Invasive Methicillin-resistant Staphylococcus Aureus Infections Research Articles

775. Comparison of Initial Vancomycin Costs and Target Attainment Between Trough- and 24-Hour Area Under the Concentration–Time Curve (AUC24)-Guided Dosing

BackgroundVancomycin is the treatment-of-choice for most invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Although serum trough concentration-guided vancomycin dosing is the current standard, dosing based on AUC24 to minimum inhibitory concentration ratio best predicts efficacy while often reducing trough concentrations associated with increased nephrotoxicity. Data regarding the impact of AUC24-guided dosing on drug costs is sparse. We compared the relative initial acquisition cost of vancomycin when utilizing AUC24- vs. trough-guided dosing. We also sought to describe current dosing practices relative to attainment of targeted vancomycin exposures.MethodsA retrospective, single-center cohort study was performed on 200 randomly-selected hospitalized adults at Duke University Hospital (DUH) in calendar year 2017 with suspected or confirmed invasive MRSA infection and stable renal function. For the primary outcome measure, a cost-minimization analysis was performed utilizing DUH wholesale vancomycin acquisition cost through 48 hours as determined from prescribed trough- and Bayesian computer-simulated AUC24-guided dosing. Descriptive statistics were utilized to characterize dosing, serum concentration monitoring practices and attainment of goal vancomycin exposures.ResultsIn the 200 enrolled subjects, the median (IQR25,75) cost difference per patient among trough- and AUC24-guided dosing was $0.00 (-15.02, 15.02). Serum vancomycin troughs were labeled correctly in 54% of samples, while 20.7% exceeded 2 hours of the next scheduled dose. Mean loading doses were 21.0 mg/kg and 24.8 mg/kg, respectively. Goal steady-state troughs were achieved in 22% of subjects. Initial dosing was predicted to achieve an AUC24 within 400–600 mg.hr/L in 66.5% and 100%, respectively. Troughs ≥15 mg/dL (a known risk factor for nephrotoxicity) were measured in 32.1% of trough-guided dosing regimens while predicted in 5.0% of AUC24-guided dosing regimensConclusionWhen compared with trough-, AUC24-guided dosing may lead to improved attainment of vancomycin target exposures, including potential reductions in excessive and incorrectly labeled trough concentrations, without impacting drug acquisition costs.Disclosures All authors: No reported disclosures.

Usnic acid modifies MRSA drug resistance through down-regulation of proteins involved in peptidoglycan and fatty acid biosynthesis.

Multidrug‐resistant Staphylococcus aureus infections place a huge burden on the healthcare sector and the wider community. An increasing rate of infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) has necessitated the development of alternative agents. We previously reported that usnic acid (UA) has activity against MRSA; here, we report the effect of UA in combination with norfloxacin on the drug resistance of MRSA clinical isolates. We observed that the combination of UA–norfloxacin significantly reduces the bacterial burden in mouse models infected with S. aureus, without causing any detectable associated toxicity. Proteomic analysis indicated that UA–norfloxacin induces oxidative stress within cells, which leads to membrane damage and inhibits metabolic activity and biosynthesis of peptidoglycan and fatty acids. Collectively, this study provides evidence that UA in combination with norfloxacin may be a potential candidate for development into a resistance‐modifying agent for the treatment of invasive MRSA infections.

Bacterial and Fungal Infections in Persons Who Inject Drugs - Western New York, 2017.

During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.* Unpublished surveillance data also indicate that an increasing proportion of all Candida spp. bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs. In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1). To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York. The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder. Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3). In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment. The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin. Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment. Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5).

Invasive Community Acquired Methicillin-resistant Staphylococcal Aureus (ca-mrsa) Infections In Children

Staphylococci are gram-positive bacteria divided into coagulase positive and coagulase negative classes, Staphylococcus aureus is the most important bacterium of this class. Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) has changed a lot. It is no more the problem of only hospitalised patients. Children coming from community has also been increasingly affected by MRSA-called community acquired methicillin-resistant (CA-MRSA) infection. The higher severity of CA-MRSA is due to its ability to produce the toxin Panton-Valentine Leukocidin (PVL) associated with staphylococcal cassette chromosome mec (SCCmec) type IV gene. Here, we are presenting five cases of CA-MRSA infection in children having age range 0.5 months to 11 years. All of them had invasive MRSA infection finally diagnosed as causing empyema thoracis, infective endocarditis, psoas abscess and necrotising fasciitis. Early surgical intervention, quick microbiological recognition of the pathogen, and appropriate antimicrobial therapy helped save their lives.

