Matthew H. Samore

Prolonged Antibiotic Prophylaxis After Cardiovascular Surgery and Its Effect on Surgical Site Infections and Antimicrobial Resistance

BACKGROUND Despite evidence supporting short antibiotic prophylaxis (ABP), it is still common practice to continue ABP for more than 48 hours after coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS To compare the effect of short (<48 hours) versus prolonged (>48 hours) ABP on surgical site infections (SSIs) and acquired antimicrobial resistance, we conducted an observational 4-year cohort study at a tertiary-care center. An experienced infection control nurse performed prospective surveillance of 2641 patients undergoing CABG surgery. The main exposure was the duration of ABP, and main outcomes were the adjusted rate of SSI and the isolation of cephalosporin-resistant enterobacteriaceae and vancomycin-resistant enterococci (acquired antibiotic resistance). Adjustment for confounding was performed by multivariable modeling. A total of 231 SSIs (8.7%) occurred after a median of 16 days, including 93 chest-wound infections (3.5%) and 13 deep-organ-space infections (0. 5%). After 1502 procedures using short ABP, 131 SSIs were recorded, compared with 100 SSIs after 1139 operations with prolonged ABP (crude OR, 1.0; CI, 0.8 to 1.3). After adjustment for possible confounding, prolonged ABP was not associated with a decreased risk of SSI (adjusted OR, 1.2; CI, 0.8 to 1.6) and was correlated with an increased risk of acquired antibiotic resistance (adjusted OR, 1.6; CI, 1.1 to 2.6). CONCLUSIONS Our findings confirm that continuing ABP beyond 48 hours after CABG surgery is still widespread; however, this practice is ineffective in reducing SSI, increases antimicrobial resistance, and should therefore be avoided.

Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea

BACKGROUND Little is known about whether patients who develop Clostridium-difficile-associated diarrhoea (CDAD) are culture-positive or culture-negative before illness. The most important risk factor is antibiotic exposure. We aimed to find out whether patients identified as primary symptom-free C difficile carriers are at higher risk of developing CDAD than patients who are culture-negative. METHOD We reviewed four longitudinal studies in which 810 patients admitted to hospital were followed up by prospective rectal-swab culture. At least two consecutive weekly cultures were obtained. We calculated the difference in risk of CDAD between colonised and non-colonised patients in each study and combined the results of the four studies in a random-effects model. FINDINGS Of 618 non-colonised patients (mean follow-up 1.7 weeks [SD 1.3]), 22 (3.6%) developed CDAD, whereas only two (1.0%) of 192 primary symptom-free carriers (1.5 [1.5]) developed CDAD (pooled risk difference -2.3% [95% CI 0.3-4.3], p=0.021). Of patients who received antibiotics, the risk difference was increased: 22 (4.5%) of 491 non-colonised patients compared with two (1.1%) of 176 colonised patients developed CDAD (-3.2% [0.4-6.0], p=0.024). Of the primary symptom-free C difficile carriers, 95 were colonised with toxigenic strains, 76 with non-toxigenic strains, 12 with both toxigenic and non-toxigenic strains (non-concurrently), and nine with strains of undetermined toxigenicity. Nine of the 12 toxogenic strains of C difficile isolates that cause CDAD were also recovered from stools of symptom-free patients. INTERPRETATION Primary symptomless C difficile colonisation is associated with a decreased risk of CDAD. Although the mechanism is unknown, risk reduction is found in colonisation with non-toxigenic and toxigenic strains.

Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea

PURPOSE A prospective clinical and molecular epidemiologic study was conducted to define the frequency of nosocomial Clostridium difficile patient-to-patient transmission in an urban tertiary referral hospital. PATIENTS AND METHODS Over a 6-month period, environmental cultures for C difficile were obtained from patients with new positive stool cytotoxin assay (index cases); stool samples were obtained from selected patient contacts (the roommate, occupants of adjacent rooms, and the patient occupying the index room after discharge of the index case); and hand cultures were obtained from personnel contacts. C difficile isolates were analyzed by pulse-field gel electrophoresis (PFGE) or, for isolates that were nontypeable by PFGE, by restriction enzyme analysis. RESULTS During the study period, we identified 98 index cases of C difficile toxin-associated diarrhea, including focal outbreaks on two wards totaling 26 cases within a 2-month interval. Environmental contamination was detected at > or = 1 sites in 58% of rooms and often involved wide dispersed areas. Among 99 prospectively identified patient contacts, C difficile was cultured from the stool of 31 (31%), including 12 with diarrhea and 19 who were asymptomatic. C difficile was cultured from the hands of 10 (14%) of 73 personnel. Molecular analysis resolved 31 typing profiles among the index isolates; the most common profile (designated strain D1) was represented by 30 isolates. Among the isolates from patient contacts, 5 of 12 from symptomatic contacts matched the corresponding index isolate, and only 1 of 19 from asymptomatically colonized contacts matched. Transmission to personnel or patient contacts of the strain cultured from the corresponding index case was correlated strongly with the intensity of environmental contamination. Strain D1 was frequently represented among isolates associated with heavy environmental contamination, with personnel carriage, and with development of symptomatic illness among prospectively identified contacts. CONCLUSIONS Intense environmental contamination and transmission to close personnel and patient contacts represented coordinated properties of an individual epidemic strain. For most epidemiologically linked contacts, positive cultures for C difficile did not result from transmission from the presumed index case.

