Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.

Infections caused by pathogens can be a significant challenge in wound healing, particularly when antimicrobial resistance is a factor. This can pose a serious threat to human health and well-being. In this scenario, it is imperative to explore novel antimicrobial agents to fight against multi-drug resistant (MDR) pathogenic bacteria. This study employed rational design strategies, including truncation, amino acid replacement, and heterozygosity, to obtain seven α-helical, cationic, and engineered peptides based on the original template of Abhisin. Among the analogs of Abhisin, AB7 displayed broad-spectrum and potent antimicrobial activity, superior targeting of membranes and DNA, and the ability to disrupt biofilms and anti-endotoxins in vitro. Additionally, we evaluated the anti-infection ability of AB7 using a murine skin wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) and found that AB7 displayed negligible toxicity both in vitro and in vivo. Furthermore, AB7 exhibited desirable therapeutic efficacy by reducing bacterial burden and pro-inflammatory mediators, modulating cytokines, promoting wound healing, and enhancing angiogenesis. These results highlight the potential of AB7 as a promising candidate for a new antibiotic. KEY POINTS: • A α-helical, cationic, and engineered peptide AB7 was obtained based on Abhisin. • AB7 exhibited potent antimicrobial activity and multiple bactericidal actions. • AB7 effectively treated infected skin wounds in mice.

Dual Drug Loaded pH-sensitive Micelles for Efficient Bacterial Infection Treatment.

PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) infection at impaired wound is associated with high risks of developing to persistent bacterial infections since bacterial biofilm is easy to form in MRSA infected wounds. An advanced therapeutic approach to effectively penetrate and eliminate bacterial biofilm and to accelerate cell proliferation and migration at the wound is crucial. METHODS: The poly(ε-caprolactone)-monomethoxyl poly (ethylene glycol) (PCL-mPEG) micelles loaded with Quercetin and Rifampicin (QRMs) were prepared. Bacterial biofilm proliferation and elimination effect of QRMs were evaluated with confocal laser scanning microscopy. Antibacterial assay was further performed to detect antibacterial activity and mechanism. The cell scratch assay and cellular uptake were performed in HaCaT skin epithelial cells. RESULTS: Our results showed that the small sized QRMs could penetrate the interior of MRSA biofilm to disperse and eradicate biofilm. Then, antibiotics are released and accumulated in the acidic biofilm environment. QRMs could kill bacteria through increasing bacterial membrane permeability and altering membrane potential and membrane fluidity. Moreover, QRMs improved intracellular and cytoplasmic delivery efficiency of drugs to epithelial cells, and in the scratch test, presented a stronger ability to promote migration and proliferation of HaCaT cells compared with free drugs. Hemolysis test further proved good biocompatibility of QRMs. CONCLUSIONS: QRMs could potentially be used as a novel dual-functional nanotherapeutic for anti-bacterial infection by eradicating biofilm and accelerating cells proliferation at MRSA infected wound.

Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has led to serious infections, especially in hospitals and clinics, where treatment and prevention have become more difficult due to the formation of biofilms. Owing to biofilm-derived antibiotic tolerance, the currently available traditional antibiotics have failed to treat MRSA infections. Hence, there is a urgent need to develop novel antibiotics for treating life-threatening MRSA infections. Lugdunin (cyclic peptide-1), a nonribosomal cyclic peptide produced by Staphylococcus lugdunensis, exhibits potent antimicrobial activity against MRSA. Amazingly, cyclic peptide-1 and its analogues cyclic peptide-11 and cyclic peptide-14 have the ability to disperse mature MRSA biofilms and show anti-clinical MRSA activity, including MRSA persister cells. In addition, these three cyclic peptide compounds have non-toxicity, lower hemolytic activity and lack of resistance development. Our results indicate that cyclic peptide-1, cyclic peptide-11, and cyclic peptide-14 have great potential as new antimicrobial drug candidates for the treatment of clinical MRSA infections.

Evaluation of MRSA Surveillance Nasal Swabs for Predicting MRSA Infection in Surgical Intensive Care Unit Patients.

