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OBJECTIVE: To describe a case of successful treatment of severe pulmonary blastomycosis with amphotericin B deoxycholate after failure of liposomal amphotericin B. CASE SUMMARY: A 35-year-old male was exposed to damp decomposing wood while cleaning his basement. He subsequently developed a cough, malaise, fever, nausea, vomiting, and diarrhea. He was admitted to the hospital and intubated for worsening pulmonary symptoms. Microscopic examination of his sputum indicated Blastomyces dermatitidis. Liposomal amphotericin B was administered for 6 days, but the patient's temperature reached 39.6 °C and his white blood cell (WBC) count reached 52,300/µL. Extensive consolidation of both lungs fields was observed on chest X-ray. Because of progressive clinical deterioration, the treatment was switched to amphotericin B deoxycholate by continuous infusion. That change resulted in clinical improvement, with abrupt reductions (within 48 hours) in temperature and the WBC count. By day 14 of therapy (day 8 of amphotericin B deoxycholate), the chest X-ray showed improvement in diffuse airspace filling. After 16 days of amphotericin B treatment, intravenous followed by oral voriconazole was administered for 3 months. Eight months later the patient's strength had improved significantly, but he still had occasional episodes of shortness of breath. DISCUSSION: The management of blastomycosis is challenging because of the lack of clinically supporting data. The gold standard for severe pulmonary blastomycosis had been amphotericin B deoxycholate; however, improved safety data with liposomal amphotericin B for other fungal infections has suggested this as an effective alternative. This report describes a patient with severe pulmonary blastomycosis failing 6 days of liposomal amphotericin B, yet he tolerated and clinically responded to continuous infusion of amphotericin B deoxycholate. Based on this case report and a simulated pharmacokinetic/pharmaco dynamic analysis, continuous infusion of amphotericin B deoxycholate may be a reasonable option for enhanced efficacy and minimal toxicity in patients with blastomycosis. CONCLUSIONS: Ours is the first case report to use continuous infusion of amphotericin B deoxycholate for the management of pulmonary blastomycosis. These results suggest that liposomal amphotericin B may not be adequate in some patients for the management of B. dermatitidis pulmonary infections.
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Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Blastomicose/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Adulto , Blastomicose/diagnóstico , Humanos , Infusões Intravenosas , Masculino , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Falha de Tratamento , Resultado do TratamentoRESUMO
INTRODUCTION: Staphylococcus aureus bacteremia is associated with considerable morbidity and mortality. In theory, reducing the turnaround time in reporting of methicillin-resistant S aureus (MRSA) among patients with bactermia could assist with the rapid optimization of antimicrobial therapy. OBJECTIVE: To evaluate the sensitivity and specificity of MRSASelect (Bio-Rad Laboratories, USA), a chromogenic medium, in the early detection of MRSA from blood cultures growing Gram-positive cocci in clusters, and to confirm that routine use of this medium would, in fact, reduce turnaround time for MRSA identification. METHODS: The present study was conducted at three microbiology laboratories in Manitoba. Between April 2010 and May 2011, positive blood cultures with Gram-positive cocci in clusters visualized on Gram stain were subcultured to both MRSASelect and routine media. MRSA isolates were identified using conventional microbiological methods from routine media and using growth with the typical colony morphology (pink colony) on MRSASelect medium. RESULTS: A total of 490 blood cultures demonstrating Gram-positive cocci in clusters on Gram stain were evaluated. S aureus was recovered from 274 blood cultures, with 51 S aureus isolates (51 of 274 [18.6%]) identified as MRSA. MRSASelect medium had a sensitivity of 98%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.8% for the recovery and identification of MRSA directly from positive blood culture bottles. In addition, use of MRSASelect medium was found to improve turnaround time in the detection of MRSA by almost 24 h relative to conventional methods. DISCUSSION: These data support the utility of MRSASelect medium for the rapid identification of MRSA from positive blood cultures. Further clinical studies are warranted to determine whether the improvement in turnaround time will result in a measurable reduction in suboptimal antimicrobial therapy and/or improvement in patient outcome.
