Clostridium difficile: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing.

Background: Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods: Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results: Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusions: Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

Host and pathogen factors for Clostridium difficile infection and colonization.

BACKGROUND: Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. METHODS: We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. RESULTS: A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. CONCLUSIONS: In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).

Antimicrobial susceptibility of clinical isolates of anaerobic bacteria in Ontario, 2010-2011.

The local epidemiology of antimicrobial susceptibility patterns in anaerobic bacteria is important in guiding the empiric treatment of infections. However, susceptibility data are very limited on anaerobic organisms, particularly among non-Bacteroides organisms. To determine susceptibility profiles of clinically-significant anaerobic bacteria in Ontario Canada, anaerobic isolates from sterile sites submitted to Public Health Ontario Laboratory (PHOL) for identification and susceptibility testing were included in this study. Using the E-test method, isolates were tested for various antimicrobials including, penicillin, cefoxitin, clindamycin, meropenem, piperacillin-tazobactam and metronidazole. The MIC results were interpreted based on guidelines published by Clinical and Laboratory Standards Institute. Of 2527 anaerobic isolates submitted to PHOL, 1412 were either from sterile sites or bronchial lavage, and underwent susceptibility testing. Among Bacteroides fragilis, 98.2%, 24.7%, 1.6%, and 1.2% were resistant to penicillin, clindamycin, piperacillin-tazobactam, and metronidazole, respectively. Clostridium perfringens was universally susceptible to penicillin, piperacillin-tazobactam, and meropenem, whereas 14.2% of other Clostridium spp. were resistant to penicillin. Among Gram-positive anaerobes, Actinomyces spp., Parvimonas micra and Propionibacterium spp. were universally susceptible to ß-lactams. Eggerthella spp., Collinsella spp., and Eubacterium spp. showed variable resistance to penicillin. Among Gram-negative anaerobes, Fusobacterium spp., Prevotella spp., and Veillonella spp. showed high resistance to penicillin but were universally susceptible to meropenem and piperacillin-tazobactam. The detection of metronidazole resistant B. fragilis is concerning as occurrence of these isolates is extremely rare. These data highlight the importance of ongoing surveillance to provide clinically relevant information to clinicians for empiric management of infections caused by anaerobic organisms.

Characterization of methicillin-resistant Staphylococcus aureus isolates from patients with persistent or recurrent bacteremia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with considerable morbidity and mortality, especially with persistent (PB) or recurrent bacteremia (RB). OBJECTIVE: To determine the frequency of PB and RB in patients with MRSA BSI, and to characterize the isolates from these patients. METHODS: Surveillance for MRSA BSI was performed for one year in 13 Canadian hospitals. PB was defined as a positive blood culture that persisted for ≥7 days; RB was defined as the recurrence of a positive blood culture ≥14 days following a negative culture. Isolates were typed using pulsed-field gel electrophoresis (PFGE). Vancomycin susceptibility was determined using Etest. RESULTS: A total of 183 patients with MRSA BSI were identified; 14 (7.7%) had PB and five (2.7%) had RB. Ten (5.5%) patients were known to have infective endocarditis, and five of these patients had PB or RB. Initial and subsequent MRSA isolates from patients with PB and RB had the same PFGE type. There were no significant differences in the distribution of PFGE types in patients with PB or RB (37% CMRSA-2/USA100; 37% CMRSA-10/USA300) compared with that in other patients (56% CMRSA-2/USA100; 32% CMRSA-10/USA300). All isolates were susceptible to vancomycin, but patients with PB or RB were more likely to have initial isolates with vancomycin minimum inhibitory concentration = 2.0 µg/mL (26% versus 10%; P=0.06). CONCLUSIONS: Persistent or recurrent MRSA bacteremia occurred in 10.4% of patients with MRSA BSIs. Initial isolates from patients with persistent or recurrent MRSA BSIs were more likely to exhibit reduced susceptibility to vancomcyin, but were not associated with any genotype.

