Introduction: Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: ‘Pneumocystis pneumonia’, ‘Pneumocystis jirovecii pneumonia’, ‘Pneumocystis carinii pneumonia’, ‘trimethoprim-sulfamethoxazole’, ‘primaquine’, ‘trimetrexate’, ‘dapsone’, ‘pentamidine’, ‘atovaquone’, ‘echinocandins’, ‘human immunodeficiency virus infection’, ‘acquired immunodeficiency syndrome’, ‘resistance to sulfamide’ and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

Objectives Rapid initiation of antiretroviral therapy (ART) engenders faster viral suppression but with suboptimal rates of durable viral suppression and engagement in care, as reported by clinical trials in resource-limited settings. Real-world experience with rapid ART initiation remains limited in resource-rich settings. Design Retrospective cohort study. Setting A tertiary hospital in metropolitan Taipei, Taiwan. Participants We included 631 patients newly diagnosed as having HIV infection between March 2014 and July 2018. Main outcome measures Rapid ART initiation was defined as starting ART within 7 days after HIV diagnosis confirmation. HIV diagnosis, ART initiation and viral suppression dates and clinical outcome data were collected by reviewing medical records. The rates of loss to follow-up (LTFU), engagement in care and virological rebound at 12 months were compared between patients with rapid ART initiation and those with standard initiation. Results Rapid ART initiation increased from 33.8% in 2014 to 68.3% in 2017, and the median interval between HIV diagnosis and viral suppression (HIV RNA load <200 copies/mL) decreased from 138 to 47 days. Patients with rapid ART initiation had a significantly higher rate of engagement in care at 12 months than did those with standard initiation (88.3% vs 79.0%; p=0.002). Patients aged <30 years had a higher risk of LTFU (HR: 2.19; 95% CI 1.20 to 3.98); and rapid ART initiation was associated with a lower risk of LTFU (HR: 0.41; 95% CI 0.24 to 0.83). Patients aged <30 years were more likely to acquire incident sexually transmitted infections (STIs) before achieving viral suppression. Conclusions Rapid ART initiation was associated with a higher rate of engagement in care at 12 months and shortened interval from diagnosis to HIV suppression. Delayed ART initiation may increase onwards HIV transmission considering the high rates of STIs. Ethics approval The study was approved by the Research Ethics Committee of National Taiwan University Hospital (Registration No. 201003112R).

The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan. Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm³ or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART. We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm³ in 2012 to 298 cells/mm³ in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04–1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04–1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33–2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04–2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14–13.65) and older age (AHR, 1.06; 95% CI, 1.03–1.10). While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population.

Increased resistance to third-generation cephalosporin (3GC) is a serious concern for community-onset Escherichia coli infection because this resistance easily delays effective treatment. This study surveyed the current antimicrobial resistance pattern among E. coli isolates that cause community-onset bacteremia, with a special focus on the prevalence of and the risk factors for 3GC resistance, and determined factors for poor outcomes among patients with community-onset E. coli bacteremia. This retrospective study was conducted at a tertiary-care teaching hospital in Taiwan. All adult patients with community-onset E. coli bacteremia between January 1, 2015, and December 31, 2015 were enrolled and were divided into two groups depending on whether the E. coli isolate was susceptible to 3GCs. Risk factors for 3GC resistance, 14-day all-cause mortality, and length of hospital stay were analyzed. The overall rate of 3GC resistance among E. coli isolates causing community-onset bacteremia was 19.7%, whereas it was 9.6% if only isolates causing community-acquired bacteremia were considered. Independent risk factors for 3GC-resistant community-onset E. coli bacteremia were hospitalization within the past 1 year (odds ratio: 2.4, 95% confidence interval: 1.6–3.7, P < 0.001), exposure to antibiotics within the past 15 days (2.6, 1.4–4.9, P = 0.002), residence in nursing home or long-term care facility (3.6, 1.0–12.3, P = 0.044), presence of underlying genitourinary disease (1.9, 1.2–2.9, P = 0.005), and presence of indwelling implantable intravenous port (2.2, 1.1–4.1, P = 0.021). 3GC resistance was independently associated with increased length of hospital stays (P < 0.001). In this study, the prevalence of 3GC resistance was high among both patients with community-onset and those with community-acquired E. coli bacteremia. 3GC resistance is a strong independent risk factor for length of hospital stay. The effectiveness of empirical antibiotic treatment would partially explain the impact of 3GC resistance, but more evidence is needed. The choice of appropriate empirical antibiotics for community-onset E. coli bacteremia might impact outcomes in terms of the length of hospital stay and need to be individualized according to the patient-specific risk for acquiring drug-resistant pathogens.