8-week period from April to May, 2001, 27 hospitals participated in a nationwide surveillance program for VISA and vancomycin-resistant S. aureus (VRSA) in Korea. After screening on brain-heart infusion agar containing 4 microg/ml of vancomycin as previously described, 100 isolates with confluent growth were tested. The medical records of the patients involved were reviewed. Even though VISA or VRSA was not detected among 3,756 MRSA isolates, 18 (0.5%) had a vancomycin MIC of 4 microg/ml. The infections in 12 of these patients, excluding 5 that were colonized, were 8 chronic osteomyelitis, 1 surgical site infection, 1 pneumonia, 1 intra-abdominal infection, and 1 catheterrelated infection. Although 11 cases were exposed to glycopeptides for a long time (median 56 days), the site of infection became culture-negative in only 1 case. Two patients died of their S. aureus infections. MRSA with a vancomycin MIC of 4 microg/ml was rare. Chronic osteomyelitis was the most common type of infection, and prolonged exposure to glycopeptides was associated with reduced susceptibility to vancomycin.

Making Vancomycin Effective Against MRSA

Link: Potential Impact

   Vancomycin as the drug of choice for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia has been called into question on the basis of therapeutic failures. In patients with MRSA pneumonia, treatment failures are probably due to the complex interplay of variables affecting the host-antimicrobial-pathogen interrelationship. However, it has been suggested that decreased penetration of vancomycin into the lungs may contribute. This review explores physiochemical and physiologic variables that affect pulmonary penetration and describes methods used in quantifying pulmonary vancomycin concentrations. Most important, findings are evaluated in the clinical context of the chemotherapeutic options available for treatment of MRSA pneumonia. The possibility of increased serum vancomycin concentrations as a method to optimize current treatment outcomes is also explored.

Japanese call for dosage change to make vancomycin more effective

Link: HubMed Abstracts.

     The clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment was evaluated by comparison with a standard dosage regimen (package insert information: vancomycin dose reduced in elderly patients and patients with renal dysfunction, with Moellering's nomogram used for renal-dysfunction patients) in adult Japanese MRSA pneumonia patients. Using Maeda's nomogram, the vancomycin dose is fixed at 1,000 mg while the dosing interval is varied in accordance with individual creatinine clearance. Using a standard dosage regimen, 5 patients out of 27 (18.5%) achieved target plasma levels of vancomycin (25-40 mug/mL for peak and 5-15 mug/mL for trough) within 2-6 days. Using Maeda's nomogram, 38 patients out of 53 (71.7%) achieved target levels in that time. A higher clinical response (complete resolution of all signs and symptoms of MRSA infection) to vancomycin therapy was also obtained with Maeda's nomogram when evaluated approximately 2-weeks after discontinuation of vancomycin therapy (43.4% versus 18.5% for the standard regimen). In conclusion, the Maeda's nomogram regimen with a 1,000 mg vancomycin dose was shown to achieve target plasma levels of vancomycin at a higher rate and provide higher clinical efficacy in vancomycin therapy of MRSA pneumonia patients, as compared with the currently available standard dosage regimen.

Effects of prolonged vancomycin administration on MRSA

Link: Journal of Antimicrobial Chemotherapy.

     Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.

Vancomycin for Surgical Prophylaxis

Link: The Annals of Pharmacotherapy.

    BACKGROUND: In 2001, vancomycin replaced cefuroxime for antibiotic prophylaxis in patients undergoing cardiac surgery at our institution due to high rates of surgical site infections caused by methicillin-resistant Staphylococcus spp. However, few data supported the use of vancomycin for surgical prophylaxis. OBJECTIVE: To determine the tolerance of vancomycin for antibiotic prophylaxis and incidence of vancomycin-resistant Enterococcus (VRE) in cardiac surgery patients. METHODS: In 2 separate studies, we assessed the adverse effects in patients given perioperative vancomycin (study 1) and the incidence of VRE in patients given perioperative vancomycin (study 2). Study 1 was a prospective cohort study of patients undergoing coronary artery bypass graft (CABG) or valve replacement surgery given vancomycin (1 dose preoperatively/2 doses postoperatively) for antibiotic prophylaxis between October 2003 and December 2004. Patients were assessed for tolerance to the antibiotic regimen. In study 2, cardiac surgery patients receiving perioperative vancomycin were screened for VRE before therapy and at day 7 of hospitalization. VRE was detected using standard microbiologic procedures. RESULTS: In study 1, 1161 patients (CABG = 75%; valve = 19%; both = 6%) were evaluated. All patients but one (99.9%) were prescribed preoperative vancomycin. Therapy was changed for 34 (2.9%) patients, of which 20 changes were due to physician preference for another antibiotic. The only toxicity that required a change in the vancomycin regimen was red man's syndrome, which was experienced by 9 (0.8%) patients. Four patients did not receive a second postoperative dose due to prior renal insufficiency. Patients were most commonly switched to cefuroxime (n = 26), linezolid (n = 2), cefepime (n = 2), gatifloxacin, cefazolin, levofloxacin, or ceftriaxone (n = 1, each). In study 2, 100 patients were screened for the emergence of VRE colonization. No patient was VRE positive at baseline and 4 (4%) were positive at day 7. CONCLUSIONS: Surgical antibiotic prophylaxis with vancomycin was reasonably well tolerated in CABGnd valve replacement surgery, with a 4% incidence of VRE colonization.

