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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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)