BACKGROUND: We aimed to examine the clinical value of serial MRSA surveillance cultures to rule out a MRSA diagnosis on subsequent cultures during a patient's surgical intensive care unit (SICU) admission. MATERIAL AND METHODS: We performed a retrospective cohort study to evaluate patients who received a MRSA surveillance culture at admission to the SICU (n = 6,915) and collected and assessed all patient cultures for MRSA positivity during their admission. The primary objective was to evaluate the transition from a MRSA negative surveillance on admission to MRSA positive on any subsequent culture during a patient's SICU stay. Percent of MRSA positive cultures by type following MRSA negative surveillance cultures was further analyzed. MEASUREMENTS AND MAIN RESULTS: 6,303 patients received MRSA nasal surveillance cultures at admission with 21,597 clinical cultures and 7,269 MRSA surveillance cultures. Of the 6,163 patients with an initial negative, 53 patients (0.87%) transitioned to MRSA positive. Of the 139 patients with an initial positive, 30 (21.6%) had subsequent MRSA positive cultures. Individuals who had an initial MRSA surveillance positive status on admission predicted MRSA positivity rates for cultures in qualitative lower respiratory cultures (64.3% versus. 3.1%), superficial wound (60.0% versus 1.6%), deep wound (39.0% versus 0.8%), tissue culture (26.3% versus 0.6%), and body fluid (20.8% versus 0.7%) cultures when compared to MRSA negative patients on admission. CONCLUSION: Following MRSA negative nasal surveillance cultures patients showed low likelihood of MRSA infection suggesting empiric anti-MRSA treatment is unnecessary for specific patient populations. SICU patient's MRSA status at admission should guide empiric anti-MRSA therapy.

How is ceftobiprole used in Canada: the CLEAR study final results.

BACKGROUND: We report the final results of the clinical usage of ceftobiprole in patients in Canada from data in the national CLEAR (Canadian Le adership on Antimicrobial Real-Life Usage) registry. RESEARCH DESIGN AND METHODS: The authors review the final data using the national ethics approved CLEAR study. Thereafter, the literature is surveyed regarding the usage of ceftobiprole to treat patients with infectious diseases via PubMed (up to March 2024). RESULTS: In Canada, ceftobiprole is primarily used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to daptomycin and/or vancomycin with high microbiological and clinical cure rates, along with an excellent safety profile. Several reports attest to the microbiological/clinical efficacy and safety of ceftobiprole. Ceftobiprole is also reported to be used empirically in select patients with community-acquired bacterial pneumonia (CABP), as well as hospital-acquired bacterial pneumonia (HABP). CONCLUSIONS: In Canada, ceftobiprole is used mostly as directed therapy to treat a variety of severe infections caused by MRSA, in patients failing previous antimicrobials. It is frequently added to, and thus used in combination with daptomycin and/or vancomycin with high microbiological/clinical cure rates, and an excellent safety profile.

Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections.

INTRODUCTION: The design of precision antimicrobials aims to personalize the treatment of drug-resistant bacterial infections and avoid host microbiota dysbiosis. OBJECTIVES: This study aimed to propose an efficient de novo design strategy to obtain specifically targeted antimicrobial peptides (STAMPs) against methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We evaluated three strategies designed to increase the selectivity of antimicrobial peptides (AMPs) for MRSA and mainly adopted an advanced hybrid peptide strategy. First, we proposed a traversal design to generate sequences, and constructed machine learning models to predict the anti-S. aureus activity levels of unknown peptides. Subsequently, six peptides were predicted to have high activity, among which, a broad-spectrum AMP (P18) was selected. Finally, the two targeting peptides from phage display libraries or lysostaphin were used to confer specific anti-S. aureus activity to P18. STAMPs were further screened out from hybrid peptides based on their in vitro and in vivo activities. RESULTS: An advanced hybrid peptide strategy can enhance the specific and targeted properties of broad-spectrum AMPs. Among 25 assessed peptides, 10 passed in vitro tests, and two peptides containing one bacterial-entrapping peptide (BEP) and one STAMP passed an in vivo test. The lead STAMP (P18E6) disrupted MRSA cell walls and membranes, eliminated established biofilms, and exhibited desirable biocompatibility, systemic distribution and efficacy, and immunomodulatory activity in vivo. Furthermore, a bacterial-entrapping peptide (BEP, SP5) modified from P18, self-assembled into nanonetworks and rapidly entrapped MRSA. SP5 synergized with P18E6 to enhance antibacterial activity in vitro and reduced systemic MRSA infections. CONCLUSIONS: This strategy may aid in the design of STAMPs against drug-resistant strains, and BEPs can serve as powerful STAMP adjuvants.

