Results. Fourteen studies described in 13 articles and a total of 1233 patients versus 1217 controls were included in the analysis. Of the 13 articles, 6 were newly published articles that had not been analysed previously and 3 were randomized controlled trials. The application of mupirocin decreased the risk by 72% [95% confidence interval (CI): 0.60–0.81] in ESI and by 70% (95% CI 0.52–0.81) in peritonitis due to S. aureus among all patients undergoing PD. Treatment of mupirocin reduced the risks of ESI and peritonitis due to all organisms by 57% (95% CI: 0.46–0.66) and 41% (95% CI: 0.24–0.54), respectively. Based on the six newly published articles, the reduced risk rate for mupirocin therapy was found to be 80% (95% CI: 0.39–0.93, P = 0.004) in ESI and 91% (95% CI: 0.72–0.97, P < 0.0001) in peritonitis due to S. aureus; 70% (95% CI: 0.47–0.82, P < 0.0001) in ESI and 42% (95% CI: 0.25–0.55, P < 0.0001) in peritonitis due to all organisms among mupirocin-treated and -untreated subjects. Based on the three randomized controlled trials, ESI and peritonitis due to S. aureus were found to be reduced by 73% (95% CI: 0.63–0.80, P < 0.0001) and 40% (95% CI: 0.17–0.56, P = 0.002), respectively. Interestingly, although mupirocin treatment can reduce the risk rate of ESI by 46% (95% CI: 0.35–0.55, P < 0.00001), it cannot decrease the risk rate of peritonitis due to all organisms (P = 0.56).
via Mupirocin for preventing exit-site infection and peritonitis in patients undergoing peritoneal dialysis — Xu et al., 10.1093/ndt/gfp411 — Nephrology Dialysis Transplantation.
Two randomly selected clinical MRSA isolates were obtained from patients with IE; both MRSA isolates quantitatively produced biofilms. Time to bactericidal activity in the presence of daptomycin was isolate dependent, but was achieved by 24h for both MRSA isolates. Vancomycin did not reach bactericidal activity throughout the experiment. At 24, 48 and 72h, daptomycin-containing regimens had significantly more activity (decline in the mean CFU/g) than any of the vancomycin-containing regimens (P=0.03). Rifampin (against MRSA B346846) and gentamicin (against both isolates) antagonized or delayed the bactericidal activity of daptomycin in the first 24h. An increase in daptomycin or vancomycin MICs were not observed. We conclude that in an IE model of biofilm-forming MRSA daptomycin monotherapy has better in vitro activity than daptomycin in combination with rifampin or gentamicin or any vancomycin-containing regimen studied within the first 24h. Biofilm formation increases the likelihood of antimicrobial resistance and reduces antibactericidal activity. Further investigations are needed to understand the initial delay of bactericidal activity observed when gentamicin or rifampin was combined with daptomycin.
via Activity of daptomycin and vancomycin alone and in combination with rifampin and gentamicin against biofilm-forming MRSA in an experimental model of endocarditis — LaPlante and Woodmansee, 10.1128/AAC.00134-09 — Antimicrobial Agents and Chemotherapy.
Staphylococcus aureus in the nose is a risk factor for endogenous staphylococcal infection. UK guidelines recommend the use of mupirocin for nasal decolonization in certain groups of patients colonized with methicillin-resistant S. aureus (MRSA). Mupirocin is effective at removing S. aureus from the nose over a few weeks, but relapses are common within several months. There are only a few prospective randomized clinical trials that have been completed with sufficient patients, but those that have been reported suggest that clearance of S. aureus from the nose is beneficial in some patient groups for the reduction in the incidence of nosocomial infections. There is no convincing evidence that mupirocin treatment reduces the incidence of surgical site infection. New antibiotics are needed to decolonize the nose because bacterial resistance to mupirocin is rising, and so it will become less effective. Furthermore, a more bactericidal antibiotic than mupirocin is needed, on the grounds that it might reduce the relapse rate, and so clear the patient of MRSA for a longer period of time than mupirocin.
via Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects — Coates et al. 64 (1): 9 — Journal of Antimicrobial Chemotherapy.
RESULTS. Of 2096 children with nondrained noncultured SSTIs, 104 (5.0%) were identified as experiencing treatment failure and were matched to 480 control subjects. Compared with β-lactam therapy, clindamycin was equally effective but trimethoprim-sulfamethoxazole was associated with an increased risk of failure. Other factors independently associated with failure included initial treatment in the emergency department, presence or history of fever, and presence of either induration or a small abscess.
CONCLUSIONS. Compared with β-lactams, clindamycin monotherapy conferred no benefit, whereas trimethoprim-sulfamethoxazole was associated with an increased risk of treatment failure in a cohort of children with nondrained noncultured SSTIs who were treated as outpatients. Even in regions with endemic community-acquired MRSA, β-lactams may still be appropriate, first-line, empiric therapy for children presenting with these infections.
via Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus — Elliott et al. 123 (6): e959 — Pediatrics.