HISTORIQUE: Les infections sanguines (IS) par le Staphylococcus aureus résistant à la méthicilline (SARM) s'associent à une morbidité et une mortalité considérables, particulièrement en présence d'une bactériémie persistante (BP) ou récurrente (BR). OBJECTIF: Déterminer la fréquence de BP et de BR chez les patients atteints d'une IS par le SARM et en caractériser les isolats. MÉTHODOLOGIE: Les chercheurs ont surveillé les IS par le SARM dans 13 hôpitaux canadiens pendant un an. La BP se définissait par une hémoculture positive qui persistait au moins sept jours, tandis que la BR désignait la récurrence d'une hémoculture positive au moins 14 jours après une hémoculture négative. Les chercheurs ont typé les isolats au moyen de l'électrophorèse sur gel en champ pulsé (ECP). Ils ont déterminé la susceptibilité à la vancomycine par Etest. RÉSULTATS: Les chercheurs ont retracé un total de 183 patients ayant une IS par le SARM. De ce nombre, 14 (7,7 %) avaient une BP et cinq (2,7 %), une BR. Dix patients (5,5 %) étaient atteints d'une endocardite infectieuse diagnostiquée, dont cinq avaient une BP ou une BR. Les isolats initiaux et subséquents de SARM chez les patients ayant une BP ou une BR présentaient le même type d'ECP. Il n'y avait pas de différence significative dans la distribution des types d'ECP chez les patients ayant une BP ou une BR (37 % de souche CSARM-2/USA100; 37% de souche CSARM-10/USA300) par rapport à celle des autres patients (56 % de souche CSARM-2/USA100; 32 % de souche CSARM-10/USA300). Tous les isolats étaient susceptibles à la vancomycine, mais les patients atteints d'une BP ou d'une BR étaient plus susceptibles de présenter des isolats initiaux de vancomycine dont la CMI = 2,0 µg/mL (26 % par rapport à 10 %; P=0,06). CONCLUSIONS: Les chercheurs ont observé une BP ou une BR par le SARM chez 10,4 % des patients atteints d'une IS par le SARM. Les isolats initiaux des patients atteints d'une IS persistante ou récurrente par le SARM risquaient davantage d'être moins susceptibles à la vancomycine, mais ne s'associaient à aucun génotype.

Antimicrobial susceptibilities of clinical isolates of HACEK organisms.

The "HACEK" organisms are a group of fastidious Gram-negative bacteria that cause a variety of infections, including infective endocarditis. Antimicrobial susceptibility testing is not universally available, and therapy for these infections is often empirical. We report the antimicrobial susceptibilities of 70 clinical HACEK isolates to 18 antimicrobials. All isolates were susceptible to ceftriaxone and levofloxacin, indicating that these agents remain appropriate empirical choices for the treatment of infections with this group of organisms.

Evaluation of the sterility testing process of hematopoietic stem cells at Canadian Blood Services.

BACKGROUND: Sterility testing of hematopoietic stem cells (HSCs) at The Canadian Blood Services Stem Cell Laboratory is performed using BacT/ALERT aerobic (SA) culture bottles. This study was conducted to verify the efficacy of this method and to assess the use of the BacT/ALERT aerobic (BPA) and anaerobic (BPN) culture bottles for microbial testing of HSCs. STUDY DESIGN AND METHODS: HSC products, including cryopreserved apheresis peripheral blood, marrow, and cord blood and fresh cord blood, were spiked with four aerobic organisms including Staphylococcus epidermidis, Bacillus cereus, Pseudomonas aeruginosa, and Candida albicans, and the anaerobe Bacteroides fragilis at a target concentration of 100 colony-forming units (CFUs)/mL. One to 2 mL of pre- and postspiked samples was inoculated into SA, BPA, and BPN bottles in duplicate and incubated for 5 to 10 days. The presence of the testing organisms in positive culture bottles was confirmed by plating on blood agar. RESULTS: The BacT/ALERT system detected the aerobic organisms in all HSCs in SA and BPA bottles within 34.1 hours while B. fragilis was detected only in BPN bottles within 68.6 hours. The mean recovered concentration of microorganisms in the HSC products ranged from 55 to 352 CFUs/mL with the exception of B. cereus, which was greater than 10(3) CFUs/mL. CONCLUSION: This study shows that the current sterility testing process at the Canadian Blood Services Stem Cell Laboratory detected the tested aerobic but not the anaerobic microbial contaminants in HSCs. The ability of the BacT/ALERT system using BPA and BPN bottles to detect bacterial contamination in HSCs was also demonstrated.

