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Link: Antimicrobial Agents and Chemotherapy.
We studied vancomycin and daptomycin susceptibility in methicillin-resistant Staphylococcus aureus from patients exposed to vancomycin, glycopeptide-intermediate S. aureus, and S. aureus passaged in vancomycin-containing medium. A correlation between vancomycin and daptomycin heteroresistance was noted in some strains, suggesting that exposure of S. aureus to vancomycin may affect susceptibility to daptomycin.
Link: Current antimicrobial
The acquisition of the mec gene complex by methicillin-susceptible Staphylococcus aureus in the community and the increased spread of methicillin-resistant Staphylococcus aureus (MRSA) from the health care setting to the community underscore a need to monitor the resistance phenotypes likely to be encountered among outpatient MRSA. Data from the LEADER 2004 surveillance program were analyzed to evaluate current resistance profiles among outpatient MRSA. Outpatient MRSA exhibited 26 different resistance phenotypes; the 4 most common were resistance to erythromycin only (40.8%), multidrug resistance to erythromycin, clindamycin, and levofloxacin (21.5%), double drug resistance to erythromycin and levofloxacin (11.3%), and double drug resistance to clindamycin and erythromycin (5.1%). These phenotypes were also the most common among inpatient MRSA (n = 946), but multidrug resistance to erythromycin, clindamycin, and levofloxacin (43.7%) was most common. Fifty percent (256) of the outpatient MRSA were resistant to 2 or more agents, whereas resistance to either vancomycin or linezolid was not encountered. The extensive similarities in resistance profiles between inpatient and outpatient MRSA have important implications for establishing outpatient management and treatment guidelines for staphylococcal infections.
Link: HighWire Press -- Medline Abstract.
Primary end points were resolution of signs and symptoms of infection and discharge from the hospital. Methicillin-resistant Staphylococcus aureus ([MRSA] 11 patients) and vancomycin-resistant entercocci ([VRE] 11 patients) were the most common pathogens, whereas 7 patients had methicillin-sensitive S. aureus infection and 1 patient had coagulasenegative Staphylococcus infection. One patient with endocarditis had a negative culture result. Overall, 24 (77%) of the 31 patients achieved clinical resolution and were discharged, including all patients infected with MRSA; 7 patients died, 6 of whom had VRE infection. Duration of treatment for infective endocarditis lasted longer (typically 22-43 days) than that for bacteremia only
Link: Guidelines
These evidence-based guidelines have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant Staphylococcus aureus (MRSA) infection. The guidelines were further informed by antibiotic susceptibility data on MRSA from the UK. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection. There are several antibiotics currently available that are suitable for use in the management of this problem and potentially useful new agents are continuing to emerge.
Link: Evaluation
Objective. Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin-resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens.Design. Single-center quasi-experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate.Setting. An 87-bed Veterans Affairs teaching hospital with an extended-care facility.Intervention. A physician-directed computer-generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked.Results. After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient-days after the study intervention (P=.02). Coagulase-negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram-negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with summer season (P=.05). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention (P=.04).Conclusion. Reduction in the institutional use of fluoroquinolones may be associated with a lower nosocomial MRSA infection rate.
Link: Methicillin-Resistant
Results. From February 2000 through December 2003, a total of 38 ICUs reported data on 499,694 patient-days and 9,552 S. aureus isolates, including 2,249 MRSA isolates and 660,029 DDDs of antimicrobials. Cumulative MRSA percentages ranged from 0% to 64.4%, with a mean of 23.6%. The MRSA incidence density ranged from 0 to 38.2 isolates per 1,000 patient-days, with a mean of 2.77 isolates per 1,000 patient-days. There was a positive correlation between MRSA percentage and imipenem and ciprofloxacin use (P<.05). Overall, comparison of data from 2001 with data from 2003 showed that MRSA percentages increased in 18 ICUs (median increase, 13.2% [range, 1.6%-38.4%]) and decreased in 14 ICUs (median decrease, 12% [range, 1.0%-48.4%]). Increased use of third-generation cephalosporins, glycopeptides, or aminoglycosides correlated significantly with an increase in the MRSA percentage (P<.05). The cumulative nosocomial MRSA infection incidence density for 141 ICUs that did not participate in SARI and, therefore, did not receive feedback increased from 0.26 to 0.35 infections per 1,000 patient-days during a 3-year period, whereas the rate in SARI ICUs decreased from 0.63 to 0.40 infections per 1,000 patient-days.Conclusion. The MRSA situation in German ICUs is still heterogeneous. Because MRSA percentages range from 0% to 64.4%, further studies are required to confirm findings that no change in the MRSA percentage and a decrease in the nosocomial MRSA infection incidence density in SARI ICUs reflect the impact of an active surveillance system.
Link: Journal of Biological Chemistry.
Emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created challenges in treatment of nosocomial infections. The recent clinical emergence of vancomycin-resistant MRSA is a new disconcerting chapter in evolution of these strains. S. aureus normally produces four PBPs, which are susceptible to modification by beta-lactam antibiotics, an event that leads to bacterial death. The gene product of mecA from MRSA is a penicillin-binding protein (PBP) designated PBP 2a. PBP 2a is refractory to the action of all available beta-lactam antibiotics. Furthermore, PBP 2a is capable of taking over the functions of the other PBPs of S. aureus in the face of the challenge by beta-lactam antibiotics. Three cephalosporins (compounds 1-3) have been studied herein, which show antibacterial activities against MRSA, including the clinically important vancomycin-resistant strains. These cephalosporins exhibit substantially smaller dissociation constants for the preacylation complex compared to the case of typical cephalosporins, but their pseudo second-order rate constants for encounter with PBP 2a (k2/Ks) are not very large (=200 M-1s-1). It is documented herein that these cephalosporins facilitate a conformational change in PBP 2a, a process that is enhanced in the presence of a synthetic surrogate for cell wall, resulting in increases in the k2/Ks parameter and in more facile enzyme inhibition. These findings argue that the novel cephalosporins are able to co-opt interactions between PBP 2a and cell wall in gaining access to the active site in the inhibition process, a set of events that leads to effective inhibition of PBP 2a and the attendant killing of the MRSA strains.
Link: HighWire Press -- Medline Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) should no longer be regarded as a strictly nosocomial pathogen. During the past decade, community-acquired MRSA (CA-MRSA) infections among young persons without healthcare-associated (HCA) risk factors have emerged in several areas worldwide. These infections are caused by strains that almost exclusively carry the staphylococcal cassette chromosome mec type IV element and the Panton-Valentine leukocidin genes and, unlike HCA-MRSA strains, are not multiresistant. Although the majority of CA-MRSA infections are mild skin and soft tissue infections, severe life-threatening cases of necrotizing pneumonia, necrotizing fasciitis, myonecrosis and sepsis have been reported. Clindamycin is an effective agent for skin and soft tissue infections, however attention should be paid to the possibility of the emergence of resistance during treatment in strains with the macrolide, lincosamide and group B streptogramin (MLS(B))-inducible resistance phenotype. For patients with invasive infections that may be caused be CA-MRSA, vancomycin, teicoplanin and linezolid represent appropriate empirical therapeutic options.
Link: Journal of Antimicrobial Chemotherapy
Objectives: This study was undertaken to determine the interaction of tigecycline with 13 select antimicrobial agents against a wide variety of Gram-negative and Gram-positive bacterial isolates. Methods: Antibiotic interactions were assayed using the chequerboard MIC format and selected synergistic combinations were confirmed using time-kill kinetic analysis. Results: Microdilution chequerboard analysis of tigecycline in combination with amikacin, ampicillin/sulbactam, azithromycin, ciprofloxacin, colistin, imipenem, levofloxacin, piperacillin, piperacillin/tazobactam, polymyxin B, rifampicin, minocycline and vancomycin resulted in an interpretation of either no interaction or synergy. Time-kill kinetic analysis resulted in an interpretation of no interaction for all but one of the drug combinations that resulted in an interpretation of synergy by the chequerboard analysis. Antagonism was not observed for any combination when assayed by either method. Conclusions: The lack of antagonism seen with tigecycline combinations in both chequerboard and time-kill kinetic studies is an encouraging outcome, suggesting that tigecycline may prove to be effective in combination therapy as well as in monotherapy.
Link: Journal of Antimicrobial Chemotherapy
Background: Infection due to methicillin-resistant Staphylococcus aureus (MRSA) is increasingly common in nosocomial and community settings. Daptomycin is a cyclic lipopeptide anti-infective with activity against MRSA, approved for treatment of complicated skin and skin structure infections. Daptomycin may be useful in systemic or local treatment of chronic osteomyelitis. Methods: We measured mechanical strength of daptomycin- and vancomycin-loaded polymethylmethacrylate (PMMA), assayed in vivo release of daptomycin and vancomycin from daptomycin- and vancomycin-loaded PMMA, respectively, and compared the efficacy of two systemic doses of daptomycin with that of vancomycin, each with or without the respective anti-infective loaded into PMMA, using a rat model of MRSA chronic osteomyelitis. Results: Neither tensile nor compressive strength of PMMA was impacted by impregnation with these antimicrobials at a concentration of 7.5% by weight. The peak concentrations of daptomycin and vancomycin in rat tibial bone surrounding a 7.5% daptomycin- and vancomycin-loaded 3 mm PMMA bead were 178 and 49 mg/L, respectively. In the treatment of experimental osteomyelitis, rats assigned to no treatment, daptomycin 50 mg/kg subcutaneously twice daily, daptomycin 60 mg/kg subcutaneously twice daily, and vancomycin 50 mg/kg intraperitoneally twice daily had 6.4, 4.1, 4.0 and 4.5 median log10 cfu/g of bone at the end of 21 days of therapy. All systemic anti-infectives studied were more active than was no treatment. Daptomycin- or vancomycin-loaded PMMA did not, however, exhibit microbiological efficacy alone or adjunctively, as assessed 21 days after implantation. Conclusions: Daptomycin is released from PMMA in vivo at a rate similar to that of vancomycin. Systemic daptomycin is as active as vancomycin in a rat model of chronic MRSA experimental osteomyelitis.
In order to gather more data on the use of teicoplanin for reducing MRSA infections in high-risk populations, the present study was conducted. At a hospital in Barcelona, Spain, there was a high prevalence of MRSA infections among patients who underwent surgery for femoral neck fracture during the first 5 months of 2002 (period A) when cefuroxime was the antibiotic prophylaxis. During the following 12 months (period B) 600 mg of teicoplanin was added to cefuroxime. The rates of overall and MRSA infection during period A were 5.07 and 2.73%, respectively. Pulsed-field gel electrophoresis demonstrated there was no clonal relationship among MRSA strains. No nasal carriers of MRSA were detected among health workers. During period B the rates of overall and MRSA infection were 2.36 and 0.19%, respectively. Both rates were statistically significantly lower than those in period A (p<0.05). These results suggest teicoplanin may be useful in patients undergoing orthopedic surgery when the prevalence of MRSA is high.