Evaluation of the statutory surveillance system for invasive MRSA infections in Germany, 2016\u20132017

BackgroundMandatory notification of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections was introduced for laboratories in Germany in 2009. The aims were to support local health authorities (LHAs) in their mandate to prevent and control infections in hospitals and to improve population-based nationwide surveillance of healthcare associated infections. We evaluated the MRSA surveillance system to assess whether its aims were met and to identify areas for improvement.MethodsUsing the updated guidelines for evaluating public health surveillance systems by the Centers for Disease Control and Prevention we assessed the attributes simplicity, timeliness, data quality, acceptability, and usefulness. In 2016/2017 we interviewed staff in LHAs, state health authorities (SHAs), and laboratories and analyzed surveillance data of cases notified between 2009 and 2016.ResultsWe interviewed 10% of LHAs (n = 38), 63% of SHAs (n = 10), 5 selected laboratories and analyzed information on 27,706 notified MRSA cases. LHAs reported that on receiving notifications from laboratories they contacted hospitals for clinical information, which was time-consuming and complicated as physicians were hard to reach or refused to answer questions, citing doctor-patient confidentiality. LHAs suggested reducing the amount of information collected as some clinical information was unnecessary for implementing control measures. LHAs stated that they received notifications on time, however surveillance data analysis showed some delay. Data completeness exceeded 90% for most variables, however it was only 68% and 80% for dates of disease onset and hospital admission respectively making it impossible to discriminate between hospital and community acquired infections in half of the cases. The surveillance system was well accepted by half of the interviewees. A third however stated that the benefits of the surveillance system were outweighed by the work associated with it. The majority rated the system to be useful for recognizing trends in the MRSA incidence and the ability to check up on infection control measures in hospitals.ConclusionsThe surveillance system proved to be useful by fulfilling its aims. It was timely, acceptable and provided complete data for most variables. However, the system was complicated; ensuring that only relevant variables are reported could simplify the system without losing any of its usefulness.

Burden of Invasive Methicillin-Resistant Staphylococcus aureus Infections in Nursing Home Residents.

To describe the epidemiology and incidence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in nursing home (NH) residents, which has previously not been well characterized. Retrospective analysis of public health surveillance data. Healthcare facilities in 33 U.S. counties. Residents of the surveillance area. Counts of NH-onset and hospital-onset (HO) invasive MRSA infections (cultured from sterile body sites) identified from the Centers for Disease Control and Prevention Emerging Infections Program (EIP) population-based surveillance from 2009 to 2013 were compared. Demographic characteristics and risk factors of NH-onset cases were analyzed. Using NH resident-day denominators from the Centers for Medicare and Medicaid Services Skilled Nursing Facility Cost Reports, incidence of NH-onset invasive MRSA infections from facilities in the EIP area was determined. A total of 4,607 NH-onset and 4,344 HO invasive MRSA cases were reported. Of NH-onset cases, median age was 74, most infections were bloodstream infections, and known risk factors for infection were common: 1,455 (32%) had previous MRSA infection or colonization, 1,014 (22%) had decubitus ulcers, 1,098 (24%) had recent central venous catheters, and 1,103 (24%) were undergoing chronic dialysis; 2,499 (54%) had been discharged from a hospital in the previous 100 days. The in-hospital case-fatality rate was 19%. The 2013 pooled mean incidence of NH-onset invasive MRSA infections in the surveillance area was 2.4 per 100,000 patient-days. More NH-onset than HO cases occurred, primarily in individuals with known MRSA risk factors. These data reinforce the importance of infection prevention practices during wound and device care in NH residents, especially those with a history of MRSA infection or colonization.

Invasive Methicillin-Resistant Staphylococcus aureus Infections Among Persons Who Inject Drugs - Six Sites, 2005-2016.

