Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis.

BACKGROUND: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION: PROSPERO CRD42018029432.

Cryptococcosis and cryptococcal meningitis: New predictors and clinical outcomes at a United States academic medical centre.

As the diagnosis of cryptococcosis is challenging in low-prevalence settings, uncovering predictive factors can improve early diagnosis and timely treatment. The aim of the study was to relate clinical outcomes to predictive variables for the presence of cryptococcosis. A retrospective case-control study matched by collection date, age and gender at a 1:2 ratio (55 cases and 112 controls) was performed in case patients diagnosed with Cryptococcus infection at the University of Colorado Hospital between 2000 and 2017 (n = 167). A bivariate and a forward, stepwise multivariable logistic regression model were performed to identify predictors of cryptococcosis infection. In an adjusted multivariable model, cryptococcal infection was significantly associated with the presence of respiratory symptoms, hyponatremia, lung disease or corticosteroids. Additionally, cryptococcal meningitis was associated with headaches, corticosteroids or increased CSF protein. Conversely, a reduced risk of cryptococcosis was associated with hypertension or peripheral monocytosis. Cryptococcal meningitis leads to subsequent hearing impairment (16% vs 4% (control), P = .013), muscle weakness (40% vs 20%, P = .021), cognitive deficits (33% vs 6%, P = .0001) or any adverse outcome (84% vs 29%, P = .0001). We uncovered novel clinical predictors for the presence of cryptococcal infection or cryptococcal meningitis. This study in patients at a low-prevalence US medical centre underscores the importance of early diagnosis in this population.