Letters

Declining antimicrobial susceptibility of Streptococcus pneumoniae in the United States: report from the SENTRY Antimicrobial Surveillance Program (1998–2009)

Streptococcus pneumoniae is a remarkably adaptable and successful human pathogen, playing dual roles of both asymptomatic carriage in the nasopharynx and invasive disease including pneumonia, bacteremia, and meningitis. Efficacious vaccines and effective antibiotic therapies are critical to mitigating morbidity and mortality. However, clinical interventions can be rapidly circumvented by the pneumococcus by its inherent proclivity for genetic exchange. This leads to an underappreciated interplay between vaccine and antibiotic pressures on pneumococcal populations. Circulating populations have undergone dramatic shifts due to the introduction of capsule-based vaccines of increasing valency imparting strong selective pressures. These alterations in population structure have concurrent consequences on the frequency of antibiotic resistance profiles in the population. This review will discuss the interactions of these two selective forces. Understanding and forecasting the drivers of antibiotic resistance and capsule switching are of critical importance for public health, particularly for such a genetically promiscuous pathogen as S. pneumoniae.

Bacterial pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma pneumoniae, and Klebsiella pneumoniae represents a frequent cause of mortality worldwide. The increased incidence of pneumococcal diseases in both developed and developing countries is alarmingly high, affecting infants and aged adult populations. The growing rate of antibiotic resistance and biofilm formation on medical device surfaces poses a greater challenge for treating respiratory infections. Over recent years, a better understanding of bacterial growth, metabolism, and virulence has offered several potential targets for developing therapeutics against bacterial pneumonia. This chapter will discuss the current and developing trends in treating bacterial pneumonia.

Streptococcus pneumoniae, which cause noninvasive pneumococcal diseases, severely impair children's health. This study analyzed serotype distribution and antimicrobial resistance of S. pneumoniae from January 2012 to December 2012 in a Children's Hospital, Shanghai.

A total of 328 pneumococcal isolates were serotyped by multiplex sequential PCR and/or capsule-quellung reaction. The minimum inhibitory concentrations for 11 antimicrobial agents were determined by broth microdilution method.

Among 328 strains, 19F (36.3%), 19A (13.4%), 6A (11.9%), 23F (11.0%), 14 (5.8%), 6B (5.2%), and 15B/C (4.3%) were the most common serotypes. The coverage rates of 7-, 10-, and 13-valent conjugate vaccines (PCV7, PCV10, and PCV13) were 58.2%, 58.2%, and 84.1%, respectively. Out of the isolates, 26 (7.9%) strains were penicillin resistant. Most of the strains displayed high resistance rate to macrolides (98.5% to erythromycin, 97.9% to azithromycin, and 97.0% to clindamycin).

The potential coverage of PCV13 is higher than PCV7 and PCV10 because of the emergence of 19A and there should be long-term and systematic surveillance for non-vaccine serotypes.

Streptococcus pneumoniae infections have periodically caused significant morbidity and outbreaks among military personnel, especially trainees. This study evaluated the effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in reducing pneumonia in healthy military trainees.

From 2000–2003, 152 723 military trainees from 5 US training camps were enrolled in a double-blind, placebo-controlled trial of PPV23. Participants were closely monitored during basic training for radiographically confirmed pneumonia etiology and loss-of-training days. Participants were also followed using electronic medical encounter data until 1 June 2007 for three additional outcomes: any-cause pneumonia, any acute respiratory disease, and meningitis.

Comparison of demographic data by study arm suggested the randomization procedures were sound. During basic training, 371 study participants developed radiographically confirmed pneumonia. None had evidence of S. pneumoniae infection, but other etiologies included adenovirus (38%), Chlamydophila pneumoniae (9%), and Mycoplasma pneumoniae (8%). During the follow-up period, many study participants, in both the vaccine and placebo groups, had clinical encounters for the medical outcomes of interest. However, Cox's proportional hazard modeling revealed no evidence of a protective vaccine effect during recruit training (radiographically confirmed pneumonia) or up to 6.7 years after enrollment (any-cause pneumonia, any acute respiratory disease, or meningitis).