Methodological Principles of Case-Control Studies That Analyzed Risk Factors for Antibiotic Resistance: A Systematic Review

Case-control studies that analyze the risk factors for antibiotic-resistant organisms have varied epidemiological methodologies, which may lead to biased estimates of antibiotic risk factors. A systematic review of case-control studies that analyzed risk factors for antibiotic-resistant organisms addressed 3 methodological principles: method of control group selection, adjustment for time at risk, and adjustment for comorbid illness. A total of 406 abstracts were reviewed. Thirty-seven studies met the inclusion and exclusion criteria and were reviewed and evaluated for the 3 methodological principles. Thirteen (35%) of 37 studies chose the preferred control group. Eleven adjusted for time at risk. Twenty-seven adjusted for comorbid illness. Future studies need to consider more closely the optimization of control group selection, adjusting for confounding caused by time at risk, and adjusting for confounding caused by comorbid illness.

Epidemiology and Clinical Outcomes of Patients with Multiresistant Pseudomonas aeruginosa

We conducted a case-series study of multiresistant Pseudomonas aeruginosa in patients who did not have cystic fibrosis. Patient characteristics, antibiotic exposures, time course of emergence of resistance, and clinical outcomes were examined. Twenty-two patients were identified from whom P. aeruginosa resistant to ciprofloxacin, imipenem, ceftazidime, and piperacillin was isolated. Nineteen (86%) had clinical infection. Patients received prolonged courses of antipseudomonal antibiotics before isolation of multiresistant P. aeruginosa. Nine of 11 patients with soft-tissue infection exhibited resolution of clinical infection but usually required surgical removal of infected tissue with or without revascularization. Overall, three patients died. In two instances in which multiple isolates with different susceptibility profiles from the same patient were available, pulsed-field gel electrophoresis profiles of serial isolates were indistinguishable or closely related. This study illustrates that multiresistant P. aeruginosa emerges in a stepwise manner after exposure to antipseudomonal antibiotics and results in adverse outcomes.

Imipenem-Resistant Pseudomonas aeruginosa: Risk Factors and Antibiotic Susceptibility Patterns

Potential risk factors for the detection of imipenem-resistant Pseudomonas aeruginosa in hospitalized patients were assessed by a case-control study. Forty patients whose first P. aeruginosa isolate was resistant or intermediate to imipenem were more likely than 387 controls to have received imipenem (odds ratio [OR] = 16.9; P < .0001) and to have undergone organ transplantation (OR = 3.9; P = .008). No significant difference was found for treatments with other antibiotics, other underlying diseases, demographic characteristics, different exposures to the hospital environment, or the culture site. Imipenem-resistant P. aeruginosa isolates were more likely to be resistant to other common antipseudomonal agents than were imipenem-susceptible isolates. It is concluded that treatment with imipenem, but not with other beta-lactam drugs, is a major risk factor for the detection of imipenem-resistant P. aeruginosa in hospitalized patients, that these organisms may relatively often be resistant to other antipseudomonal agents, and that the hospital environment per se might not play a major role in their epidemiology.

Antecedent Treatment with Different Antibiotic Agents as a Risk Factor for Vancomycin-Resistant Enterococcus

We conducted a matched case-control study to compare the effect of antecedent treatment with various antibiotics on subsequent isolation of vancomycin-resistant Enterococcus (VRE); 880 in-patients; 233 VRE cases, and 647 matched controls were included. After being matched for hospital location, calendar time, and duration of hospitalization, the following variables predicted VRE positivity: main admitting diagnosis; a coexisting condition (e.g., diabetes mellitus, organ transplant, or hepatobiliary disease); and infection or colonization with methicillin-resistant Staphylococcus aureus or Clostridium difficile within the past year (independent of vancomycin treatment). After controlling for these variables, we examined the effect of various antibiotics. Intravenous treatment with third-generation cephalosporins, metronidazole, and fluoroquinolones was positively associated with VRE. In our institution, when we adjusted the data for temporo-spatial factors, patient characteristics, and hospital events, treatment with third-generation cephalosporins, metronidazole, and fluoroquinolones was identified as a risk factor for VRE. Vancomycin was not a risk factor for isolation of VRE.

