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Infectious disease AND Urinary tract infection [keywords]
- Role of Capsule and O Antigen in the Virulence of Uropathogenic Escherichia coli. [Journal Article]
- PLoS One 2014; 9(4):e94786.
Urinary tract infection (UTI) is one of the most common bacterial infections in humans, with uropathogenic Escherichia coli (UPEC) the leading causative organism. UPEC has a number of virulence factors that enable it to overcome host defenses within the urinary tract and establish infection. The O antigen and the capsular polysaccharide are two such factors that provide a survival advantage to UPEC. Here we describe the application of the rpsL counter selection system to construct capsule (kpsD) and O antigen (waaL) mutants and complemented derivatives of three reference UPEC strains: CFT073 (O6:K2:H1), RS218 (O18:K1:H7) and 1177 (O1:K1:H7). We observed that while the O1, O6 and O18 antigens were required for survival in human serum, the role of the capsule was less clear and linked to O antigen type. In contrast, both the K1 and K2 capsular antigens provided a survival advantage to UPEC in whole blood. In the mouse urinary tract, mutation of the O6 antigen significantly attenuated CFT073 bladder colonization. Overall, this study contrasts the role of capsule and O antigen in three common UPEC serotypes using defined mutant and complemented strains. The combined mutagenesis-complementation strategy can be applied to study other virulence factors with complex functions both in vitro and in vivo.
- Safety and Efficacy of Long-Term Outpatient Ertapenem Therapy. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Apr 7.
Ertapenem is increasingly utilized in outpatient parenteral antimicrobial therapy (OPAT), but data regarding efficacy and safety of long-term ertapenem therapy are limited. We conducted a retrospective cohort study of adult patients who received outpatient ertapenem therapy at our center between 2010 and 2013. Among 306 unique patients who were discharged on ertapenem therapy, the most common indications were intra-abdominal infections (38%), followed by pneumonia (12%), bone and joint infections (11%), bloodstream infections (10%), urinary tract infections (10%), surgical site infections (5%) and skin and soft tissue infections (4%). Of them, 68 received regular outpatient follow-up visits at our infectious disease clinic, where the majority of patients (91%) were successfully treated with ertapenem by the end of therapy. Of the 6 patients who experienced clinical failure, 2 had adverse events leading to discontinuation of therapy and 4 required additional source control for clinical success. In addition, two patients had recurrent infection at 6 months.
- Fever of unknown origin: a retrospective study of 95 children in an Iranian referral hospital. [Journal Article]
- Br J Biomed Sci 2014; 71(1):40-2.
Fever of unknown origin (FUO) is a common manifestation in paediatrics and is a diagnostic problem especially in primary care. The present study aims to revue the causes of FUO in an Iranian referral tertiary care hospital. Information on 95 patients referred to the Children's Medical Center Hospital, Tehran, between 2004 and 2006 with a primary diagnosis of FUO was evaluated retrospectively. Infectious diseases were diagnosed in 26.3% (n = 25) of the cases, while malignant and non-infectious inflammatory diseases constituted 7.4% (n = 7) and 14.7% (n = 14), respectively. Urinary tract infections, acute lymphoid leukaemia and Kawasaki disease were the most commonly diagnosed conditions. Urinary tract infection accounted for approximately half of the infectious cases (n = 14). Conclusive diagnostic factors included history and examination in 21 cases, analysis of different specimens (i.e., urine analysis, urine culture, serology, peripheral blood and cerebrospinal fluid [CSF] examination) in 12 cases, culture in nine cases and serological tests in four cases. Infection and malignancy in patients aged under three years, and inflammatory diseases in patients aged over three years were more common. In patients aged under three years urine culture, bone marrow aspiration and peripheral blood smear proved more helpful in arriving at a final diagnosis of FUO, while in patients aged over three years, history and physical examination also contributed to the final diagnosis.
- Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era. [Journal Article]
- Expert Rev Anti Infect Ther 2014 May; 12(5):549-54.
In the era of multidrug resistance, it is critical to utilize antibiotics in an appropriate manner and to identify new treatments or revisit the use of 'forgotten' drugs. Because urinary tract infections (UTIs) are common, particularly in an increasing elderly population, the 'forgotten' drug, methenamine, may become important as a preventive therapy for recurrent UTIs. Methenamine, a urinary antibacterial agent, can be used as methenamine hippurate or methenamine mandelate preparations and is United States Food and Drug Administration-approved. This article discusses the place of preventive therapy for recurrent UTIs, chemistry, mechanism of action, pharmacology, clinical uses, dosage, adverse reactions and safety, and drug interactions of methenamine. Because of its unique antiseptic property, the authors suggest that methenamine should be considered when more commonly used antibiotics fail to suppress recurrent UTIs.
- Nosocomial infections in the Intesive Care Unit, Univerisity Hospital for Infectious and Tropical Diseases, Belgrade, Serbia. [Journal Article]
- Vojnosanit Pregl 2014 Feb; 71(2):131-6.