Vancomycin side effects charted

Link: The Annals of Pharmacotherapy

   BACKGROUND: Vancomycin is frequently used to manage serious resistant gram-positive infections. Neutropenia, whose epidemiology has not been well characterized, is a potentially serious adverse event associated with the use of vancomycin. OBJECTIVE: To characterize the incidence and risk factors for development of vancomycin-induced neutropenia in patients treated with home intravenous vancomycin therapy. METHODS: A retrospective chart review was conducted of adult patients receiving vancomycin therapy through the University of New Mexico Home Intravenous Infusion Clinic between January 1998 and December 2004. Data collection included demographics, comorbid conditions, dose and duration of vancomycin therapy, indications for vancomycin use, vancomycin concentrations, all concurrent medications, laboratory data, culture and susceptibility data, reasons for antibiotic alteration or discontinuations, all other recorded adverse events, management of adverse events, and outcomes of adverse events. RESULTS: A total of 372 charts of patients managed through the clinic were reviewed and 114 patients treated with vancomycin were identified. Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%) cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less. The mean � SD duration of vancomycin therapy and time to neutropenia were 32 � 29 and 26 � 15 days, respectively. Laboratory monitoring was performed on a weekly basis and resolution of vancomycin-induced neutropenia occurred promptly after discontinuation. Total vancomycin doses used and serum concentrations were not associated with the development of neutropenia. CONCLUSIONS: Vancomycin-induced neutropenia may occur at a higher frequency than previously reported. Clinicians should monitor hematologic parameters at least weekly in patients receiving home intravenous vancomycin therapy.

CA MRSA may respond to Vancomycin for some while yet

Link: In vitro

     Vancomycin is the preferred parenteral antibiotic for the treatment of all methicillin-resistant Staphylococcus aureus (MRSA) infections, including the newly emerging community-associated MRSA (CA-MRSA) infections. Vancomycin-intermediate nosocomial MRSA strains have developed in vitro and in vivo after exposure to vancomycin. The aim of this study was to determine whether daily serial passage of CA-MRSA strains onto vancomycin-supplemented agar selects for the development of vancomycin resistance. Twelve clinical isolates of the six commonest Australian and US strains of CA-MRSA were serially passaged daily for 25 days onto brain-heart infusion agar plates supplemented with 4mug/mL vancomycin and then subcultured for a further 15 days onto antibiotic-free agar to assess the stability of the resistance phenotype. Minimum inhibitory concentrations (MICs) were determined by standard Etest every 5 days from day 0 to day 40. Serial passaging resulted in increased MICs in all strains but the rises were modest, with an increase of <2 doubling dilutions. All strains remained vancomycin susceptible throughout the experiment according to Clinical Laboratory Standards Institute criteria.

Two drugs better than one?

Link: Comparative evaluation of tigecycline and vancomycin

Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. . RESULTS: Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.

Linezolid will work if VRSA grows

Link: HighWire Press -- Medline Abstract.

OBJECTIVES: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA isolates recovered from hospitalized patients. METHODS: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin) and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method. RESULTS: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC90 was 2.0 microg/ml for vancomycin and teicoplanin (range 0.5-2.0 microg/ml and 0.125-2.0 microg/ml, respectively), and 0.5 microg/ml for pristinamycin and linezolid (range 0.125-0.75 microg/ml and 0.125-0.5 microg/ml, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ (P < 0.01) and an apparent increase in resistance to other antibiotics. CONCLUSION: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.

Vancomycin resistance - the clinical evidence

Link: Journal of Pharmacy Practice.