Link: Yahoo! Finance
Chiron Corporation (Nasdaq:CHIR - News) today announced that the European Commission has granted marketing approval for CUBICIN� (daptomycin), a first-in-class IV antibiotic. The marketing approval was granted in the 25 member states of the European Union, Iceland, Liechtenstein and Norway. Under the approval, CUBICIN is indicated for the treatment of complicated skin and soft-tissue infections (cSSTI) caused by Gram-positive bacteria. CUBICIN is expected to become available in the United Kingdom and the Netherlands within the next few weeks, followed by additional European countries, in accordance with local legal regulations. Gram-positive bacteria are a major cause of problematic infections in many healthcare facilities and institutions. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate S. aureus (GISA) and glycopeptide-resistant enterococci (VRE or GRE), particularly E. faecium, which are driving the need for new antibacterial agents. The novel mechanism of action of CUBICIN means that it is unaffected by the high-level cross-resistance that occurs with many other antibiotic classes.(1),(2)
Link: Decreased susceptibility
OBJECTIVES: To assess the evolution of glycopeptide susceptibility in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in a large French teaching hospital from 1983 to 2002. METHODS: Determination of glycopeptide MICs by using the Etest method in Mueller-Hinton agar on a sample of randomly selected MRSA strains. RESULTS: A total of 1445 MRSA strains were tested, and one vancomycin-intermediate MRSA (VISA) and 31 teicoplanin-intermediate MRSA (TISA) strains were detected. The first strains were detected in 1985, and all strains were gentamicin resistant (GR). None of the gentamicin-susceptible strains had a glycopeptide MIC > 3 mg/L. In addition, there was a significant increase in glycopeptide MIC geometric means over the years, and this increase was higher for teicoplanin than for vancomycin. CONCLUSIONS: The higher increase in teicoplanin MICs, and the good correlation between vancomycin and teicoplanin MICs, suggests systematic determination of teicoplanin MIC to screen for abnormal glycopeptide susceptibility among GR-MRSA.
Link: News
A new drug in a similar class as vancomycin -- a last resort antibiotic -- appears to clear up dangerous methicillin-resistant Staphylococcus aureus (MRSA) skin infections more effectively than standard treatment.
"Usually that standard of care is vancomycin," said Martin Stryjewski, MD, Attending Physician, Internal Medicine and Infectious Diseases, Cemic Hospital, Buenos Aires, Argentina.
"Telavancin achieved significantly [P = .04] higher eradication rates in patients infected with MRSA. Although not statistically significant [P= .07], in patients infected with S. aureus, the clinical response rates at test of cure were higher in telavancin treated patients," Dr. Stryjewski said in his poster presentation December 18th at the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
Telavancin is a bactericidal lipoglycopeptide now in phase 3 clinical studies.
Link: HighWire Press -- Medline Abstract.
Erysipelas is a bacterial infection of the dermis and hypodermis, mostly of streptococcal origin. Bullous erysipelas represents a severe form of the disease. OBJECTIVE: To evaluate the clinical and microbiological characteristics and treatment of bullous erysipelas. Staphylococcus aureus was isolated from 7 (50%), while S. warneri, Streptococcus pyogenes and Escherichia coli grew from the lesions of 3 other patients. Six out of 7 S. aureus strains were methicillin resistant (MRSA) but susceptible to several other non-beta-lactam antibiotics such as quinolones, vancomycin, rifampicin and trimethoprim/sulfamethoxazole. CONCLUSION: Our findings suggest that S. aureus is frequently involved in and probably contributes in synergy with beta-hemolytic streptococci to the complicated course of bullous erysipelas. The frequency of MRSA isolation suggests that beta-lactam antibiotics may not be sufficient for the treatment of bullous erysipelas anymore, at least in areas with a high incidence of MRSA strains. The role of other classes of antibiotics providing adequate coverage for MRSA has to be evaluated in prospective clinical trials.
Link: Infection Control Today
Decision Resources, Inc., a leading research and advisory firm focusing on pharmaceutical and healthcare issues, finds that the increasing prevalence of drug-resistant pathogens will significantly drive the sales of antibacterial agents that can effectively treat drug-resistant infections. Such drugs include Pfizer's Zyvox (linezolid), Cubist/Chiron's Cubicin (daptomycin), and Sanofi-Aventis's Ketek (telithromycin). According to a new Pharmacor report titled, “Antibacterial Drug Resistance,” antibacterial resistance is limiting the efficacy of many older antibiotics and the pipeline of new agents remains relatively sparse. Drug-resistant pathogens that concern health care professionals include penicillin-resistant and macrolide-resistant Streptococcus pneumoniae in the community setting and methicillin-resistant Staphylococcus aureus and Pseudomonas in the hospital setting. The report analyzes the unmet need presented by different types of infections in the hospital and community setting and provides an assessment of the most promising segments for drug developers to target. Although the report finds that late-stage compounds such as Basilea/Johnson & Johnson's ceftobiprole and Pfizer's dalbavancin may partially address the need for drug-resistant gram-positive infections, novel classes of antibacterials are needed to combat multi-drug resistant infections and expand physician treatment options.
