Larissa Grigoryan

Effectiveness of an Antimicrobial Stewardship Approach for Urinary Catheter–Associated Asymptomatic Bacteriuria

IMPORTANCE Overtreatment of asymptomatic bacteriuria (ASB) in patients with urinary catheters remains high. Health care professionals have difficulty differentiating cases of ASB from catheter-associated urinary tract infections. OBJECTIVES To evaluate the effectiveness and sustainability of an intervention to reduce urine culture ordering and antimicrobial prescribing for catheter-associated ASB compared with standard quality improvement methods. DESIGN, SETTING, AND PARTICIPANTS A preintervention and postintervention comparison with a contemporaneous control group from July 2010 to June 2013 at 2 Veterans Affairs health care systems. Study populations were patients with urinary catheters on acute medicine wards and long-term care units and health care professionals who order urine cultures and prescribe antimicrobials. INTERVENTION A multifaceted guidelines implementation intervention. MAIN OUTCOMES AND MEASURES The primary outcomes were urine cultures ordered per 1000 bed-days and cases of ASB receiving antibiotics (overtreatment) during intervention and maintenance periods compared with baseline at both sites. Patient-level analysis of inappropriate antimicrobial use adjusted for individual covariates. RESULTS Study surveillance included 289,754 total bed-days. The overall rate of urine culture ordering decreased significantly during the intervention period (from 41.2 to 23.3 per 1000 bed-days; incidence rate ration [IRR], 0.57; 95% CI, 0.53-0.61) and further during the maintenance period (to 12.0 per 1000 bed-days; IRR, 0.29; 95% CI, 0.26-0.32) (P < .001 for both). At the comparison site, urine cultures ordered did not change significantly across all 3 periods. There was a significant difference in the number of urine cultures ordered per month over time when comparing the 2 sites using longitudinal linear regression (P < .001). Overtreatment of ASB at the intervention site fell significantly during the intervention period (from 1.6 to 0.6 per 1000 bed-days; IRR, 0.35; 95% CI, 0.22-0.55), and these reductions persisted during the maintenance period (to 0.4 per 1000 bed-days; IRR, 0.24; 95% CI, 0.13-0.42) (P < .001 for both). Overtreatment of ASB at the comparison site was similar across all periods (odds ratio, 1.32; 95% CI, 0.69-2.52). When analyzed by type of ward, the decrease in ASB overtreatment was significant in long-term care. CONCLUSIONS AND RELEVANCE A multifaceted intervention targeting health care professionals who diagnose and treat patients with urinary catheters reduced overtreatment of ASB compared with standard quality improvement methods. These improvements persisted during a low-intensity maintenance period. The impact was more pronounced in long-term care, an emerging domain for antimicrobial stewardship.

Diagnosis and Management of Urinary Tract Infections in the Outpatient Setting: A Review

IMPORTANCE Urinary tract infection is among the most common reasons for an outpatient visit and antibiotic use in adult populations. The increasing prevalence of antibacterial resistance among community uropathogens affects the diagnosis and management of this clinical syndrome. OBJECTIVES To define the optimal approach for treating acute cystitis in young healthy women and in women with diabetes and men and to define the optimal approach for diagnosing acute cystitis in the outpatient setting. EVIDENCE REVIEW Evidence for optimal treatment regimens was obtained by searching PubMed and the Cochrane database for English-language studies published up to July 21, 2014. FINDINGS Twenty-seven randomized clinical trials (6463 patients), 6 systematic reviews, and 11 observational studies (252,934 patients) were included in our review. Acute uncomplicated cystitis in women can be diagnosed without an office visit or urine culture. Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days), nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5-7 days), and fosfomycin trometamol (3 g in a single dose) are all appropriate first-line therapies for uncomplicated cystitis. Fluoroquinolones are effective for clinical outcomes but should be reserved for more invasive infections. β-Lactam agents (amoxicillin-clavulanate and cefpodoxime-proxetil) are not as effective as empirical first-line therapies. Immediate antimicrobial therapy is recommended rather than delayed treatment or symptom management with ibuprofen alone. Limited observational studies support 7 to 14 days of therapy for acute urinary tract infection in men. Based on 1 observational study and our expert opinion, women with diabetes without voiding abnormalities presenting with acute cystitis should be treated similarly to women without diabetes. CONCLUSIONS AND RELEVANCE Immediate antimicrobial therapy with trimethoprim-sulfamethoxazole, nitrofurantoin, or fosfomycin is indicated for acute cystitis in adult women. Increasing resistance rates among uropathogens have complicated treatment of acute cystitis. Individualized assessment of risk factors for resistance and regimen tolerability is needed to choose the optimum empirical regimen.