Surveillance data demonstrate that the majority of gram-positive bacterial isolates obtained in the intensive care unit (ICU) setting are staphylococci and enterococci. Staphylococci, mainly Staphylococcus aureus and coagulase-negative staphylococci, compose the majority of clinical isolates. Data from 25 North American ICUs reported methicillin-resistant Saureus (MRSA) in more than 50% of the Saureus organisms isolated mainly from a respiratory source. In addition to MRSA, Saureus with reduced susceptibility to vancomycin has been reported. Enterococci are typically considered opportunistic pathogens, infecting immunocompromised hosts. Resistance of enterococci to vancomycin, along with the newer gram-positive antimicrobials, is an increasing problem. Investigators have demonstrated that nearly 30% of enterococci isolated in the ICU are resistant to vancomycin. The high level of resistance and limited therapeutic options make treating resistant gram-positive organisms such as MRSA and vancomycin-resistant enterococci particularly problematic. While vancomycin has long been considered the gold standard for the treatment of resistant gram-positive infections, newer agents (eg, quinupristin-dalfopristin, linezolid, and daptomycin) offer therapeutic alternatives.

Superbug deaths 'set to double'

Link: BBC NEWS.

This story begs several questions. Click the link above for the whole story. Is Vancomycin the only drug used in the UK?  Linzelolid is believed to be more effective as we will suggest in an article next week. Why is not used more in the UK? Could it be a budget issue

Deaths from the hospital superbug MRSA could double over the next five years, experts have warned. UK scientists say the methicillin-resistant Staphylococcus aureus bacteria is becoming increasingly resistant to the antibiotic vancomycin. Around 5,000 Britons die each year from infections acquired in hospital. But the researchers, whose study is published in Emerging Infectious Diseases, say more lives will be lost if vancomycin can no longer be used. If we lose vancomycin completely as a treatment, we could see a doubling in deaths over the next five years Dr Mark Enright, University of Bath It had been thought that vancomycin-resistance was only a problem in one strain of MRSA - seen in the US and Japan. But scientists from the University of Bath, University of Bristol and Southmead Hospital say all five major types of MRSA - including those seen in the UK - show signs of resistance to vancomycin.

Vancomycin Resistance Spreading

Link: HighWire Press -- Medline Abstract.

We report the first case of ventriculitis due to hVISA. It was successfully treated with intrathecal vancomycin and intravenous linezolid. We also believe this to be the first documented case of clinical infection due to hVISA in South Africa.

Helping drug stay potent

Link: HighWire Press -- Medline Abstract.

One of the cell wall-synthesizing enzymes (known as PBP2') of this pathogen has low affinity to beta-lactams, and therefore the bacterial cells continue to grow even under high concentrations of the agents. However, this drug resistance does not seem to be total. They seem to have some weak spots and several substances are known to sensitize strains of MRSA to beta-lactams. This review discusses the ability of polyoxotungstates (POTs) to sensitize MRSA to beta-lactams by reducing the expression of PBP2'. It is also possible that the sensitization is a type of stress response of MRSA to POTs. This idea may provide a hint for the development of a new antimicrobial agent.

DHEA & Vancycomin resistance

Link: HighWire Press -- Medline Abstract.

Aims: To investigate whether dehydroepiandosterone (DHEA), an androgen present throughout life, alters the response of Staphylococcus aureus clinical isolates to vancomycin. Methods and Results: DHEA in physiologically relevant concentrations (0.1, 0.5, 1.0 and 5.0 mumol l(-1)) was tested for its effect on methicillin-sensitive S. aureus (MSSA, n = 53) and methicillin-resistant S. aureus (MRSA, n = 73) response to vancomycin using standard protocols. Mutant selection was determined by serial transfer of selected isolates (n = 5). DHEA-mediated at least a fourfold increase in vancomycin MIC for 42% of MSSA and 21% of MRSA. For five of the isolates (0.1 and 0.5 mumol l(-1) DHEA) the MIC was increased to levels (8 mug ml(-1)) defined as vancomycin-intermediate resistance. Conclusion: Resistance was detected only in the presence of DHEA, and was not related to altered generation time, indicating induction of phenotypic resistance. Significance and Impact of the Study: These findings require further investigation to determine what role DHEA plays in clinical vancomycin treatment failure that has been reported in the absence of vancomycin genotypic resistance or heteroresistance.

Safety and efficacy of glycopeptide antibiotics

Link: Journal of Antimicrobial Chemotherapy.

It is not entirely surprising, therefore, that despite more than 40 years of clinical use and the interim appearance of bacterial strains resistant to this drug class, there remains continued interest in the development of newer members of the glycopeptide antibiotic class. This paper is intended to provide a global overview of the efficacy and safety of glycopeptide antibiotics currently in use, as background to understanding the need for and potential roles of new agents of this class.