Link: ShropshireStar.com
Please note the bold line - any insights via the comments box welcome
A Mid Wales pensioner died after contracting the hospital superbug MRSA following a hip operation at the Royal Shrewsbury Hospital, an inquest heard. Mrs Dilys Jones, 76, of Tynewydd, Llanfair Caereinion, died on June 15 after being admitted to the hospital for a fractured hip on May 27 following a fall in the street. The inquest at Shrewsbury yesterday heard she had a hip replacement as a result of the accident but the wound from the operation had become infected. Dr Graham Harvey, consultant medical microbiologist at the Royal Shrewsbury Hospital, said Mrs Jones had died of septicaemia caused by MRSA. He said anti-inflammatory drugs she was on for her arthritis may have limited her body’s ability to fight the infection.
Link: Chest Meeting Abstracts.
Determine if a clinical guideline increased the initial administration of appropriate empiric anti-microbial treatment to trauma patients with ventilator associated pneumonia (VAP). Secondary objectives evaluated duration of mechanical ventilation, ICU and hospital lengths of stay (LOS), drug cost of VAP treatment, and development of super-infection. METHODS: A VAP guideline for diagnosis and treatment was developed with the guidelines of the American College of Chest Physicians and the institution’s antibiogram. Once VAP was diagnosed, cultures were obtained and intravenous antibiotics were started within twelve hours - vancomycin 15 mg/kg (renal ajusted dosing), ciprofloxacin 400 mg every eight hours, and piperacillin/tazobactam 4.5 grams every six hours. Once culture and susceptibilities were received, treatment was modified, and limited to seven days. Prospectively enrolled patients were compared to a retrospective cohort before the guideline. Super infection was defined as developing an infection with Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter, or MRSA.T-test and Chi squared analysis had significance assigned at p< 0.05. RESULTS: Forty-nine trauma patients comprise this study; 36 retrospective (12/2002 through 7/2003) and 13 prospective (12/2003 through 12/2004). Before the guideline only 1/36 (2.8%) received appropriate initial antibiotics; after implementation 4/13 patients (30.8%) received appropriate initial antibiotics at maximal doses, a significant improvement. Prospective patients had shoter duration of ventilation and ICU LOS just missing statitiscal validity and hospital lengths of stay were statistically lower in the prospective study group. The mean cost of VAP antibiotic treatment per patient for the retrospective group was significantly higher than the prospective group. Super-infection developed in 29/36 patients (80.6%) in the retrospective group, 8/13 patients (61.5%) developed a super-infection in the prospective group, a decrease which just missed statistical significance. CONCLUSION: The guideline diagnosed VAP more carefully decreasing unnecessary antibiotics and ultimately cost of treatment. It also increased appropriate intial treatment and decreased length of hospital stay, time on mechanical ventilation and super infections. CLINICAL IMPLICATIONS: Precisely defining diagnosis, evidence based treatment plans and reduced therapeutic variation improved outcome in complex trauma ICU patients.
Link: Antimicrobial Agents and Chemotherapy.
In a randomized, double-blind, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. The primary end point was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable (CE) populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed. Safety was assessed by physical examination, laboratory results, and adverse event reporting. Five hundred twenty patients were included in the c-mITT population (tigecycline group, n = 261; combination group, n = 259), and 436 were clinically evaluable (tigecycline group, n = 223; combination group, n = 213). The clinical responses in the tigecycline and the combination vancomycin and aztreonam groups were similar in the c-mITT population (84.3% versus 86.9%; difference, –2.6% [95% confidence interval, –9.0, 3.8]; P = 0.4755) and the CE population (89.7% versus 94.4%; difference, –4.7% [95% confidence interval, –10.2, 0.8]; P = 0.1015). Microbiologic eradication (documented or presumed) occurred in 84.8% of the patients receiving tigecycline and 93.2% of the patients receiving vancomycin and aztreonam (difference, –8.5 [95% confidence interval, –16.0, –1.0]; P = 0.0243). The numbers of patients reporting adverse events were similar in the two groups, with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the combination vancomycin and aztreonam group. Tigecycline was shown to be safe and effective for the treatment of complicated skin and skin structure infections.
Link: Antimicrobial Agents and Chemotherapy.
After 7 days of therapy with ceftobiprole medocaril or vancomycin, average counts of MRGR3 decreased significantly (P < 0.02) by 0.68 0.28 (n = 29) and 0.88 0.22 (n = 28) log CFU/ml of tissue cage fluid, respectively, compared with cages of untreated animals, but were not significantly different from each other. No resistant mutants were detected on ceftobiprole-supplemented agar following therapy with this cephalosporin. The in vivo activity of ceftobiprole medocaril against chronic MRSA foreign-body infections was equivalent to that of vancomycin and did not lead to the emergence of resistant subpopulations.
Link: American Journal of Health-System Pharmacy.
Nafcillin is a penicillinase-resistant antistaphylococcal antibiotic that has been used for various indications, such as endocarditis and skin infections.1 In the setting of home infusion, nafcillin is not considered a very user-friendly medication because of the substantial risk of phlebitis2,3 and the need for frequent administration. To meet these challenges, central i.v. lines are placed in home care patients receiving nafcillin, and programmable portable infusion pumps are used to deliver medications every four to six hours. Unlike the infusion-pump reservoirs used in the inpatient setting, those used in home care usually contain enough medication for 24 hours or more. In this case, the amount and concentration of nafcillin in the reservoir are determined by the drug’s stability.
