Methicillin-resistant Staphylococcus Aureus Infective Endocarditis Research Articles

Subtherapeutic Doses of Vancomycin Synergize with Bacteriophages for Treatment of Experimental Methicillin-Resistant Staphylococcus aureus Infective Endocarditis.

Background. Recurrent therapeutic failures reported for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) with vancomycin may be due to poor bactericidal activity. Alternative antibacterial approaches using bacteriophages may overcome this limitation. Objectives. An experimental rat model of MRSA IE (EE) was used to examine the efficacy of vancomycin combined with a 1:1 bacteriophage (phage) cocktail composed of Herelleviridae vB_SauH_2002 and Routreeviridae 66. Methods. Six hours after inoculation with ca. 5 log10 colony forming units (CFU) of MRSA strain AW7, animals were treated with either: (i) saline, (ii) an equimolar two-phage cocktail (bolus of 1 mL followed by a 0.3 mL/h continuous infusion of 10 log10 plaque forming units (PFU)/mL phage suspension), (iii) vancomycin (at a dose mimicking the kinetics in humans of 0.5 g b.i.d.), or (iv) a combination of both. Bacterial loads in vegetations, and phage loads in vegetations, liver, kidney, spleen, and blood, were measured outcomes. Results. Phage cocktail alone was unable to control the growth of strain AW7 in cardiac vegetations. However, when combined with subtherapeutic doses of vancomycin, a statistically significant decrease of ∆4.05 ± 0.94 log10 CFU/g at 24 h compared to placebo was detected (p < 0.001). The administration of vancomycin was found to significantly impact on the local concentrations of phages in the vegetations and in the organs examined. Conclusions. Lytic bacteriophages as an adjunct treatment to the standard of care antibiotics could potentially improve the management of MRSA IE. Further studies are needed to investigate the impact of antibiotics on phage replication in vivo.

Epidemiologic and clinical characteristics of infective endocarditis: a single-center retrospective study in the Bronx, New York.

There is paucity of data on the epidemiological, microbiological, and clinical characteristics of patients admitted with infective endocarditis (IE) in the Bronx, New York. We conducted a retrospective study at Jacobi Medical Center, a tertiary care hospital in the Bronx. All adult patients who were hospitalized with a primary diagnosis of new-onset IE between January 1st, 2010 and September 30th, 2020 were included. The primary outcome was in-hospital mortality. A logistic regression model was used to identify baseline variables associated with in-hospital mortality. 182 patients were included in this analysis (female sex: 38.5%, median age: 54years). 46 patients (25.3%) reported intravenous drug use. 153 patients (84.1%) had positive blood cultures. Staphylococcus aureus (S. aureus) was the most common isolated pathogen (45.1% of monomicrobial IE). Nearly half of the cases secondary to S. aureus were methicillin resistant Staphylococcus aureus (MRSA) (34/69). 164 patients (90.1%) were diagnosed with native valve IE. The mitral valve was involved in 32.4% of patients followed by the aortic valve (19.8%). The in-hospital mortality was 18.1%. The mortality was higher in the cohort 2010-2015 compared to the cohort 2016-2020 (22.1% vs 14.6%). Increasing age, MRSA IE, and active malignancy were the only variables found to have significant association with in-hospital death. S. aureus was the most common causative agent and MRSA accounted for about half of the S. aureus IE cases. The incidence of IE in patients with intravenous drug use increased over time, while the median age decreased. The in-hospital death rate was higher in 2010-2015 compared to 2016-2020.