Penicillin and other antibiotics in the beta-lactam family work as well as other antibiotics to treat MRSA (methicillin-resistant Staphylococcuss aureus) infections in the skin and soft-tissue of children and may help prevent further resistance to antibiotic treatment, according to a new study.
The study, published in the June, 2009 issue of Pediatrics, compared treatment outcomes for three different antibiotics – beta-lactums (which include penicillin, cephalosporins, carbapenems and monobactams), clindamycin, and trimethoprim-sulfamethoxazole. The study concluded that children treated with clindamycin for skin and soft tissue infections potentially caused by MRSA did not show greater improvement compared to those treated with beta-lactam therapy. Children treated with trimethoprim-sulfamethoxazole were less likely to show improvement.
via Common Antibiotics May Be Best First Treatment For Children With MRSA-related Infections.
Ceftobiprole is a cephalosporin with potent activity against Methicillin-Resistant Staphylococcus aureus (MRSA). In order to treat patients with severe Staphylococcal pneumonia, it is important to understand the drug exposure required to mediate multiple Log10 cell kill in a preclinical infection model. In a murine model of Staphylococcal pneumonia, we demonstrated that ceftobiprole penetrated into Epithelial Lining Fluid (ELF) from the plasma at a median value of nearly 69% (25-75 percentile range 0.25-1.87), as indexed to the ratio of AUC values. The standard dose for ceftobiprole is 0.5 g every 8 hours as a 2 hour infusion. The target attainments remained above 90% for a 1 Log10 and 2 Log10 target at MIC values of 1 mg/L and 0.5 mg/L, respectively. Taking the expectation over a 4958 isolate MIC distribution of MRSA to ceftobiprole showed an overall target attainment of 85.6% for a 1 log10 kill and 79.7% for a 2 Log10 kill. It is important to derive exposure targets in pre-clinical infection models in the infection site to be explored in clinical trials in order to optimize the probability of a good clinical outcome.
via Identifying Exposure Targets for the Treatment of Staphylococcal Pneumonia with Ceftobiprole — Rodvold et al., 10.1128/AAC.00144-09 — Antimicrobial Agents and Chemotherapy.
Recent medical studies have found that natural plant cannabinoids are capable of reducing the spread of drug-resistant bacteria, including methicillin-resistant Staphyloccus aureus (MRSA). Researchers at Italy’s Universita del Piemonte Orientale and Britain’s University of London reported similar findings in the Journal of Natural Products. Five cannabinoids – THC, CBD, CBG, CBC, and CBN – apparently demonstrated “potent and exceptional” antibacterial activity against two epidemic MRSA oubtreaks in UK hospitals. “Although the use of cannabinoids as systemic antibacterial agents awaits rigorous clinical trials, their topical application to reduce skin colonization by MRSA seems promising. Cannabis sativa represents an interesting source of antibacterial agents to address the problem of multidrug resistance in MRSA and other pathogenic bacteria,” the authors concluded.
via TG Daily – Cannabis compounds help reduce the spread of dangerous bacteria.
MRSA expert Dr Bill Love has called for the NHS to use faster acting drugs to implement Sir Richard Branson’s proposal for MRSA screening for hospital staff. Dr Love’s drug development company Destiny Pharma is currently undertaking clinical trials for a new anti MRSA drug codenamed XF-73 which aims to allow a faster eradication of the hospital ‘Superbug’.
In his role as Vice President of the Patients Association, Sir Richard Branson is campaigning for all hospital staff to be regularly screened for MRSA and treated immediately if found to be carrying the Superbug. Despite discouraging reactions from the British Medical Association, Dr Love has given his support to the campaign in a statement released today.
One of the main objections to screening and decolonising staff MRSA carriers is that it can take up to two weeks to effect MRSA eradication and taking staff off wards for this long would put massive pressure on NHS resources. Dr Love argues that this could be overcome with faster-acting drugs that could eradicate MRSA in a much shorter period. In addition, the new drug, XF-73, has shown to have continued effectiveness against MRSA after multiple exposures, indicating MRSA may find it hard to become resistant to this new drug’s action. Therefore XF-73 could be used in a more widespread fashion allowing for a greater proportion of MRSA carriers in hospitals to be cleared of the Superbug, and assist in reducing MRSA infections even further.
via Hospital Healthcare Europe – Faster acting drugs needed to combat MRSA.
Theravance Inc.’s once-a-day injectable antibiotic — aimed at so-called “superbugs” in skin infections — must include a boxed warning for pregnant women but won’t require additional clinical trials for FDA approval. The Food and Drug Administration’s requirements delay approval of telavancin, which was submitted in December 2006 for the agency’s review. But the FDA’s “complete response letter” doesn’t require more expensive tests or a stronger “black box” warning.
