Miriam R. Elman

Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients

BackgroundUrinary tract infections (UTIs) are one of the most common infections treated in ambulatory care settings, however the epidemiology differs by age and sex. The incidence of UTI is far greater in females than males, and infection in pediatric patients is more often due to anatomical abnormalities. The purpose of this research was to describe age- and sex-specific trends in antibiotic susceptibility to common urinary anti-infectives among urinary isolates of Escherichia coli from ambulatory primary care patients in a regional health maintenance organization.MethodsClinical microbiology data were collected for all urine cultures from patients with visits to primary care clinics in a regional health maintenance organization between 2005 and 2010. The first positive culture for E. coli tested for antibiotic susceptibilities per patient per year was included in the analysis dataset. The frequency of susceptibility to ampicillin, amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole (TMP/SMX) was calculated for male and female patients. The Cochrane-Mantel-Haenzel test was used to test for differences in age-stratified susceptibility to each antibiotic between males and females.ResultsA total of 43,493 E. coli isolates from 34,539 unique patients were identified for study inclusion. After stratifying by age, E. coli susceptibility to ampicillin, amoxicillin-clavulanate, ciprofloxacin, and nitrofurantoin differed significantly between males and females. However, the magnitude of the differences was less than 10% for all strata except amoxicillin-clavulanate susceptibility in E. coli isolated from males age 18–64 compared to females of the same age.ConclusionsWe did not observe clinically meaningful differences in antibiotic susceptibility to common urinary anti-infectives among E. coli isolated from males versus females. These data suggest that male sex alone should not be used as an indication for empiric use of second-line broad-spectrum antibiotic agents for the treatment of UTIs.

Comparison of Antibiograms Developed for Inpatients and Primary Care Outpatients

To support antimicrobial stewardship, some healthcare systems have begun creating outpatient antibiograms. We developed inpatient and primary care outpatient antibiograms for a regional health maintenance organization (HMO) and academic healthcare system (AHS). Antimicrobial susceptibilities from 16,428 Enterococcus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa cultures from 2010 were summarized and compared. Methicillin susceptibility among S. aureus was similar in inpatients and primary care outpatients (HMO: 61.2% versus 61.9%, P = 0.951; AHS: 62.9% versus 63.3%, P > 0.999). E. coli susceptibility to trimethoprim/sulfamethoxazole was also similar (HMO: 81.8% versus 83.6%, P = 0.328; AHS: 77.2% versus 80.9%, P = 0.192), but ciprofloxacin susceptibility differed (HMO: 88.9% versus 94.6%, P < 0.001; AHS: 81.2% versus 90.6%, P < 0.001). In the HMO, ciprofloxacin-susceptible P. aeruginosa were more frequent in primary care outpatients than in inpatients (91.4% versus 79.0%, P = 0.007). Comparison of cumulative susceptibilities across settings yielded no consistent patterns; therefore, outpatient primary care antibiograms may more accurately inform prudent empiric antibiotic prescribing.

Frequency of Outpatient Antibiotic Prescription on Discharge to Hospice Care

ABSTRACT The use of antibiotics is common in hospice care despite limited evidence that it improves symptoms or quality of life. Patients receiving antibiotics upon discharge from a hospital may be more likely to continue use following transition to hospice care despite a shift in the goals of care. We quantified the frequency and characteristics for receiving a prescription for antibiotics on discharge from acute care to hospice care. This was a cross-sectional study among adult inpatients (≥18 years old) discharged to hospice care from Oregon Health & Science University (OHSU) from 1 January 2010 to 31 December 2012. Data were collected from an electronic data repository and from the Department of Care Management. Among 62,792 discharges, 845 (1.3%) patients were discharged directly to hospice care (60.0% home and 40.0% inpatient). Most patients discharged to hospice were >65 years old (50.9%) and male (54.6%) and had stayed in the hospital for ≤7 days (56.6%). The prevalence of antibiotic prescription upon discharge to hospice was 21.1%. Among patients discharged with an antibiotic prescription, 70.8% had a documented infection during their index admission. Among documented infections, 40.3% were bloodstream infections, septicemia, or endocarditis, and 38.9% were pneumonia. Independent risk factors for receiving an antibiotic prescription were documented infection during the index admission (adjusted odds ratio [AOR] = 7.00; 95% confidence interval [95% CI] = 4.68 to 10.46), discharge to home hospice care (AOR = 2.86; 95% CI = 1.92 to 4.28), and having a cancer diagnosis (AOR = 2.19; 95% CI = 1.48 to 3.23). These data suggest that a high proportion of patients discharged from acute care to hospice care receive an antibiotic prescription upon discharge.

Use of electronic health record data to identify skin and soft tissue infections in primary care settings: a validation study.

BackgroundEpidemiologic studies of skin and soft tissue infections (SSTIs) depend upon accurate case identification. Our objective was to evaluate the positive predictive value (PPV) of electronic medical record data for identification of SSTIs in a primary care setting.MethodsA validation study was conducted among primary care outpatients in an academic healthcare system. Encounters during four non-consecutive months in 2010 were included if any of the following were present in the electronic health record: International Classification of Diseases, Ninth Revision (ICD-9) code for an SSTI, Current Procedural Terminology (CPT) code for incision and drainage, or a positive wound culture. Detailed chart review was performed to establish presence and type of SSTI. PPVs and 95% confidence intervals (CI) were calculated among all encounters, initial encounters, and cellulitis/abscess cases.ResultsOf the 731 encounters included, 514 (70.3%) were initial encounters and 448 (61.3%) were cellulitis/abscess cases. When the presence of an ICD-9 code, CPT code, or positive culture was used to identify SSTIs, 617 encounters were true positives, yielding a PPV of 84.4% [95% CI: 81.8–87.0%]. The PPV for using ICD-9 codes alone to identify SSTIs was 90.7% [95 % CI: 88.5–92.9%]. For encounters with cellulitis/abscess codes, the PPV was 91.5% [95% CI: 88.9–94.1%].ConclusionsICD-9 codes may be used to retrospectively identify SSTIs with a high PPV. Broadening SSTI case identification with microbiology data and CPT codes attenuates the PPV. Further work is needed to estimate the sensitivity of this method.

Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women

AIM(S) While it is known that CYP3A4/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4/5 activity in obese women. METHODS Thirty-four, obese (body mass index, BMI > 30 kg m(-2)) women of reproductive age (18-35 years old) were placed on a COC pill containing 20 µg ethinylestradiol/100 µg levonorgestrel for 21 days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21 days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non-compartmental method. RESULTS Midazolam clearance, a surrogate measure of CYP3A4/5 activity, was significantly decreased upon COC use (63.3 l h(-1) vs. 53.9 l h(-1), P < 0.05). A median decrease of 5.6 l h(-1) (95% CI -4.1, 13.3 l h(-1)) was observed. However, the magnitude of change was similar to that reported in women with normal BMI. CONCLUSIONS Although we hypothesized that obesity might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug-drug interactions in obese COC users as CYP3A4/5 is a major enzyme in the metabolism of many marketed drugs.

Incidence and Outcomes of Cytomegalovirus (CMV) Infection among Hematopoietic Stem Cell Transplant (HSCT) Recipients

Abstract Background Outcomes of CMV infection among HSCT recipients likely vary by patient population and treatment modality. However, data on these outcomes have been reported by relatively few centers. Methods This was a retrospective cohort study of allogenic HSCT recipients age ≥18 years at Oregon Health and Science University Hospital (OHSU) between 2010–2015. During the study period, OHSU standard practice was to preemptively treat CMV-viremic patients (quantitative PCR assay ≥ 200 copies/mL or consecutive PCR assays <200 copies/mL) with first-line valganciclovir or ganciclovir and second line foscarnet if there were contraindications to first-line agents. Study data were collected from an electronic health record repository and local Center for International Blood and Marrow Transplant Research (CIBMTR) database. Primary outcomes were clinical manifestations of CMV disease, death, and cause of death within 1 year of transplant. Results Among 409 HSCT recipients, mean age was 53 (standard deviation: 13) years and 41% were female. 192 (47%) patients had CMV viremia and the median (interquartile range) time to CMV reactivation was 42 (31–53) days (Figure 1). Patients with acute myeloid leukemia were significantly less likely to have CMV reactivation (39% vs. 55%, P < 0.01) and those with myelodysplastic syndromes had a non-significantly higher risk (24% vs. 17%, P = 0.06). 4 (1%) patients had a documented clinical manifestation of CMV disease (3 pneumonia and 1 pancreatitis). One-year mortality was 36% (148/409); there was no significant difference in mortality (37.5% vs. 35.0%, P = 0.60) or cause of death (P = 0.30) between patients with and without CMV reactivation (Figure 2). The most frequent causes of death among CMV viremic patients were recurrent/persistent disease (35%), acute graft vs. host disease (GVHD) (22%), infection (19%), and chronic GVHD (11%). CMV was documented as the primary cause of death for 2 patients. Conclusion Nearly half of HSCT recipients had CMV reactivation and more than a third died within one year of transplant. However, incidence of CMV disease was rare and reactivation was not associated with increased mortality. Further study is needed to identify risk factors for CMV reactivation, infection and mortality in this population. Disclosures J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. L. Strasfeld, Merck: Independent Contractor, Salary. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant

Impact of Urine Testing on Unnecessary Antibiotic use for Asymptomatic Bacteriuria

Abdominal pain 6 (6.0) 23(23.0) Other symptomse 1 (1.0) 10(10.0) IQR = Interquartile range, NR = Not Reported. aData are n(%) and compared with Chi-square testing unless otherwise specified; bWilcoxon rank-sum test; cOnepatient with a positive urine screen had no comorbidity identified; dIncludes quadriplegia, paraplegia, multiple sclerosis, spina bifida, amyotrophic lateral sclerosis, and Parkinsons disease; eIncludes dysuria, frequency, urgency, retention, and flank pain. Table 2. Characteristics of antibiotic utilizationa

874Risk Factors for Complicated Urinary Tract Infection (cUTI) due to Pseudomonas

Study Design  Retrospective cohort of hospitalized patients with cUTI admitted to an academic medical center between May 1, 2009 and December 31, 2013  Pregnant patients and those without microbiology data excluded  Each eligible patient allowed to enter the cohort once Data Collection and Definitions  Medical records and clinical data collected electronically from a research data warehouse • UTI and other conditions determined by ICD-9 diagnosis code, surgeries and procedures from ICD-9 and CPT procedure codes  cUTI defined as catheter-associated UTI; acute pyelonephritis; UTI in patients with uropathy or other urinary tract functional abnormality (UT abnormality), urogenital/anorectal surgery, urinary calculi, quadriplegia/paraplegia, spinal cord injury/disorder, kidney transplant, or end-stage renal disease; or UTI in males METHODS Oregon State University/Oregon Health & Science University College of Pharmacy Jessina C. McGregor, Miriam R. Elman, Brie N. Noble, Jon P. Furuno Risk Factors for Complicated Urinary Tract Infection (cUTI) due to Pseudomonas