686. Comparing Treatments of Methicillin-Resistant Staphylococcus aureus Infective Endocarditis by People Who Inject Drugs

Abstract Background People who inject drugs (PWID) are at high risk for infective endocarditis (IE) with high-mortality pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Stigma against PWID may cause differences in treatment and outcomes between these patients infected with MRSA IE. Methods Single center retrospective cohort study from August 2006 to February 2021 that includes adult patients diagnosed with IE. Primary outcomes included 90-day all-cause mortality, 60-day MRSA recurrence, 60-day readmission, and hospital length of stay (LOS). Statistical analysis was performed by chi-square, t-test, and Mann-Whitney-U as appropriate. Results A total of 214 patients were diagnosed with MRSA IE; 89 PWID and 125 non-PWID. The mean (SD) age was 47.4±12.4 years (PWID) vs 59.3 ±16.0 years (non-PWID) (p&amp;lt; 0.001). Patients were primarily male (56%), but differed in terms of race 34% African-American (AA) (PWID) vs 66% AA (non-PWID) (p&amp;lt; 0001). Mean APACHE II scores differed between groups: 16(±9.9) (PWID) vs 19(±8.1) (non-PWID) (p&amp;lt; 0.008). Among patients who cleared bacteremia, mean (SD) duration was 5.7(±3.9) days and was not significant between groups (p&amp;lt; 0.64). Valve-type was 93% native and 7% prosthetic and not different between groups (p&amp;lt; 0.16). Infectious Diseases consult did not differ at 96% overall (p&amp;lt; 0.31), but pursuit of source control nearly reached significance at 27% for PWID vs 41% non-PWID (p&amp;lt; 0.06). Similarly, use of combination therapy daptomycin and ceftaroline was nearly significant: 21% (PWID) vs 12% (non-PWID) (p&amp;lt; 0.09). Odds ratio of PWID and combination therapy remained non-significant after regression: 0.39(0.14-1.1,p&amp;lt; 0.07). Primary 90-day mortality was lower in PWID vs non-PWID (15% vs 30%) respectively (p&amp;lt; 0.01), but did not differ in 60-day MRSA recurrence (p&amp;lt; 1.0) at 9%, 60-day readmission (p&amp;lt; 1.0) at 33%, or median LOS (IQR) (p&amp;lt; 0.46) at 15 (10-24) days overall. Conclusion While PWID are significantly younger, less critically ill, and have lower mortality compared to non-PWID, they have similar LOS, MRSA recurrence, and readmission rates. Analyses suggest a potential difference in the pursuit of source control and combination therapy among PWID, however more studies may be needed to achieve significance. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

Comparing Echocardiographic Modalities in Native-Valve Infective Endocarditis Due to Methicillin-Resistant Staphylococcus Aureus in People Who Inject Drugs.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is associated with high morbidity and mortality. Current IE guidelines recommend transesophageal echocardiogram (TEE) over transthoracic echocardiogram (TTE) to diagnose infective endocarditis. Management of IE in people who inject drugs (PWID) in many medical centers is mainly conservative with prolonged intravenous antibiotics. Cardiac valve replacement in these patients remains controversial, given the high risk of reinfection. This study’s purpose is to evaluate whether obtaining sequential TEE after TTE in PWID with MRSA native-valve IE changes the management plan in these patients.Methods: A retrospective cohort of patients who are 18 years of age or older and inject drugs with definite MRSA IE between 2013 and 2019 were studied. Their echocardiographic reports and overall management plans were reviewed.Results: One hundred and twenty-six patients met the inclusion criteria. TTE was performed in 121 patients and, of these patients, 69 (57%) had detectable valvular vegetations while 52 (43%) did not. Of the 52 patients with a negative TTE, 44 underwent TEE, 28 (53%) of which showed vegetation. A total of 18 (14%) patients underwent surgery. Of these, six (33%) patients had a positive TTE only, with no subsequent TEE. Ten (56%) patients had both a positive TTE and TEE, and two (11%) patients had a negative TTE but positive TEE.Conclusion: In this retrospective cohort, obtaining a sequential TEE after a TTE in PWID with proven MRSA native IE by modified Duke’s criteria changed the management plan in two patients. The decision to perform a TEE in these patients needs to be individualized. Larger studies are needed to better evaluate the role of TEE in this patient population.