High prevalence of ST131 isolates producing CTX-M-15 and CTX-M-14 among extended-spectrum-beta-lactamase-producing Escherichia coli isolates from Canada.

Phenotypic and genotypic methods were used to characterize extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli isolated in 2007 from 11 different Canadian medical centers. Of the 209 ESBL-producing E. coli isolates tested, 148 (71%) produced CTX-M-15, 17 (8%) produced CTX-M-14, 5 (2%) produced CTX-M-3, and 1 produced CTX-M-27. Overall, 96 (46%) of the ESBL producers belonged to clonal complex ST131, with the highest prevalence in Brampton, Calgary, and Winnipeg. ST131 is an important cause of community onset urinary tract infections due to ESBL-producing E. coli across Canada.

Detection of plasmid-mediated KPC-producing Klebsiella pneumoniae in Ottawa, Canada: evidence of intrahospital transmission.

Klebsiella pneumoniae isolates from three patients admitted to the Ottawa Hospital, a 1,040-bed teaching hospital, were found to contain the plasmid-borne K. pneumoniae carbapenemase (KPC)-producing bla gene (bla(KPC)). There was evidence of person-to-person transmission for two patients. Screening of 186 clinical isolates revealed no additional bla(KPC)-containing isolates.

Contemporary Microbiology and Antimicrobial Treatment of Complicated Appendicitis: The Value of a Short-term Study.

BACKGROUND: Antimicrobial stewardship interventions to curtail the use of third-generation cephalosporins and antipseudomonal penicillins for the treatment of complicated appendicitis in children are challenging given the tendency to treat complicated disease with broad-spectrum antimicrobials. Reasons for this are unclear, but there is a paucity of contemporary microbiologic data associated with the child presenting with either acute perforated or gangrenous appendicitis. This study aimed to justify the appropriateness of an empiric regimen consisting of ampicillin, tobramycin/gentamicin plus metronidazole and to analyze duration of postoperative therapy. METHODS: We conducted a retrospective cohort study from February 1, 2017, to October 31, 2018, in children who underwent appendectomy or interventional radiologic drainage for primary complicated appendicitis. The primary outcome was the proportion of patients who had a pathogen isolated from peritoneal fluid culture that was not susceptible to the recommended empiric therapy. The secondary outcomes were the total duration of antimicrobial therapy and the proportion of patients with a postoperative infectious complication within 30 days after intervention. RESULTS: Of 425 children with primary acute appendicitis, 158 (37%) had complicated appendicitis at presentation. Culture was performed in 53 (40%) of the 133 who underwent a surgical or interventional radiologic intervention. The group with peritoneal cultures was more likely to present with longer symptom duration before admission [3 (interquartile range, 2-5) vs 2 (interquartile range, 1-2) days; P < 0.001] and with purulent peritonitis [47% (25/53) vs 13% (10/80); P < 0.001]. The most common pathogens isolated were anaerobes (81%), Escherichia coli (74%) and Streptococcus anginosus group (62%). Only 4% of isolated bacteria were resistant to empiric therapy. Postoperative infectious complications were documented in 23 (17%) patients and were not associated with the presence of a resistant pathogen or the choice of antimicrobial agents but with more severe disease and higher C-reactive protein values (303 vs 83 mg/L; P=0.03) at presentation. CONCLUSIONS: In a cohort of previously healthy children presenting with complicated appendicitis requiring surgical drainage, the most common bacteria from peritoneal cultures continue to be S. anginosus, aminoglycoside-susceptible Gram-negative bacilli and anaerobes. In an attempt to reduce extended-spectrum cephalosporin use, these data were useful in supporting the use of metronidazole with ampicillin and an aminoglycoside, rather than third-generation cephalosporins.