Comparison of disease and economic burden between MRSA infection and MRSA colonization in a university hospital: a retrospective data integration study.

BACKGROUND: Although there is a growing concern and policy regarding infections or colonization caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), the prognosis of MRSA infections compared to that of methicillin-susceptible Staphylococcus aureus (MSSA) infections remains controversial. Moreover, there have not been any studies comparing both the burden of disease and its impact on the healthcare economy between MRSA infection and colonization while adjusting for confounding factors. These comparisons are crucial for developing effective infection control measures and healthcare policies. We aimed to compare the disease and economic burden between MRSA and MSSA infections and between MRSA infection and colonization. METHODS: We retrospectively investigated data of 496 in-patients with MRSA or MSSA infections and of 1178 in-patients with MRSA infections or MRSA colonization from a university hospital in Japan from 2016 to 2021. We compared in-hospital mortality, length of stay, and hospital charges between in-patients with MRSA and MSSA infections and those with MRSA infections and MRSA colonization using multiple regressions. We combined surveillance data, including all microbiological test results, data on patients with infections, treatment histories, and clinical outcomes, to create the datasets. RESULTS: There was no statistically significant difference in in-hospital mortality rates between matched MRSA vs. MSSA infections and MRSA infection vs. colonization. On the contrary, the adjusted effects of the MRSA infection compared to those of MSSA infection on length of stay and hospital charges were 1.21-fold (95% confidence interval [CI] 1.03-1.42, P = 0.019) and 1.70-fold (95% CI 1.39-2.07, P < 0.00001), respectively. The adjusted effects of the MRSA infection compared to those of MRSA colonization on length of stay and hospital charges were 1.41-fold (95% CI 1.25-1.58, P < 0.00001) and 1.53-fold (95% CI 1.33-1.75, P < 0.00001), respectively. Regarding confounding factors, hemodialysis or hemofiltration was consistently identified and adjusted for in the multiple regression analyses comparing MRSA and MSSA infections, as well as MRSA infection and MRSA colonization. CONCLUSIONS: MRSA infection was associated with longer length of stay and higher hospital charges than both MSSA infection and MRSA colonization. Furthermore, hemodialysis or hemofiltration was identified as a common underlying factor contributing to increased length of stay and hospital charges.

Bleeding Complications in Vancomycin-Induced Thrombocytopenia: A Real-world Postmarketing Pharmacovigilance Analysis.