Comparison of mortality, stroke, and relapse for methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infective endocarditis: a retrospective cohort study

The purpose of this study was to compare survival, relapse, and stroke for patients with methicillin-resistant Staphylococcus aureus (MRSA) vs methicillin-susceptible S. aureus (MSSA) infective endocarditis (IE). In this retrospective study, the primary outcome of death and secondary outcomes of stroke and relapse were compared using multivariable Cox proportional hazards regression. Surgical treatment was adjusted for as a time-dependent variable. In total, 355 patients with at least one episode of IE caused by S. aureus were included. Patients with MRSA IE had higher mortality than those with MSSA IE (HR 1.34, 95% CI 1.01-1.77), but did not have a higher risk of stroke (HR 0.75, 95% CI 0.43-1.32) or relapse (HR 0.89, 95% CI 0.26-3.05). The cumulative incidence of relapse was very small. Among patients with IE caused by S. aureus MRSA infection is associated with higher mortality than MSSA infection.

A Randomized Controlled Clinical Trial on Therapeutic Effects of Teicoplanin and Vancomycin after Cardiac Surgery due to MRSA infective endocarditis in ICU Patients

Background: Infective endocarditis (IE) is a relatively rare disease but with significant rates of morbidity and mortality. The goal of IE treatment is to eradicate the foci of infection, including antimicrobial therapy with or without surgery. The decision on the selection of an empirical therapy regimen is diverse and based on patient characteristics. Vancomycin and teicoplanin are bacteriostatic glycopeptide antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, including MRSA-IE, and patients allergic to penicillin who are infected with methicillin-sensitive Staphylococcus aureus. Objective: The current study aimed to compare the efficacy and adverse effects of vancomycin and teicoplanin in the treatment of patients with MRSA-IE. Materials and Methods: This parallel, randomized, and controlled trial study was carried out on the efficacy and safety of teicoplanin versus vancomycin in the treatment of MRSA endocarditis within August 2012 and April 2017. The present study recruited adult patients with a definite or possible diagnosis of IE based on the Modified Duke Criteria. A central computer-generated random number list was used to allocate the patients (1:1) to the treatment with teicoplanin or vancomycin. Vancomycin was intravenously administered at a dose of 30 mg/kg/day in two doses. Teicoplanin was administered at a loading dose of 6-12 mg/kg every 12 h in four doses and then continued once a day. Results: Out of 86 patients screened with suspected IE, 66 patients were randomly assigned to the vancomycin (n=33) and teicoplanin (n=33) groups. The mean age values of the study subjects were 41±11.8 and 39±13.1 years in the vancomycin and teicoplanin groups, respectively. In addition, 27 patients (81.8%) in the vancomycin group met the criteria for microbiological cure, compared to 25 subjects (89.3%) in the teicoplanin group. In this regard, the observed difference was not statistically significant (P=0.41). Moreover, 26 (78.8%) and 23 (82.1%) patients in the vancomycin and teicoplanin groups achieved clinical cure, respectively (P=0.97). Overall, the patients in the vancomycin group experienced more adverse events in comparison to those of the teicoplanin group (P=0.04). The rate of acute kidney injury over time, especially in the first week of therapy, was higher in the vancomycin group than that reported for the teicoplanin group (P=0.05). Six and four patients in the vancomycin and teicoplanin groups required dialysis, respectively. The use of dialysis was not different between the two groups (P=0.88). Seven (21.3%) and five (17.9%) patients in the vancomycin and teicoplanin groups died, respectively, which was not statistically different between the two groups (P=0.74). Conclusions: It was concluded that the administration of vancomycin or teicoplanin does not significantly change the outcome of patients undergoing empirical treatment for MRSA-IE. This finding indicates the patients are similar in clinical outcomes and mortalities despite some adverse effects, such as skin rashes; therefore, teicoplanin can be considered a treatment choice for these diseases.