Carriage of Methicillin-Resistant Staphylococcus Aureus at Hospital Admission

OBJECTIVES To measure the prevalence of, and to establish predictors for, the nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission. To evaluate mannitol-salt agar with oxacillin for the simultaneous detection and identification of MRSA from nasal swabs. DESIGN Three-month prospective case-control survey, with data collected from interviews and computerized databases. The criterion standard for MRSA detection was culture on Mueller-Hinton agar with oxacillin 6 microg/mL (National Committee for Clinical Laboratory Standards method). SETTING 320-bed tertiary-care hospital. PATIENTS 387 patients screened within 24 hours after admission, including 10 MRSA carriers (cases), 291 patients with no S aureus, and 86 patients with methicillin-susceptible S aureus. RESULTS The prevalence of MRSA nasal carriage was 2.6%, whereas the prevalence of carriage was 3.1% when both nasal and wound cultures were performed. The significant predictors of carriage were a prior detection of MRSA, open wounds, diabetes mellitus, treatments by injection, prior nursing home stays, visits at home by a nurse, and prior antibiotic treatments. Cases had stayed for longer periods in hospitals and had received longer antibiotic treatments within a year. Eighty patients (including the 10 cases) had diabetes, had been exposed to healthcare facilities within a year, and had antibiotics within 6 months. The sensitivity and negative predictive value of nasal swabs on mannitol-salt agar with oxacillin were 60% and 71%, respectively. CONCLUSION MRSA carriage on admission to the hospital may be an increasing and underestimated problem. Further studies are needed to develop and validate a sensitive and specific prediction rule.

Risk Factors for Nosocomial Candiduria Due to Candida glabrata and Candida albicans

The aims of this study were to analyze the clinical characteristics and risk factors associated with catheter-associated candiduria due to Candida glabrata and due to Candida albicans and to compare patients with candiduria due to C. glabrata or C. albicans (cases) with controls. Controls were a randomly chosen sample of inpatients with Foley catheters for whom urine cultures were negative for Candida species. Univariate and multivariate analyses were performed. There were 40 cases of C. glabrata candiduria and 289 cases of C. albicans candiduria. Factors strongly associated with both C. albicans candiduria and C. glabrata candiduria were female gender (P <. 05) and being in the intensive care unit (P <. 01). Fluconazole use (adjusted odds ratio, 4.37; P <. 01) and quinolone use (adjusted odds ratio, 3.16; P <. 01) were specifically associated with C. glabrata candiduria but not with C. albicans candiduria. In conclusion, patients receiving fluconazole treatment are at risk of developing C. glabrata candiduria.

Objective surveillance definitions for ventilator-associated pneumonia.

Objectives:The subjectivity and complexity of surveillance definitions for ventilator-associated pneumonia preclude meaningful internal or external benchmarking and therefore hamper quality improvement initiatives for ventilated patients. We explored the feasibility of creating objective surveillance definitions for ventilator-associated pneumonia. Design:We identified clinical signs suitable for inclusion in objective definitions, proposed candidate definitions incorporating these objective signs, and then applied these definitions to retrospective clinical data to measure their frequencies and associations with adverse outcomes using multivariate regression models for cases and matched controls. Setting:Medical and surgical intensive care units in eight U.S. hospitals (four tertiary centers, three community hospitals, and one Veterans Affairs institution). Patients:Eight thousand seven hundred thirty-five consecutive episodes of mechanical ventilation for adult patients. Interventions:We evaluated 32 different candidate definitions composed of different combinations of the following signs: three thresholds for respiratory deterioration defined by sustained increases in daily minimum positive end-expiratory pressure or FIO2 after either 2 or 3 days of stable or decreasing ventilator settings, abnormal temperature, abnormal white blood cell count, purulent pulmonary secretions defined by neutrophils on Gram stain, and positive cultures for pathogenic organisms. Measurements and Main Results:Ventilator-associated pneumonia incidence, attributable ventilator days, hospital days, and hospital mortality. All candidate definitions were significantly associated with increased ventilator days and hospital days, but only definitions requiring objective evidence of respiratory deterioration were significantly associated with increased hospital mortality. Significant odds ratios for hospital mortality ranged from 1.9 (95% confidence interval 1.2–2.9) to 6.1 (95% confidence interval 2.2–17). Requiring additional clinical signs beyond respiratory deterioration alone decreased event rates, had little impact on attributable lengths of stay, and diminished sensitivity and positive predictive values for hospital mortality. Conclusions:Objective surveillance definitions that include quantitative evidence of respiratory deterioration after a period of stability strongly predict increased length of stay and hospital mortality. These definitions merit further evaluation of their utility for hospital quality and safety improvement programs.