Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

Introduction: Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns.

Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model’, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly.

Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.     

Antigen-specific B memory cell responses to lipopolysaccharide (LPS) and invasion plasmid antigen (Ipa) B elicited in volunteers vaccinated with live-attenuated Shigella flexneri 2a vaccine candidates

We evaluated B memory responses in healthy adult volunteers who received one oral dose of live-attenuated Shigella flexneri 2a vaccine. LPS-specific B_M cells increased from a median of 0 at baseline to 20 spot forming cells (SFC)/10⁶ expanded cells following vaccination (p = 0.008). A strong correlation was found between post-vaccination anti-LPS B_M cell counts and peak serum anti-LPS IgG titers (rs = 0.95, p = 0.0003). Increases in B_M specific for IpaB approaching significance were also observed. In sum, oral vaccination with live-attenuated S. flexneri 2a elicits B_M cells to LPS and IpaB, suggesting that B_M responses to Shigella antigens should be further studied as a suitable surrogate of protection in shigellosis.     

Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.     

B cell responses in gastric antrum and duodenum following oral inactivated Helicobacter pylori whole cell (HWC) vaccine and LT(R192G) in H pylori seronegative individuals

To investigate whether B cell-specific responses could be elicited in the gastric mucosa of Helicobacter pylori (HP) naive subjects, five volunteers ingested three doses of a HP killed whole cell (HWC) vaccine with 25 microg of recombinant heat-labile toxin (LT(R192G)). Two of three subjects had detectable LT(R192G) and HWC IgA antibody secreting cell (ASC) gastric responses. LT(R192G) and HWC responses in duodenal were 5-14-fold higher than those detected in antral biopsies (P<0.01 and P=0.05, respectively). These results provide the first evidence that specific gastric B cell responses can be induced in HP-non-infected individuals following oral immunization.     

Assessment of the prevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among college students using three survey methods

To evaluate the seroprevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among undergraduate college students, the authors simultaneously conducted three types of surveillance on a large university campus (27,902 undergraduates) in the Baltimore-Washington metropolitan area: a voluntary HIV-1 serosurvey with a linked risk assessment questionnaire (n = 3,394), a blinded serosurvey using blood specimens collected for routine purposes in the Student Health Center (n = 1,829), and a random sample risk assessment and case identification mail survey (n = 1,017 respondents of 3,000 solicited). The proportion of students belonging to a known risk group (a homosexual or bisexual man, intravenous drug user, or a sexual partner of a bisexual man, an HIV-1-infected person, a female prostitute, or an intravenous drug user) was 5.9% in the mail survey and 8.8% in the voluntary serosurvey. Whereas no infections were detected in the blinded serosurvey, two infected persons were identified in the mail survey (0.2%) and two in the voluntary serosurvey (0.06%), all among high-risk persons. Although derived from independent samples and subject to different biases, these three survey methods yielded a consistent pattern of HIV-1 epidemiology on this campus, whereby the overall prevalence of infection was low and confined to members of high-risk groups, despite the common occurrence of behaviors that might facilitate sexual transmission of HIV-1 among many other students.