Risk of New Bloodstream Infections and Mortality Among People Who Inject Drugs With Infective Endocarditis

People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU). To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality. This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or older admitted with infective endocarditis. Data were analyzed from April 1, 2007, to June 29, 2018. New BSIs and factors associated with their development, treatment setting of infective endocarditis episodes (ie, inpatient vs outpatient), and 90-day mortality. The analysis identified 420 unique episodes of infective endocarditis in 309 PWID (mean [SD] patient age, 35.7 [9.7] years; 213 episodes [50.7%] involving male patients), with 82 (19.5%) complicated by new BSIs. There were 138 independent new BSIs, of which 68 (49.3%) were polymicrobial and 266 were unique isolates. Aerobic gram-negative bacilli (143 of 266 [53.8%]) and Candida species (75 of 266 [28.2%]) were the most common microorganisms. Ongoing inpatient IVDU was documented by a physician in 194 infective endocarditis episodes (46.2%), and 127 of these (65.5%) were confirmed by urine toxicology results. Multivariable time-dependent Cox regression demonstrated that previous infective endocarditis (hazard ratio [HR], 1.89; 95% CI, 1.20-2.98), inpatient treatment (HR, 4.49; 95% CI, 2.30-8.76), and physician-documented inpatient IVDU (HR, 5.07; 95% CI, 2.68-9.60) were associated with a significantly higher rate of new BSIs, whereas inpatient addiction treatment was associated with a significantly lower rate (HR, 0.53; 95% CI, 0.32-0.88). New BSIs were not significantly associated with 90-day mortality (HR, 1.76; 95% CI, 0.78-4.02); significant factors associated with mortality included inpatient infective endocarditis treatment (HR, 3.39; 95% CI, 1.53-7.53), intensive care unit admission (HR, 9.51; 95% CI, 4.91-18.42), and methicillin-resistant Staphylococcus aureus infective endocarditis (HR, 1.77; 95% CI, 1.03-3.03), whereas right-sided infective endocarditis was associated with a significantly lower mortality rate (HR, 0.41; 95% CI, 0.25-0.67). In this study, new BSIs were common in PWID receiving parenteral treatment for infective endocarditis. Discharging patients to outpatient treatment was not associated with an increase in new BSI incidence or mortality; carefully selected PWID may therefore be considered for such treatment.

Role of Vancomycin Minimum Inhibitory Concentrations by Modified Population Analysis Profile Method and Clinical Outcomes in High Inoculum Methicillin-Resistant Staphylococcus aureus Infections.

IntroductionVancomycin remains the standard of care for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Treatment failures from heteroresistant vancomycin-intermediate subpopulations (hVISA) are challenging to detect. Minimum inhibitory concentrations (MIC) identified by modified population analysis profile (PAP) is an alternative testing method. The aim of this study was to evaluate the role of PAP MIC on vancomycin failures in two high inoculum infections: MRSA infective endocarditis and pneumonia.MethodsRetrospective, observational study at Detroit Medical Center from 2008 to 2016. Adults ≥ 18 years with ≥ 1 positive MRSA blood culture from IE or pneumonia source and received ≥ 48 h vancomycin were included. The primary outcome was composite failure: MRSA bacteremia ≥ 7 days or 30-day all-cause mortality.ResultsA total of 191 patients were included; 47.6% IE and 52.4% pneumonia. About 19% were hVISA isolates, median vancomycin PAP MIC of 3 (2, 3). More than half (54.5%) experienced composite failure with a larger proportion of PAP MIC ≥ 4 mg/L in this group (25 vs. 15%, p = 0.086). Patients with IE experienced prolonged bacteremia whereas patients with pneumonia experienced higher 30-day mortality. On logistic regression analysis, age [adjusted odds ratio (aOR), 1.026; 95% confidence interval (CI), 1.005–1.047; p = 0.014] and APACHE II score (aOR 1.039; 95% CI, 1.004–1.076; p = 0.029) independently predicted composite failure.ConclusionVancomycin PAP MIC may be a more relevant predictor of patient outcomes in persistent bacteremic MRSA infections (e.g., IE). This susceptibility method is less applicable in other high inoculum infections with shorter bacteremia durations and higher mortality rates (e.g., pneumonia).

