Colistin and Fusidic Acid, a Novel Potent Synergistic Combination for Treatment of Multidrug-Resistant Acinetobacter baumannii Infections.

The spread of multidrug-resistant Acinetobacter baumannii (MDRAB) has led to the renaissance of colistin (COL), often the only agent to which MDRAB remains susceptible. Effective therapy with COL is beset with problems due to unpredictable pharmacokinetics, toxicity, and the rapid selection of resistance. Here, we describe a potent synergistic interaction when COL was combined with fusidic acid (FD) against A. baumannii. Synergy in vitro was assessed against 11 MDRAB isolates using disc diffusion, checkerboard methodology (fractional inhibitory concentration index [FICI] of ≤ 0.5, susceptibility breakpoint index [SBPI] of >2), and time-kill methodology (≥2 log10 CFU/ml reduction). The ability of FD to limit the emergence of COL resistance was assessed in the presence and absence of each drug alone and in combination. Synergy was demonstrated against all strains, with an average FICI and SBPI of 0.064 and 78.85, respectively. In time-kill assays, COL-FD was synergistic and rapidly bactericidal, including against COL-resistant strains. Fusidic acid prevented the emergence of COL resistance, which was readily selected with COL alone. This is the first description of a novel COL-FD regimen for the treatment of MDRAB. The combination was effective at low concentrations, which should be therapeutically achievable while limiting toxicity. Further studies are warranted to determine the mechanism underlying the interaction and the suitability of COL-FD as an unorthodox therapy for the treatment of multidrug-resistant Gram-negative infections.

Carbapenemase-producing organism (CPO) colonisation at a district general hospital: universal screening may help reduce transmission.

OBJECTIVE: Assess the potential of hospital-wide routine screening by determining the prevalence and incidence of carbapenemase-producing organisms (CPOs) isolated from rectal screens at Barnet and Chase Farm Hospitals. METHODS: 3,553 samples were collected between 01/12/2018 and 31/08/2019: from adult critical care wards (universal screening - admission, discharge and weekly), from medical wards with risk-factor based screening according to the prevailing Public Health England (PHE) carbapenemase-producing Enterobacteriaceae (CPE) screening guidelines, or on an ad hoc basis. Prevalence was defined as previously documented positive CPO colonisation, or new positive status, as a proportion of all eligible samples. Incidence was defined as all newly positive patients per 1,000 patient-days. RESULTS: Overall CPO prevalence was 2.1% (95% CI: 1.61-2.58%). Inpatient prevalence was significantly higher at 2.6% vs outpatient at 0.5% (p < 0.001). Incidence was 0.44 per 1,000 patient-days (95% CI: 0.33-0.57), with a rate ratio between Barnet and Chase Farm of 4.9 (p = 0.013). Incidence was highest where universal screening strategy was applied (3.9 per 1000 patient-days, 95% CI: 2.4-5.91). This was 2.5 times higher than risk-factor based screening (p = 0.005) and 23.5 times that of wards without routine surveillance implemented (p < 0.001). CONCLUSION: Surveillance remains a cornerstone in controlling CPO transmission. Our local incidence, lacking hospital-wide screening, significantly exceeded the reported UK average. Universal screening could help to uncover the true prevalence and incidence of CPO, thereby providing the necessary information to properly control transmission, reducing nosocomial outbreaks and ultimately reducing the overall cost to healthcare.

An unusual case of seronegative, 16S PCR positive Brucella infection.

INTRODUCTION: Brucella is a zoonotic infection commonly diagnosed by isolation of the organism from blood culture or positive serological testing. It is an uncommon cause of a pyrexia of unknown origin in the United Kingdom. CASE PRESENTATION: We describe the case of a 14-year-old girl with no history of travel who presented with pyrexia, weight loss, arthralgia, multiple splenic abscesses and a subsequent pleural effusion, the latter of which isolated a Brucella species on 16S rRNA PCR. The patient responded well to initiation of treatment for brucellosis and on repeat imaging, after 3 months, the splenic abscesses had resolved. CONCLUSION: This unique case demonstrates uncommon complications of brucellosis and the challenges of diagnosing the organism, the latter of which can be alleviated by the utilization of molecularbased technologies. This patient had a negative serology result for brucellosis, which highlights the need to interpret serology results with caution in non-endemic regions for brucellosis.