Postoperative outcomes after receipt of ertapenem antimicrobial prophylaxis for colon surgery: a multicenter retrospective cohort study.

OBJECTIVE: To evaluate postoperative outcomes among patients undergoing colon surgery who receive perioperative prophylaxis with ertapenem compared to other antibiotic regimens. DESIGN AND SETTING: Multicenter retrospective cohort study among adults undergoing colon surgery in seven hospitals across three health systems from 1/1/2010 to 9/1/2015. METHODS: Generalized linear mixed logistic regression models were applied to assess differential odds of select outcomes among patients who received perioperative prophylaxis with ertapenem compared to other regimens. Postoperative outcomes of interest included surgical site infection (SSI), Clostridioides difficile infection (CDI) and clinical culture positivity for carbapenem-resistant Enterobacteraciae (CRE). Inverse probability weights were applied to account for differing covariate distributions across ertapenem and non-ertapenem groups. RESULTS: A total of 2,109 patients were included for analysis. The odds of postoperative SSI was 1.56 times higher among individuals who received ertapenem than among those receiving other perioperative antimicrobial prophylaxis regimens in our cohort (46 [3.5%] vs 20 [2.5%]; IPW-weighted OR 1.56, [95% CI, 1.08-2.26], P = .02). No statistically significant differences in odds of postoperative CDI (24 [1.8%] vs 16 [2.0%]; IPW-weighted OR 1.07 [95% CI, .68-1.68], P = .78) were observed between patients who received ertapenem prophylaxis compared to other regimens. Clinical CRE culture positivity was rare in both groups (.2%-.5%) and did not differ statistically. CONCLUSIONS: Ertapenem use for perioperative prophylaxis was associated with increased odds of SSI among patients undergoing colon surgery in our study population, though no differences in CDI or clinical CRE culture positivity were identified. Further study and replication of these findings are needed.

Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study.

Background: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). Methods: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences. Findings: Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages. Interpretation: The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. Funding: This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin. METHODS: We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was -12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT03341273. FINDINGS: Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference -6%, 95% CI -15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference -7% [95% CI -15 to 0]; p=0·066). INTERPRETATION: Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration. FUNDING: National Institute of Allergy and Infectious Diseases, bioMérieux.

Stopping Hospital Infections With Environmental Services (SHINE): A Cluster-randomized Trial of Intensive Monitoring Methods for Terminal Room Cleaning on Rates of Multidrug-resistant Organisms in the Intensive Care Unit.

BACKGROUND: Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of 2 methods for monitoring of terminal cleaning effectiveness. METHODS: Six intensive care units (ICUs) at 3 medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in 5 rooms weekly, after terminal cleaning, with adenosine triphosphate (ATP) monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, whereas secondary analysis included the baseline. RESULTS: The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared with the UV/F period (incidence rate ratio [IRR] 0.876; 95% confidence interval [CI], 0.807-0.951; P = .002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924; 95% CI, 0.855-0.998; P = .04), and MDR-GNB infection or colonization (IRR 0.856; 95% CI, 0.825-0.887; P < .001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turnaround time increased by a median of 1 minute with the ATP intervention and 4.5 minutes with UV/F compared with baseline. CONCLUSIONS: Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization.

Implementation of a Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study.

BACKGROUND: Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection. METHODS: We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our pediatric intensive care unit (PICU). The algorithm suggested that PICU clinicians stop antibiotics if (1) C-reactive protein <4 mg/dL and procalcitonin <1 ng/mL at SIRS onset and (2) no evidence of bacterial infection by exam/testing by 48 hours. We evaluated excess broad-spectrum antibiotic use, defined as administration on days 3-9 after SIRS onset in uninfected children. Incidence rate ratios (IRRs) compared unadjusted excess length of therapy (LOT) in the 34 months before (Period 1) and 12 months after (Period 2) implementation of this algorithm, stratified by biomarker values. Segmented linear regression evaluated excess LOT among all uninfected episodes over time and between the periods. RESULTS: We identified 457 eligible SIRS episodes without bacterial infection, 333 in Period 1 and 124 in Period 2. When both biomarkers were below the algorithm's cut-points (n = 48 Period 1, n = 31 Period 2), unadjusted excess LOT was lower in Period 2 (IRR, 0.53; 95% confidence interval, 0.30-0.93). Among all 457 uninfected episodes, there were no significant differences in LOT (coefficient 0.9, P = .99) between the periods on segmented regression. CONCLUSIONS: Implementation of a biomarker-based algorithm did not decrease overall antibiotic exposure among all uninfected patients in our PICU, although exposures were reduced in the subset of SIRS episodes where biomarkers were low.

