Case report: Mycobacterium bovis orchitis post intravesical Bacillus Calmette Guerin.

Bacillus Calmette-Guérin (BCG) therapy is a common adjunctive therapy for superficial bladder carcinoma but there has been noted to be complications from this treatment ranging from general disseminated infections to osteomuscular involvement. We report a case regarding a 63 year old gentleman who presented with right testicular swelling and pain and later found to have evidence consistent with Mycobacterium bovis orchitis. We also detail a literature review regarding genitourinary infections secondary to BCG therapy and discussion regarding current testing modalities.

Clinical Outcomes in Patients With Gram-Negative Infections Treated With Optimized Dosing Cefepime Over Various Minimum Inhibitory Concentrations.

BACKGROUND: The Clinical and Laboratory Standards Institute (CLSI) revised cefepime interpretive criteria, introducing the susceptible dose-dependent category for Enterobacteriaceae with a minimum inhibitory concentration (MIC) of 4 to 8 µg/mL in 2014. Limited clinical data support these new categories. This study compares outcomes of patients treated with standard and high-dose cefepime across various MICs. METHODS: We retrospectively reviewed cases of pneumonia or bacteremia caused by gram-negative organisms treated with adequate doses of cefepime for ≥48 hours. Outcomes were compared for MICs of ≤2 (low), 4 (medium), and 8 µg/mL (high). The primary end point was clinical failure, the secondary end point was microbiological failure. RESULTS: Ninety cases met the inclusion criteria: 46, 25, and 19 patients with low, medium, or high MIC, respectively. Multivariate logistic regression revealed that the medium (odds ratio [OR]: 9.13, P < .01) and high (OR: 6.79, P = .01) MIC groups had increased clinical failure. CONCLUSION: Cefepime therapy, even at CLSI-recommended doses, had an increased risk of clinical failure for gram-negative pathogens with MICs of 4 or 8 µg/mL. This finding suggests that higher dosing regimens (2 g every 8 hours or 1 g every 6 hours) may be necessary to treat serious gram-negative infections with elevated MICs.

Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report.

BACKGROUND: : Travelers' diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts. METHODS: : This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers' diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology. RESULTS: : New definitions for severity of travelers' diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted. CONCLUSIONS: : Prevention and treatment of travelers' diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers' diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea.

Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia.

Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state. Additionally, clinical outcomes for 33 patients with Gram-negative bacterial pneumonia who received cefepime monotherapy were determined. The free minimum concentration (fCmin) to MIC ratio for each patient was determined by conditioning the validated pharmacokinetic model using patient-specific creatinine clearance (CLCr), dosing regimen and cefepime MIC of the organism isolated, and was subsequently correlated with clinical failure. Classification and regression tree (CART) analysis was used to determine the most significant drug exposure breakpoint. Mean±S.D. CLCr and cefepime Cmin in the 12 patients were 87.5±21.2mL/min and 6.2±3.8mg/L, respectively. In comparison, the Cmin predicted by the pharmacokinetic model was 5.8mg/L using a CLCr of 90mL/min. MICs of organisms ranged from 0.5mg/L to 8mg/L. Percent time free drug above MIC of 100% was achieved in 32/33 patients, but 12 patients experienced clinical failure. CART analysis determined patients with an fCmin/MIC≥2.1 had a significantly lower risk of clinical failure (OR=0.11, 95% CI 0.02-0.67; P=0.017). The fCmin/MIC ratio is a useful predictor of clinical failure in Gram-negative bacterial pneumonia. The clinical utility of fCmin/MIC in therapeutic drug monitoring should be further explored.

Vibrio parahemolyticus septicaemia in a liver transplant patient: a case report.

