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Microbiological and Host Features Associated with Corynebacteriosis in Cancer Patients: a Five-Year Study

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Microbiological and Host Features Associated with Corynebacteriosis in Cancer Patients: a Five-Year Study Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 104(6): 905-913, September 2009 905 Microbiological and host features associated with corynebacteriosis in cancer patients: a five-year study CAS Martins1, 3, LMD Faria1, MC Souza3, TCF Camello3, E Velasco1, R Hirata Jr3, LCS Thuler2, AL Mattos-Guaraldi3/+ 1Instituto Nacional do Câncer, Ministério da Saúde, Rio de Janeiro, RJ, Brasil 2Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil 3Disciplina de Microbiologia e Imunologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro 87 fundos, 3º andar, 20551-030 Rio de Janeiro, RJ, Brasil During a five-year period, 932 clinical isolates from cancer patients treated in a Brazilian reference centre were identified as corynebacteria; 86% of the cultures came from patients who had been clinically and microbiologically classified as infected and 77.1% of these patients had been hospitalised (71.1% from surgical wards). The adult solid tumour was the most common underlying malignant disease (66.7%). The univariate and multivariate analyses showed that hospitalised patients had a six-fold greater risk (OR = 5.5, 95% CI = 1.15-26.30 p = 0.033) related to 30-day mor- tality. The predominant species were Corynebacterium amycolatum (44.7%), Corynebacterium minutissimum (18.3%) and Corynebacterium pseudodiphtheriticum (8.5%). The upper urinary tracts, surgical wounds, lower respiratory tracts, ulcerated tumours and indwelling venous catheters were the most frequent sources of C. amycolatum strains. Corynebacterium jeikeium infection occurred primarily in neutropenic patients who have used venous catheters, while infection caused by C. amycolatum and other species emerged mainly in patients with solid tumours. Key words: Corynebacterium amycolatum - Corynebacterium infection - cancer Corynebacterium species have recently been recog- Zalas et al. 2004); for example, mutations in the gyrase nised as important pathogens that infect immunocom- genes are determinants of the resistance to quinolones in promised patients. Despite the increase in the number Corynebacterium striatum and Corynebacterium amy- of reports of severe infection caused by non-diphtheria colatum strains (Sierra et al. 2005). corynebacteria, these organisms are still frequently In Rio de Janeiro, Brazil, recent studies conducted at dismissed as contaminants. Corynebacterium spp have a teaching hospital showed that 68% of the clinical iso- been cited with an increased frequency as pathogens of lates of corynebacteria species corresponded to Coryne- nosocomial infections associated with septicaemias, en- bacterium pseudodiphtheriticum, C. amycolatum, docarditis, infections of surgical wounds, prostheses and Corynebacterium propinquum and Corynebacterium infections related to the central venous catheter. Geo- minutissimum. The urinary tract and the venous access graphical variations in the frequency of isolated species were the sites most commonly affected. In the blood and variations in the natural and acquired antimicrobial and the respiratory tract, there was a predominance of resistance have been described (Osterwalder et al. 1986, C. pseudodiphtheriticum and C. propinquum, while Rozdzinski et al. 1991, van der Lelie et al. 1995). Corynebacterium xerosis and C. amycolatum were the Recent advances in Corynebacterium identification most commonly observed species in central venous have shown that the genus exhibits considerable taxo- catheters. C. propinquum and C. minutissimum were the nomic complexity and that the phenotypic markers used most frequently observed species in surgical wounds. in the past for its identification can be ambiguous (Bar- Data indicated the occurrence of multi-resistant pheno- reau et al. 1993, Brandenburg et al. 1996, Oteo et al. types and the possibility of severe infections due to C. 2001, Camello et al. 2003, Meyer & Reboli 2005, Otsuka pseudodiphtheriticum, a pathogen usually overlooked in et al. 2006). When these infections are linked to multi- emerging countries (Camello et al. 2003, 2009). resistant species, they are difficult to treat (Bodey 1995, Infection has been recognised as one of the major Funke et al. 1996, Camello et al. 2003, Funke & Bernard obstacles to the successful management of patients with 2003). Multiple resistance to antimicrobial agents has malignant diseases. Few studies have described non-diph- been described among some species (Lagrou et al. 1998, theria corynebacteria species as emerging pathogens in patients with solid tumours, with the exception of those that highlighted the importance of Corynebacterium jeikeium (Rozdzinski et al. 1991, van der