In the United States, age-adjusted opioid overdose death rates increased by >200% during 1999-2015, and heroin overdose death rates increased nearly 300% during 2011-2015 (1). During 2011-2013, the rate of heroin use within the past year among U.S. residents aged ≥12 years increased 62.5% overall and 114.3% among non-Hispanic whites, compared with 2002-2004 (2). Increases in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections related to increases in injection drug use have been recently highlighted (3,4); likewise, invasive bacterial infections, including endocarditis, osteomyelitis, and skin and soft tissue infections, have increased in areas where the opioid epidemic is expanding (5-7). To assess the effects of the opioid epidemic on invasive methicillin-resistant Staphylococcus aureus (MRSA) infections during 2005-2016, surveillance data from CDC's Emerging Infections Program (EIP) were analyzed (8). Persons who inject drugs were estimated to be 16.3 times more likely to develop invasive MRSA infections than others. The proportion of invasive MRSA cases that occurred among persons who inject drugs increased from 4.1% in 2011 to 9.2% in 2016. Infection types were frequently those associated with nonsterile injection drug use. Continued increases in nonsterile injection drug use are likely to result in increases in invasive MRSA infections, underscoring the importance of public health measures to curb the opioid epidemic.

Methicillin-resistant Staphylococcus aureus has greater risk of transmission in the operating room than methicillin-sensitive S aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic S aureus strain characteristic associated with increased patient morbidity and mortality. The health care system needs to understand MRSA transmissibility in all settings to improve basic preventive measures to generate sustained reductions in invasive MRSA infections. Our primary aim was to compare intraoperative transmissibility of MRSA versus methicillin-sensitive S aureus (MSSA) isolates. S aureus isolates (N = 173) collected from 274 randomly selected operating room environments (first and second case of the day in each operating room, a case pair) at 3 hospitals underwent systematic-phenotypic and genomic processing to identify clonally related transmission events. Confirmed transmission events were defined as at least 2 S aureus isolates obtained from ≥2 distinct intraoperative reservoirs sampled within or between cases in a study unit that were epidemiologically and clonally related. We explored the relationship between clonal transmission and methicillin resistance with Poisson regression analysis. We identified 58 clonal transmission events. MRSA isolates were associated with increased risk of clonal transmission compared with MSSA isolates (adjusted incidence risk ratio [IRR], 1.68; 95% confidence interval [CI], 1.13-2.49; P = .010; unadjusted IRR, 1.85; 95% CI, 1.23-2.77; P = .003, respectively). MRSA isolates are associated with increased risk of intraoperative transmission. Future work should examine the impact of the attenuation of intraoperative MRSA transmission on the incidence of invasive MRSA infections.

Methicillin-Resistant Staphylococcus aureus in a Trauma Population: Does Decolonization Prevent Infection?

The purpose of this study was to determine if a decolonization regimen reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections and if colonization isolates are genetically related to subsequent infectious strains. Trauma patients admitted to the intensive care unit with positive MRSA nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths and mupirocin (MUP) ointment to the nares or soap and water baths and placebo ointment for five days. Nasal swabs performed at the end of treatment and invasive MRSA infections during the remaining hospitalization were compared with the original nasal isolate via polymerase chain reaction for genetic relatedness as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal swabs over a 22-month period ending in 3/2014. After the five day treatment period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%) for soap and water baths and placebo, P = 0.114. No isolates tested positive for the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr. There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap, P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present in the original nasal swab. There was no difference in all-cause Gram-negative or positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467. CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may reduce the incidence of infection. Subsequent invasive MRSA infections are typically caused by the endogenous colonization strain.