Incidental post-partum isolation of Brucella melitensis in an asymptomatic woman.

A 25-year-old Somali-born female was admitted to the hospital in active labour. Following post-partum hemorrhage, Brucella melitensis grew from a blood culture and the placenta. Identification and relatedness were determined through reverse transcriptase polymerase chain reaction (RT-PCR), single nucleotide polymorphism (SNP), and whole genome sequencing. The patient and her child were completely asymptomatic at their initial assessment.

Une femme d'origine somalienne de 25 ans a été hospitalisée en travail actif. Après une hémorragie postpartum, le Brucella melitensis s'est développé dans une hémoculture et dans le placenta. La réaction de transcriptase inverse et d'amplification en chaîne de la polymérase (RT-PCR), le polymorphisme du nucléotide simple (SNP) et le séquençage du génome entier ont permis d'identifier la bactérie et d'établir sa parenté génétique. La patiente et son enfant étaient complètement asymptomatiques à l'évaluation initiale.

Direct molecular detection of amoxicillin-susceptible E. coli in urine samples from children with suspected urinary tract infection: A potential tool to improve antibiotic stewardship and patient care.

Background: Rapid detection of amoxicillin-susceptible Escherichia coli (ASEC) urinary tract infections (UTIs) could have a significant impact on patient care and improve antibiotic stewardship. This is especially true for infants and children, for whom antibiotic choices are more limited than for adults. Methods: A real-time polymerase chain reaction (PCR) uniplex panel for detection of ASEC using PCR assays for E. coli and five resistance genes (bla TEM, bla SHV, bla OXA, bla CTX-M, and bla CMY) and an internal control was designed. PCR was then performed directly on pediatric urine samples using an inhibitor-resistant DNA polymerase. The main outcome measure was the performance of the PCR panel (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], accuracy) for the detection of ASEC. ASEC samples were defined as those that were E. coli PCR positive and PCR negative for all five resistance genes. PCR results were compared with the reference standard for culture and susceptibility testing. Results: Two hundred and six urine samples with pyuria (>10 white blood cells/high power field) were tested with the PCR panel. Two samples showed PCR inhibition (1%). For ASEC detection, the PCR panel showed a sensitivity of 91.53% (95% CI 81.32% to 97.19%), specificity of 98.21% (95% CI 90.45% to 99.95%), PPV of 98.18% (95% CI 88.54% to 99.74%), NPV of 91.67% (95% CI 82.61% to 96.22%), and accuracy of 94.78% (95% CI 88.99% to 98.06%). Conclusions: This PCR method could potentially enable amoxicillin or ampicillin to be used in a greater proportion of children with E. coli UTIs, improving antibiotic stewardship.