Fosfomycin plus β-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Telavancin for refractory methicillin-resistant Staphylococcus aureus bacteremia and infective endocarditis

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and infective endocarditis (IE) have become increasingly difficult to treat over the past decade, with suboptimal response rates of less than 50%. Although vancomycin and daptomycin are standard therapeutic options, treatment failures with either or both agents are common. Telavancin is a lipoglycopeptide antibiotic with activity against MRSA. In vitro, telavancin displays bactericidal activity and has lower minimum inhibitory concentrations to MRSA than vancomycin. Methods: We present a retrospective, case-series report of 14 patients treated with telavancin for refractory MRSA bacteremia with and without IE at our institution from 9 September 2010 to 2 April 2012. Results: Of the 14 patients who received telavancin for refractory MRSA bacteremia and IE, eight survived their inpatient admission and were able to be followed for 30 days. The overall survival rate was 57% (n = 8). Of the eight surviving patients, five were diagnosed with MRSA IE and the remaining three were diagnosed with complicated MRSA bacteremia. All six patients who did not survive the inpatient admission were diagnosed with left-sided IE involving the mitral valves. Conclusions: This retrospective case series provides clinical evidence for the use of telavancin as a treatment option for refractory MRSA bacteremia and IE. With limited effective agents in the treatment of MRSA-complicated bacteremia and IE, telavancin represents a potential treatment option. Further randomized, controlled trials are necessary to define the optimal role of telavancin in the treatment of MRSA bacteremia and IE.

Persistent methicillin-resistantStaphylococcus aureusbacteremia: do we need a new therapeutic strategy?

Persistent methicillin-resistant<i>Staphylococcus aureus</i>bacteremia: do we need a new therapeutic strategy?

Efficacy of NZ2114, a Novel Plectasin-Derived Cationic Antimicrobial Peptide Antibiotic, in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Cationic antimicrobial peptides (CAPs) play important roles in host immune defenses. Plectasin is a defensin-like CAP isolated from the saprophytic fungus Pseudoplectania nigrella. NZ2114 is a novel variant of plectasin with potent activity against Gram-positive bacteria. In this study, we investigated (i) the in vivo pharmacokinetic and pharmacodynamic (PK/PD) characteristics of NZ2114 and (ii) the in vivo efficacy of NZ2114 in comparison with those of two conventional antibiotics, vancomycin or daptomycin, in an experimental rabbit infective endocarditis (IE) model due to a methicillin-resistant Staphylococcus aureus (MRSA) strain (ATCC 33591). All NZ2114 regimens (5, 10, and 20 mg/kg of body weight, intravenously [i.v.], twice daily for 3 days) significantly decreased MRSA densities in cardiac vegetations, kidneys, and spleen versus those in untreated controls, except in one scenario (5 mg/kg, splenic MRSA counts). The efficacy of NZ2114 was clearly dose dependent in all target tissues. At 20 mg/kg, NZ2114 showed a significantly greater efficacy than vancomycin (P < 0.001) and an efficacy similar to that of daptomycin. Of importance, only NZ2114 (in 10- and 20-mg/kg regimens) prevented posttherapy relapse in cardiac vegetations, kidneys, and spleen, while bacterial counts in these target tissues continued to increase in vancomycin- and daptomycin-treated animals. These in vivo efficacies were equivalent and significantly correlated with three PK indices investigated: fC(max)/MIC (the maximum concentration of the free, unbound fraction of a drug in serum divided by the MIC), fAUC/MIC (where AUC is the area under the concentration-time curve), and f%T(>MIC) (%T(>MIC) is the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions), as analyzed by a sigmoid maximum-effect (E(max)) model (R(2) > 0.69). The superior efficacy of NZ2114 in this MRSA IE model suggests the potential for further development of this compound for treating serious MRSA infections.