Lelie et al. 1995). Vancomycin has been demonstrated to be the primary treatment option for C. jeikeium. The choice of using gly- copeptides to empirically treat patients with neutropenic Financial support: INCA, FAPERJ, CNPq, CAPES, SR-2/UERJ, PRONEX fever and persistent fever has been criticised since the + Corresponding author: [email protected] advent of the vancomycin-resistant Enterococcus and the Received 15 May 2009 heterogeneous vancomycin-intermediate Staphylococcus Accepted 20 August 2009 aureus (Furtado et al. 2006). The new options for therapy online | memorias.ioc.fiocruz.br 906 Corynebacterium in cancer patients • CAS Martins et al. are also not completely safe for the treatment of gram pos- polyuria) or systemic signs of infection; pyuria was only itive life-threatening infections partially due to the emer- required in non-neutropenic patients. Tracheal secretions gence of microbial resistance (Boucher et al. 2000, Dobbs in intubated patients, sputum or tracheal aspirations in et al. 2006, Schoen et al. 2009). non-intubated patients were considered as positive if The aim of this descriptive study was to assess they were associated with clinical or radiological signs the microbiological and clinical aspects as well as that indicated an infection. Protected sampling was not factors related to 30-day mortality in cancer patients performed in bronchoscopy (Garner et al. 1988, Hughes with corynebacteriosis. et al. 1996, Berghmans et al. 2003). PATIENTS, MATERIALS AND METHODS Bacterial strains and identification - We retrospec- Study setting - In this descriptive study, we retro- tively reviewed 932 strains identified as Corynebacte- spectively reviewed clinical and microbiological data rium spp that were recovered from representative clini- over a five-year period (from January 2000-December cal sites of cancer patients with signs and symptoms of bacterial infection. Corynebacterium-like colonies 2004). The patient information originated from one were selected for further identification when they were of the units (Cancer Hospital I with 200 beds, Cancer grown in any quantity from normally sterile body fluid Hospital II with 90 beds and Cancer Hospital III with or when they were isolated in significant numbers or 60 beds) of the National Cancer Institute (INCA) in in pure culture from other specimens obtained at clini- Rio de Janeiro, Brazil. cal sites in which infection was suspected (Funke & The analysis included bacteriological data from Bernard 2003). All clinical samples yielding more than 88,541 cultures and 1,100 irregular gram-positive rods three organisms were regarded as contaminated and isolated from cancer patients. The operational units in- discarded (Thomson 2007). cluded the Laboratory of Microbiology and the Hospital The Maki’s semi-quantitative method was used to Infection Control Committee (HICC) at the INCA and distinguish infection (> 15 colonies) from contamination the Laboratory of Diphtheria and Corynebacteria, State of catheter-tips (Maki et al. 1977). For quantitative BAL University of Rio de Janeiro (UERJ), Brazil. fluid cultures, a colony count > 103 colony-forming units During the period of the study, there were no chang- (CFU) mL-1 of potential pathogens was considered posi- es in the technical team who processed the material tive. Isolation of two or three species of microorganisms for bacteriological cultures or in the medical team who was regarded as a polymicrobial infection for catheter assisted the patients. tips and the lower respiratory tract, respectively. Mi- Ethics - This paper was submitted and approved by croorganisms were identified from the urine cultures in the Ethical Research Committee at INCA (CEP 008/06) cystine lactose electrolytes deficient agar (CLED; Mer- and complies with the Brazilian Government’s Ethical ck, Darmstadt, Germany) and were considered to be po- Guidelines for research involving human beings (resolu- tential pathogens when the growth was > 104 CFU mL-1 tion of the National Health Council/Ministry of Health). as the only isolate or > 105 CFU mL-1 as the predominant 3 -1 Diagnostic measures - The study analysed the clini- isolate; > 10 CFU mL , in cases of nephropathies, was cal characteristics of 315 patients with Corynebacterium also considered a potential pathogen. Blood cultures isolates who had malignant diseases or underwent bone were always obtained in pairs, wherein at least one of marrow transplantation in the last two years of the study. the samples was collected through the central venous Data assessment was performed on the basis of a medi- catheter, if present. Blood specimens were inoculated cal records review of patients. in Bactec Plus anaerobic⁄aerobic vials and processed in The hospitalised patients were monitored by at least a Bactec 9240 continuous-monitoring system (Becton- one member of the HICC as a part of the antimicrobial
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