Risk factors for multidrug-resistant organisms among deceased organ donors.

Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.

A Clinical Prediction Tool for Extended-Spectrum Cephalosporin Resistance in Community-Onset Enterobacterales Urinary Tract Infection.

BACKGROUND: Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB). METHODS: A case-control study was performed. The source population included patients presenting to an emergency department (ED) or outpatient practice with an EB UTI between 2010 and 2013. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched to cases 1:1 on study year. Multivariable conditional logistic regression was performed to develop the predictive model by maximizing the area under the receiver-operating curve (AUC). Internal validation was performed via bootstrapping. RESULTS: A total of 302 patients with a community-onset EB UTI were included, with 151 cases and 151 controls. After multivariable analysis, we found that presentation with an ESC-R EB community-onset UTI could be predicted by the following: (1) a history of malignancy; (2) a history of diabetes; (3) recent skilled nursing facility or hospital stay; (4) recent trimethoprim-sulfamethoxazole exposure; and (5) pyelonephritis at the time of presentation (AUC 0.73, Hosmer-Lemeshow goodness-of-fit P value 0.23). With this model, each covariate confers a single point, and a patient with ≥ 2 points is considered high risk for ESC-R EB (sensitivity 80%, specificity 54%). The adjusted AUC after bootstrapping was 0.71. CONCLUSIONS: Community-onset ESC-R EB UTI can be predicted using the proposed scoring system, which can help guide diagnostic and therapeutic interventions.

Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis.

OBJECTIVES: Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. DESIGN: Cohort study. SETTING: The medical and surgical ICUs at an academic medical center. SUBJECTS: We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. INTERVENTIONS: We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. MEASUREMENTS AND MAIN RESULTS: Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). CONCLUSIONS: Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.

Comparison of Culture-Based Methods for Identification of Colonization with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus in the Context of Cocolonization.

Two screening methods to detect staphylococcal colonization in humans were compared. Direct plating to CHROMagar (BD Diagnostics) was compared to a broth preenrichment followed by plating to Baird-Parker agar. The broth-enrichment method was comparable to CHROMagar for methicillin-resistant Staphylococcus aureas (MRSA) detection, but the enrichment method was optimum for recovery of coagulase-positive Staphylococcus spp.

Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa.

OBJECTIVE: The major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations. DESIGN: Case-case-control study SETTING: Two adult academic acute-care hospitals PATIENTS: Case 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations. Controls were a random sample of all inpatients with a stay of 3 days or more. METHODS: Each case group was compared to the control group in separate multivariate models on the basis of demographics and inpatient antibiotic exposure, and risk factors were qualitatively compared. RESULTS: Of 298 PSA isolates, 172 (57.7%) had at least 1 mutation. Exposure to vancomycin and other agents with extended Gram-positive activity was a risk factor for both cases (case 1 odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04-1.13; OR, 1.14; 95% CI, 1.03-1.26; case 2 OR, 1.09; 95% CI, 1.03-1.14; OR, 1.13; 95% CI, 1.01-1.25, respectively). CONCLUSIONS: Exposure to agents with extended Gram-positive activity is a risk factor for isolation of PSA overall but not for gyrA/parC mutations. FQ exposure is not associated with isolation of PSA with mutations.

Impact of a new practice guideline on antibiotic use with pediatric tonsillectomy.