Invasive MRSA infections in neurosurgical patients – a decade of progress

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of bloodstream infection (BSI), which is declining in many countries, including Ireland. However, it also causes other invasive infections, such as meningitis in neurosurgical patients. It is unclear whether the decline in MRSA BSI is reflected in other invasive infections and in specialist units.Aim: To investigate trends in the incidence of MRSA invasive infection in a national neurosurgical centre over a 10-year period.Methods: A retrospective review of neurosurgical patients with MRSA recovered from sterile sites and indicating invasive infection, according to internationally agreed definitions was conducted between January 2006 and December 2015. Rates per 10,000 bed days used (BDU) and neurosurgical bed days used (NBDU) were calculated and trends were analysed.Results: Forty-four cases of invasive MRSA infection were identified over the study period. The majority were BSI (26, 59%) followed by ventriculitis (8, 18%). Invasive MRSA infections declined significantly from 0.52 per 10,000 BDU (or 4.65 per 10,000 NBU) in 2006 to 0.22 per 10,000 BDU (or 2.04 per 10,000 NBDU) in 2015, p < .01, despite an increase in neurosurgical clinical activity. Half of the infections occurred in patients with no previous history of MRSA colonisation/infection. The mean length-of-stay for neurosurgical patients with invasive MRSA infections was 67 days (median 32.5 days), significantly greater for other neurosurgical patients (p < .01).Conclusion: There has been a significant decrease in invasive MRSA infections in neurosurgical patients, reflecting national and international trends for MRSA BSI. This indicates that infection prevention and control measures have been effective in reducing invasive MRSA infections overall, thus contributing to improved patient care.

Risk Factors for Invasive Methicillin-Resistant Staphylococcus aureus Infection After Recent Discharge From an Acute-Care Hospitalization, 2011-2013.

Significant progress has been made in reducing methicillin-resistant Staphylococcus aureus (MRSA) infections among hospitalized patients. However, the decreases in invasive MRSA infections among recently discharged patients have been less substantial. To inform prevention strategies, we assessed risk factors for invasive MRSA infection after acute-care hospitalizations. We conducted a prospective, matched case-control study. A case was defined as MRSA cultured from a normally sterile body site in a patient discharged from a hospital within the prior 12 weeks. Eligible case patients were identified from 15 hospitals across 6 US states. For each case patient, 2 controls were matched for hospital, month of discharge, and age group. Medical record reviews and telephone interviews were performed. Conditional logistic regression was used to identify independent risk factors for postdischarge invasive MRSA. From 1 February 2011 through 31 March 2013, 194 case patients and 388 matched controls were enrolled. The median time between hospital discharge and positive culture was 23 days (range, 1-83 days). Factors independently associated with postdischarge MRSA infection included MRSA colonization (matched odds ratio [mOR], 7.71; 95% confidence interval [CI], 3.60-16.51), discharge to a nursing home (mOR, 2.65; 95% CI, 1.41-4.99), presence of a chronic wound during the postdischarge period (mOR, 4.41; 95% CI, 2.14-9.09), and discharge with a central venous catheter (mOR, 2.16; 95% CI, 1.13-4.99) or a different invasive device (mOR, 3.03; 95% CI, 1.24-7.39) in place. Prevention efforts should target patients with MRSA colonization or those with invasive devices or chronic wounds at hospital discharge. In addition, MRSA prevention efforts in nursing homes are warranted.

External validity of a randomised controlled trial on the treatment of severe infections caused by MRSA

ObjectivesTo assess the external validity of a pragmatic, investigator-initiated RCT on treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA), we compared patient characteristics and treatment effect estimates for...

Risk of MRSA Infection in Patients with Intermittent versus Persistent MRSA Nares Colonization.

To determine the relative risk of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection among non-colonized (NC) patients, intermittently colonized (IC) patients, and persistently colonized (PC) patients. Observational cohort study of patient data collected longitudinally over a 41-month period. Department of Veterans Affairs Eastern Colorado Healthcare System, a tertiary care medical center. Any patient who received ≥5 MRSA nasal swab tests between February 20, 2010, and July 26, 2013. In total, 3,872 patients met these criteria, 0 were excluded, 95% were male, 71% were white, and the mean age was 62.9 years on the date of study entry. Patients were divided into cohorts based on MRSA colonization status. Physicians reviewed medical records to identify invasive infection and were blinded to colonization status. Cox and Kaplan-Meier analyses were used to assess the relationship between colonization status and invasive infection. In total, 102 patients developed invasive MRSA infections, 16.3% of these were PC patients, 11.2% of these were IC patients, and 0.5% of these were NC patients. PC patients were at higher risk of invasive infection than NC patients (hazard ratio [HR] 36.8; 95% CI, 18.4-73.6; P<.001). IC patients were also at higher risk than NC patients (HR, 22.8; 95% CI, 13.3-39.3; P<.001). The difference in risk between PC and IC patients was not statistically significant (HR, 1.61; 95% CI, 0.94-2.78, P=.084). Alternate analysis methods confirmed these results. The risk of invasive MRSA infection is much higher among PC and IC patients, supporting routine clinical testing for colonization. However, this risk is similar among PC and IC patients, suggesting that distinguishing between the 2 colonization states may not be clinically important.