Glycopeptide and daptomycin resistance in community-associated MRSA in the UK

Methicillin-resistant Staphylococcus aureus (MRSA) infections are commonly treated with glycopeptides. When glycopeptide resistance occurs, one of the few remaining therapeutic options is daptomycin. We describe the in vivo development of both glycopeptide and daptomycin resistance in a patient from the UK with community-associated (CA) MRSA infective endocarditis. A 35-year-old man presented to our hospital in Liverpool, UK, in 2008. A diagnosis of tricuspid valve infective endocarditis was made, secondary to intravenous drug use. Both MRSA and group G haemolytic streptococcus grew from the blood cultures. Antimicrobial therapy was initiated with teicoplanin and rifampicin, but after 3 weeks of treatment MRSA was cultured again from the patient’s blood, suggesting that resistance may have developed. Glycopeptide minimum inhibitory concentration (MIC) testing was therefore performed. The MIC to teicoplanin was determined to be 8 mg/L, identifying the MRSA isolate as glycopeptide-resistant S. aureus (GRSA). Daptomycin therapy was prescribed, but 1 week later, after an initial clinical improvement, the patient suffered cerebral emboli. Blood cultures again recovered MRSA, leading to daptomycin MIC testing. Daptomycin resistance was confirmed with an MIC to daptomycin of 4 mg/L. Linezolid, ciprofloxacin and gentamicin were then administered to the patient (Fig. 1). The patient clinically responded to this treatment, and mitral valve replacement was subsequently completed. A total of 6 weeks of oral ciprofloxacin and linezolid were prescribed post-operatively, and the patient was well upon review in January 2010. This patient was initially infected with a glycopeptidesusceptible MRSA, with initial teicoplanin and vancomycin MICs of B2 mg/L [MICs by Etest method (bioMerieux, Marcy l’Etoile, France)]. However, following treatment with teicoplanin, the isolate became glycopeptide resistant, with teicoplanin and vancomycin MICs of 8 and 3 mg/L, respectively. The MIC breakpoint for glycopeptide resistance is[2 mg/L according to the European Committee on Antimicrobial Susceptibility testing (EUCAST 2010: http://www.eucast.org). The development of glycopeptide resistance was associated with that of daptomycin resistance. The daptomycin MIC increased from a range of 0.19–0.25 to 1.5–3 mg/L, and this occurred prior to in vivo exposure to daptomycin (EUCAST MIC breakpoint for daptomycin resistance is [1 mg/L). Daptomycin therapy was associated with a further rise in the daptomycin MIC to 4 mg/L (Table 1). The MRSA isolate was confirmed as CA-MRSA [1] based on its susceptibility to ciprofloxacin [2], positivity for the Panton–Valentine Leukocidin (PVL) gene [3] and spa type t127 [4]. SCCmec typing, which is also used to differentiate CA-MRSA and health care-associated MRSA (HA-MRSA) is not valid in the UK as HA-MRSA and CA-MRSA are both commonly SCCmec type IV [5]. Pulsed field gel electrophoresis (PFGE) confirmed the A. Kirby (&) C. M. Broughton Institute of Infection and Global Health, Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, 8th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK e-mail: amk@liv.ac.uk

MRSA tricuspid valve infective endocarditis with multiple embolic lung abscesses treated by combination therapy of vancomycin, rifampicin, and sulfamethoxazole/trimethoprim

A 26-year-old pregnant woman who was an intravenous drug user (IDU) was admitted to our hospital for the treatment of tricuspid valve infective endocarditis (IE) and lung abscesses due to methicillin-resistant Staphylococcus aureus (MRSA). We started to treat her with vancomycin (VCM) alone and then in combination with rifampicin (RFP), but her condition did not improve. Then we added sulfamethoxazole/trimethoprim (SMZ/TMP) to VCM and RFP. After that, she improved rapidly. In Japan, there are very few reports about tricuspid valve IE caused by MRSA in IDUs. This case suggests that the combination of VCM, RFP, and SMZ/TMP may be effective for the treatment of severe MRSA infections.

