Chronic Bone Infections Due to Enterobacter cloacae: Current Therapeutic Trends and Clinical Outcome

Abstract

Chronic osteomyelitis is a difficult-to-treat infection which often necessitates surgical debridement and prolonged administration of antibiotics 1. enterobacter cloacae are a very rare cause of osteomyelitis and of septic arthritis with adjacent osteomyelitis and spondylodiskitis. Published experience is limited to sporadic cases 2-4 and little is known about the clinical course and outcome of the disease. A case-series of 15 adult patients with chronic bone infections by e. cloacae is presented. A retrospective analysis of 15 cases of bone infections caused by e. cloacae was made. Data for analysis derived from an electronic registry of 768 patients with chronic bone and joint infections followed-up in the Outpatients Department of infectious Diseases of the 4th Department of internal Medicine during the period 1998-2008. Written informed consent for use of each patient’s data for publication was provided upon admission. Described cases met the following inclusion criteria: i) documentation of chronic bone infection by clinical and radiological criteria; and ii) implication of e. cloacae as the responsible pathogen. More precisely, e. cloacae was isolated either from cultures of infected bone and/or surrounding tissues sampled intra-operatively or from cultures of an orthopedic implant device or from pus aspirated proximally to the infected tissue by radiological guidance. Patients not eligible for analysis were: i) those with isolation of e. cloacae from a sinus tract; and ii) those with isolated e. cloacae considered as a superinfection of a previous staphylococcal infection. Diagnosis of bone infection was performed by the following criteria 5: i) presence of local signs of inflammation and/or sinus tract formation at the infection site; ii) erythrocyte sedimentation rate (EsR) more than 30 mm/h and C-reactive protein (CRP) more than 15 mg/L (normal values below 5 mg/L); and iii) radiological proof of infection by positive findings on x-ray and magnetic resonance imaging. identification of e. cloacae was performed by testing of its biochemical properties (APi20E, bioMerieux, Mercy L’Etoile, France). Antimicrobial susceptibility testing was done by the Kirby-Bauer disk diffusion assay with interpretation criteria according to the Clinical and Laboratory standards institute 6. The production of extended-spectrum b-lactamase (EsBL) was defined by the double disk approximation test and of AmpC b-lactamases by the application of a cefoxitin disk. The type of antimicrobial therapy was based on the susceptibility testing of the pathogen. All patients were followed-up on a monthly basis. Duration of therapy was decided by the attending physician. For each patient the following data were recorded: age, gender, co-existing diseases, type, dose and duration of therapy and performance of surgical debridement. Clinical arrest of the infection was considered as any resolution of clinical and radiological findings accompanied by restoration of EsR and CRP within normal ranges. All other cases were considered treatment failures. Patients with arrest of the infection and those who failed treatment were compared regarding the performance of surgical debridement by the Fischer’s exact test; and for the duration of treatment by the Mann-Whitney U test. Any value of p <0.05 was considered significant. Clinical characteristics of described cases are shown in table 1. in six cases, osteomyelitis followed an orthopedic operation; none of these patients was admitted to an intensive Care Unit (iCU) after operation. All isolates were EsBL and AmpC b-lactamase producers. susceptibility testing of the offending pathogens was as follows: carbapenems 100%, trimethoprim/sulfamethoxazole 60%, ciprofloxacin 86%. Based on the susceptibility of the pathogens, the most commonly prescribed regimens were ciprofloxacin in 12 cases and carbapenems in 3 cases. surgical debridement was performed in 9 cases. Arrest of the infection was achieved in 9 cases. These patients did not relapse within the first year after cessation of therapy. surgical debridement was performed in 6 out of 9 patients with arrest of the infection; and in 4 out of 6 patients with treatment failure (pns). Median duration of therapy for patients with arrest of the 4th Department of internal Medicine, University of Athens, Medical school, Greece