HISTORIQUE: La bactériémie à Staphylococcus aureus s'associe à une morbidité et une mortalité considérables. En théorie, la réduction du délai à confirmer un S aureus résistant à la méthicilline (SARM) chez les patients ayant une bactériémie pourrait contribuer à l'optimisation rapide de la thérapie antimicrobienne. OBJECTIF: Évaluer la sensibilité et la spécificité du MRSASelect (Bio-Rad Laboratories, États-Unis), un milieu de culture chromogène, pour déceler rapidement le SARM dans des cultures sanguines contenant des coccobacilles à Gram positif en grappes et confirmer que l'utilisation systématique de ce milieu de culture réduit véritablement le délai de dépistage du SARM. MÉTHODOLOGIE: Les chercheurs ont mené la présente étude dans trois laboratoires de microbiologie du Manitoba. Entre avril 2010 et mai 2011, les cultures sanguines positives aux coccobacilles à Gram positif en grappes visualisées sur une coloration de Gram ont été repiquées à la fois dans un milieu de culture MRSASelect et dans un milieu de culture habituel. Les chercheurs ont repéré des isolats de SARM au moyen des méthodes microbiologiques classiques dans les milieux de culture habituels et des milieux de culture ayant la morphologie classique des colonies (colonie rose) sur les milieux de culture MRSASelect. RÉSULTATS: Au total, les chercheurs ont évalué 490 cultures sanguines démontrant des cocccobacilles à Gram positif en grappes sur une coloration de Gram. Ils ont prélevé le S aureus sur 274 analyses sanguines et déterminé que 51 isolats de S aureus (51 sur 274 [18,6 %]) étaient un SARM. Le milieu de culture MRSASelect avait une sensibilité de 98 %, une spécificité de 100 %, une valeur prédictive positive de 100 % et une valeur négative prédictive de 99,8 % à l'égard de la récupération et du dépistage du SARM directement dans les fioles de culture sanguine. De plus, l'utilisation du milieu de culture MRSASelect raccourcissait de près de 24 heures le délai de dépistage du SARM par rapport aux méthodes classiques. EXPOSÉ: Ces données appuient l'utilité du milieu de culture MRSASelect pour dépister rapidement le SARM dans les cultures sanguines positives. D'autres études cliniques s'imposent pour déterminer si l'obtention plus rapide des résultats s'associera à une réduction mesurable de la thérapie antimicrobienne sous-optimale ou à une amélioration de l'issue des patients.
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OBJECTIVES: Escherichia coli resistance to antimicrobials varies according to many factors. E coli isolates from Canadian intensive care units (ICUs) were studied to determine the distribution and demographics associated with antimicrobial resistance in this population. METHODS: The Canadian National Intensive Care Unit (CAN-ICU) study characterized pathogens isolated in Canadian ICUs from July 2005 to June 2006. E coli susceptibility to 10 antimicrobials was determined and a multivariate logistic regression model was designed to determine whether region, sex, isolation from a sterile site and age (younger than 30 years) were significantly associated with susceptibility to the tested antimicrobials, to multidrug resistance or pan-susceptibility. RESULTS: Four hundred ninety-three E coli isolates, representing 12.6% of all isolates collected in the CAN-ICU study were examined. Susceptibilities were highest for meropenem and tigecycline (100%), cefepime (98.2%), piperacillin-tazobactam (97.0%), ceftriaxone (93.1%) and gentamicin (92.3%), and lowest for cefazolin (76.7%), trimethoprim-sulfamethoxazole (75.7%) and the fluoroquinolones (ciprofloxacin, 78.3%; and levofloxacin, 78.9%). In the multivariate model, fluoroquinolone resistance was lowest in patients younger than 30 years of age. Cefazolin and ceftriaxone susceptibility was lowest in Nova Scotia. Susceptibility to all tested antimicrobials was lowest in Nova Scotia and British Columbia. Isolation from a sterile site was associated with trimethoprim-sulfamethoxazole, piperacillin-tazobactam and multidrug resistance. CONCLUSIONS: E coli antimicrobial susceptibility varies across Canadian ICUs. Age, region and site of infection should be considered when prescribing empirical antimicrobial therapy. For infections caused by or suspected to be caused by E coli, fluoroquinolones, cefazolin and sulfonamides should be avoided due to low susceptibilities. Local antimicrobial prescribing practices, in particular the liberal use of fluoroquinolones and cephalosporins, and inadequate infection control practices are likely reducing susceptibility rates.