Historique: La détection rapide des infections urinaires à Escherichia coli susceptibles à l'amoxicilline (ECSA) peut avoir des effets importants sur les soins aux patients et améliorer la gérance des antibiotiques. C'est particulièrement vrai chez les nourrissons et les enfants, pour qui les choix d'antibiotiques sont plus limités que pour les adultes. Méthodologie: Les chercheurs ont fait appel à un panel uniplex d'amplification en chaîne par polymérase (PCR) pour déceler l'ECSA au moyen d'épreuves PCR d'E. coli et de cinq gènes de résistance (bla TEM, bla SHV, bla OXA, bla CTX-M et bla CMY) et ont conçu un contrôle interne. Ils ont ensuite effectué la PCR directement sur les échantillons d'urine pédiatrique à l'aide d'une polymérase d'ADN résistante aux inhibiteurs. La principale mesure de résultat était l'exécution du panel de PCR (sensibilité, spécificité, valeur prédictive positive [VPP], valeur prédictive négative [VPN], précision) pour déceler l'ECSA. Les échantillons d'ECSA étaient définis comme ceux dont la PCR était positive à l'E. coli et négative aux cinq gènes de résistance. Les chercheurs ont comparé les résultats de la PCR aux normes de référence des tests de culture et susceptibilité. Résultats: Les chercheurs ont testé 206 échantillons d'urine pyurique (>10 globules blancs/champ à fort grossissement) avec le panel de PCR. Deux échantillons ont révélé une inhibition de la PCR (1 %). Pour déceler l'ECSA, le panel de PCR a révélé une sensibilité de 91,53 % (IC à 95 %, 81,32 % à 97,19 %), une spécificité de 98,21 % (IC à 95 %, 90,45 % à 99,95 %), une VPP de 98,18 % (IC à 95 %, 88,54 % à 99,74 %), une VPN de 91,67 % (IC à 95 %, 82,61 % à 96,22 %) et une précision de 94,78 % (IC à 95 %, 88,99 % à 98,06 %). Conclusions: Cette méthode de PCR pourrait permettre de prescrire de l'amoxicilline ou de l'ampicilline à une plus grande proportion d'enfants ayant une infection urinaire à E. coli, ce qui améliorera la gérance des antibiotiques.

Surveillance for hospital outbreaks of invasive group a streptococcal infections in Ontario, Canada, 1992 to 2000.

BACKGROUND: Streptococcus pyogenes can cause severe disease in the individual patient and dramatic hospital outbreaks. OBJECTIVE: To describe the epidemiology of hospital outbreaks of invasive group A streptococcal infection in order to understand the potential benefit of proposed outbreak investigation and management strategies. DESIGN: Prospective, population-based surveillance. SETTING: Short-term care hospitals in Ontario, Canada. PATIENTS: Persons with a positive culture for group A streptococcus from a normally sterile site between 1 January 1992 and 31 December 2000. MEASUREMENTS: Laboratory-based surveillance identified patients with nosocomial invasive group A streptococcal infection. Epidemiologic and microbiological investigations were used to detect transmission. RESULTS: Of 2351 cases of invasive group A streptococcal disease, 291 (12%) were hospital acquired. Twenty-nine (10%) nosocomial cases occurred as part of 20 outbreaks. Seventy percent (14 of 20) of outbreaks involved nonsurgical, nonobstetric patients. Community-acquired cases initiated 25% of outbreaks; most were cases of necrotizing fasciitis in patients admitted to the intensive care unit. Outbreaks were small (median, 2 cases [range, 2 to 10 cases]) and short (median duration, 6 days [range, 0 to 30 days]). The median time between the first 2 cases was 4.5 days. The most common mode of propagation was patient-to-patient transmission. A staff carrier was the primary mode of transmission in 2 (10%) outbreaks, but 1 or more health care workers were colonized with the outbreak strain in 6 of 18 (33%) other outbreaks. LIMITATIONS: Some outbreaks with 1 case of invasive disease may have been missed; advice provided to participating hospitals may have reduced the number and size of outbreaks. CONCLUSIONS: Practices to prevent hospital transmission of group A streptococci should include isolation of patients admitted to the intensive care unit with necrotizing fasciitis, investigation after a single nosocomial case, and emphasis on identifying and treating health care worker carriers on surgical and obstetric services and patient reservoirs on other wards.

A comparison of the Allplex™ bacterial and viral assays to conventional methods for detection of gastroenteritis agents.