INTRODUCTION: Vibrio parahemolyticus is the leading cause of vibrio-associated gastroenteritis in the United States of America, usually related to poor food handling; only rarely has it been reported to cause serious infections including sepsis and soft tissue infections. In contrast, Vibrio vulnificus is a well-known cause of septicaemia, especially in patients with cirrhosis. We present a patient with V. parahemolyticus sepsis who had an orthotic liver transplant in 2007 and was on immunosuppression for chronic rejection. Clinical suspicion driven by patient presentation, travel to Gulf of Mexico and soft tissue infection resulted in early diagnosis and institution of appropriate antibiotic therapy. CASE PRESENTATION: A 48 year old Latin American man with a history of chronic kidney disease, orthotic liver transplant in 2007 secondary to alcoholic end stage liver disease on immunosuppressants, and chronic rejection presented to the emergency department with fever, vomiting, abdominal pain, left lower extremity swelling and fluid filled blisters after a fishing trip in the Gulf of Mexico. Samples from the blister and blood grew V. parahemolyticus. The patient was successfully treated with ceftriaxone and ciprofloxacin. CONCLUSION: Febrile patients with underlying liver disease and/or immunosuppression should be interviewed regarding recent travel to a coastal area and seafood ingestion. If this history is obtained, appropriate empiric antibiotics must be chosen. Patients with liver disease and/or immunosuppresion should be counselled to avoid eating raw or undercooked molluscan shellfish. People can prevent Vibrio sepsis and wound infections by proper cooking of seafood and avoiding exposure of open wounds to seawater or raw shellfish products.

Prevention of travelers' diarrhea with rifaximin in US travelers to Mexico.

BACKGROUND: Because bacterial pathogens are the primary cause of travelers' diarrhea (TD), antibiotic prophylaxis is effective in TD prevention. This study assessed the efficacy and safety of the nonsystemic antibiotic rifaximin in preventing TD in US travelers to Mexico. METHODS: Healthy adult students traveling to Mexico received rifaximin 600 mg/d or placebo for 14 days and were followed for 7 days post-treatment. Stool pattern and gastrointestinal symptoms were recorded in daily diary entries. The primary end point was prevention of TD during 14 days of treatment measured by time to first unformed stool. RESULTS: A total of 210 individuals received rifaximin (n = 106) or placebo (n = 104) and were included in the safety population. Median age was 21 years (range, 18-75 y), and the majority of participants were female (65%). Efficacy analyses were conducted in a modified intent-to-treat population of 201 patients who received rifaximin (n = 99) or placebo (n = 102). Rifaximin prophylaxis reduced risk of developing TD versus placebo (p < 0.0001). A smaller percentage of individuals who received rifaximin versus placebo developed all-cause TD (20% vs 48%, respectively; p < 0.0001) or TD requiring antibiotic therapy (14% vs 32%, respectively; p = 0.003). More individuals in the rifaximin group (76%) completed treatment without developing TD versus those in the placebo group (51%; p = 0.0004). Rifaximin provided a 58% protection rate against TD and was associated with fewer adverse events than placebo. CONCLUSIONS: Prophylactic treatment with rifaximin 600 mg/d for 14 days safely and effectively reduced the risk of developing TD in US travelers to Mexico. Rifaximin chemoprevention should be considered for TD in appropriate individuals traveling to high-risk regions.

Noroviruses as a cause of diarrhea in travelers to Guatemala, India, and Mexico.

Noroviruses (NoVs) are increasingly being recognized as an important enteric pathogen of gastroenteritis worldwide. The prevalence of NoVs as a cause of diarrhea acquired by travelers in developing countries is not well known. We examined the prevalence and importance of NoV infection in three international traveler cohorts with diarrhea acquired in three developing regions of the world, Mexico, Guatemala, and India. We also characterized the demographics and symptoms associated with NoV diarrhea in these travelers. Stool samples from 571 international travelers with diarrhea were evaluated for traditional enteropathogens. NoVs were identified using reverse transcription-PCR and probe hybridization. NoVs were identified in 10.2% of cases of travelers' diarrhea and, overall, was the second most common pathogen, following diarrheagenic Escherichia coli. The detection of NoV diarrhea significantly varied over the three study time periods in Guadalajara, Mexico, ranging from 3 of 98 (3.0%) diarrheal stools to 12 of 100 (12.0%) fecal specimens (P=0.03). The frequency of NoV diarrhea was also dependent upon the geographic region, with 17 of 100 (17.0%) travelers to Guatemala, 23 of 194 (11.9%) travelers to India, and 3 of 79 (3.8%) travelers to Mexico testing positive for NoVs from 2002 to 2003 (P=0.02). NoVs are important pathogens of travelers' diarrhea in multiple regions of the world. Significant variation in the prevalence of NoV diarrhea and in the predominant genogroup infecting travelers was demonstrated, dependent upon the specific geographic location and over time.

Travelers' preferences for the treatment and prevention of acute diarrhea.