Link: European Respiratory Journal.
The aim of this study was to evaluate C-reactive protein (CRP) levels, body temperature and white cell count (WCC) after prescription of antibiotics in order to describe the clinical resolution of ventilator-associated pneumonia (VAP). A cohort of 47 VAP patients with microbiological confirmation of disease was assessed. CRP levels, body temperature and WCC were monitored daily. On day 4 of the antibiotic therapy, the CRP level of survivors was 0.62 times the initial value, whereas, in nonsurvivors, it was 0.98. Body temperature and WCC remained almost unchanged. By day 4, a CRP of >0.6 times the initial level was a marker of poor outcome (sensitivity 0.92; specificity 0.59). Patients were divided according to their CRP patterns of response to antibiotics: fast response, slow response, nonresponse, and biphasic response. All patients with fast and slow response patterns survived, whereas those showing nonresponse and a biphasic response pattern exhibited a mortality of 78 and 75%, respectively. The adequacy of the initial antibiotic therapy had a marked influence on the rate of CRP decrease, as well as on mortality. In conclusion, daily C-reactive protein measurements after antibiotic prescription were useful in the identification, as early as day 4, of ventilator-associated pneumonia patients with poor outcome. The identification of the pattern of C-reactive protein response to antibiotics was useful in the recognition of individual clinical course, improving or worsening, as well as of the rate of improvement.
Link: American Journal of Health-System Pharmacy.
Daptomycin, a novel cyclic lipopeptide antimicrobial, is bactericidal against a range of gram-positive bacteria, including many multiple-drug-resistant isolates. It has only minimal activity against anaerobic bacteria and no activity against gram-negative bacteria. Daptomycin exhibits linear pharmacokinetics, and the plasma concentration-versus-time relationship is best described by a two-compartment model with first-order elimination. The initial bactericidal activity is rapid, extensive, and concentration related. In clinical trials, daptomycin has shown efficacy in treating complicated skin and skin-structure infections (CSSSIs); the drug carries FDA-approved labeling for same. The adverse effects of daptomycin appear comparable to those of vancomycin and semisynthetic penicillins. The dosage for CSSSIs is 4 mg/kg by i.v. infusion every 24 hours. Conclusion. Daptomycin is bactericidal against gram-positive organisms and offers an option in the treatment of CSSSIs.
Link: Journal of Antimicrobial Chemotherapy.
Twenty-seven patients were identified with osteoarticular infections. Twenty-four cases involved Staphylococcus aureus (multiresistant MRSA in 21 cases); three involved Staphylococcus epidermidis sensu stricto; four cases involved multiple organisms. Nineteen cases received pristinamycin monotherapy; the others received various combinations (fusidic acid with five; other antibiotics with three). Therapy was generally well tolerated; no haematological or biochemical toxicity was detected. Seven patients had minor gastrointestinal disturbance; and one developed rash. Four patients required dose reduction. Only four patients ceased pristinamycin due to intolerance. Treatment outcome was evaluated in 23 cases; cure was effected in 16 cases, five were successfully suppressed and two failed. There were no deaths. Conclusions: Oral pristinamycin is well tolerated and an important additional agent to treat osteoarticular infections with multiresistant MRSA and other staphylococci.
Few data exist on the efficacy of the long-acting tetracyclines doxycycline and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: The medical records of 24 patients with serious tetracycline-susceptible MRSA infections who were treated with doxycycline or minocycline were reviewed. A review of the literature on the use of these antibiotics for treatment of both methicillin-susceptible and methicillin-resistant S. aureus infection was also performed. RESULTS: Complicated skin and skin-structure infections were most common (67%). Clinical cure was achieved in 20 (83%) of 24 patients in our case series. Both drugs were well-tolerated. The review of the literature on a total of 85 patients with S. aureus infection revealed similar results. CONCLUSIONS: Long-acting tetracyclines may be a reasonable treatment alternative for patients with certain types of MRSA infection.
Link: Successful oral pristinamycin therapy
Twenty-seven patients were identified with osteoarticular infections. Twenty-four cases involved Staphylococcus aureus (multiresistant MRSA in 21 cases); three involved Staphylococcus epidermidis sensu stricto; four cases involved multiple organisms. Nineteen cases received pristinamycin monotherapy; the others received various combinations (fusidic acid with five; other antibiotics with three). Therapy was generally well tolerated; no haematological or biochemical toxicity was detected. Seven patients had minor gastrointestinal disturbance; and one developed rash. Four patients required dose reduction. Only four patients ceased pristinamycin due to intolerance. Treatment outcome was evaluated in 23 cases; cure was effected in 16 cases, five were successfully suppressed and two failed. There were no deaths. CONCLUSIONS: Oral pristinamycin is well tolerated and an important additional agent to treat osteoarticular infections with multiresistant MRSA and other staphylococci.
Link: Hubmed.
