Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung.

BACKGROUND AND OBJECTIVES: Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung. METHODOLOGY: Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 13 MLST loci. RESULT: Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these were clinically resistant and 15% multi-drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and ß-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype. CONCLUSIONS AND IMPLICATIONS: Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients.

Case report: severe gastrointestinal inflammation and persistent HHV-6B infection in a paediatric cancer patient.

Lymphotropic herpesviruses such as human herpesvirus type 6 (HHV-6) have enhanced pathogenicity in some immunocompromised hosts, such as transplant recipients and HIV-infected patients. The clinical relevance of HHV-6 infections in cancer patients undergoing conventional cytotoxic therapy is undetermined, however. Here we report on a 10-month-old boy with an anaplastic astrocytoma, who acquired an HHV-6 variant B infection during chemotherapy. HHV-6B infection caused or triggered severe gastrointestinal inflammation with intractable diarrhoea and failure to thrive over several months. The clinical symptoms were associated with pronounced (CD4) lymphopenia and a marked increase in serum immunoglobulin A levels. After unsuccessful therapy with ganciclovir and foscarnet, combined antiviral and anti-inflammatory treatment with cidofovir and prednisolone controlled the HHV-6 infection and enabled resolution of clinical symptoms.

Fanconi syndrome caused by antiepileptic therapy with valproic Acid.

PURPOSE: Valproic acid (VPA) is commonly used as an antiepileptic drug (AED). Regular screening for renal side effects is uncommon. Fanconi syndrome, a generalized dysfunction of renal proximal tubular cells, occurs with some inborn errors of metabolism. In addition, it can be acquired by exposure to several toxic substances. We report a case of Fanconi syndrome after long-term therapy with VPA. METHODS: An 8-year-old severely disabled and developmentally retarded boy with epilepsy was treated with VPA over a period of 7 years. He was hospitalized after a status epilepticus with laboratory findings suggesting a Fanconi syndrome. A PubMed-based worldwide review of the literature revealed that Fanconi syndrome is a rare side effect in children during long-term VPA treatment. We analyzed all 10 previously published cases by comparing age, underlying diseases, medication, and outcome. RESULTS: Examination revealed metabolic acidosis suggestive of renal tubular malfunction. Based on typical clinical and laboratory findings, an acquired Fanconi syndrome was diagnosed. This was treated with large doses of sodium bicarbonate. After discontinuation of VPA, renal function completely normalized within 2 months. CONCLUSIONS: Fanconi syndrome appears to be a rare but severe consequence of long-term VPA therapy. Therefore patients treated with VPA should be checked regularly for the possible development of VPA-induced Fanconi syndrome.