Data from this large, double-blind, placebo controlled trial do not support routine use of PPV23 among healthy new military trainees. This clinical trial was registered at clinicaltrials.gov (registration number NCT02079701, http://www.clinicaltrials.gov/ct2/show/NCT02079701?term=NCT02079701&rank=1).

The Assessing Worldwide Antimicrobial Resistance Evaluation Program monitors the activity of ceftaroline and comparator agents tested against pathogens causing either respiratory or skin and soft tissue infections. A total of 7733 isolates from patients in 80 medical centers across the United States (USA) identified as respiratory tract pathogens by the infection type and/or specimen site recorded by the submitting laboratory during 2009–2011 were evaluated. There were 3360 isolates of Streptococcus pneumoniae, 1799 Haemophilus influenzae, 1087 Staphylococcus aureus, 678 Moraxella catarrhalis, 459 Klebsiella pneumoniae, 223 Escherichia coli, and 127 Klebsiella oxytoca. Annual penicillin resistance among S. pneumoniae ranged from 21.9 to 24.3%. All S. pneumoniae strains were inhibited at a ceftaroline MIC of ≤0.5 μg/mL with 100.0% of isolates categorized as susceptible. Ceftaroline was 16-fold more active than ceftriaxone and 32-fold more active than amoxicillin-clavulanate against penicillin-resistant pneumococci. Only 49.8% of the penicillin-resistant isolates were susceptible to ceftriaxone. There were a total of 1087 S. aureus (48.9% methicillin-resistant S. aureus [MRSA]) isolates, and the yearly MRSA rate ranged from 47.9 to 49.7%. The ceftaroline MIC_50/90 for S. aureus was at 0.25/1 μg/mL; 98.2% susceptible and no resistant strains (≥4 μg/mL). Ceftaroline activity against methicillin-susceptible S. aureus (MSSA) isolates (MIC₅₀ and MIC₉₀, 0.25 and 0.25 μg/mL, respectively; 100% susceptible) was 2- to 4-fold greater than for MRSA (MIC_50/90, 0.5/1 μg/mL; 96.2% susceptible). The ceftriaxone MIC₉₀ for MSSA was 4 μg/mL. Ceftaroline was active against H. influenzae (MIC_50/90 ≤0.015/0.03 μg/mL; 100.0% susceptible) and against M. catarrhalis (MIC_50/90, 0.06/0.12 μg/mL). Ceftaroline was active against non–extended spectrum β-lactamase (ESBL) phenotype strains of Enterobacteriaceae but not against ESBL-positive phenotype strains. In summary, ceftaroline was highly active against a large collection of bacterial pathogens isolated from patients with respiratory tract infections in the USA during 2009 through 2011.

This study evaluated pneumococci cultured from blood or lower respiratory tract specimens from hospitalized patients in the USA (all age groups) during 2011–2012 (N = 1190) and compared findings with those from a similar study performed in 2008 (N = 694). Isolates were tested for susceptibility by broth microdilution and serotypes determined by cpsB sequencing, supplemented with multiplex PCR and capsular swelling assays. Relative percentages of 7-valent pneumococcal conjugate vaccine (PCV7) types were 6.3 and 4.9% in 2008 and 2011–2012, respectively, and the most common PCV7 serotypes (19F and 6B) comprised only 3.7% and 4.0% of all isolates from both periods, respectively. Thirteen-valent pneumococcal conjugate vaccine (PCV13) serotypes represented 42.9% of isolates in 2008 and 30.1% in the second period, and this decrease was driven by 19A and 7F. Non-PCV13 serogroups/serotypes 23A, 15B/15C, 7C, 8, and 31 increased. Penicillin non-susceptibility rates were 9.6–10.0% and 38.9–42.7% when applying the parenteral (i.e. ≥4 μg/mL) and oral breakpoints (i.e. ≥0.12 μg/mL), respectively. Ceftaroline was the most potent agent tested based on MIC₅₀ and MIC₉₀ values (≤0.015 and 0.12 μg/mL, respectively) for both time periods.