During the screening of compounds that potentiate the effect of antimicrobial agents against methicillin-resistant Staphylococcus aureus(MRSA), we found that an extract of thyme (Thymus vulgaris L) leaves greatly reduced the minimum inhibitory concentration (MIC) of tetracycline against MRSA. We isolated the effective compound and identified it as baicalein (5, 6, 7-trihydroxyflavone). One of the clinically isolated MRSA strains possessed tetK, a gene encoding active efflux pump for tetracycline. We examined the effect of baicalein on the efflux of tetracycline, using Escherichia coli KAM32/pTZ1252 carrying the tetK. The E. coli KAM32/pTZ1252 showed 8 to 16 times higher MIC than E. coli KAM32. We observed strong inhibition of transport of tetracycline by baicalein with membrane vesicles prepared from E. coli KAM32/pTZ1252. Baicalein also showed synergy with tetracycline in a MRSA strain that doesn't possess tetK, or with beta-lactams. Thus, mechanisms of the synergies seem to be versatile.
Link: European Respiratory Journal.
The adequacy of the initial antibiotic therapy had a marked influence on the rate of CRP decrease, as well as on mortality. In conclusion, daily C-reactive protein measurements after antibiotic prescription were useful in the identification, as early as day 4, of ventilator-associated pneumonia patients with poor outcome. The identification of the pattern of C-reactive protein response to antibiotics was useful in the recognition of individual clinical course, improving or worsening, as well as of the rate of improvement.
Link: Daptomycin-resistant, methicillin-resistant Staphylococcus aureus bacteremia..
We describe a patient who developed daptomycin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) during an episode of presumed septic thrombophlebitis of the portal vein. Although daptomycin is an alternative agent for treatment of drug-resistant gram-positive bacterial infections, development of resistance during prolonged use may occur with MRSA bacteremia from a persistent focus.
Link: Chest.
We found few differences between the groups regarding cure rate, duration of IV medication, and occurrence of adverse effects with the tested therapies. However, clindamycin therapy was less expensive and was associated with a lower rate of posttreatment occurrence of methicillin-resistant Staphylococcus aureus. Conclusions: Clindamycin therapy for mild-to-moderate aspiration pneumonia is clinically effective, and provides economic advantages as compared to SBT/ABPC or PAPM/BP therapy.
Link: HighWire Press -- Medline Abstract.
To review available data regarding the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). DATA SOURCES: A MEDLINE search was performed (January 1966-December 2003) using the search terms Staphylococcus aureus , sulfamethoxazole, trimethoprim, co-trimoxazole, and methicillin resistance. Abstracts from infectious diseases meetings also were reviewed. DATA SYNTHESIS: The reported rate of TMP-SMX resistance in S. aureus is highly variable. From a mechanistic standpoint, TMP-SMX resistance among MRSA appears to be distinct from multidrug resistance, although some anecdotal reports suggest otherwise. Clonal outbreaks of MRSA resistant to TMP-SMX have been described; of these, the Brazilian clone has more often been resistant to TMP-SMX than the Iberian clone. Rates of TMP-SMX resistance are particularly high in institutions serving large numbers of patients infected by the human immunodeficiency virus, due to increased exposure for Pneumocystis prophylaxis. Limited studies and case reports have found TMP-SMX useful against infections caused by MRSA. CONCLUSIONS: A large body of anecdotal data, but only one randomized clinical trial, indicates the effectiveness of TMP-SMX as a treatment for MRSA infections. Double-blind, randomized controlled trials are needed to compare the two available oral agents-TMP-SMX and linezolid-against MRSA.
Link: Telegraph
The world may run out of effective antibiotics by the end of this decade and faces a gap of at least five years before new drugs can be developed to combat superbugs, according to one of the world’s most influential scientists. The warning that the age of infectious disease control is almost over has come from Prof George Poste, Director of the Biodesign Institute at Arizona State University and an advisor to the US president. Click to enlarge “Frankly, most governments are asleep at the switch,” said Prof Poste. He predicts that from 2010 to 2015 will be a “window of vulnerability” when the toll of the superbug will reach its peak as a result of antibiotic resistance. “We are facing a relentless increase in antibiotic resistance across all classes of drug,” said Prof Poste, who began his 40-year career in Britain. The superbugs of most concern are strains of MRSA, methicillin-resistant staphylococcus aureus.
Link: Learning to fight an adversary that won't stay down.
New biomolecular technologies have largely failed to deliver the hoped-for knockout punch breakthrough against the defences of disease-causing bacteria, says a leading Canadian specialist in antibiotic resistance. Techniques such as genomic sequencing and high throughput screening were expected to make the development of new antibiotic compounds easier and more productive. But in most cases the microbes continue to hold the upper hand – and if three billion years of bacterial history is any kind of track record, we're in for an endless running battle, says Dr. Julian Davies, a microbiologist at the University of British Columbia. "We haven't evolved in our thinking sufficiently to be able to match the microbes," says Dr. Davies, Scientific Director of the Canadian Bacterial Diseases Network. "Pharmaceutical companies and other researchers have put hundreds of millions of dollars into 'modern' approaches to antibiotic discovery over the past six or seven years and this has failed miserably." The scientist, whose work is supported by Science and Engineering Research Canada (NSERC), has organized a symposium on the evolutionary genetics of antibiotic resistance at the 2005 meeting of the American Association for the Advancement of Science in Washington D.C.
Link: Affinium
Affinium Pharmaceuticals announced today that it has selected a drug candidate for development of a novel MRSA antibiotic to be used in hospital and community settings. The candidate is one of multiple compounds from Affinium's Galapagos program. ADVERTISEMENT "It is important that our development candidate operates via a novel mechanism of action with very novel chemistry, and distinct from any other antibiotic on the market. Our drug candidates selectively inhibit a bacterial pathway to kill bacteria without any detectable side effects to the analogous human pathway. Because of their unique way of working, we believe resistance will be slow to develop." said Judd Berman, Ph.D., Senior Vice President of Chemistry. "Our team selected Affinium's first development candidate after evaluating animal data from over 150 front runner compounds with potent MRSA activity from this new antibiotic class. We selected the first compound for its potential as an IV and oral antibiotic for hospital and community MRSA."