Nosocomial infections (NIs) are an important cause of morbidity, mortality and prolonged hospitalizations. Fifty percent of NIs have been reported in Intensive Care Units. The aim of this study was to determine the frequency and type of NIs among critically ill patients treated in the University Hospital for Infectious and Tropical Diseases, Clinical Centre of Serbia, as well as risk factors for acquiring them.This prospective cohort study included 52 patients treated in the Intensive Care Unit from January to June 2004. The diagnosis of NI was established according to the Centers for Disease Control and Prevention (CDC) definition, based on clinical presentation, radiological and microbiological findings, etc. Statistical data processing was done by using the electronic data base organized in SPSS for Windows version 10.0. The level of statistical significance was defined as p < 0.05.NIs were found in 33 (63.4%) of 52 inpatients. Urinary tract infections (UTIs), pneumonia, and soft tissue infections, the most common nosocomial infections in our setting, were recorded in 41.0%, 25.6%, and 23.1%, of patients, respectively. Several factors contributed to a high incidence of these infections: chronic comorbidities (p < 0.01), the presence of indwelling devices such as urinary tract catheters (p < 0.01), endotracheal tubes (p < 0.05) along with mechanical ventilation (p < 0.05).The majority of patients with NIs had chronic underlying comorbidities. All the patients with UTIs had urinary catheters. The most important risk factors for the development of nosocomial pneumonias were endotracheal intubation and mechanical ventilation. The patients with pneumonia had the highest mortality.
- How well do discharge diagnoses identify hospitalised patients with community-acquired infections? - a validation study. [Journal Article]
- PLoS One 2014; 9(3):e92891.
Credible measures of disease incidence, trends and mortality can be obtained through surveillance using manual chart review, but this is both time-consuming and expensive. ICD-10 discharge diagnoses are used as surrogate markers of infection, but knowledge on the validity of infections in general is sparse. The aim of the study was to determine how well ICD-10 discharge diagnoses identify patients with community-acquired infections in a medical emergency department (ED), overall and related to sites of infection and patient characteristics.We manually reviewed 5977 patients admitted to a medical ED in a one-year period (September 2010-August 2011), to establish if they were hospitalised with community-acquired infection. Using the manual review as gold standard, we calculated the sensitivity, specificity, predictive values, and likelihood ratios of discharge diagnoses indicating infection.Two thousand five hundred eleven patients were identified with community-acquired infection according to chart review (42.0%, 95% confidence interval [95%CI]: 40.8-43.3%) compared to 2550 patients identified by ICD-10 diagnoses (42.8%, 95%CI: 41.6-44.1%). Sensitivity of the ICD-10 diagnoses was 79.9% (95%CI: 78.1-81.3%), specificity 83.9% (95%CI: 82.6-85.1%), positive likelihood ratio 4.95 (95%CI: 4.58-5.36) and negative likelihood ratio 0.24 (95%CI: 0.22-0.26). The two most common sites of infection, the lower respiratory tract and urinary tract, had positive likelihood ratios of 8.3 (95%CI: 7.5-9.2) and 11.3 (95%CI: 10.2-12.9) respectively. We identified significant variation in diagnostic validity related to age, comorbidity and disease severity.ICD-10 discharge diagnoses identify specific sites of infection with a high degree of validity, but only a moderate degree when identifying infections in general.
- Factors associated with ciprofloxacin- and cefotaxime-resistant Escherichia coli in women with acute pyelonephritis in the emergency department. [JOURNAL ARTICLE]
- Int J Infect Dis 2014 Mar 19.
High rates of antimicrobial resistance in Escherichia coli isolated from patients with urinary tract infections have been reported worldwide. The aim of this study was to identify risk factors for resistance to ciprofloxacin (CIP) and cefotaxime (CTX) in E. coli isolated from patients with acute pyelonephritis (APN).We prospectively identified women over 18 y of age who visited the emergency department of one of 10 hospitals with APN and whose urine culture grew E. coli. The study was conducted from April 16 to June 10, 2012.Of the 229 patients identified, 173 (75.5%) had community-associated (CA) infections and 56 (24.5%) had healthcare-associated (HCA) infections. Sixty-seven isolates (29.3%) were resistant to CIP, 45 (19.7%) to CTX, and 29 (12.7%) to both CIP and CTX. Multivariate analyses revealed that hematologic disease, chronic kidney disease, a bed-ridden state, indwelling urinary catheter, antibiotic treatment in the preceding 3 months, and isolation of CIP-resistant E. coli in the urine within the preceding 3 months, were significantly associated with resistance to both CIP and CTX.Chronic conditions and healthcare-associated factors were related to resistance to both fluoroquinolones and third-generation cephalosporins in women with APN. Continued and vigilant surveillance is necessary to monitor the dissemination of antimicrobial resistance in uropathogens.
- Procoagulant tissue factor activity on microparticles is associated with disease severity and bacteremia in febrile urinary tract infections. [JOURNAL ARTICLE]
- Thromb Res 2014 Mar 6.