IMPORTANCE: More than 500,000 children undergo tonsillectomy each year in the United States. Although prior studies suggest that most patients received perioperative antibiotics, practice varies across centers. In 2011, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) published a practice guideline recommending against perioperative antibiotic use for pediatric tonsillectomy. The impact of this recommendation has not been thoroughly examined. OBJECTIVE: To determine the impact of the AAO-HNS guideline on the use of perioperative antibiotics and patient outcomes for pediatric tonsillectomy. DESIGN, SETTING, AND PARTICIPANTS: This was a quasi-experimental study including 9265 children who underwent routine tonsillectomy from January 2009 through August 2012 within a large pediatric health care network containing hospital-based and ambulatory surgical facilities. Data were collected from a shared electronic health record and validated through manual medical record review. We used an interrupted time series analysis with segmented logistic regression and a nonequivalent dependent variable (tympanoplasty) to assess acute changes and differences in trends over time relative to guideline publication. INTERVENTIONS: Publication of the AAO-HNS clinical practice guideline. MAIN OUTCOMES AND MEASURES: The primary outcome was antibiotic administration on the day of surgery. Secondary outcomes included otolaryngology clinic encounters, emergency department encounters, hospital admissions, and surgical procedures for bleeding in the 30 days following tonsillectomy. RESULTS: Of 9265 tonsillectomies during the study period, 5359 met inclusion criteria. Immediately after guideline publication, perioperative antibiotic use dropped by 86.5% (P < .001) and was sustained throughout the postintervention period. Rates of otolaryngology clinic encounters, emergency department encounters, and hospital admissions did not change significantly over time. There was a small but statistically significant increase in surgical procedures for bleeding following the intervention from 1.35% (95% CI, 0.57%-2.14%) to 3.48% (95% CI, 1.85%-5.10%). CONCLUSIONS AND RELEVANCE: AAO-HNS guideline publication decreased perioperative antibiotic use for pediatric tonsillectomy across a large pediatric health care network. Although there were no changes in otolaryngology clinic visits, emergency department visits, or admissions, we found a small but significant increase in surgery for bleeding following guideline publication. Additional studies are necessary to verify this unexpected association.

Coagulase-negative Staphylococcus culture in chronic rhinosinusitis.

BACKGROUND: Coagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity. METHODS: Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture. RESULTS: A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034). CONCLUSION: Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates.

Quality of life improvement from sinus surgery in chronic rhinosinusitis patients with asthma and nasal polyps.

BACKGROUND: It is unclear whether chronic rhinosinusitis (CRS) patients with both nasal polyps and asthma have different quality of life (QOL) improvement after functional endoscopic sinus surgery (FESS). We aimed to determine whether CRS patients with asthma and nasal polyps had a greater QOL improvement after FESS compared to patients without asthma or polyps. METHODS: This retrospective analysis included adult CRS patients who underwent FESS between 2007 and 2011. QOL was measured using the 22-item Sino-Nasal Outcome Test (SNOT-22). Variables collected included baseline demographics, clinical factors, SNOT-22 scores before FESS, and 1 month, 3 months, and 6 months post-FESS. Groups tested were asthma alone, polyps alone, asthma and polyps, and no asthma or polyps. Linear mixed-effects regression model was performed to calculate ß-coefficients, which represent the adjusted mean QOL differences. RESULTS: Among the 376 patients included, 40.16% had both asthma and polyps (n = 151), 14.36% had asthma alone (n = 54), 19.45% had polyps alone (n = 75), and 25.53% had no asthma or polyps (n = 96). After adjusting for all factors, there were significantly more QOL improvements in patients with both asthma and nasal polyps from baseline to 1-month (ß-coefficient = -10.05; 95% CI, -15.86 to -4.23; p = 0.001) and 3-month follow-up (ß-coefficient = -8.27; 95% CI, -14.98 to -1.56; p = 0.016), and patients with asthma alone from baseline to 6-month follow-up (ß-coefficient = -8.78; 95% CI, -17.45 to -0.11; p = 0.047), when compared to patients without asthma or nasal polyps. CONCLUSION: CRS patients with both asthma and nasal polyps or asthma alone experience a larger QOL benefit from FESS immediately after FESS compared to CRS patients without asthma or polyps.

The effect of diabetes mellitus on chronic rhinosinusitis and sinus surgery outcome.

