Multidrug and Mupirocin Resistance in Environmental Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Homes of People Diagnosed with Community-Onset MRSA Infection.

Patients with community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline (n = 104 isolates) and 51% (33/65) of homes 3 months later (n = 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.)IMPORTANCE MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis.

The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35 g/L) receiving teicoplanin 12 mg/kg 12-hourly intravenously for 48 h followed by 12 mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15-24) g/L. After 48 h, the median (IQR) free trough (fC(min)) and total trough (tC(min)) concentrations were 2.90 (2.67-3.47) mg/L and 15.54 (10.28-19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9-47.8) L/h and 7.0 (IQR 6.8-9.8) L/h, respectively (P<0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations (P=0.174), albumin concentration did (P<0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients.

Anatomical patterns of colonization of pets with staphylococcal species in homes of people with methicillin-resistant Staphylococcus aureus (MRSA) skin or soft tissue infection (SSTI).

Methicillin-resistant strains of Staphylococcus aureus (MRSA), Staphylococcus pseudintermedius (MRSP), and other pathogenic staphylococci can cause infections in companion animals and humans. Identification of colonized animals is fundamental to research and practice needs, but harmonized methods have not yet been established. To establish the optimal anatomic site for the recovery of methicillin-resistant coagulase positive staphylococci (CPS), survey data and swabs were collected from 196 pets (dogs, cats, reptiles, birds, fish and pocket pets) that lived in households with an MRSA-infected person. Using broth-enrichment culture and PCR for speciation, S. aureus was identified in 27 of 179 (15%) pets sampled at baseline and 19 of 125 (15%) pets sampled at a three-month follow-up home visit. S. pseudintermedius was isolated from 33 of 179 (18%) pets sampled at baseline and 21 of 125 (17%) of pets sampled at follow-up. The baseline MRSA and MRSP prevalence was 8% and 1% respectively from 145 mammalian pets. The follow-up MRSA and MRSP prevalence was 7% and <1% respectively from 95 mammalian pets. The mouth was the most sensitive single site sampled for isolation of S. aureus and S. pseudintermedius in mammals. In a subset of pets, from which all available isolates were identified, dual carriage of S. aureus and S. pseudintermedius was 22% at baseline and 11% at follow-up. These results identify the mouth as the most sensitive site to screen for pathogenic staphylococci and suggest that it should be included in sampling protocols.

Derivation and validation of clinical prediction rules for reduced vancomycin susceptibility in Staphylococcus aureus bacteraemia.

Reduced vancomycin susceptibility (RVS) may lead to poor clinical outcomes in Staphylococcus aureus bacteraemia. We conducted a cohort study of 392 patients with S. aureus bacteraemia within a university health system. The association between RVS, as defined by both Etest [vancomycin minimum inhibitory concentration (MIC) >1·0 µg/ml] and broth microdilution (vancomycin MIC ≥1·0 µg/ml), and patient and clinical variables were evaluated to create separate predictive models for RVS. In total, 134 (34·2%) and 73 (18·6%) patients had S. aureus isolates with RVS by Etest and broth microdilution, respectively. The final model for RVS by Etest included methicillin resistance [odds ratio (OR) 1·51, 95% confidence interval (CI) 0·97-2·34], non-white race (OR 0·67, 95% CI 0·42-1·07), healthcare-associated infection (OR 0·56, 95% CI 0·32-0·96), and receipt of any antimicrobial therapy ≤30 days prior to the culture date (OR 3·06, 95% CI 1·72-5·44). The final model for RVS by broth microdilution included methicillin resistance (OR 2·45, 95% CI 1·42-4·24), admission through the emergency department (OR 0·54, 95% CI 0·32-0·92), presence of an intravascular device (OR 2·24, 95% CI 1·30-3·86), and malignancy (OR 0·51, 95% CI 0·26-1·00). The availability of an easy and rapid clinical prediction rule for early identification of RVS can be used to help guide the timely and individualized management of these serious infections.

Risk of invasive pneumococcal disease varies by neighbourhood characteristics: implications for prevention policies.