OBJECTIVE: Molecular methods to detect diarrheal pathogens are increasingly being used in place of conventional methods. We compared a new multiplex real-time PCR assay for detection of both bacterial and viral gastroenteritis agents, the Allplex™ Gastrointestinal Panel Assays (AGPA), to conventional methods (stool culture for bacterial pathogens and electron microscopy (EM) for viral pathogens). RESULTS: Gastrointestinal viruses, in particular norovirus genogroup II viruses, were detected by the AGPA in a high number of specimens that were negative by EM. For bacterial pathogens, the AGPA was able to detect the organisms grown in culture with high sensitivity and additionally detected several types of E. coli, such as enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), and non-O157 Shiga toxin-producing E. coli (STEC), that could not be detected with conventional culture methods. Overall, the AGPA had a > 2-fold higher detection rate than the conventional methods, with 24/135 (17.8%) samples positive by conventional methods and 60/135 (44.4%) by AGPA. Thus, diarrhea pathogen detection rates increased substantially with the use of the AGPA as compared to conventional methods.

Prevalence of methicillin-resistant Staphylococcus aureus in a Canadian inner-city shelter.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is increasingly of concern in community settings. However, despite a recent outbreak in Calgary, Alberta, data on the prevalence of MRSA in Canadian communities are lacking. Globally, few studies have been performed in high-risk groups such as inner-city populations. METHODS: A cross-sectional study of the prevalence of MRSA among residents and staff at three Ottawa, Ontario, shelters was conducted. All participants completed a questionnaire, and provided nasal swabs as well as one of rectal, anal or groin swabs. RESULTS: Among 84 participants, the prevalence of MRSA colonization was 2.4%. Among the resident subgroup, the prevalence was 4.5%, while no MRSA isolates were found among 40 staff participants. All isolates were USA100 (CMRSA-2) subtypes. CONCLUSIONS: The prevalence of MRSA colonization among residents is higher than baseline population rates, but is consistent with other inner-city populations. Although community outbreaks of USA300 and USA400 strains are increasingly reported, movement of nosocomial strains (ie, USA100 [CMRSA-2]) into communities remains an important avenue in the spread of MRSA and underscores the importance of nosocomial MRSA control.

Outcomes in a nurse-led peripherally inserted central catheter program: a retrospective cohort study.

BACKGROUND: Peripherally inserted central catheters (PICCs) provide enormous benefit to patients. However, recent publications have highlighted relatively high PICC-associated complication rates. We report on patient and device outcomes from a nurse-led program. METHODS: We performed a retrospective analysis of a prospective cohort of consecutive patients undergoing PICC insertion at The Ottawa Hospital between Jan. 1, 2013 and Dec. 31, 2014. Of the 8314 BioFlo PASV PICCs inserted, we randomly selected a sample of 700 and obtained a complete data set for 656. We measured the cumulative incidence of major complications (catheter-related bloodstream infections and deep vein thrombosis) and use of a thrombolytic to alleviate occlusions. RESULTS: The total number of catheter days was 58 486, and the median dwell time 45 days. We observed 4 cases of catheter-related bloodstream infection (0.6% [95% CI 0.17%-1.55%]) (0.07/1000 catheter days). Ten patients (1.5% [95% CI 0.83%-2.78%]) (0.17/1000 catheter days) had catheter-related deep venous thrombosis. At least 1 dose of thrombolytic was required in 75 catheters (11.4% [95% CI 8.61%-13.39]), 31 (7.1%) of the 436 single-lumen catheters and 113 (25.7%) of the 440 lumina of dual-lumen catheters (p < 0.001). INTERPRETATION: We attribute our low rates of major complications to a nurse-led expert insertion team, standardized care and maintenance protocols, high insertion volumes, novel catheter material and continuous quality-improvement initiatives that are implemented and evaluated regularly. We conclude that the considerable benefits PICCs provide to patients are attained with a low risk of major complications.