PURPOSE: Vancomycin and linezolid are first-line drugs used for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin is well known as the best alternative drug when linezolid-induced thrombocytopenia occurs. However, several cases with vancomycin-induced thrombocytopenia, especially with bleeding complications, have been reported recently, which has attracted attention. The objective of this study is to assess the potential relevance between vancomycin and bleeding complications in thrombocytopenia. METHODS: This is a real-world pharmacovigilance study conducted in October 2022 using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We performed a disproportional analysis to assess the risk of bleeding complications in vancomycin-induced thrombocytopenia by calculating reporting odds ratios (RORs) and information components (ICs), with a weak signal defined as a lower limit of the IC 95% CI of 0 to 1.5, a middle signal defined as a lower limit of the IC 95% CI of 1.5 to 3.0, and a strong signal defined as a lower limit of the IC 95% CI of >3.0. FINDINGS: There were 21,854 cases in the FAERS database that listed vancomycin as a suspected drug from quarter 1 of 2004 to quarter 2 of 2022. There were 800 cases of vancomycin-induced thrombocytopenia and 125 cases of bleeding complications in vancomycin-induced thrombocytopenia. Teicoplanin, tigecycline, and vancomycin (3 middle signals) were sequentially less associated with thrombocytopenia than linezolid (strong signal). However, bleeding complications in thrombocytopenia were significant associated with vancomycin (ROR = 9.641; 95% CI, 8.105-11.468; IC = 3.184; 95% CI, 2.929-3.440 [middle signal]), followed by linezolid (ROR = 9.350; 95% CI, 7.318-11.947; IC = 3.106; 95% CI, 2.745-3.466 [middle signal]), teicoplanin (ROR = 6.399; 95% CI, 2.869-14.272; IC = 2.059; 95% CI, 0.881-3.283 [weak signal]), and daptomycin (ROR = 2.784; 95% CI, 1.496-5.180; IC = 1.287; 95% CI, 0.374-2.201 [weak signal]). Tigecycline and daptomycin were the least likely anti-MRSA drug to cause thrombocytopenia (middle signal and weak signal, respectively) and bleeding complications in thrombocytopenia (no signal and weak signal, respectively). Middle signals of bleeding complication in vancomycin-induced thrombocytopenia were found in all group except those <45 to ≥80 years of age (weak signal). IMPLICATIONS: Bleeding complications in thrombocytopenia were significantly associated with vancomycin use, and the risk was highest among all the anti-MRSA drugs. Physicians should be aware of this possible serious adverse reaction.

Biocontrol of methicillin-resistant Staphylococcus aureus using a virulent bacteriophage derived from a temperate one.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to global public health due to its resistance to specific antibiotics. Bacteriophages particularly the lytic ones are promoted as a potential powerful-tool to combat infections caused by drug resistant bacteria; while several disadvantages limited the application of the temperate ones. In this study, we isolated 14 phages against MRSA strains, and found three ones showed the capacity of killing most of the target MRSA strains. However, whole genome sequencing and generation of lysogens indicated that these three bacteriophage candidates were temperate ones. Therefore, we mutated one (4PHSA25) of them to a virulent bacteriophage (4PHCISA25). Phenotypical characterization assays revealed that 4PHCISA25 had similar lytic spectrum, temperature, pH, and UV sensitivities to 4PHSA25. However, 4PHCISA25 displayed increased lytic activities and decreased bacteriophage insensitive mutant frequency. Biofilm removing assays showed that 4PHCISA25 exhibited a better capacity than 4PHSA25 on eliminating biofilms formed by MRSA strains. Mouse experiments demonstrated that injection of 4PHCISA25 was safe to the mice and treatment with it (109 PFU per mouse) inhibited the development of abscess induced by MRSA within 24 h and promoted the recovery from the clinical signs. Taken together, this study highlights the use of phages combating MRSA.

MRSA compendium of epidemiology, transmission, pathophysiology, treatment, and prevention within one health framework.

Staphylococcus aureus is recognized as commensal as well as opportunistic pathogen of humans and animals. Methicillin resistant strain of S. aureus (MRSA) has emerged as a major pathogen in hospitals, community and veterinary settings that compromises the public health and livestock production. MRSA basically emerged from MSSA after acquiring SCCmec element through gene transfer containing mecA gene responsible for encoding PBP-2α. This protein renders the MRSA resistant to most of the ß-lactam antibiotics. Due to the continuous increasing prevalence and transmission of MRSA in hospitals, community and veterinary settings posing a major threat to public health. Furthermore, high pathogenicity of MRSA due to a number of virulence factors produced by S. aureus along with antibiotic resistance help to breach the immunity of host and responsible for causing severe infections in humans and animals. The clinical manifestations of MRSA consist of skin and soft tissues infection to bacteremia, septicemia, toxic shock, and scalded skin syndrome. Moreover, due to the increasing resistance of MRSA to number of antibiotics, there is need to approach alternatives ways to overcome economic as well as human losses. This review is going to discuss various aspects of MRSA starting from emergence, transmission, epidemiology, pathophysiology, disease patterns in hosts, novel treatment, and control strategies.