BACKGROUND: Patients with diabetes mellitus (DM) are known to be prone to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS). METHODS: We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from October 1, 2007 to December 31, 2011. Patient demographics, comorbidities, medication use, and Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-month, 3-month, and 6-month postoperative QOL was measured by scores on the 22-item Sinonasal Outcome Test (SNOT-22). A mixed effects model was performed for analysis. RESULTS: Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% vs 7.56%; p = 0.004) and Gram-negative rods (26.32% vs 8.96%; p = 0.013), but there was no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean = 11.14, 95% CI (0.14, 22.15), p = 0.047) after adjusting for all the other risk factors for CRS. CONCLUSION: DM patients may be prone to Gram-negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM.

Culture-inappropriate antibiotic therapy decreases quality of life improvement after sinus surgery.

BACKGROUND: Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS). METHODS: This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed. RESULTS: Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences. CONCLUSION: Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome.

The effect of a hospital-wide urine culture screening intervention on the incidence of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella species.

OBJECTIVE: Optimal strategies for limiting the transmission of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella spp (ESBL-EK) in the hospital setting remain unclear. The objective of this study was to evaluate the impact of a urine culture screening strategy on the incidence of ESBL-EK. DESIGN: Prospective quasi-experimental study. SETTING: Two intervention hospitals and one control hospital within a university health system from 2005 to 2009. PATIENTS AND INTERVENTION: All clinical urine cultures with E. coli or Klebsiella spp were screened for ESBL-EK. Patients determined to be colonized or infected with ESBL-EK were placed in a private room with contact precautions. The primary outcome of interest was nosocomial ESBL-EK incidence in nonurinary clinical cultures (cases occurring more than 48 hours after admission). Changes in monthly ESBL-EK incidence rates were evaluated with mixed-effects Poisson regression models, with adjustment for institution-level characteristics (eg, total admissions). RESULTS: The overall incidence of ESBL-EK increased from 1.42/10,000 patient-days to 2.16/10,000 patient-days during the study period. The incidence of community-acquired ESBL-EK increased nearly 3-fold, from 0.33/10,000 patient-days to 0.92/10,000 patient-days (P < .001). On multivariable analysis, the intervention was not significantly associated with a reduction in nosocomial ESBL-EK incidence (incidence rate ratio, 1.38 [95% confidence interval, 0.83-2.31]; P - .21). CONCLUSIONS: Universal screening of clinical urine cultures for ESBL-EK did not result in a reduction in nosocomial ESBL-EK incidence rates, most likely because of increases in importation of ESBL-EK cases from the community. Further studies are needed on elucidating optimal infection control interventions to limit spread of ESBL-producing organisms in the hospital setting.

Impact of antibiotic use during hospitalization on the development of gastrointestinal colonization with Escherichia coli with reduced fluoroquinolone susceptibility.

OBJECTIVE: Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization. DESIGN: A prospective cohort study was conducted from 2002 to 2004 within a university health system. METHODS: Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates. RESULTS: Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1-1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21-0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10-1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00-1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization. CONCLUSIONS: The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.

The effect of staphylococcal cassette chromosome mec (SCCmec) type on clinical outcomes in methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVES: The impact of staphylococcal cassette chromosome mec (SCCmec) type on mortality in methicillin-resistant Staphylococcus aureus (MRSA) infections remains unclear. The objective of this study was to determine the association between SCCmec type and mortality in MRSA bacteremia. METHODS: A cohort study of patients who were hospitalized with MRSA bacteremia was conducted within a university health system. A multivariable logistic regression model was developed to evaluate the association of SCCmec type with 30-day in-hospital mortality. RESULTS: Thirty-four of a total of 184 patients with MRSA bacteremia died, resulting in a mortality rate of 18.5%. Adjusted risk factors for 30-day mortality included APRDRG Risk of Mortality score (odds ratio [OR], 5.33; 95% confidence interval [CI], 2.28-12.4; P<0.001), white blood cell count (OR, 1.09; 95% CI, 1.03-1.15; P=0.002), and malignancy (OR, 3.25; 95% CI, 1.17-9.02; P=0.02). On multivariable analyses, SCCmec II was not significantly associated with mortality in patients with MRSA bacteremia (OR, 1.85; 95% CI, 0.69-4.92; P=0.22). CONCLUSIONS: Mortality in MRSA bacteremia was independent of SCCmec type. SCCmec type II is most likely a marker for disease severity rather than a direct mediator of mortality. Further research is needed to elucidate the factors associated with poor clinical outcomes in MRSA infections.