This study investigates neighbourhood variation in rates of pneumococcal bacteraemia and community-level factors associated with neighbourhood heterogeneity in disease risk. We analysed data from 1416 adult and paediatric cases of pneumococcal bacteraemia collected during 2005-2008 from a population-based hospital surveillance network in metropolitan Philadelphia. Cases were geocoded using residential address to measure disease incidence by neighbourhood and identify potential neighbourhood-level risk factors. Overall incidence of pneumococcal bacteraemia was 36∙8 cases/100,000 population and varied significantly (0-67∙8 cases/100,000 population) in 281 neighbourhoods. Increased disease incidence was associated with higher population density [incidence rate ratio (IRR) 1∙10/10,000 people per mile², 95% confidence interval (CI) 1∙0-1∙19], higher percent black population (per 10% increase) (IRR 1∙07, 95% CI 1∙04-1∙09), population aged ≤5 years (IRR 3∙49, CI 1∙8-5∙18) and population aged ≥65 years (IRR 1∙19, CI 1∙00-1∙38). After adjusting for these characteristics, there was no significant difference in neighbourhood disease rates. This study demonstrates substantial small-area variation in pneumococcal bacteraemia risk that appears to be explained by neighbourhood sociodemographic characteristics. Identifying neighbourhoods with increased disease risk may provide valuable information to optimize implementation of prevention strategies.

Potential for pet animals to harbour methicillin-resistant Staphylococcus aureus when residing with human MRSA patients.

Colonization by methicillin-resistant Staphylococcus aureus (MRSA) may be persistent in people and is horizontally transmissible. The scientific literature suggests that domestic pets may also participate in cross-transmission of MRSA within households. The objectives of this study were to evaluate the prevalence of and risk factors for MRSA carriage by pets residing in households with an MRSA-infected person. From 66 households in which an MRSA-infected patient resided, we screened 47 dogs and 52 cats using a swab protocol. Isolates from pets and humans were genotyped using two techniques and compared for concordance. Human participants completed a 22-question survey of demographic and epidemiologic data relevant to staphylococcal transmission. Eleven of 99 pets (11.5%) representing 9 (13.6%) of households were MRSA-positive, but in only six of these households were the human and animal-source strains genetically concordant. Human infection by strain USA 100 was significantly associated with pet carriage [OR = 11.4 (95% CI 1.7, 76.9); P = 0.013]. Yet, for each day of delay in sampling the pet after the person's MRSA diagnosis, the odds of isolating any type of MRSA from the pet decreased by 13.9% [(95% CI 2.6, 23.8); P = 0.017)]. It may be concluded that pets can harbour pandemic strains of MRSA while residing in a household with an infected person. However, the source of MRSA to the pet cannot always be attributed to the human patient. Moreover, the rapid attrition of the odds of obtaining a positive culture from pets over time suggests that MRSA carriage may be fleeting.

Combination therapy with an aminoglycoside for Staphylococcus aureus endocarditis and/or persistent bacteremia is associated with a decreased rate of recurrent bacteremia: a cohort study.

PURPOSE: Although limited data exist on the efficacy and potential risk of synergistic aminoglycoside therapy for persistent Staphylococcus aureus bacteremia and endocarditis, aminoglycosides are frequently used in clinical practice. METHODS: As our study population, we included subjects fulfilling the modified Duke criteria for S. aureus endocarditis and/or having greater than 72 h of S. aureus bacteremia. Among these subjects, we compared patients who did and did not receive aminoglycoside therapy for their S. aureus bloodstream infection. These groups were compared for the primary outcome of recurrent bacteremia, as well as for the duration of bacteremia, mortality, complication rate, and incident renal failure. RESULTS: Eighty-seven subjects fulfilled the inclusion criteria. Of these, 49 received aminoglycoside therapy, whereas 38 did not. There were no significant differences in the baseline characteristics when comparing groups who did or did not receive aminoglycoside therapy. Four (8.2%) subjects treated with aminoglycoside therapy experienced recurrent bacteremia versus nine (23.7%) who did not receive aminoglycoside therapy [relative risk and 95% confidence interval [RR (95%CI)] = 0.51 (0.22-1.17), p = 0.04]. In multivariable analyses, aminoglycoside use remained significantly associated with a decrease in recurrent bacteremia [adjusted odds ratio (OR) (95%CI) = 0.26 (0.07-0.98), p = 0.046]. No significant differences were seen between groups treated with and without an aminoglycoside in terms of the 6-month all-cause mortality (51.0 vs. 42.1%, p = 0.41), complication rate (71.4 vs. 73.7%, p = 0.82), or incident renal failure (54.5 vs. 46.9%, p = 0.54). CONCLUSIONS: The use of combination therapy with an aminoglycoside in persistent S. aureus bacteremia and/or endocarditis may be associated with a lower rate of recurrent bacteremia without significant differences in the incident renal failure.