A descriptive analysis of PVL-positive multidrug-resistant Staphylococcus aureus in hospital-associated infections in Saudi Arabia.

Methicillin resistant Staphylococcus aureus infections impose a huge risk to public health in healthcare and community settings worldwide. Therefore, it is of interest to document data on the anti-biogramas and genotypes of isolates from Saudi Arabia. We assessed the antimicrobial susceptibility, determined spa (protein A gene) and analyzed multilocus MLST genotypes, and detected PVL gene in these isolates. We collected 28 clinical MRSA isolates, cultured and determined the minimum inhibitory concentrations of 17 antimicrobial agents using Vitek2 system (BioMerieux, USA) from 3 hospitals in Saudi Arabia during the year 2012. Polymorphic region of the spa and seven housekeeping genes were amplified and sequenced. BioNumerics v.5.1 (Applied Maths) was used for spa typing and MLST. Samples were screened for the presence of PVL and mecA genes using polymerase chain reaction (PCR). Analysis shows that all isolates were susceptible to chloramphenicol, rifampicin, nitrofurantoin, teicoplanin, daptomycin and vancomycin. The T4573/ST22 strains are found to be prevalent in the Saudi Arabia (N=6, 21%). We further noted that three isolates (t363/ST240 strain) were resistant to eight antimicrobial agents. Most of t4573/ST22 strains were PVL positive, resistant to ciprofloxacin and linked to HA-MRSA infections. We document data for the presence of emerging multi drug resistant S. aureus strains carrying the PVL gene circulating within hospitals. This highlights the urgent need for continuous active surveillance and implementation of prevention measures.

Vancomycin MIC and agr dysfunction in invasive MRSA infections in southern Brazil.

In methicillin-resistant Staphylococcus aureus (MRSA) treatment, the vancomycin minimum inhibitory concentration (MIC) increase, vancomycin heteroresistance (hVISA) presence, and accessory gene regulator (agr) dysfunction are predictors of vancomycin therapy failure. This study evaluated the association between vancomycin MIC (≥ 1.0 µg/mL) and agr dysfunction in invasive MRSA isolates. Vancomycin MIC, hVISA phenotype, agr group, and function were determined in 171 MRSA isolates obtained between 2014 and 2019 from hospitals in Porto Alegre, Brazil. All MRSA were susceptible to vancomycin; 16.4% of these had MIC ≥ 1.0 µg/mL. Seventeen MRSA isolates expressed the hVISA phenotype; 35.3% of them had MIC of 1.5 µg/mL. agr groups I (40.9%) and II (47.1%) were the most found groups for MRSA and hVISA isolates, respectively. The proportion of MRSA with vancomycin MIC ≥ 1.0 µg/mL in agr group II was significantly higher than in agr groups I and III (p = 0.002). agr dysfunction was observed in 4.7% (8/171) of MRSA, especially those with vancomycin MIC ≥ 1.0 µg/mL (p < 0.001). In addition, six isolates (35.3%; 6/17) with hVISA phenotype presented agr dysfunction, which was significantly higher than that in non-hVISA phenotype (p < 0.001). In conclusion, agr dysfunction in MRSA is associated with vancomycin MIC ≥ 1.0 µg/mL and hVISA phenotype, which suggests that agr dysfunction might confer potential advantages on MRSA to survive in invasive infections.

Swift Cure of a Chronic Wound Infected With Multiresistant Staphylococcus aureus in an Elderly Patient With Stage 5 Renal Disease.