Impact of antimicrobial stewardship programme changes on unnecessary double anaerobic coverage therapy.

BACKGROUND: Concern has been raised over the practice of unnecessary double anaerobic coverage therapy (DACT) in the hospital setting. However, the incidence of and risk factors for unnecessary DACT are not well studied. On 8 September 2008, the antimicrobial stewardship programme (ASP) at our institution was modified such that several antibiotics, including ampicillin/sulbactam and metronidazole, no longer required pre-approval. We anticipated that this change would increase both unnecessary DACT and target antibiotic consumption. METHODS: A nested case-control study was conducted to determine the cumulative incidence of and risk factors for unnecessary DACT. Cases were subjects who received unnecessary DACT while controls were subjects who did not receive DACT or who received necessary DACT. Segmented regression analysis was subsequently performed to evaluate the impact of ASP changes on unnecessary DACT and consumption of target antibiotics. RESULTS: From October 2007 to September 2009, the cumulative incidence of unnecessary DACT was 2.3% [95% confidence interval (CI) 1.7-3.1]. Independent risk factors for unnecessary DACT [adjusted odds ratio (95% CI); P value] included hospitalization on a surgical ward [3.51 (1.03-12.02); P = 0.002], hospitalization on an obstetrics and gynaecology ward [9.07 (2.54-32.40); P = 0.002] and underlying metastatic malignancy [3.18 (1.38-7.09); P = 0.006]. The ASP change was associated with an increase in ampicillin/sulbactam and metronidazole consumption. However, there was no significant impact on unnecessary DACT prescribing. CONCLUSIONS: Although uncommon, unnecessary DACT is more prevalent in specific services. Future qualitative studies focusing on these specific subgroups would be useful in elucidating this problem more clearly. The ASP changes were not associated with increases in unnecessary DACT.

The use of antimicrobial agents after diagnosis of viral respiratory tract infections in hospitalized adults: antibiotics or anxiolytics?

OBJECTIVE: Because extensive antibiotic use by inpatients has been associated with the development of multidrug-resistant organisms, we aimed to determine which variables were associated with the use of antibiotics after viral respiratory tract infection diagnosis among adult patients admitted to the hospital with respiratory symptoms. METHODS: A retrospective cohort study was conducted at 2 affiliated urban hospitals in Pennsylvania. We identified all adult patients admitted to the hospital during the period from November 1, 2005, through August 1, 2007, with a viral assay positive for influenza A or B, parainfluenza, adenovirus, or respiratory syncytial virus. Among these patients, we identified those who received antibiotics after the diagnosis of viral RTI. Data on demographics; comorbidities; and physical examination, laboratory, and radiographic findings were ascertained to identify risk factors for antimicrobial use among these patients. RESULTS: A total of 196 hospitalized patients with positive viral assay results were included; 125 of 131 patients administered antibiotics continued to receive them after viral RTI diagnosis. Among 52 patients with an abnormal chest radiograph, 46 continued antibiotic therapy. An abnormal chest radiograph was independently associated with continued antibiotic use (adjusted odds ratio, 4.28 [95% confidence interval, 1.71-10.77]; P = .002). However, the majority of patients (79 of 125 [63%]) who continued antibiotic therapy had normal chest imaging findings. Eight patients (6%) who continued antibiotic therapy and no patients who stopped developed C. difficile infection (95% CI, 1.5-∞; P = .05), but there was no significant difference in length of stay or mortality. CONCLUSIONS: Antibiotics are commonly used to treat hospitalized patients with known acute viral RTIs. Continued use is strongly associated with abnormal radiograph findings at admission. However, the reasons for continuation of antibiotics in the treatment of the majority of patients with normal radiographs are unclear and may represent inappropriate use.