Risk factors for fluoroquinolone resistance in Enterococcus urinary tract infections in hospitalized patients.

Past studies exploring risk factors for fluoroquinolone (FQ) resistance in urinary tract infections (UTIs) focused only on UTIs caused by Gram-negative pathogens. The epidemiology of FQ resistance in enterococcal UTIs has not been studied. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System in order to identify risk factors for FQ resistance in enterococcal UTIs. Subjects with positive urine cultures for enterococci and meeting CDC criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant enterococcal UTI. Controls were subjects with FQ-susceptible enterococcal UTI and were frequency matched to cases by month of isolation. A total of 136 cases and 139 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors [adjusted OR (95% CI)] for FQ resistance included cardiovascular diseases [2·24 (1·05-4·79), P=0·037], hospitalization within the past 2 weeks [2·08 (1·05-4·11), P=0·035], hospitalization on a medicine service [2·15 (1·08-4·30), P<0·030], recent exposure to ß-lactamase inhibitors (BLIs) [14·98 (2·92-76·99), P<0·001], extended spectrum cephalosporins [9·82 (3·37-28·60), P<0·001], FQs [5·36 (2·20-13·05), P<0·001] and clindamycin [13·90 (1·21-10·49), P=0·035]. Use of BLIs, extended spectrum cephalosporins, FQs and clindamycin was associated with FQ resistance in enterococcal uropathogens. Efforts to curb FQ resistance should focus on optimizing use of these agents.

Risk factors for fluoroquinolone resistance in Gram-negative bacilli causing healthcare-acquired urinary tract infections.

The prevalence of urinary tract infections caused by fluoroquinolone-resistant Gram-negative bacilli (FQ-resistant GNB-UTIs) has been increasing. Previous studies that explored risk factors for FQ resistance have focused only on UTIs caused by Escherichia coli and/or failed to distinguish colonisation from infection. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System to identify risk factors for FQ resistance among healthcare-acquired GNB-UTIs. Subjects with positive urine cultures for GNB and who met Centers for Disease Control and Prevention criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant GNB-UTI and controls were subjects with FQ-susceptible GNB-UTI matched to cases by month of isolation and species of infecting organism. In total, 251 cases and 263 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors (adjusted odds ratio; 95% confidence interval) for FQ resistance included male sex (2.03; 1.21-3.39; P=0.007), African-American race (1.80; 1.10-2.94; P=0.020), chronic respiratory disease (2.58; 1.18-5.62; P=0.017), residence in a long term care facility (4.41; 1.79-10.88; P=0.001), hospitalisation within the past two weeks (2.19; 1.31-3.64; P=0.003), hospitalisation under a medical service (2.72; 1.63-4.54; P<0.001), recent FQ exposure (15.73; 6.15-40.26; P<0.001), recent cotrimoxazole exposure (2.49; 1.07-5.79; P=0.033), and recent metronidazole exposure (2.89; 1.48-5.65; P=0.002).

The impact of household transmission on duration of outpatient colonization with methicillin-resistant Staphylococcus aureus.

We identified eight consecutive patients who presented with a skin or soft tissue infection due to MRSA. Of seven household members of these cases, three were colonized with MRSA. The mean duration of MRSA colonization in index cases was 33 days (range 14-104), while mean duration of colonization in household cases was 54 days (range 12-95). There was a borderline significant association between having a concurrent colonized household member and a longer duration of colonization (mean 44 days vs. 26 days, P=0.08).

Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.

Pediatric Crohn's disease: risk factors for postoperative recurrence.