We present a case of a 91-year-old female with stage 5 renal disease, diabetes type 2, and considerable weakness, suffering from a 2-month-old wound infected by a multiresistant Staphylococcus aureus. The wound measured 7 cm in length, 5 cm in width, and 1.5 cm in depth, having purulent white edges and exudates exceeding the size of the wound. The systemic antibiotic use was opposing to improve the patient's clinical condition due to underlying nephrotoxicity that may have deteriorated renal failure and resistance of the infecting pathogen. The halogenated taurine (Tau) derivatives N-chlorotaurine (NCT) and N-bromotaurine (NBrT) with potent anti-inflammatory and antimicrobial efficacy were alternatively employed as combination topical treatment to provide a therapeutic solution. Each agent was applied separately with an interval of 5 minutes as a 1% spray in aqueous solution every 30 minutes during the day for 3 days. This treatment was very well tolerated and led to rapid disappearance of the purulent exudate, rapid epithelialization, and complete healing. To avoid relapse, the application was continued 4 times daily for a further 4 days. No complications occurred in the course of treatment. This case report confirms the therapeutic efficacy of NCT in chronic purulent wounds. NBrT is well tolerated, too, and can be used in combination with NCT in emergency clinical settings. Its potential as a single agent should be investigated in further studies. Advancement of wound closure by these agents proved to be life-saving for this patient. Further molecular research is needed to identify mechanisms that promote wound healing.

Molecular analysis of meticillin-resistant Staphylococcus aureus strains isolated from different types of infections from patients hospitalized in 12 regional, non-teaching hospitals in southern Poland.

BACKGROUND: Accumulated data indicate that meticillin-resistant Staphylococcus aureus (MRSA) infections are associated with a worse prognosis than methicillin-susceptible S. aureus infections. AIM: To assess the epidemiological profile of S. aureus infections and the genetic diversity of clinical strains of MRSA in 12 hospitals in southern Poland. METHODS: Samples from bloodstream infections, pneumonia, and skin and soft tissue infections from adult patients were examined. S. aureus isolates were tested for MRSA and macrolide-lincosamide-streptogramin B (MLSB) phenotypes. Staphylococcal cassette chromosome mec (SCCmec) typing and S. aureus protein A (spa) typing were performed. Analysis of the genetic similarity was performed by pulsed-field gel electrophoresis. RESULTS: This study included 555 patients. An MRSA phenotype was detected in 15.1% of strains. The prevalence of MRSA infection was higher in patients aged >80 years. An MLSB phenotype was detected in 18.2% of strains. Analysis of SmaI profiles did not reveal a dominant clone. Spa typing showed 25 different spa types, and spa type t003 was the most common (49% of strains). Among MRSA strains, SCCmecII (49%) and SCCmecIV (27.4%) were predominant. CONCLUSION: The characteristics of MRSA showed considerable heterogeneity. The results demonstrate the need for caution when drawing conclusions on direct epidemiological relationships between isolates based on a single typing method. As the cases of infection in this study were not associated with the hospital environment and horizontal transfer, a focus on screening at hospital admission, and appropriate infection control, may help to reduce the risk of MRSA infections.

Novel antimicrobial peptide-modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus.

Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections.

Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis.

STUDY OBJECTIVE: Daptomycin is a therapeutic option for patients with underlying renal insufficiency who are vulnerable to nephrotoxicity from vancomycin. We evaluated the efficacy and safety of daptomycin in patients with renal impairment. DESIGN: Multicenter, retrospective, observational, case series analysis. SETTING: Two academic medical centers. PATIENTS: One hundred and sixty adults with creatinine clearance (Clcr ) of 50 ml/minute or less who received daptomycin for at least 72 hours for complicated Gram-positive infections from 2008-2011. MEASUREMENTS AND MAIN METHODS: Clinical and microbiologic outcomes were assessed at the end of daptomycin therapy. Safety evaluations were documented for all patients, and when available, creatine phosphokinase (CPK) levels were recorded. Thirty-eight (23.8%) patients were on hemodialysis, and 122 (76.3%) had a decreased baseline renal clearance not requiring hemodialysis with a median interquartile range (IQR) Clcr of 32.4 ml/minute (24.2-40.4 ml/min). The median (IQR) daptomycin dose was 6.0 mg/kg (5.8-7.8 mg/kg) administered every 24 hours in 68 patients (42.5%) and every 48 hours in 92 patients (57.5%). Daptomycin success, including cure or improvement, (Cure: signs and symptoms resolved and no additional antibiotic therapy required, or infection cleared with negative cultures reported at the end of daptomycin therapy; Improvement: partial resolution of signs and symptoms and additional antibiotic therapy necessary at the end of daptomycin therapy) was achieved in 128 of 160 (80.0%) patients at the end of therapy. Methicillin-resistant Staphylococcus aureus (MRSA) was the most common pathogen (45%) isolated. The most frequent reason for using daptomycin was due to vancomycin-associated nephrotoxicity (20%). Daptomycin therapy was discontinued in six patients (3.8%) because of elevated CPK (median time to onset, 11.5 days). Loss of daptomycin susceptibility occurred in two patients with complex endovascular infections who were on hemodialysis. CONCLUSIONS: Daptomycin demonstrated clinical and microbiologic success rates comparable with prior studies. Discontinuation of therapy because of elevated CPK levels may have been avoided in some patients with adjustment to every 48-hour dosing for Clcr less than 30 ml/minute. The relatively early time to onset suggests the need for CPK monitoring more frequently than once/week in renally impaired patients receiving daptomycin. The treatment of bacteremia in patients with renal insufficiency warrants further study.

