Successful Treatment of Postneurosurgical Ventriculitis Caused by Extensively Drug-resistant Acinetobacter baumannii in a Child: Case Report

Introduction: The incidence of postneurosurgical Acinetobacter baumannii ventriculitis/meningitis, primarily due to drug-resistant strains, has increased considerably in recent years. However, limited therapeutic options are available because most antibiotics poorly penetrate the blood-brain barrier, especially in pediatric patients. Case Presentation: A five-year-old boy developed ventriculitis due to extensively drug-resistant A. baumannii (XDRAB) after bilateral frontal external ventricular drainage for spontaneous intraventricular hemorrhage. The boy was safely and successfully treated with intraventricular (IVT)/intrathecal (ITH) polymyxin B together with intravenous tigecycline plus cefoperazone/sulbactam. Conclusions: In the present case, postneurosurgical XDRAB ventriculitis was closely associated with intraventricular hemorrhage and the placement of external ventricular drainage. IVT/ITH polymyxin B combined with intravenous tigecycline and cefoperazone sulbactam could be a therapeutic option against XDRAB ventriculitis in children.

Antibacterial Activity of Manuka Honey Against Azithromycin Resistant Extensively Drug Resistant Salmonella Typhi Clinical Isolates: In-Vitro Study

Typhoid fever is a significant health problem in developing countries like Pakistan. Salmonella Typhi the causative agent of typhoid has developed resistant to almost all recommended antibiotics. Emergence of resistance to third generation cephalosporins has further complicated the situation and such strains are called as extensively drug resistant (XDR) Salmonella Typhi. Currently only available options are azithromycin and cabapenems. Recently few reports of azithromycin resistance have emerged from countries like Pakistan, India, Bangladesh and Nepal. As azithromycin is the only oral option available to treat XDR Typhoid, development of resistance may change treatment strategy altogether from out patient management to hospitalization of every patient. This may increase the burden on already weak health care system of countries like Pakistan. So there is dire need to look for the alternative treatment options. Manuka honey is well known for its therapeutic potential against wide range of bacteria including Salmonella Typhimurium. In this study 3 azithromycin resistant isolates were isolated and identified using disc diffusion, E-test and broth micro dilution methods and antibacterial activity, MIC and MBC of manuka honey was performed by agar well diffusion assay and broth micro dilution assay respectively. Manuka honey manifested significant antibacterial activity against all test isolates with zone of inhibition ranging from 7.3mm to 7.5mm, MIC and MBC values were between 10 to 15% v/v Here, we conclude that Manuka honey possess potent antibacterial activity and might be used as an alternative treatment option against azithromycin resistant XDR Typhid. However, further clinical trials are mandatory to validate our initial findings.

The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized an extensively drug-resistant Klebsiella pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistant plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Except for tigecycline resistance, three plasmids, mediating resistance to colistin, Fosfomycin, and ceftazidime–avibactam, respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation systems. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies, respectively, but also could co-transfer to E. coli J53 effectively, which was additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we characterized and reported the uncommon co-existence and co-transferring of FosA3-, NDM-5, and MCR-1-encoding plasmids in a K. pneumoniae isolate, which may increase the risk of spread of these resistant phenotypes and needing great concern.

Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis

IntroductionBedaquiline, pretomanid and linezolid (BPaL) is a new all oral, 6-month regimen comprised of bedaquiline, the new drug pretomanid and linezolid, endorsed by the WHO for use under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB). We quantified per-patient treatment costs and the 5-year budgetary impact of introducing BPaL in Indonesia, Kyrgyzstan and Nigeria.MethodsPer-patient treatment cost of BPaL regimen was compared head-to-head with the conventional XDR-TB treatment regimen for respective countries based on cost estimates primarily assessed using microcosting method and expected frequency of each TB service. The 5-year budget impact of gradual introduction of BPaL against the status quo was assessed using a Markov model that represented patient’s treatment management and outcome pathways.ResultsThe cost per patient completing treatment with BPaL was US$7142 in Indonesia, US$4782 in Kyrgyzstan and US$7152 in Nigeria – 57%, 78% and 68% lower than the conventional regimens in the respective countries. A gradual adoption of the BPaL regimen over 5 years would result in an 5-year average national TB service budget reduction of 17% (US$128 780) in XDR-TB treatment-related expenditure in Indonesia, 15% (US$700 247) in Kyrgyzstan and 32% (US$1 543 047) in Nigeria.ConclusionOur study demonstrates that the BPaL regimen can be highly cost-saving compared with the conventional regimens to treat patients with XDR-TB in high drug-resistant TB burden settings. This supports the rapid adoption of the BPaL regimen to address the significant programmatic and clinical challenges in managing patients with XDR-TB in high DR-TB burden countries.

Antimicrobial Resistance, Serologic and Molecular Characterization of E. coli Isolated from Calves with Severe or Fatal Enteritis in Bavaria, Germany

Worldwide, enterotoxigenic Escherichia coli (ETEC) cause neonatal diarrhea and high mortality rates in newborn calves, leading to great economic losses. In Bavaria, Germany, no recent facts are available regarding the prevalence of virulence factors or antimicrobial resistance of ETEC in calves. Antimicrobial susceptibility of 8713 E. coli isolates obtained from 7358 samples of diseased or deceased diarrheic calves were investigated between 2015 to 2019. Considerably high rates of 84.2% multidrug-resistant and 15.8% extensively drug-resistant isolates were detected. The resistance situation of the first, second and third line antimicrobials for the treatment, here amoxicillin-clavulanate, enrofloxacin and trimethoprim-sulfamethoxazole, is currently acceptable with mean non-susceptibility rates of 28.1%, 37.9% and 50.0% over the investigated 5-year period. Furthermore, the ETEC serotypes O101:K28, O9:K35, O101:K30, O101:K32, O78:K80, O139:K82, O8:K87, O141:K85 and O147:K89, as well as the virulence factors F17, F41, F5, ST-I and stx1 were identified in a subset of samples collected in 2019 and 2020. The substantially high rates of multi- and extensively drug-resistant isolates underline the necessity of continuous monitoring regarding antimicrobial resistance to provide reliable prognoses and adjust recommendations for the treatment of bacterial infections in animals.