Link: This little piggy may help fight super-bugs.
AN ANTI-BACTERIAL agent produced by pigs can help prevent skin infection in humans, researchers have revealed. The molecule, from a family of protective proteins called cathelicidins, may provide an extra weapon in the war against hospital super-bugs. When scientists delivered the molecule PR39 to human skin cells in the laboratory, the cells were better able to fend off infection by the bugs. Mice engineered to produce PR39 showed increased resistance. Each year, an estimated 5,000 patients in the UK die as a result of infections picked up in hospital including MRSA, an antibiotic-resistant form of the bug Staphylococcus aureus. With super-bugs on the rise, scientists are searching for possible alternatives to conventional antibiotics.
Link: Journal of Antimicrobial Chemotherapy.
Among 133 patients with a diabetic ulcer infection, 103 were clinically evaluable; 47 received daptomycin and 56 received a comparator. Most infections were monomicrobial, and Staphylococcus aureus was the predominant pathogen. Success rates for patients treated with daptomycin or the comparators were not statistically different for clinical (66% versus 70%, respectively; 95% CI, –14.4, 21.8) or microbiological (overall or by pathogen) outcomes. Both treatments were generally well tolerated, with most adverse events of mild to moderate severity. Conclusions: The clinical and microbiological efficacy and safety of daptomycin were similar to those of commonly used comparator antibiotics for treating infected diabetic foot ulcers caused by Gram-positive pathogens. Daptomycin should be considered for treating these infections, especially those caused by resistant Gram-positive pathogens. Keywords: diabetic ulcers , foot infections , soft tissue infections , antibiotic resistance , Gram-positive infections
Link: HighWire Press -- Medline Abstract.
BACKGROUND: Catheter-related bloodstream infections (CR-BSIs) are associated with substantial mortality, prolongation of hospital stay, and increased cost of care. Dalbavancin, a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen, possesses excellent activity against clinically important gram-positive bacteria, suggesting utility in the treatment of patients with CR-BSIs. METHODS: A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days. Gram-positive bacteria isolated in this study included coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). RESULTS: Infected patients who received weekly dalbavancin (n=33) had an overall success rate (87.0%; 95% confidence interval [CI], 73.2%-100.0%) that was significantly higher than that of those who received vancomycin (n=34) (50.0%; 95% CI, 31.5%-68.5%). Adverse events and laboratory abnormalities were generally mild and were comparable for the 2 drugs. CONCLUSIONS: Dalbavancin thus appears to be an effective and well-tolerated treatment option for adult patients with CR-BSIs caused by CoNS and S. aureus, including MRSA.
Link: HighWire Press -- Medline Abstract.
We found that ethyl gallate purified from a dried pod of tara (Caesalpinia spinosa) intensified beta-lactam susceptibility in methicillin-resistant and methicillin-sensitive strains of Staphylococcus aureus (MRSA and MSSA strains, respectively). This compound and several known alkyl gallates were tested with MRSA and MSSA strains to gain new insights into their structural functions in relation to antimicrobial and beta-lactam susceptibility-intensifying activities.
Link: Coalition for Medical Progress
Human trials of a potential new vaccine against hospital superbug MRSA are due to begin this month, after British researchers proved in animal tests that it successfully arms the body’s defence mechanisms to fight off invading bacteria. The new vaccine prompts the immune system to produce antibodies capable of warding off dangerous organisms and then ‘patrol’ the bloodstream for signs of infection, killing off any bacteria they come across. “Laboratory results have been very encouraging,” says Dr Afshan Ahmad, from West Midlands firm Vaccines Research International, which developed the vaccine. “Eventually we would like to vaccinate patients who are having elective surgery – the ones who know when they are going into hospital and how long they will be in.”
Link: HighWire Press -- Medline Abstract.
Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants. ABK alleviated clinical symptoms and inflammations in all cases. CONCLUSION: Nine newborns and infants with MRSA infection and various underlying diseases were successfully treatedwith TDM-based administration of ABK with no severe adverse reactions
Link: HighWire Press -- Medline Abstract.
Clindamycin has been used successfully to treat pneumonia and soft-tissue and musculoskeletal infections due to MRSA in adults and children. However, concern over the possibility of emergence of clindamycin resistance during therapy has discouraged some clinicians from prescribing that agent. Simple laboratory testing (e.g., the erythromycin-clindamycin "D-zone" test) can separate strains that have the genetic potential (i.e., the presence of erm genes) to become resistant during therapy from strains that are fully susceptible to clindamycin.
Link: HighWire Press -- Medline Abstract.
All three new strategies were only rarely or very rarely used in Germany even in universities and hospitals with more than 1000 beds. This appears to be very astonishing because all substances were subject to extensive marketing campaigns, received scientific prices (linezolid) or were strongly recommended by some scientific societies (aPC). One major concern to the use of the new approaches was based on the high pricing. Prices were assessed as excessive or very excessive. In spite of a mass of information about the substances, a lot of the intensivists reviewed the scientific basis as weak and not justifiying the use of the costly substances. CONCLUSIONS: Moderne, costly pharmaceutical approaches in intensive care medicine are widely not accepted in Germany. Especially a tight financial corset hinders most intensivists to use these strategies that may be life-saving in some patients. A solution to this problem is urgently required that can be reached only in intensive exchange with all who are responsible for this dilemma.