Ceftaroline: clinical and microbiology experience with focus on methicillin-resistant Staphylococcus aureus after regulatory approval in the USA

Ceftaroline fosamil was approved in 2010 by the United States Food and Drug Administration (USA-FDA) for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP). After approval, several studies and case reports have described the postmarketing clinical experience with ceftaroline in ABSSSIs and CABP and in patients with invasive methicillin-resistant Staphylococcus aureus (MRSA) infections, many of whom had failed prior antibiotics. Successful clinical outcomes observed among the majority of these patients were supported by preapproval and postapproval in vitro surveillance of ceftaroline activity using breakpoint criteria that have been harmonized between the USA-FDA and CLSI. MIC90 values/percentage of strains susceptible to ceftaroline has remained stable over the period 2009–2012. Taken together, these postapproval studies support the use of ceftaroline for ABSSSI as well as CABP. Importantly, these data also suggest that ceftaroline can be effective in patients with serious invasive MRSA infections who have failed other therapies.

Association between vancomycin trough concentration and area under the concentration-time curve in neonates.

National treatment guidelines for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections recommend targeting a vancomycin 24-h area under the concentration-time curve (AUC0-24)-to-MIC ratio of >400. The range of vancomycin trough concentrations that best predicts an AUC0-24 of >400 in neonates is not known. This understanding would help clarify target trough concentrations in neonates when treating MRSA. A retrospective chart review from a level III neonatal intensive care unit was performed to identify neonates treated with vancomycin over a 5-year period. Vancomycin concentrations and clinical covariates were utilized to develop a one-compartment population pharmacokinetic model and examine the relationships between trough and AUC0-24 in the study neonates. Monte Carlo simulations were performed to examine the effect of dose, postmenstrual age (PMA), and serum creatinine level on trough and AUC0-24 achievement. A total of 1,702 vancomycin concentrations from 249 neonates were available for analysis. The median (interquartile range) PMA was 39 weeks (32 to 42 weeks) and weight was 2.9 kg (1.6 to 3.7 kg). Vancomycin clearance was predicted by weight, PMA, and serum creatinine level. At a trough of 10 mg/liter, 89% of the study neonates had an AUC0-24 of >400. Monte Carlo simulations demonstrated that troughs ranging from 7 to 11 mg/liter were highly predictive of an AUC0-24 of >400 across a range of PMA, serum creatinine levels, and vancomycin doses. However, a trough of ≥10 mg/liter was not readily achieved in most simulated subgroups using routine starting doses. Higher starting doses frequently resulted in troughs of >20 mg/liter. A vancomycin trough of ∼10 mg/liter is likely adequate for most neonates with invasive MRSA infections based on considerations of the AUC0-24. Due to pharmacokinetic and clinical heterogeneity in neonates, consistently achieving this target vancomycin exposure with routine starting doses is difficult. More robust clinical dosing support tools are needed to help clinicians with dose individualization.

Vancomycin and Piperacillin-Tazobactam Against Methicillin-Resistant Staphylococcus aureus and Vancomycin-Intermediate Staphylococcus aureus in an In Vitro Pharmacokinetic/Pharmacodynamic Model

