Successful treatment of extensively drug-resistant Pseudomonas aeruginosa osteomyelitis using a colistin- and tobramycin-impregnated PMMA spacer.

Discovered in 1949, the antibiotic colistin was initially used for therapeutic purposes. Parenteral use of colistin was gradually abandoned because of its side-effect profile, especially its nephrotoxicity and neurotoxicity. Despite the risk of these potentially serious adverse effects, increasing resistance of Gram-negative bacteria has led to a renaissance of intravenous use of colistin in the last few years. Local administration of colistin is an alternative method to minimise the risk of systemic toxicity. We present a case of extensively drug-resistant Pseudomonas aeruginosa osteomyelitis treated successfully with high-dose colistin- and tobramycin-impregnated bone cement as a drug delivery vehicle. For the first time, local colistin concentrations in drainage and synovial fluid were quantified in order to determine the optimal dose and to minimise serious side effects. Insertion of a bone cement spacer loaded with a high dose of tobramycin and colistin resulted in local colistin levels at the infection site that exceeded the minimum inhibitory concentration (MIC) of colistin against the isolated P. aeruginosa five-fold on Day 4. Thus, the treatment may be expected to exert a prolonged effect. Whereas systemic administration of colistin alone was not sufficient to treat the infection, combined local and parenteral therapy led to eradication of P. aeruginosa in this patient. Plasma colistin levels remained in the therapeutic range, which confirms the systemic safety of the method.

Outcome and management of invasive candidiasis following oesophageal perforation.

The regular colonisation of the oesophagus with a Candida species can, after oesophageal perforation, result in a contamination of the mediastinum and the pleura with a Candida species. A patient cohort of 80 patients with oesophageal perforation between 1986 and 2010 was analysed retrospectively. The most common sources with positive results for Candida were mediastinal biopsies and broncho-alveolar secretions. Candida species were detected in 30% of the patients. The mortality rate was 41% in patients with positive microbiology results for Candida, whereas it was 23% in the remaining patient cohort. This difference did not reach statistical significance (P = 0.124). Mortality associated with oesophageal perforation was attributed mainly to septic complications, such as mediastinitis and severe pneumonia. During the study period we observed a shift towards non-albicans species that were less susceptible or resistant to fluconazole. In selected patients with risk factors as immunosuppression, granulocytopenia and long-term intensive-care treatment together with the finding of Candida, an antimycotic therapy should be started. A surgical approach offers the possibility to obtain deep tissue biopsies. The antimycotic therapy should start with an echinocandin, as the resistance to fluconazole is growing and to cover non-albicans Candida species, too.