Predictors of antihypertensive medication adherence in two urban health-care systems.

BACKGROUND Most studies on patient-related predictors of adherence used self-reported measures or pharmacy databases to measure adherence. We identified predictors of antihypertensive medication adherence measured by Medication Event Monitoring System (MEMS), the gold standard for adherence assessment, in uncontrolled, predominantly African-American (AA) hypertensives from large urban public and private primary care clinics. METHODS As part of the baseline data collection of a cluster-randomized trial for hypertension control, we measured adherence in a random sample of 124 participants using MEMS caps. We also included the data of 52 patients in intervention clinics who subsequently completed MEMS monitoring on referral from their provider. Participants were classified as adherent if they took ≥ 80% of all prescribed doses. Multivariate logistic regression was used to predict adherence. RESULTS Of 176 patients monitored, 61 (34.6%) took <80% of prescribed doses. AA ethnicity (odds ratio (OR) AA vs. Hispanic = 0.36; 95% confidence interval (CI) 0.15-0.86), female sex (OR = 0.38; 95% CI 0.15-0.91), and public clinics as source of care (OR public clinics vs. private clinics = 0.45; 95% CI 0.20-0.97) were independently associated with lower adherence. Higher adherence was seen in patients monitored by clinician order in the intervention clinics (OR intervention sample vs. random baseline sample = 2.15; 95% CI 0.96-4.81) and diabetic patients (OR = 2.05; 95% CI 1.01-4.15). All analyses were adjusted for education, employment status, and other potentially confounding factors. CONCLUSIONS AA ethnicity, female gender and attending a publicly funded primary care clinic were associated with lower adherence. Whether targeting these groups for special interventions would improve overall adherence needs further study.

Approach to a Positive Urine Culture in a Patient Without Urinary Symptoms

Asymptomatic bacteriuria (ASB) is a condition in which bacteria are present in a noncontaminated urine sample collected from a patient without signs or symptoms related to the urinary tract. ASB must be distinguished from symptomatic urinary tract infection (UTI) by the absence of signs and symptoms compatible with UTI or by clinical determination that a nonurinary cause accounts for the patients symptoms. The overall purpose of this review is to promote an awareness of ASB as a distinct condition from UTI and to empower clinicians to withhold antibiotics in situations in which antimicrobial treatment of bacteriuria is not indicated.

Patterns of nonadherence to antihypertensive therapy in primary care.

Nonadherence to medications is an important cause of poor blood pressure control. Long‐acting antihypertensive agents could theoretically be beneficial in partially adherent patients, who are commonly seen in contemporary practice. Little has been reported about the duration of drug holidays (DHs) in treated hypertensives outside of generally compliant patients in phase 4 clinical trials. The authors described patterns of nonadherence to single and multiple antihypertensives in a random sample of 120 primary care patients with uncontrolled hypertension. Adherence to up to 3 antihypertensives was measured by electronic monitoring. Frequencies of single‐day omissions and DHs of 2 consecutive days (DH2), 3 days (DH3), or ≥4 days (DH ≥4) for each drug were calculated. Overall, 89 (74%) of patients had at least a 1‐day omission. A single day omission was found in 61.4% of the patients taking 1 drug, followed by DH ≥4 (28.1%), DH2 (26.3%), and DH3 (8.8%). In patients using multiple drugs, single‐day omissions were also most common, followed by DH ≥4, DH2, and DH3. Omissions of ≤3 days comprise on average 74% of all omissions. Although encouraging full adherence remains important, it may be prudent to prescribe long‐acting antihypertensive agents, which can compensate for the majority of dose omissions. J Clin Hypertens (Greenwich). 2012; 00:00–00. ©2012 Wiley Periodicals, Inc.

Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: Network meta-analysis of randomized trials

BACKGROUND The efficacies and adverse effects of different antibiotics for uncomplicated urinary tract infections (UTIs) have been studied by standard meta-analytic methods using pairwise direct comparisons of antimicrobial treatments: the effects of one treatment are compared to those of either another treatment or placebo. However, for clinical decisions, we need to know the effectiveness of each possible treatment in comparison with all relevant alternatives, not with just one. OBJECTIVES To compare the efficacies and adverse effects of all relevant antibiotics for UTI treatment simultaneously by performing a network meta-analysis using direct and indirect treatment comparisons. METHODS Using logistic regression analysis, we performed a network meta-analysis of randomized controlled trials (RCTs) published after 1999 that compared different oral antibiotic or placebo regimens for UTI treatment in general practice or outpatient settings. We looked at five binary outcomes: early clinical, early bacteriological, late clinical and late bacteriological outcomes, as well as adverse effects. Consequently, a ranking of the antibiotic regimens could be composed. RESULTS Using a network structure, we could compare and rank nine treatments from 10 studies. Overall, ciprofloxacin and gatifloxacin appeared the most effective treatments, and amoxicillin-clavulanate appeared the least effective treatment. In terms of adverse effects, there were no significant differences. DISCUSSION Network meta-analysis shows some clear efficacy differences between different antibiotic treatments for UTI in women. It provides a useful tool for clinical decision making in everyday practice. Moreover, the method can be used for meta-analyses of RCTs across primary care and beyond.

Low Concordance With Guidelines for Treatment of Acute Cystitis in Primary Care.

We found low concordance with the updated 2010 IDSA guidelines for both the choice of drug and duration of therapy for acute cystitis. Interventions to decrease overuse of fluoroquinolones are needed to preserve the antimicrobial efficacy of these important antimicrobials.

Nonprescription Antimicrobial Use in a Primary Care Population in the United States

ABSTRACT Community antimicrobial resistance rates are high in communities with frequent use of nonprescription antibiotics. Studies addressing nonprescription antibiotic use in the United States have been restricted to Latin American immigrants. We estimated the prevalence of nonprescription antibiotic use in the previous 12 months as well as intended use (intention to use antibiotics without a prescription) and storage of antibiotics and examined patient characteristics associated with nonprescription use in a random sample of adults. We selected private and public primary care clinics that serve ethnically and socioeconomically diverse patients. Within the clinics, we used race/ethnicity-stratified systematic random sampling to choose a random sample of primary care patients. We used a self-administered standardized questionnaire on antibiotic use. Multivariate regression analysis was used to identify independent predictors of nonprescription use. The response rate was 94%. Of 400 respondents, 20 (5%) reported nonprescription use of systemic antibiotics in the last 12 months, 102 (25.4%) reported intended use, and 57 (14.2%) stored antibiotics at home. These rates were similar across race/ethnicity groups. Sources of antibiotics used without prescriptions or stored for future use were stores or pharmacies in the United States, “leftover” antibiotics from previous prescriptions, antibiotics obtained abroad, or antibiotics obtained from a relative or friend. Respiratory symptoms were common reasons for the use of nonprescription antibiotics. In multivariate analyses, public clinic patients, those with less education, and younger patients were more likely to endorse intended use. The problem of nonprescription use is not confined to Latino communities. Community antimicrobial stewardship must include a focus on nonprescription antibiotics.

A comparison of the microbiologic profile of indwelling versus external urinary catheters

We studied the microbiology reports of urine cultures collected from external (condom catheters) versus indwelling (Foley) catheters. The equal prevalence of Enterobacteriaceae and Enterococci in samples from both catheter types calls into question the practice of switching from indwelling to external catheters to decrease catheter-associated bacteriuria.

