Annie Brooks

MANAGEMENT OF COMPLICATED URINARY TRACT INFECTIONS IN THE ERA OF ANTIMICROBIAL RESISTANCE

Abstract Complicated urinary tract infections (cUTIs) are a major cause of hospital admissions and are associated with significant morbidity and health care costs. Patients presenting with a suspected UTI should be screened for the presence of complicating factors, such as anatomic and functional abnormalities of the genitourinary tract. In the setting of cUTIs, the etiology and susceptibility of the causative organism is not predictable; therefore, when infection is suspected, patients should undergo a urinalysis in addition to culture and sensitivity testing. Although not warranted in all cases of complicated pyelonephritis, blood cultures are appropriate in some clinical settings. With the increased prevalence of antimicrobial resistance, and the lack of well-designed clinical trials, treatment of cUTIs can be challenging for clinicians. Although resistant organisms are not always implicated as the causative agent, all patients with cUTIs should be assessed for predisposing risk factors. Consideration of an optimal antimicrobial agent should be based on local resistance patterns, patient-specific factors, including anatomic site of infection and severity of disease, pharmacokinetic and pharmacodynamic principles, and cost. Resistance to first-line antimicrobial agents, including fluoroquinolones, has become increasingly common in Escherichia coli. Fluoroquinolones should not be used as a first-line option for empiric treatment of serious cUTIs, especially when patients exhibit risk factors for harboring a resistant organism, such as previous or recent use of fluoroquinolones. Fluoroquinolones, trimethoprim-sulfamethoxazole, and nitrofurantoin are still appropriate empiric options for mild lower cUTIs. However, empiric treatment for serious cUTIs, where risk factors for resistant organisms exist, should include broad-spectrum antibiotics such as carbapenems or piperacillintazobactam. Once organisms and susceptibilities are identified, treatment should be targeted accordingly. Nitrofurantoin and fosfomycin have limited utility in the setting of cUTIs and should be reserved as alternative treatment options for lower cUTIs following confirmation of the causative organism. Aminoglycosides, tigecycline, and polymyxins can be used for the treatment of serious cUTIs when first-line options are deemed to be inappropriate or patients fail therapy. The duration of treatment for cUTIs has not been well established; however, treatment durations can range from 1 to 4 weeks based on the clinical situation.

An update on the management of urinary tract infections in the era of antimicrobial resistance.

ABSTRACT Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs are categorized according to location (upper versus lower urinary tract) and severity (uncomplicated versus complicated). Increasing rates of antibiotic resistance necessitate judicious use of antibiotics through the application of antimicrobial stewardship principles. Knowledge of the common causative pathogens of UTIs including local susceptibility patterns are essential in determining appropriate empiric therapy. The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin tromethamine. Second-line options include fluoroquinolones and β-lactams, such as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- β -lactamase-producing organisms include fosfomycin, nitrofurantion, fluoroquinolones, cefepime, piperacillin–tazobactam and carbapenems. In addition, treatment options for UTIs due to ESBLs–producing Enterobacteriaceae include nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides. Based on identification and susceptibility results, alternatives to carbapenems may be used to treat mild-moderate UTIs caused by ESBL-producing Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance. Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options.

Inappropriate use of antibiotics and Clostridium difficile infection

We assessed appropriateness of preceding and concurrent antibiotics in 126 consecutive patients with hospital-associated Clostridium difficile infection. In 93 (73.8%) episodes, at least 1 preceding course of antibiotics was inappropriate. We provided feedback on concurrent antibiotics on the day of diagnosis during the final 8 months: 17 of 74 (23.0%) patients were on inappropriate antibiotics. Our recommendations were well received. Reviewing C difficile-infected patients allowed for identification of opportunities to improve antibiotic utilization and potentially improved patient outcomes.

A Controlled Quasi-Experimental Study of an Educational Intervention to Reduce the Unnecessary Use of Antimicrobials For Asymptomatic Bacteriuria