Inhibition of tissue factor, the primary initiator of coagulation in sepsis, attenuates morbidity in primates infused with Escherichia coli. In a human endotoxemia model, microparticles expressing procoagulant TF (MP-TF) are released in blood concurrently with markers of inflammation and coagulation. We investigated whether the release of MP-TF into blood is accompanied by procoagulant and inflammatory changes in patients with E. coli urinary tract infection.In a multicenter cohort study, we determined clinical disease severity using APACHE II scores and measured plasma MP-TF activity, TAT, sE-selectin, sVCAM-1, procalcitonin and monocyte count in blood of 215 patients with community-acquired febrile E. coli urinary tract infections.Plasma MP-TF activity on admission corresponded with clinical disease severity (APACHE II score; P=0.006) and correlated significantly but weakly with plasma markers of disease severity (sE-selectin, sVCAM-1, procalcitonin). Additionally, median plasma MP-TF activity was higher in patients than in healthy controls (197 vs. 79 fM Xa/min; P<0.0001), and highest in bacteremic patients (325 fM Xa/min). MP-TF activity showed a weak inverse correlation with monocyte count (rs -0.22; P=0.016) and a weak correlation with TAT (rs 0.23, P=0.017). After 3days of antibiotic treatment, upon resolution of the infection, plasma MP-TF activity and TAT concentrations declined.Microparticle-associated procoagulant tissue factor activity is related to disease severity and bacteremia in febrile E. coli UTI patients and may contribute to the prothrombotic state in gram-negative sepsis.
- Predictors of Clinical Success Among a National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus aureus Pneumonia. [Journal Article]
- Clin Ther 2014 Apr 1; 36(4):552-9.
The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is exceedingly complicated, which is concerning because of the high mortality rate associated with the infection. Identification of independent predictors of clinical success can optimize patient care by assisting clinicians in treatment decisions.Our goal was to identify independent predictors of clinical success in a national Veterans Affairs (VA) cohort of patients with MRSA pneumonia.A nested case-control study was conducted among a cohort of VA patients with MRSA pneumonia receiving linezolid or vancomycin between January 2002 and September 2010. Cases included those demonstrating clinical success, defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Control subjects represented nonsuccess, defined as therapy change, intubation, intensive care unit admission, readmission, or death between treatment initiation and day 14. The potential predictors assessed included treatment, patient demographic and admission characteristics, previous health care and medication exposures, comorbidities, and medical history. Odds ratios (ORs) and 95% CIs were calculated from logistic regression.Our study included 2442 cases of clinical success and 1290 control subjects. Demographic characteristics varied between the clinical success and nonsuccess groups, including age, race, and region of facility. A current diagnosis of chronic respiratory disease (46% vs 42%) and diagnosis of pneumonia in the year before the MRSA pneumonia admission (37% vs 32%) were both more common in the clinical success group. Despite these significant differences, only 2 predictors of clinical success were identified in our study: previous complication of an implant or graft, including mechanical complications and infections, in the year before the MRSA pneumonia admission (adjusted OR, 1.55 [95% CI, 1.17-2.06]) and treatment with linezolid (adjusted OR, 1.53 [95% CI, 1.12-2.10]). Predictors of nonsuccess (adjusted OR [95% CI) included diagnosis of concomitant urinary tract infection (0.82 [0.70-0.96]), intravenous line (0.76 [0.66-0.89]), previous coagulopathy (0.74 [0.56-0.96]), previous amputation procedure (0.72 [0.53-0.98]), current coagulopathy diagnosis (0.71 [0.53-0.96]), dialysis (0.54 [0.38-0.76]), multiple inpatient procedures (0.53 [0.45-0.62]), inpatient surgery (0.48 [0.41-0.57]), and previous endocarditis (0.24 [0.07-0.81]).MRSA pneumonia tends to affect patients with complex care, and identification of the predictors of clinical success is useful when considering different therapeutic approaches. In this national cohort of VA patients with MRSA pneumonia, treatment was the only modifiable variable predicting clinical success.
- Beyond malaria--causes of fever in outpatient Tanzanian children. [Journal Article, Research Support, Non-U.S. Gov't]
- N Engl J Med 2014 Feb 27; 370(9):809-17.
As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children.We recruited children younger than 10 years of age with a temperature of 38°C or higher at two outpatient clinics--one rural and one urban--in Tanzania. Medical histories were obtained and clinical examinations conducted by means of systematic procedures. Blood and nasopharyngeal specimens were collected to perform rapid diagnostic tests, serologic tests, culture, and molecular tests for potential pathogens causing acute fever. Final diagnoses were determined with the use of algorithms and a set of prespecified criteria.Analyses of data derived from clinical presentation and from 25,743 laboratory investigations yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses), 62.2% had an acute respiratory infection; 5.0% of these infections were radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic infection other than malaria or typhoid fever was found in 13.3% of children, nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%, malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%, typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%. The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease.These results provide a description of the numerous causes of fever in African children in two representative settings. Evidence of a viral process was found more commonly than evidence of a bacterial or parasitic process. (Funded by the Swiss National Science Foundation and others.).