PurposeSynergy between β-lactams and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate Staphylococcus aureus (VISA) has been observed in vitro and in vivo. However, studies investigating piperacillin-tazobactam with vancomycin against MRSA and VISA are limited despite broad clinical use of these antibiotics in combination. This study evaluated vancomycin and piperacillin-tazobactam against MRSA and VISA by using an in vitro pharmacokinetic/pharmacodynamic model. MethodsTwo clinical MRSA strains (M3425 and M494) and one VISA strain (Mu50) were tested in duplicate by using a 72-hour, 1-compartment pharmacokinetic/pharmacodynamic model with the following exposures: growth control, vancomycin only, piperacillin-tazobactam only, and vancomycin with piperacillin-tazobactam. Vancomycin 1 g every 12 hours (free trough concentration, 8.75 mg/L; Cmin, 17.5 mg/L) and piperacillin-tazobactam 13.5 g per 24 hours’ continuous infusion (free steady-state concentration, 27 mg/L) were simulated. Time–kill curves were constructed, and reductions in log10 CFU/mL at all time points were compared between regimens tested. FindingsVancomycin and piperacillin-tazobactam MICs for M494, M3425, and Mu50 were 1, 1, and 4 and 1.5, 32, and >256 mg/L, respectively. All isolates had an oxacillin MIC ≥4 mg/L. Against all 3 isolates, vancomycin with piperacillin-tazobactam achieved a significant reduction in inoculum at 72 hours compared with vancomycin alone (all, P ≤ 0.015). The superiority of vancomycin with piperacillin-tazobactam compared with vancomycin alone became detectable at 8 hours for M3425 (P < 0.001) and at 24 hours for M494 and Mu50 (both, P ≤ 0.008). Although vancomycin with piperacillin-tazobactam achieved enhanced antibacterial activity at 72 hours against M3425 compared with vancomycin alone, bacterial regrowth occurred. Reduced susceptibility to vancomycin at 72 hours for M3425 was confirmed by using population analysis profile/AUC analysis. At 72 hours, M3425 had a PAP/AUC ratio of 0.77 compared to 0.51 at baseline. ImplicationsVancomycin with piperacillin-tazobactam demonstrated enhanced antimicrobial activity against MRSA and VISA compared with vancomycin alone. These results further enhance existing data that support using vancomycin in combination with a β-lactam for invasive MRSA infections. Combination therapy with vancomycin and a β-lactam against MRSA warrants clinical consideration.

Risk factors affecting nasal colonization of methicillin-resistant Staphylococcus aureus when admitted in intensive care unit

Background Colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for subsequent invasive MRSA infection, particularly in patients admitted for critical care. The purpose of this study was to investigate the risk factors affecting nasal colonization of MRSA in patients admitted to intensive care units (ICU). Methods Between August 1, 2011 and June 30, 2012, we screened for MRSA nasal colonization in 350 patients by Real-time PCR within 24 hours of admission by means of swab samples taken from the anterior nares. According to the results of PCR, the patients were divided into 2 groups: the positive group with nasal MRSA colonization and the negative group without nasal MRSA colonization. The 31 (8.86%) patients were MRSA positive. The risk factors evaluated included thirteen variables, which were analyzed by t test for continuous variables and χ 2 test for discrete variables. The variables with significance (P &lt;0.05) were analyzed with stepwise Logistic regression. Results There were differences (P &lt;0.05) in four variables between two groups. The duration of stay in hospital prior to ICU admission in the positive group was (35.7±16.1) days, vs. (4.5±3.1) days in the negative group. The average blood albumin level was (28.4±2.9) g/L in the positive group, vs. (30.5±4.3) g/L in the negative group. Of 31 patients in the positive group, seven had been treated with antibiotics longer than seven days vs. 34 of 319 patients in the negative group. In the positive group, four of 31 patients received treatment with more than two classes of antibiotics prior to admission in ICU, contrasted to 13 of 319 patients in the negative group. Furthermore, stepwise Logistic regression analysis for these four variables indicates that the duration of stay in hospital prior to ICU admission may be an independent risk factor. Conclusions MRSA colonization in ICU admission may be related to many factors. The duration of stay in hospital prior to ICU admission is an independent risk factor.

Genome Sequences of Sequence Type 45 (ST45) Persistent Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia Strain 300-169 and ST45 Resolving MRSA Bacteremia Strain 301-188

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (positive blood cultures after ≥7 days) represents a challenging subset of invasive MRSA infections. The comparison of genome sequences of persistent (300-169) and resolving (301-188) MRSA bacteremia isolates with similar genetic background (sequence type 45 [ST45]) will help us to better understand underlying mechanisms of persistent MRSA bacteremia.

