Volume 64, Issue 7, 1 April 2017

The development of nontoxic broad-spectrum antimicrobial drugs in the mid-20th century led to a culture of empiricism, underdevelopment of diagnostics, neglect of immunotherapy, and selection for drug resistance, which together created the conditions that underlie the current crisis.

In 1996 an article in this journal predicted a crisis in infectious diseases, which subsequently unfolded with a paucity of new drugs, increases in antimicrobial resistance, and underdevelopment in both immunotherapy and diagnostics. This article argues that the root cause of the current-day problems lies in the enormous success of the mid-20th century antibiotic revolution. The availability of low-toxicity broad-spectrum drugs fostered a culture of empiricism and widespread use, which in turn stunted the development of both the specialty and rapid diagnostics while promoting increases in resistance. Two decades later, there are promising signs that widespread recognition of these problems is leading to fundamental changes in the approach to the therapy of infectious diseases. Ultimately, a concerted effort to simultaneously develop pathogen-specific drugs, immunotherapy, and improved diagnostics could provide a qualitatively new platform for confronting the challenge of infectious diseases, which now also includes host dysbiosis.

The use of 2 doses of influenza vaccine is safe and immunologically relevant in solid organ transplant recipients, with a number needed to treat for seroprotection and seroconversion <10, supporting the use of 2 vaccination doses after transplantation.

Carbapenem-resistant Klebsiella pneumoniae is a major public health threat, including in the long-term acute care hospital (LTACH) setting. We found a carbapenem resistance rate of 25% among K. pneumoniae clinical isolates from a network of 64 LTACHs in the United States. Resistance rates to gram-negative agents were also high, including a strikingly high prevalence of colistin/polymyxin B resistance of 16%.

We investigated the association between proton pump inhibitors (PPIs) and risk of listeriosis in Denmark, 1994-2012, using register data. The matched comorbidity adjusted odds ratio was 2.8 (95%CI: 2.1–3.7). PPIs may increase the risk of listeriosis in vulnerable populations groups.

Our study demonstrated immune memory and antibody persistence for 6 years following 1 dose of quadrivalent HPV vaccine (4vHPV). Two doses of 4vHPV induced similar vaccine-type specific antibody response as 3 doses in girls who were vaccinated 6 years ago.

Using longitudinal data from geographically diverse community cohorts, this study informs disease etiology by describing hepatitis C virus (HCV) incidence temporal trends and related exposure behaviors, highlighting the impact early and sustained harm reduction strategies can have on HCV trends.

Adjunctive intravenous immunoglobulin (IVIG) was infrequently used in patients with necrotizing fasciitis and shock at US academic hospitals. IVIG had no significant impact on mortality, even when administered within 2 days of hospitalization or specifically to patients with streptococcal or staphylococcal infections.

We generated genome sequence data from 293 Enterococcus faecium isolates from patients with bacteremia spanning 7 years in one hospital. Cases were connected to numerous transmission routes, the complexity of which placed them beyond detection by conventional infection control methods.

We investigated and mitigated a 2-phase clonal outbreak of Mycobacterium abscessus linked to hospital tap water. A combination of tap water avoidance among high-risk patients, including lung transplant and cardiac surgery patients, and water engineering interventions terminated the outbreak.

Zika virus startled the world with reports of increased microcephaly cases. Here, we demonstrate that Zika virus infects microglia in human fetal brain cells. This highlights a role for microglia and the development of neuroinflammation during congenital Zika virus pathogenesis.

This manuscript describes a prospective study of early-onset neonatal candidiasis (congenital candidiasis) in extremely low birth weight infants and compares them to infants with late-onset disease and to controls. Early-onset disease predicts dissemination, cardiovascular end-organ damage, and high mortality.

Patients with Lyme disease often have pronounced T_H17 inflammatory responses. Early in the infection, during erythema migrans, T_H17 responses correlate with Borrelia burgdorferi antibodies, whereas late in the disease, in patients with antibiotic-refractory Lyme arthritis, these responses correlate with autoantibodies.

We have noted a recent upsurge in blackwater fever among children presenting to hospitals in eastern Uganda and speculate that this may relate to a change in policy toward new artemisinin-based combination therapies for malaria.

Samples from >750 patients with presumptive TB in two continents were tested with a field-based IgG serological assay incorporating 57 M. tuberculosis antigens, and showed that responses to single antigens or multiple antigen sets have no clinically useful discriminating power.

We conducted a spatial analysis to identify epidemic foci and trends of HIV among men who have sex with men (MSM) in China. Assorted spatial analyses reveal concentrated HIV epidemic among young MSM in Chinese cities, calling for intensive interventions.

The continued rise in infections caused by extended-spectrum β-lactamase (ESBL)–producing pathogens is recognized globally as one of the most pressing concerns facing the healthcare community. We review the available data for the use of cephamycins, cefepime, piperacillin-tazobactam, ceftolozane-tazobactam, and ceftazidime-avibactam for the treatment of ESBL infections.