Pneumocystis pneumonia outbreak among renal transplant recipients at a North American transplant center: Risk factors and implications for infection control.

BACKGROUND: Pneumocystis pneumonia is a severe opportunistic fungal infection. Outbreaks among renal transplant recipients have been reported in Europe and Japan, but never in North America. METHODS: We conducted a retrospective case-control study among adult renal transplant recipients at a Canadian center, using a 3:1 matching scheme. Ten cases and 30 controls were matched based on initial transplantation date, and all patients received prophylaxis with trimethoprim-sulfamethoxazole for 1 year posttransplantation. RESULTS: The median time between transplantation and infection was 10.2 years, and all patients survived. Compared with controls, case patients had statistically lower estimated glomerular filtration rate (29.3 mL/min vs 66.3 mL/min; P = .028) and lymphopenia (0.51 × 10(9)/L vs 1.25 × 10(9)/L; P = .002). Transmission mapping revealed significant overlap in the clinic and laboratory visits among case vs control patients (P = .0002). One hundred percent of patients (4 out of 4) successfully genotyped had the same strain of Pneumocystis jirovecii. CONCLUSIONS: Our study demonstrated an outbreak of pneumocystis more than 10 years following initial transplantation, despite using recommended initial prophylaxis. We identified low estimated glomerular filtration rate and lymphopenia as risk factors for infection. Overlapping ambulatory care visits were identified as important potential sources of infection transmission, suggesting that institutions should re-evaluate policy and infrastructure strategies to interrupt transmission of respiratory pathogens.

Mycobacterium abscessus infection after use of tumor necrosis factor alpha inhibitor therapy: case report and review of infectious complications associated with tumor necrosis factor alpha inhibitor use.

Tumor necrosis factor alpha (TNF-alpha) inhibitors, such as infliximab and etanercept, are now frequently used in the treatment of inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease. As an apparent result of their immune modulating activity, there has been an observed association between the use of these agents and the development of a wide range of infections, most notably Mycobacterium tuberculosis. We describe a case of infection with Mycobacterium abscessus in a 67-year-old woman receiving infliximab as a component of her therapy for RA. This case, along with extensive reports in the medical literature, illustrate how treatment with inhibitors of TNF-alpha has the potential to result in a wide range of infectious complications, including rapid growing Mycobacterium.

Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study.

BACKGROUND: Coagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods. METHODS: A retrospective study was conducted of infants > or =4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups. RESULTS: There were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2. CONCLUSION: Although we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU.

Risk Factors for and Outcomes of Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella Species at a Canadian Tertiary Care Hospital.

BACKGROUND: Antimicrobial resistance due to production of extended-spectrum ß-lactamases by Escherichia coli and Klebsiella species (ESBL-EK) is concerning. Previous studies have shown that bacteremia due to ESBL-producing organisms is associated with increases in length of stay and/or mortality rate. Rates of infection by ESBL-EK vary worldwide, and regional differences in the prevalence of risk factors are likely. Few Canadian studies assessing risk factors for ESBL-EK infections or the outcomes of empiric therapy have been published. OBJECTIVES: To determine risk factors for and patient outcomes associated with ESBL-EK bacteremia. The appropriateness of empiric antibiotic therapy and the effect of inappropriate empiric therapy on these outcomes were also examined. METHODS: In a retrospective, 1:1 case-control study conducted in a tertiary care hospital between 2005 and 2010, data for 40 patients with ESBL-EK bacteremia were compared with data for 40 patients who had non-ESBL-EK bacteremia. RESULTS: Of all variables tested, only antibiotic use within the previous 3 months was found to be an independent risk factor for acquisition of ESBL-EK bacteremia (odds ratio 5.2, 95% confidence interval 1.6-16.9). A greater proportion of patients with non-ESBL-EK bacteremia received appropriate empiric therapy (88% [35/40] versus 15% [6/40], p < 0.001). Time to appropriate therapy was longer for those with ESBL-EK bacteremia (2.42 days versus 0.17 day, p < 0.001). Patient outcomes, including length of stay in hospital, admission to the intensive care unit (ICU), length of stay in the ICU (if applicable), and in-hospital mortality were not affected by the presence of ESBL-EK or the appropriateness of empiric therapy. CONCLUSIONS: Previous antibiotic use was a significant, independent risk factor for acquiring ESBL-EK. Thus, prior antibiotic use is an important consideration in the selection of empiric antibiotic therapy and should increase the concern for resistant pathogens.