Assessing the Rising Cases of Methicillin-resistant Staphylococcus Aureus: Hospital and Community-associated Cases

Methicillin-resistant Staphylococcus aureus (MRSA) has since become a major cause of illness and death in our healthcare setting. Risk factors for HA-MRSA include hospitalization, older age, invasive devices, and residence in long-term care facility, including exposure to antimicrobial agents. HA-MRSA isolates are often resistant to several antimicrobial drug classes in addition to beta-lactams. The CA-MRSA infections usually affects young, healthy persons and associated with sharing towels or athletic equipment, participating in contact sports, living in unsanitary and crowded areas, using illegal intravenous drugs. The number of invasive MRSA infections reported and the number of invasive infections caused by CA-MRSA is on the increase. The increase of CA-MRSA poses a unique public health threat. It is now clear that CA-MRSA no longer causes only SSTIs but now causes an increased proportion of invasive infections in a rural state. This should further inform and direct prospective researches and policies in developing specific tools to meet the needs.

Methicillin-ResistantStaphylococcus aureus

Despite the availability of effective preventative and therapeutic strategies, methicillin-resistant Staphylococcus aureus (MRSA) remains amajor cause of health care–associated and, more recently, community-acquired infections. Since the introduction of methicillin in 1959, epidemics due to different clones ofMRSAhave occurred in diverse geographic regions.1 The result has been the persistence of MRSA as an important pathogen worldwide. In the United States, themost recentMRSA epidemic has been due to the clone USA300. USA300 has been responsible for themajorityof communityandhealth care–associatedoutbreaks since the early 1990s.1 Until recently, thenumber of infections has continued to rise, especially in urban centers. While themajority of these have been skin and soft-tissue infections (SSTIs), a notable minority have been invasive and life-threatening.1 Two articles in this issueof JAMAInternalMedicineprovide additional insight into both the incidence and the risks associatedwithdevelopmentofMRSA infections.Danteset al2provide evidence that the overall incidence of invasiveMRSA infections nationally is declining. Casey et al3 perform an ecological investigation; they find that individuals livingnear high-density farming operations (ie, farms having an animal density of 2 animals or 1000-lbs live weight per acre) or near crop fieldsusingmanure exported from thehigh-density livestock farms are at increased risk of developingMRSA or other bacterial SSTIs. Both studies raise questions thatwarrant further investigation. Dantes et al2 useddata from theActiveBacterial Core Surveillance Program (ABCSP) to compare the national incidence rate of invasive MRSA infections for the years 2005 through 2011. The findings are of special importance because of the surveymethods that areusedand the size of the sample population (approximately 15 million). The ABCSP is an active surveillance program that is population based and includes a reviewofmedical records. It serves as amodel for this type of surveillance. The results show that the incidence of health care–associated community-onset and hospital-onset invasive MRSA infections have declined by 27.7% and 54.2%, respectively. The findings are consistent with several earlier reports including one from the same group. This impressive declinemaywellbeduetothe implementationof infectioncontrol efforts at thehospital level; however, it is alsopossible that the epidemic MRSA strains circulating in the health care setting have evolved, becoming less virulent. In contrast to the decline inhealth care–associatedMRSA, the estimated reduction in incidence of community-associated infections was a modest 5%. In addition to the evidence that the incidenceofMRSA infections is declining, the study highlights 2 important points. The first is the observation that there is an increased risk of recurrent infection among recentlyhospitalizedpatientswith healthcare–associatedcommunity-onset infections.Thesepatients had a 64% risk of infection at 3 months or less followingdischarge.Others have also reported ahigh risk of reinfection in discharged patients either infected or colonized with MRSA.4 Possible explanations for the patients’ increased risk include underlyingmedical comorbidities, persistent colonizationor recolonizationwithMRSA,orexposure tosimilar risks of MRSA infection following discharge. This subset of patients would appear to be candidates for studies directed at reducing their high risk of recurrent infection. The second finding is the limited change in the incidence of communityassociated infections. This is in marked contrast with the reduction in the incidence of health care–associated infections. As noted by the authors, the study highlights the need for a greater understanding of how these epidemic MRSA strains spread and initiate infection within the community. Related articles pages 1970 and 1980 Research Original Investigation National Burden of Invasive MRSA Infections