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BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and vancomycin-resistant enterococci (VRE) are important hospital pathogens in Canada and worldwide. OBJECTIVES: To genotypically and phenotypically characterize the isolates of MRSA, VRE and ESBL-producing E coli collected from patients in Canadian intensive care units (ICUs) in 2005 and 2006. METHODS: Between September 1, 2005, and June 30, 2006, 19 medical centres participating in the Canadian National Intensive Care Unit (CAN-ICU) study collected 4133 unique patient isolates associated with infections in ICUs. Isolates of MRSA underwent mecA polymerase chain reaction (PCR) and Panton-Valentine leukocidin analysis; they were typed using pulsed-field gel electrophoresis. All isolates of E coli with ceftriaxone minimum inhibitory concentrations greater than or equal to 1 mug/mL were tested for the presence of an ESBL using the Clinical Laboratory Standards Institute double-disk diffusion method. Subsequently, PCR and sequence analysis were used to identify bla(SHV), bla(TEM) and bla(CTX-M). Isolates of VRE were tested for the presence of vanA and vanB genes by PCR. RESULTS: Of the 4133 ICU isolates collected, MRSA accounted for 4.7% (193 of 4133) of all isolates. MRSA represented 21.9% (193 of 880) of all S aureus collected during the study; 90.7% were health care-associated MRSA strains and 9.3% were community-associated MRSA strains. Resistance rates for the isolates of MRSA were 91.8% to levofloxacin, 89.9% to clarithromycin, 76.1% to clindamycin and 11.7% to trimethoprim-sulfamethoxazole; no isolates were resistant to vancomycin, linezolid, tigecycline or daptomycin. ESBL-producing E coli accounted for 0.4% (18 of 4133) of all isolates and 3.7% (18 of 493) of E coli isolates. All 18 ESBL-producing E coli were PCR-positive for CTX-M, with bla(CTX-M-15) occurring in 72% (13 of 18) of isolates. All ESBL-producing E coli displayed a multidrug-resistant phenotype (resistant to third-generation cephalosporins and one or more other classes of antimicrobials), with 77.8% of isolates resistant to ciprofloxacin, 55.6% resistant to trimethoprim-sulfamethoxazole, 27.8% resistant to gentamicin and 26.3% resistant to doxycycline; all isolates were susceptible to ertapenem, meropenem and tigecycline. VRE accounted for 0.4% (17 of 4133) of all isolates and 6.7% (17 of 255) of enterococci isolates; 88.2% of VRE had the vanA genotype. Isolated VRE that were tested were uniformly susceptible to linezolid, tigecycline and daptomycin. CONCLUSIONS: MRSA isolated in Canadian ICUs in 2005 and 2006 was predominately health care-associated (90.7%), ESBL-producing E coli were all CTX-M producers (72% bla(CTX-M-15)) and VRE primarily harboured a vanA genotype (88.2%). MRSA, ESBL-producing E coli and VRE were frequently multidrug resistant.
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OBJECTIVE: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are increasingly common in nosocomial and community settings. Furthermore, fluoroquinolone (FQ) and even multidrug resistance (MDR) appear to be associated with certain ESBL genotypes. The purpose of the present study was to determine which ESBL genotypes are associated with FQ and MDR in E coli urinary isolates in Manitoba. METHODS: The authors determined the antimicrobial susceptibility, genetic similarity and ESBL genotype of 27 FQ-resistant and seven FQ-susceptible, ESBL-producing urinary isolates submitted to the clinical microbiology laboratories of two teaching hospitals between October 2000 and April 2005. Susceptibilities to beta-lactams, FQs, trimethoprim-sulfamethoxazole (SXT), doxycycline (DOX), gentamicin (GM) and tigecycline were determined by microbroth dilution; pulsed-field gel electrophoresis (PFGE) was used to determine genetic relatedness, and ESBL genotype was determined by polymerase chain reaction and sequencing. RESULTS: Of 34 ESBL-producing organisms, 27 (79.4%) were found to be ciprofloxacin (CIP) resistant, 27 (79.4%) were SXT resistant, eight (23.5%) were GM resistant and 29 (85.3%) were DOX resistant. Twenty-three (67.6%) had MDR, with concomitant resistance to CIP and SXT; 16 had concomitant resistance to CIP, SXT and DOX; and seven (20.6%) had MDR, with concomitant resistance to CIP, SXT, DOX and GM. All isolates were susceptible to tigecycline. Of 27 FQ-resistant ESBL-producing organisms, seven (25.9%) were genotype CTX-M-14, 19 (70.4%) were genotype CTX-M-15 and one (3.7%) was genotype CTX-M-24. Among the seven FQ-susceptible strains, three (42.8%) expressed SHV-type enzymes, three (42.8%) expressed TEM-type enzymes and one (14.3%) expressed CTX-M-9. CTX-M-15 was the most common MDR-associated genotype. Of a total of 19 strains, 18 (94.7%) were resistant to FQs and SXT; 15 (78.9%) were resistant to FQs, SXT and DOX; and five (26.3%) were resistant to FQs, SXT, DOX and GM. PFGE analysis revealed genetic similarity within CTX-M-15-producing isolates only. CONCLUSION: CTX-M-15 in E coli is strongly associated with an MDR phenotype compared with other genotypes. CTX-M-14 is associated with FQ resistance only. PFGE suggests clonality of CTX-M-15-producing isolates within and among hospitals.
