Efflux Pump Overexpression Profiling in Acinetobacter baumannii and Study of New 1-(1-Naphthylmethyl)-Piperazine Analogs as Potential Efflux Inhibitors.

Overexpression of efflux pumps extruding antibiotics currently used for the treatment of Acinetobacter baumannii infections has been described as an important mechanism causing antibiotic resistance. The first aim of this work was to phenotypically evaluate the overexpression of efflux pumps on a collection of 124 ciprofloxacin-resistant A. baumannii strains. An overexpression of genes encoding one or more efflux pumps was obtained for 19 out of the 34 strains with a positive phenotypic efflux (56%). The most frequent genes overexpressed were those belonging to the RND family, with adeJ being the most prevalent (50%). Interestingly, efflux pump genes coding for MATE and MFS families were also overexpressed quite frequently: abeM (32%) and abaQ (26%). The second aim was to synthesize 1-(1-naphthylmethyl)-piperazine analogs as potential new efflux pump inhibitors and biologically evaluate them against strains with a positive phenotypic efflux. Quinoline and pyridine analogs were found to be more effective than their parent compound, 1-(1-naphthyl methyl)-piperazine. Stereochemistry also played an important part in the inhibitory activity, as quinoline derivative (R)-3a was identified as being the most effective and less cytotoxic. Its inhibitory activity was also correlated with the number of efflux pumps expressed by a strain. The results obtained in this work suggest that quinoline analogs of 1-(1-naphthylmethyl)-piperazine are promising leads in the development of new anti-Acinetobacter baumannii therapeutic alternatives in combination with antibiotics for which an efflux-mediated resistance is suspected.

Prospective evaluation of a screening algorithm for carbapenemase-producing Enterobacteriaceae.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) have become a major public health issue. The objective of the present study was to prospectively assess the analytical performance of a CPE detection algorithm based on phenotypic tests (the screening test) and MALDI-ToF hydrolysis (the confirmatory test). METHODS: Over a 6-month period and based on a disk diffusion method, 74 carbapenem-resistant strains were included in this study. RESULTS: Of the collected isolates, 54 turned out to be negative after phenotypic tests. Hence, 20 strains (including all of the CPEs) were checked with the confirmation test. Seven strains were positive. After molecular biology assessments in a reference center, three of the seven were found to be false positives. The algorithm had a negative predictive value and a sensitivity of 100%, a specificity of 77%, and a positive predictive value of 20%. CONCLUSION: The algorithm has a 24-hour turnaround time and helps to avoid using expensive molecular biology tests; we consider that it can be used on a routine basis for screening clinical strains.

A case of acute clival osteomyelitis in a 7-year-old boy secondary to infection of a Thornwaldt cyst.

Clival osteomyelitis is a potentially life-threatening infection that can occur in healthy children. It can be related to congenital anomalies. We report the case of a 7-year-old boy with Streptococcus intermedius and Fusobacterium clival osteomyelitis arising from a Thornwaldt cyst situated in a fossa navicularis magna of the occipital bone. Multidisciplinary management is necessary to ensure rapid improvement and complete healing.

Bartholinitis due to Aggregatibacter aphrophilus: a case report.

BACKGROUND: Aggregatibacter aphrophilus, a commensal of the oro-pharyngeal flora and member of the HACEK group of organisms, is an uncommonly encountered clinical pathogen. It has already been described as the causative agent of brain abscesses, empyema, meningitis, sinusitis, otitis media, bacteriemia, pneumonia, osteomyelitis, peritonitis, endocarditis and wound infections. Herein we report the first case of bartholinitis due to A. aphrophilus. CASE PRESENTATION: A 33-year-old woman was admitted for a 3-day genital pain without fever and urinary functional signs. The abscess was incised and drained; A. aphrophilus was the only micro-organism that grew from the pus. The patient received no antibiotics; the clinical course was favourable. CONCLUSION: This case highlights the importance of an effective treatment of recurrent bartholinitis such as a cold resection of the gland. It is presented for its rarity.