Antimicrobial resistance and molecular epidemiology of Staphylococcus aureus from Ulaanbaatar, Mongolia.

This study aimed to characterize Staphylococcus aureus (S. aureus) strains isolated from human infections in Mongolia. Infection samples were collected at two time periods (2007-08 and 2011) by the National Center for Communicable Diseases (NCCD) in Ulaanbaatar, Mongolia. S. aureus isolates were characterized using polymerase chain reaction (PCR) for mecA, PVL, and sasX genes and tested for agr functionality. All isolates were also spa typed. A subset of isolates selected by frequency of spa types was subjected to antimicrobial susceptibility testing and multilocus sequence typing. Among 251 S. aureus isolates, genotyping demonstrated methicillin resistance in 8.8% of isolates (22/251). Approximately 28% of the tested S. aureus isolates were observed to be multidrug resistant (MDR). Sequence type (ST) 154 (spa t667) was observed to be a strain with high virulence potential, as all isolates for this spa type were positive for PVL, had a functional agr system and 78% were MDR. S. aureus isolates of ST239 (spa t037) were observed to cause infections and roughly 60% had functional agr system with a greater proportion being MDR. Additionally, new multilocus sequence types and new spa types were identified, warranting continued surveillance for S. aureus in this region.

The prevalence of methicillin resistant organisms among pacemaker and defibrillator implant recipients.

INTRODUCTION: Pacemaker and defibrillator infections are an uncommon, but catastrophic complication of device implantation. The present study examined the prevalence of device-related infections, the patterns of antibiotic resistance, and the presence of methicillin resistant staphylococcus aureus (MRSA) nares colonization in device implant recipients. METHODS: Two protocols were employed using a retrospective and a prospective analysis. A retrospective chart review of 218 patients with suspected device infection from 1/2000 to 1/2011 was performed. Demographics, infection rates, and patterns of antibiotic resistance were compared. The prospective analysis enrolled one hundred eighty two patients undergoing device implantations or generator replacements. The nares were swabbed and analyzed for the presence of staphylococcus aureus, and tested for methicillin sensitivity. RESULTS: Over a period of ten years, 12,771 device implants/generator changes/system revisions were performed, with an infection rate of 1.2%. Methicillin resistance (MR) was identified in 98/218 (44.9%) of patients. Those with MR infection had more diabetes and cardiomyopathy. There was no significant increase in methicillin resistance over time (p=0.30). Our prospective analysis included 110 men. A total of 32 patients (17.6%) had positive cultures for SA: 6.6% with MRSA. Patients positive for MRSA nares colonization had a statistically significant greater length of hospital stay 8.5 days (mean) versus 4.4 days (P=0.049). CONCLUSIONS: Methicillin resistant organisms appear to be emerging and persistent pathogens in device implants. The screening of MRSA colonization may identify new populations at risk. Further studies and analysis are needed to determine the cost effectiveness of a screening protocol.