OBJECTIVE: Postoperative recurrence of Crohn's disease in adults has been extensively studied; however, the course of Crohn's disease after surgery in children has not been well defined. The aim of this study was to examine the postoperative course of pediatric Crohn's disease and the factors that may predict early postoperative recurrence. METHODS: We identified 100 resective surgeries in 79 children with Crohn's disease seen at the Children's Hospital of Philadelphia between 1978 and 1996. A retrospective, multivariable analysis of factors potentially influencing postoperative clinical recurrence was performed. Preoperative and postoperative height measurements were compared, and z scores were computed for height-for-age. Two-tailed t test was used for the analysis. RESULTS: Clinical recurrence rates were 17% at 1 yr, 38% at 3 yr, and 60% at 5 yr. Patients with colonic Crohn's disease had a significantly shorter postoperative recurrence-free interval (median 1.2 yr) than patients with ileocecal (median 4.4 yr) or diffuse disease (median 3.0 yr) (p = 0.01). On multivariable analysis, a high Pediatric Crohn's Disease Activity Index at the time of surgery (p = 0.01) and preoperative use of 6-mercaptopurine (6-MP) (p < 0.005) were also independently associated with higher postoperative recurrence rates. There was a significant improvement in z scores for height (p = 0.04) after surgery. CONCLUSIONS: In children undergoing resective surgery for Crohn's disease, high rates of postoperative Crohn's disease recurrence are associated with severe disease at the time of surgery, colonic Crohn's disease, and the preoperative use of 6-MP. Patients who require preoperative use of 6-MP are likely to suffer from a more aggressive disease and would benefit from postoperative 6-MP prophylaxis. Height growth was improved after intestinal resection for Crohn's disease.

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes.

The prevalence of antibiotic resistance among extended-spectrum beta-lactamase (ESBL)--producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03--1.18; P=.006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P<.001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P=.01 and P<.001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.

Enterococcal bacteremia: risk factors for vancomycin resistance and predictors of mortality.

OBJECTIVE: To identify risk factors for vancomycin resistance and mortality in enterococcal bacteremia. DESIGN: Historical cohort study. SETTING: A large academic medical center with a high prevalence of vancomycin-resistant enterococci (VRE). PATIENTS: Two hundred sixty patients with enterococcal bacteremia, of whom 72 (28%) had VRE. RESULTS: Independent risk factors for infection with VRE were the mean number of antibiotic days (P<.001), renal insufficiency (P<.001), mean days of vancomycin use (P = .005), and neutropenia (P = .013). A trend toward a significant association between metronidazole use and VRE also was noted (P = .068). Mortality was attributable to the bacteremia in 96 patients (37%). Severity of illness (P<.001) and age (P = .020) were independent risk factors for mortality. Vancomycin resistance was not, however, an independent predictor of mortality. CONCLUSION: These results suggest that restrictions on antibiotic use, particularly in patients with renal insufficiency and neutropenia, may help to combat the rising incidence of VRE. Although patients with VRE bacteremia demonstrated higher mortality rates than patients with infection due to susceptible isolates, vancomycin resistance was not an independent predictor of mortality in these patients and likely serves more as a marker of underlying severity of illness.

The role of chloramphenicol in the treatment of bloodstream infection due to vancomycin-resistant Enterococcus.

The incidence of bacteremia due to vancomycin-resistant Enterococcus (VRE) has increased markedly in recent years. We investigated the role of chloramphenicol in its treatment. All cases of VRE bacteremia occurring at our facility during a 45-month period were analyzed. The response to chloramphenicol, its effect on mortality, and the incidence of adverse effects were assessed. Fifty-one patients (65.4%) received chloramphenicol. Among patients in whom a response could be assessed, 22 (61.1%) of 36 demonstrated a clinical response, while 34 (79.1%) of 43 showed a microbiological response. Forty-two patients (53.8%) died as a result of the bacteremia. Although the mortality rate was lower for patients treated with chloramphenicol, the difference was not significant (odds ratio = 0.72; 95% confidence interval, 0.28-1.85; P = .49), nor was there an association between earlier initiation of therapy and reduced mortality (P = .45). In cases with central line-related bacteremia, there was no difference in mortality among patients treated with chloramphenicol, line removal, or both (P = .36). Although 16 patients (31.4%) had adverse effects, none could be definitely attributed to chloramphenicol. Although chloramphenicol was well-tolerated, no significant effect of its use on mortality could be demonstrated.