Theravance CEO Rick Winningham said the company will respond to the FDA’s demands “promptly.” It could take another six months before telavancin would face approval. “There was nothing really surprising in here,” Theravance CFO Michael Aguiar said about the FDA’s letter to the company. “There’s a relatively clear path forward.” The FDA will require data on patients with kidney risk factors — from Theravance’s telavancin studies for skin infections and hospital-acquired pneumonia — and a “risk evaluation and mitigation strategy,” including a medication guide.
via FDA wants warning, more info on Theravance ‘superbug’ fighter – San Francisco Business Times:.
Oritavancin exhibited concentration-dependent bactericidal activity against stationary-phase inocula of methicillin-susceptible S. aureus (MSSA) ATCC 29213, methicillin-resistant S. aureus (MRSA) ATCC 33591, and vancomycin-resistant S. aureus (VRSA) VRS5 inoculated into nutrient-depleted cation-adjusted Mueller-Hinton broth. As has been described for exponential-phase cells, oritavancin induced membrane depolarization, increased membrane permeability, and caused ultrastructural defects including a loss of nascent septal cross walls in stationary-phase MSSA. Furthermore, oritavancin sterilized biofilms of MSSA, MRSA, and VRSA at minimal biofilm eradication concentrations (MBECs) of between 0.5 and 8 µg/ml. Importantly, MBECs for oritavancin were within 1 doubling dilution of their respective planktonic broth MICs, highlighting the potency of oritavancin against biofilms. These results demonstrate a significant activity of oritavancin against S. aureus in phases of growth that exhibit tolerance to other antimicrobial agents.
via Oritavancin Kills Stationary-Phase and Biofilm Staphylococcus aureus Cells In Vitro — Belley et al. 53 (3): 918 — Antimicrobial Agents and Chemotherapy.
Tigecycline is a currently marketed antimicrobial agent with activity against resistant gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA). Despite the proven efficacy of tigecycline in the treatment of infections caused by these pathogens, questions remain as to the exposure-response relationship best associated with its efficacy. Tigecycline pharmacokinetics were best described by a two-compartment model, with a mean half-life of 9.9 h. Protein binding was dose dependent (range, 92.9 to 81.2%). MICs were 0.25 µg/ml for all isolates, except for HA-MRSA 56 (MIC, 0.5 µg/ml) and CA-MRSA 156 (MIC, 0.125 µg/ml). Tigecycline displayed efficacy against all isolates, producing maximum decreases in log10 numbers of CFU/ml of 1.8 to 2.3 from 0-h controls. Mean correlation coefficients for free-drug (f) concentration exposures derived from the parameters fT>MIC (the percentage of time during which the concentration of f remains above the MIC), fCmax/MIC (the ratio of the maximum concentration of f to the MIC), and fAUC/MIC (the ratio of the area under the concentration-time curve of f to the MIC) were 0.622, 0.812, and 0.958, respectively. Values for the mean effective exposure index at 80% (EI80) and 50% (EI50) for fAUC/MIC were 5.4 µg/ml (range, 2.8 to 13 µg/ml) and 2.6 µg/ml (range, 0.6 to 5.1 µg/ml), respectively. Experiments with nonneutropenic mice infected with CA-MRSA 156 resulted in maximum kill at all fAUC/MIC exposures tested (1.8 to 8.8 µg/ml). The fAUC/MIC ratio is the pharmacodynamic parameter most predictive of tigecycline efficacy. Furthermore, the presence of a functioning immune system markedly reduces the required exposure.
via Pharmacodynamics of Tigecycline against Phenotypically Diverse Staphylococcus aureus Isolates in a Murine Thigh Model — Crandon et al. 53 (3): 1165 — Antimicrobial Agents and Chemotherapy.
RESULTS: Gentamicin plus EDTA (G+EDTA) and tigecycline plus EDTA (Ti+EDTA) resulted in significant reductions (p < 0.05) of log10 cfu/mL at 24 hours for all organisms tested. Daptomycin, reconstituted in LR, plus heparin (D+LR+H) demonstrated potent activity against all staphylococcal species (p < 0.05). With respect to MRSA, G+EDTA displayed significantly better activity than Ti+EDTA and cefazolin plus heparin (p < 0.05), but there was no significant difference compared with D+LR+H. No antagonism was noted with the addition of anticoagulants to the solutions.
CONCLUSIONS: Gentamicin, tigecycline, and daptomycin in combination with anticoagulants as lock solutions displayed potent activity against common pathogens responsible for CRBSIs. Each of these lock solutions deserves strong consideration for study in a clinical trial. Further data on compatibility and stability of these solutions are needed before routine clinical use can be recommended.
via Activity of Novel Antibiotic Lock Solutions in a Model Against Isolates of Catheter-Related Bloodstream Infections — Bookstaver et al. 43 (2): 210 — The Annals of Pharmacotherapy.
