Use of Ceftazidime-Avibactam in the Treatment of Clinical Syndromes With Limited Treatment Options: A Retrospective Study.

Background With rising trends of multi-drug organism infections and the limited availability of new antimicrobials, management of such cases has become a hassle for the clinician. Ceftazidime-Avibactam (CEF-AVI) is evolving as an effective alternative to polymyxins in the management of Carbapenem-Resistant Organisms (CRO) infections. The Food and Drug Administration (FDA) has approved CEF-AVI in a restricted group of clinical syndromes where the drug could have potential use. Objective The goal of this study was to evaluate the clinical outcome in terms of 14-day all-cause mortality and clinical cure at seven days in patients on CEF-AVI. Methodology A retrospective study was conducted on patients who received CEF-AVI in a period of one year in our hospital. Patients were included in the study if they have received CEF-AVI for more than one day of therapy (DOT) and samples from relevant sites have been sent for culture and sensitivity. Variables and outcomes were collected from the hospital information system and medical records. Results A total of 78 patients were included, 52 (66.7%) were started empirically on CEF-AVI while 26 (33.3%) were on targeted therapy. Out of the 78 patients, 43 patients had positive cultures among which 32 patients had Carbapenem-Resistant Enterobacteriaceae (CRE)/Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) infection. The most common clinical syndrome in which the drug was used was occult sepsis (27/78; 34.6%) followed by primary bacteremia (20/78; 25.6%) and neutropenic sepsis (11/78; 14.1%). The clinical efficacy which was primarily assessed in terms of clinical cure was met for 55 (70.5%) patients. The 14-day mortality for the studies group was found to be 18 (23%). Conclusion The analysis of results shows encouraging clinical cure rates and 14-day mortality rates in a subset of severe infections which has limited treatment options.

Typhoid and paratyphoid fever: a clinical seminar.

Rationale for review: Enteric fever (EF) caused by Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi) and S. Paratyphi (Salmonella Paratyphi) remains an important cause of infectious morbidity and mortality in many low-income countries and, therefore, still poses a major infectious risk for travellers to endemic countries. Main findings: Although the global burden of EF has decreased over the past two decades, prevalence of EF remains high in Asia and Africa, with the highest prevalence reported from the Indian subcontinent. These statistics are mirrored by data on travel-related EF. Widespread and increasing antimicrobial resistance has narrowed treatment options for travel-related EF. Ceftriaxone- and azithromycin-based therapies are commonly used, even with the emergence of extremely drug-resistant typhoid in Pakistan. Preventive measures among locals and travellers include provision of safe food and water and vaccination. Food and water precautions offer limited protection, and the efficacy of Salmonella Typhi vaccines is only moderate signifying the need for travellers to be extra cautious. Recommendations: Improvement in the diagnosis of typhoid with high degree of clinical suspicion, better diagnostic assays, early and accurate detection of resistance, therapy with appropriate drugs, improvements in hygiene and sanitation with provision of safe drinking water in endemic areas and vaccination among travellers as well as in the endemic population are keys to controlling typhoid. While typhoid vaccines are recommended for travellers to high-risk areas, moderate efficacy and inability to protect against Salmonella Paratyphi are limitations to bear in mind. Improved Salmonella Typhi vaccines and vaccines against Salmonella Paratyphi A are required.

Drug resistance in Salmonella Typhi: implications for South Asia and travel.

PURPOSE OF REVIEW: Recent attempts at mapping Typhoid epidemiology have revealed an enormous burden of disease in developing countries. Countries hitherto believed to have a low incidence, such as the African subcontinent, on accurate mapping were found to have a significant burden of disease. Drug resistance, because of rampant overuse of antibiotics, has driven selection pressure to extensively drug-resistant typhoid becoming a reality in the Indian subcontinent. With widespread travel, importation of this variety of typhoid to nonendemic countries is likely to lead to outbreaks in a nonimmune population. RECENT FINDINGS: A strain of extensively drug-resistant Salmonella Typhi isolated in Pakistan in 2016 has been responsible for multiple outbreaks in Pakistan and multiple travel-related cases all over the world in United States, UK, and Australia. This novel strain belongs to H58 lineage harbouring a plasmid encoding additional resistance elements like blaCTX-M-15 and a qnrS fluoroquinolone resistance gene. This resistance pattern has rendered many therapeutic options like Ceftriaxone and Fluoroquinolones clinically inactive impacting care in endemic and traveller populations alike. SUMMARY: Changing epidemiology and drug resistance in typhoid indicates that it may be prudent to vaccinate nonimmune travellers travelling to typhoid endemic areas, especially the Indian subcontinent.