Urinary Tract Infection

Urinary tract infections (UTIs) are common in both outpatient and inpatient settings. Clinical entities encompassed by the term UTI include asymptomatic bacteriuria (ASB), acute uncomplicated cystitis, recurrent cystitis, catheter-associated ASB, catheter-associated UTI (CAUTI), prostatitis, and pyelonephritis. These categories are further distinguished by the presence or absence of symptoms referable to the urinary tract and the patients sex, comorbid conditions, and genitourinary history, including the presence of stones, stents, or catheters. Because acute cystitis is the most common manifestation of UTI and is most prevalent in women, most clinical research on UTI has been done in women. Clinicians must consider whether recommendations derived from this evidence base are applicable to their patient populations. In the absence of known abnormalities of the urinary tract, women are at higher risk for UTIs than men. Premenopausal women are at especially high risk for acute cystitis—incidence is 0.50.7 case per person-year among sexually active women (1). Other populations at risk for UTI include patients with voiding abnormalities related to diabetes; neurogenic bladder; spinal cord injury; pregnancy; prostatic hypertrophy; or urinary tract instrumentation, including long-term (30 days) indwelling catheters. As men age, acquired abnormalities of the urinary tract impair normal bladder emptying, which narrows the sex-based difference in UTI rates (2). The strongest risk factors in premenopausal women include sexual intercourse, use of spermicides, and previous UTI. A history of maternal UTI and age at first UTI are also important risk factors in this group, suggesting a genetic component to susceptibility (3). Pregnant women are also at increased risk. Changes in vaginal microbial flora in perimenopausal women may increase risk for UTI. In contrast to the predominant role of behavioral risk factors in premenopausal women, mechanical and physiologic factors that affect bladder emptying are important in postmenopausal women (4). Diabetes increases risk for all urinary infectious disorders, from ASB to perirenal abscess and emphysematous pyelonephritis (5). In men, risk for UTI is primarily related to prostatic hypertrophy that occurs with advancing age. Temporary urinary catheterization is the major medical intervention that increases risk for UTI. Other comorbid conditions that increase risk in both sexes include the presence of stones or foreign bodies (such as ureteral stents) in the urinary system and diseases associated with neurogenic bladder. Screening and Prevention Is there a role for screening for UTI or ASB? In men and nonpregnant women, screening for ASB is generally not recommended because treatment does not improve clinical outcomes (6). ASB does not lead to hypertension, chronic kidney disease, or decreased duration of survival (7). Women with ASB are at increased risk for symptomatic UTI, but treatment does not decrease this risk (8). ASB is a marker for poor overall health status in diabetic patients, noncatheterized women in retirement homes, and catheterized inpatients but is not an independent risk factor for death. ASB during pregnancy (4%7% of pregnant women) is associated with progression to symptomatic UTI, including pyelonephritis (9). Acute pyelonephritis occurs in up to 2% of pregnancies in the United States and is the most common nonobstetric cause of hospitalization during pregnancy (9). ASB during pregnancy is also associated with low birthweight and preterm labor, although a causative relationship has not been established. The most recent Cochrane review (10) on this topic found that antibiotic treatment of ASB was associated with significantly decreased risk for pyelonephritis, premature birth, and low birthweight compared with no treatment. However, the 14 included studies were done between 1960 and 1987, and the risk of bias was judged to be high. The quality of the evidence was judged to be very low (pyelonephritis) and low (prematurity and low birthweight). A cohort study of 4283 healthy pregnant women in the Netherlands who had very low risk for preterm delivery found much lower rates of pyelonephritis than previous studies (11). The proportion of pregnant women with untreated ASB who developed pyelonephritis was 5 of 208 (2.4%) compared with 24 of 4034 (0.6%) without ASB (odds ratio [OR], 3.9 [95% CI, 1.411.4]). Women with untreated ASB were also more likely than those without ASB to have subsequent UTI treated with antibiotics during pregnancy (OR, 2.9 [CI, 2.04.2]) and recurrent UTI treated with antibiotics during pregnancy (OR, 3.5 [CI, 1.86.7]). Screening for and treatment of ASB are also recommended before transurethral resection of the prostate (TURP) or other urinary tract instrumentation resulting in mucosal bleeding. Studies have shown that TURP in bacteriuric men can precipitate bacteremia with associated sepsis and that antimicrobial treatment of