Methicillin-resistant versus methicillin-sensitive Staphylococcus aureus infective endocarditis

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is increasing. This study compared clinical characteristics and mortality in patients with methicillin-sensitive S. aureus (MSSA) IE versus MRSA IE, based on a prospectively collected series of 72 consecutive patients with definite S. aureus IE according to the modified Duke criteria between June 2000 and December 2006. Sixteen of 72 IE patients (22%) were caused by MRSA. Nosocomial origin, surgical site infection, surgery in the previous 6 months, the presence of a catheter and persistent bacteremia were significantly associated with MRSA. MSSA patients had significantly more unknown origin of bacteremia and experienced a significantly higher rate of major embolism than MRSA patients. MSSA patients underwent more frequently combined surgical and antimicrobial therapy, and MRSA patients were treated more frequently with antimicrobial therapy due to a contraindication to surgery. The 6-month mortality was higher in patients with MRSA than MSSA. In the MSSA group treated with antimicrobial therapy without an indication to surgery, all patients survived, and in the combined surgical and antimicrobial group 29% died. The mortality in MRSA patients was lowest if combined surgical and antimicrobial therapy was performed. Both in MSSA and MRSA patients with antimicrobial therapy due to a contraindication to surgery, the mortality was extremely high. These data suggest that in S. aureus IE patients with a nosocomial origin, the presence of a catheter or recent surgery, initial therapy should include antimicrobial agents active against MRSA. Antimicrobial therapy alone with close monitoring of the therapeutic effect and signs of complicated course is an acceptable approach in selected patients with MSSA IE. Denial of surgery because of local or general factors in patients that meet criteria for surgical intervention in acute IE is prognostically ominous.

Treatment of infective endocarditis caused by methicillin-resistant Staphylococcus aureus: Teicoplanin versus vancomycin in a retrospective study

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) is increasing. Vancomycin and teicoplanin are 2 intravenous glycopeptides appropriate for its treatment. There is no human study comparing teicoplanin and vancomycin for the treatment of MRSA endocarditis. Between 1996 and 2006, 51 MRSA endocarditis patients were treated at the authors' hospital. There were 29 patients with nosocomial infection; 15 were treated with teicoplanin. Teicoplanin was used as the first therapeutic agent in 3 patients because of renal insufficiency. Vancomycin was used as the first therapeutic agent in 12 patients. Treatment was changed to teicoplanin because of adverse reactions in 10 and persistent bacteremia in 2 patients. Early operation was performed in 2 patients because of persistent MRSA bacteremia. Overall, 7 patients died in hospital. There was no statistically significant difference in hospital mortality rate (42% vs 47%) and bacteriologic failure rate (34% vs 40%) between 36 patients treated with vancomycin and 15 patients treated with teicoplanin. Teicoplanin can be an alternative therapy of MRSA infective endocarditis.

Risk Factors for Nosocomial Infective Endocarditis in Patients with Methicillin-ResistantStaphylococcus AureusBacteremia

Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are increasing. Only a few studies of MRSA infective endocarditis have been conducted, and none have reported its risk factors. We sought to determine the host-related risk factors for infective endocarditis in patients with nosocomial MRSA bacteremia. A 2,000-bed, university-affiliated, tertiary-care hospital. Thirty-one patients with nosocomial MRSA infective endocarditis between October 1996 and May 2003. A retrospective chart review was conducted. Data were compared with those from a control group of patients with nosocomial MRSA bacteremia. Logistic regression was used to identify independent risk factors for nosocomial infective endocarditis. Compared with patients who had nosocomial MRSA bacteremia and no infective endocarditis, patients who had infective endocarditis had a higher incidence of chronic liver disease and a lower incidence of immunodeficiency. The risk of developing infective endocarditis was approximately 10% for patients with nosocomial MRSA bacteremia. Patients with MRSA bacteremia and underlying chronic liver disease were prone to infective endocarditis.