Link: HighWire Press -- Medline Abstract.
Because thioridazine, a relatively mild neuroleptic as compared to its parental compound chlorpromazine, kills intracellular MDRTB and MRSA at clinical concentrations, its use for the management of these infections may be considered. The review also discusses the activity of phenothiazines against protozoa and parasites, the mechanisms by which phenothiazines promote their antimicrobial effects, their potential for regulating efflux pumps that are a cause for mono or multidrug resistance, as well as their potential for the therapy of problematic infections caused by bacteria that have acquired plasmid-antibiotic-resistant genes.
Link: HighWire Press -- Medline Abstract.
The results of the present study demonstrated that quinupristin/ dalfopristin and linezolid, have good in vitro activity against MRSA, MRCoNS and vancomycin resistant E. faecium in Turkey. These drugs could be promising therapeutic options in an era of rapidly growing antibiotic resistance in all parts of world.
Link: The Annals of Pharmacotherapy.
To study the pharmacokinetics and antibacterial activity of linezolid against selective skin/soft tissue pathogens in obese patients. CONCLUSIONS: Serum concentrations of oral linezolid in this patient population were diminished compared with those of healthy volunteers, but still provided prolonged serum inhibitory activity against common pathogens associated with skin/soft tissue infections. One treatment concern would be an obese patient receiving oral linezolid who was infected with a less susceptible (MIC ≥4.0 �g/mL) strain of S. aureus. Bactericidal activity was also observed against selective pathogens.
Link: HighWire Press -- Medline Abstract.
Chlorpromazine (CPZ) is concentrated by human macrophages where it kills intracellular mycobacteria when the concentration outside the macrophage is sub-clinical. We have previously demonstrated that thioridazine (TZ), a much milder phenothiazine, has similar activity and kills intracellular methicillin-susceptible S. aureus at sub-clinical concentrations. We have extended this latter study to include methicillin-resistant S. aureus (MRSA) and show that TZ kills intracellular MRSA at clinically relevant concentrations. Because macrophage intracellular MRSA is not killed by the macrophage and its intracellular location protects it from antibiotics that are unable to reach that site, recurrent infections which result may be successfully managed with the use of TZ.
Link: HighWire Press -- Medline Abstract.
Vancomycin has been the cornerstone of therapy for serious MRSA infections including bacteremia and endocarditis. Clinicians have noted that MRSA bacteremias treated with vancomycin often fail to clear even with prolonged therapy. Persistent or prolonged MRSA bacteremia unresponsive to vancomycin therapy has led to the treatment of these infections by other agents, that is, quinupristin, dalfopristin, linezolid, or daptomycin. These antibiotics have been found particularly useful in treating MRSA bacteremias unresponsive to vancomycin therapy. We report a case of a patient who presented with MRSA PVE complicated by perivalvular aortic abscess with persistent MRSA bacteremia unresponsive to vancomycin therapy. The patient's MRSA bacteremia was cleared with daptomycin therapy (6 mg/kg/d). Because the patient refused surgery, daptomycin therapy was continued in hopes of curing the endocarditis and sterilizing the perivalvular aortic abscess.
Link: CytoGenix .
Johns Hopkins AIDS Service reports, "The emergence of CA-MRSA infections is an additional threat to the growing global public health crisis of antimicrobial resistance. Efforts to control MRSA infections can no longer depend solely on surveillance, infection control efforts, and judicious antibiotic prescribing practices within the hospital setting. Proactive patient education, aggressive diagnostic efforts, and effective treatment for CA-MRSA infections by outpatient clinicians, will not only improve patient care, but also protect our communities and hospitals from an increasingly prevalent pathogen."
Link: Infection and Immunity.
Staphylococcal enterotoxin C (SEC), a bacterial superantigenic exotoxin, is commonly produced by invasive Staphylococcus aureus isolates, especially methicillin-resistant strains and isolates from animal diseases. We constructed and expressed a nontoxic mutant SEC (mSEC) and investigated whether immunization with mSEC, which is devoid of superantigenic activity, can protect against S. aureus infection. Mice were immunized with mSEC and challenged with viable S. aureus. The bacterial counts in the organs of mSEC-immunized mice were significantly lower and the survival rate was higher than the corresponding values for the control group.
Link: Antimicrobial Agents and Chemotherapy.
At 24 h postinfusion, serum from subjects given telavancin demonstrated potent bactericidal activity against methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae strains. The results suggest that telavancin may be an effective once-daily therapy for serious bacterial infections caused by these pathogens.
Link: Antimicrobial Agents and Chemotherapy.
We investigated various regimens of cefepime alone and in combination against two clinical MRSA isolates (R2481 and R2484) in an established in vitro pharmacodynamic model. . A 99.9% kill was achieved with cefepime plus aminoglycoside combinations as early as 2 h and maintained throughout the 48-h period. Overall, the most potent combinations noted were cefepime in combination with low- and high-dose aminoglycosides. Further investigations with combination therapies are warranted.
Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.
Link: Scotsman.com
A CHANCE meeting with a student who was chewing on a piece of wood has sparked a major breakthrough in food safety. Researchers at the c