BACKGROUND: A survey was designed to assess travelers' willingness to take antibiotic chemoprophylaxis against travelers' diarrhea (TD) or to intervene with antibiotic or symptomatic treatments. METHODS: A brief written questionnaire was administered to clients in North American (United States and Canadian) and European (UK and German) travel clinic waiting rooms to assess length, purpose, and destination of their upcoming trips; their perceived risk of developing TD at their destination; and their preferences for hypothetical treatment or chemoprophylaxis options, which included descriptions, but no mention of brand names, of a systemically absorbed antibiotic based on a fluoroquinolone, a nonabsorbed antibiotic based on rifaximin, and an over-the-counter antidiarrheal similar to loperamide. RESULTS: The 209 UK and German travelers planned significantly longer travel than the 277 US and Canadian travelers (25 vs 15 d, p < 0.001) and correctly recognized high risk of TD more often than the North Americans (81% vs 61%, p < 0.001). More of the North Americans preferred any therapy options compared with the Europeans; only 14% of the North Americans preferred no treatment compared with 29% of the Europeans (p < 0.001). More of the North Americans and the Europeans preferred the nonabsorbed antibiotic than the systemically absorbed antibiotic, regardless of if combined with the antidiarrheal agent. Significantly more of the Europeans preferred not to take antibiotic chemoprophylaxis than North Americans (66% vs 37%, p < 0.001). Among the North Americans, significantly more travelers preferred chemoprophylaxis with the nonabsorbed than the systemic antibiotic (45% vs 33%, p= 0.003). CONCLUSIONS: Among the relatively small groups of travelers studied, the UK and German travelers were more cognizant of TD risk than US and Canadian travelers. The Europeans were less inclined to take chemoprophylaxis or treatment. Both groups preferred treatment or prophylaxis with the nonabsorbed antibiotic over the systemically absorbed antibiotic or the antidiarrheal agent.

Expert review of the evidence base for prevention of travelers' diarrhea.

The most frequent illness among persons traveling from developed to developing countries is travelers' diarrhea. Travelers to high-risk regions traditionally have been educated to exercise care in food and beverage selection. Innovative research is needed to identify ways to motivate people to exercise this care and to determine its value. Chemoprophylaxis can be recommended for certain groups while monitoring for safety, drug resistance, and efficacy against all forms of bacterial diarrhea. Research to evaluate the value of immunoprophylaxis is recommended. In the following document, the authors used an evidence base when available to determine strength and quality of evidence and when data were lacking, the panel experts provided consensus opinion.

Enterotoxigenic Escherichia coli and diffusely adherent E. coli as likely causes of a proportion of pathogen-negative travelers' diarrhea--a PCR-based study.

BACKGROUND: Enteropathogens cannot be identified in 40% to 50% of subjects with travelers' diarrhea (TD). METHODS: We used polymerase chain reaction (PCR) methods to look for the presence of two bacterial causes of diarrhea in a large group of international travelers after failing to detect a pathogen by conventional tests. DNA was isolated from the diarrheal stool and subjected to PCR from 162 subjects from whom we earlier failed to identify a pathogen in a previous study and included 54 from Antigua, Guatemala, 39 from Guadalajara, Mexico, 29 from Kolkata, India, and 40 from Goa, India. Gene products for enterotoxigenic Escherichia coli (ETEC)--LT (heat-labile enterotoxin) and ST (heat-stable enterotoxin)--and diffusely adherent E. coli (DAEC), afa/dr (Afa fimbrial and Dr nonfimbrial family of adhesins), were used. RESULTS: At least one gene product was identified in diarrhea stool samples of 47 of 162 (29%) subjects. ETEC virulence genes (LT, ST) were found in 34 (21%) samples studied, with rates of occurrence ranging from 8% in Goa to 39% for the samples from Guatemala (p = 0.0006). A large number of ST-only strains explained the high ETEC rate in Guatemala. DAEC afa/dr family of adhesions was identified in between 8 and 14% of the samples. CONCLUSIONS: ETEC and DAEC were implicated in nearly one-third of the subjects initially diagnosed as pathogen negative. Direct PCR results from stools are consistent with the previous assumption that most undiagnosed TD is bacterial in nature and also highlights the potential value that PCR can add to studies designed to evaluate treatment and preventive interventions for TD, including vaccines.