the bacteriuria can prevent these complications. The level of risk associated with specific invasive urologic procedures other than TURP in patients with preexisting bacteriuria is not well-defined. However, the Infectious Diseases Society of America (IDSA) recommends that procedures anticipated to cause mucosal bleeding warrant screening by urine culture and treatment of ASB before the procedure (6). Simple catheter placement and cystoscopy without biopsy do not warrant screening for ASB. Renal transplant recipients who have ASB are at higher risk for pyelonephritis, but whether pyelonephritis affects graft function is controversial (12, 13). The relationship of ASB to UTI and sepsis in patients with neutropenia has not been well-studied. Bacteriuria diagnosed in neutropenic patients as part of a fever work-up is by definition symptomatic. How can UTI be prevented? Prevention of symptomatic UTI in patients with ASB is recommended only in pregnant women or before an invasive urologic procedure. Urine culture should be done and infection should be treated with directed antimicrobial therapy based on culture results. Symptomatic UTI in women with recurrent episodes can be prevented with antimicrobial prophylaxis. This decision should be individualized. Given increasing antimicrobial resistance, regular use of antimicrobials to prevent UTI may not be appealing, and approaches other than antimicrobial prophylaxis, such as patient-initiated therapy or nonantimicrobial prevention, may be preferred even if they are less effective in reducing symptomatic events. If antibiotics are used to prevent recurrent UTI, they may be prescribed postcoitally or continuously. Postcoital antibiotic prophylaxis has been shown to be highly effective in preventing symptomatic recurrences in women with 34 UTIs per year, particularly if these are temporally associated with coitus. A randomized, double-blind, placebo-controlled trial found that among women with at least 2 culture-documented UTIs in the previous year, postcoital use of a single dose of trimethoprimsulfamethoxazole (TMPSMX) (40 mg plus 200 mg) resulted in an infection rate of 0.3 per patient per year compared with 3.6 per patient per year in the control group (14). Adverse effects were infrequent and minor. In women who are intolerant of or resistant to TMPSMX, an alternative agent (such as nitrofurantoin macrocrystals or a fluoroquinolone) may be as effective as TMPSMX for postcoital prophylaxis, although clinical evidence specifically related to postcoital use is not available for these agents. For women with more frequent recurrences, more frequent coitus, or recurrences temporally unrelated to coitus, continuous (daily, thrice-weekly, or weekly) prophylaxis may be preferable, with dosing frequency tailored to the individual patients response. However, rates decrease only during the active prophylaxis period and in many cases return to baseline levels after antimicrobial therapy is discontinued. Because some women may not wish to take prophylactic antibiotics regularly, patient-initiated therapy may have greater appeal. In a meta-analysis of 19 trials of prophylactic antibiotics for acute cystitis, 17 of which tested daily antibiotic use, the range of having 1 clinical recurrence was 00.27 person-years in the antibiotic group and 1.123.6 person-years in the placebo group (15). Increased awareness of the role of the microbiome in overall health, concern for selection for antibiotic-resistant bacteria, and the difficulty of treating resistant urinary pathogens have led to exploration of nonantimicrobial approaches to UTI prevention. These include probiotics (typically lactobacilli), cranberry products, D-mannose, and vaccines. A Cochrane meta-analysis of trials of lactobacilli concluded that probiotics did not significantly reduce risk for UTI compared with placebo or antibiotics (16). Currently, no vaccines are approved for use in UTI prevention in the United States, although preclinical testing has identified promising candidates (17). Debate is ongoing about the effectiveness of cranberry products in the prevention of UTI. A randomized trial found a potentially protective effect on recurrent UTI with cranberry products compared with placebo; however, the study was underpowered (18). Another randomized controlled trial of twice-daily cranberry juice consumption versus placebo found no between-group difference in the rate of UTI recurrence (19). In a recent randomized double-blind trial of women in nursing homes, no significant difference was observed for any of the clinical or microbiologic outcomes (20). In another trial that included premenopausal women with complicated and uncomplicated recurrent UTI, TMPSMX was more effective at preventing recurrent UTI than cranberry capsules, but at the expense of promoting antibiotic resistance (21). Daily consumption of a cranberry beverage decreased the number of clinical UTIs in a randomized, double-blind, placebo-controlled, multicent