Background Asymptomatic bacteriuria (ABU) should only be treated in cases of pregnancy or in-patients undergoing urologic procedures; however, unnecessary treatment of ABU is common in clinical practice. Objective To identify risk factors for unnecessary treatment and to assess the impact of an educational intervention focused on these risk factors on treatment of ABU. Design Quasi-experimental study with a control group. Setting Two tertiary teaching adult care hospitals. Participants Consecutive patients with positive urine cultures between January 30th and April 17th, 2012 (baseline) and January 30th and April 30th, 2013 (intervention). Intervention In January 2013, a multifaceted educational intervention based on risk factors identified during the baseline period was provided to medical residents (monthly) on one clinical teaching unit (CTU) at one hospital site, with the CTU of the other hospital serving as the control. Results During the baseline period, 160/341 (46.9%) positive urine cultures were obtained from asymptomatic patients at the two hospitals, and 94/160 (58.8%) were inappropriately treated with antibiotics. Risk factors for inappropriate use included: female gender (OR 2.1, 95% CI 1.1-4.3), absence of a catheter (OR 2.5, 1.2-5), bacteriuria versus candiduria (OR 10.6, 3.8-29.4), pyuria (OR 2.0, 1.1-3.8), and positive nitrites (OR 2.2, 1.1-4.5). In 2013, only 2/24 (8%) of ABU patients were inappropriately treated on the intervention CTU as compared to 14/29 (52%) on the control CTU (OR 0.10; 95% CI 0.02-0.49). A reduction was also observed as compared to baseline on the intervention CTU (OR 0.1, 0.02-0.7) with no significant change noted on the control CTU (OR 0.47, 0.13-1.7). Conclusions A multifaceted educational intervention geared towards medical residents with a focus on identified risk factors for inappropriate management of ABU was effective in reducing unnecessary antibiotic use.

Antimicrobial stewardship in the intensive care setting--a review and critical appraisal of the literature.

BACKGROUND Many antimicrobial stewardship programmes (ASPs) target the intensive care unit owing to high antimicrobial utilisation. In this review, we summarise and assess the quality of evidence supporting the implementation of various ASP strategies in the intensive care unit setting with a focus on publications between 2010 and 2015. METHODS We searched Medline up to April 2015 and screened publications of interest for additional relevant articles. We grouped the strategies into four categories: audit and feedback, formulary restrictions, guidelines/clinical pathways, and procalcitonin. We used GRADE terminology to describe the quality of evidence. RESULTS AND CONCLUSIONS We identified several studies reporting optimisation and reduction of antibiotic utilisation as well as cost reduction in all four strategies. Randomised controlled trials reviewing the role of procalcitonin demonstrate a moderate level of evidence. Given the lack of randomised controlled trials to support the role of guidelines, formulary restrictions, and audit and feedback, the level of evidence supporting these strategies is low. Importantly, there is no convincing evidence to support the main goal of ASP, namely to improve patient outcomes. Larger, rigorous long-term studies using a cluster randomised controlled trial or at least a controlled quasi-experimental design with time series are required to assess the impact of ASP on patient-important outcomes and on the emergence of resistance in the intensive care unit setting.

Medical Management of Diabetic Foot Infections

Abstract Diabetic foot infections (DFIs) are a commonly encountered medical problem. They are associated with an increased frequency and length of hospitalization and risk for lower–extremity amputation. Furthermore, they have substantial economic consequences. Patients with diabetes mellitus are particularly susceptible to foot infections because of neuropathy, vascular insufficiency, and diminished neutrophil function. The approach to managing DFIs starts with determining if an infection exists. If an infection exists, then the type, severity, extent of infection, and risk factors for resistant organisms should be determined through history, physical examination, and additional laboratory and radiological testing. Optimal management requires surgical debridement, pressure offloading, effective antibiotic therapy, wound care and moisture, maintaining good vascular supply, and correction of metabolic abnormalities, such as hyperglycemia, through a multidisciplinary team. Empiric antibiotics for DFIs vary based on the severity of the infection, but must include anti–staphylococcal coverage.

Postexposure management of healthcare personnel to infectious diseases

Abstract Healthcare personnel (HCP) are at risk of exposure to various pathogens through their daily tasks and may serve as a reservoir for ongoing disease transmission in the healthcare setting. Management of HCP exposed to infectious agents can be disruptive to patient care, time-consuming, and costly. Exposure of HCP to an infectious source should be considered an urgent medical concern to ensure timely management and administration of postexposure prophylaxis, if available and indicated. Infection control and occupational health departments should be notified for management of exposed HCP, identification of all contacts of the index case, and application of immediate infection control measures for the index case and exposed HCP, if indicated. This article reviews the main principles of postexposure management of HCP to infectious diseases, in general, and to certain common infections, in particular, categorized by their route of transmission, in addition to primary prevention of these infections.

Postexposure management of infectious diseases

Anyone exposed to an infectious disease—whether a healthcare provider, patient, or contact of a patient—should be evaluated promptly and the source of the infection identified. A systematic response entails postexposure prophylactic therapy if available and indicated, infection control measures to prevent further transmission, counseling and educating those involved, and assessing those who may require work restriction or modification. People who have been exposed to an infectious disease should be evaluated promptly and systematically.