CONTEXTE: La résistance aux antimicrobiens attribuable à la production de ß-lactamases à spectre étendu (BLSE) par les espèces Escherichia coli et Klebsiella est préoccupante. Des études antérieures ont démontré que les bactériémies causées par les organismes producteurs de BLSE sont associées à une augmentation de la durée du séjour à l'hôpital ou du taux de mortalité. Les taux d'infection par les espèces E. coli ou Klebsiella productrices de BLSE varient de par le monde et les différences régionales de la prévalence des facteurs de risque sont vraisemblables. Peu d'études canadiennes évaluant les facteurs de risque de ces infections ou les résultats cliniques des antibiothérapies empiriques ont été publiées. OBJECTIFS: Déterminer quels sont les facteurs de risque des bactériémies à E. coli ou à Klebsiella productrices de BLSE ainsi que les résultats cliniques associés à ces bactériémies. De plus, étudier la pertinence de l'antibiothérapie empirique ainsi que l'effet d'une antibiothérapie empirique inappropriée sur ces résultats. MÉTHODES: Au cours d'une étude cas-témoins rétrospective d'un ratio de 1 pour 1 et réalisée dans un centre hospitalier de soins tertiaires entre 2005 et 2010, les données de 40 patients présentant une bactériémie à E. coli ou Klebsiella productrices de BLSE ont été comparées aux données de patients présentant une bactériémie à organisme non producteur de BLSE. RÉSULTATS: Parmi toutes les variables évaluées, seul l'emploi d'une antibiothérapie dans les trois derniers mois s'est révélé être un facteur de risque indépendant du développement d'une bactériémie à E. coli ou Klebsiella productrices de BLSE (risque relatif approché de 5,2, intervalle de confiance à 95 % de 1,6­16,9). Une plus grande proportion de patients présentant une bactériémie autre que celles à E. coli ou Klebsiella productrices de BLSE ont reçu une antibiothérapie empirique appropriée (88 % [35/40] contre 15 % [6/40], p < 0,001). Le temps requis pour trouver le traitement adéquat était plus long pour ceux présentant une bactériémie à E. coli ou Klebsiella productrices de BLSE (2,42 jours contre 0,17 jour, p < 0,001). La présence des espèces E. coli ou Klebsiella productrices de BLSE de même que la pertinence d'une antibiothérapie empirique n'ont pas eu de répercussion sur les résultats cliniques, notamment la durée du séjour à l'hôpital, l'admission à l'unité des soins intensifs (USI), la durée du séjour à l'USI (le cas échéant) ainsi que le taux de mortalité en hôpital. CONCLUSIONS: L'emploi d'une antibiothérapie préalable représentait un important facteur de risque indépendant de la survenue des espèces E. coli ou Klebsiella productrices de BLSE. Ce faisant, l'emploi d'une antibiothérapie préalable représente un facteur important à considérer au moment du choix d'une antibiothérapie empirique et devrait rendre sensible aux dangers des pathogènes résistants.

Disseminated histoplasmosis associated with acquired hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening clinical syndrome caused by uncontrolled activation of lymphocytes and histiocytes resulting in high levels of cytokines. Acquired HLH occurs in autoimmune, inflammatory, infectious, and immunosuppressive disorders. Prompt identification and treatment of an underlying triggering cause improves clinical outcome.