Kristin Dascomb

Streptococcus pneumoniae serotypes in Utah adults at the end of the PCV7 era

While heptavalent pneumococcal conjugate vaccine (PCV) has decreased vaccine type invasive pneumococcal disease (IPD) nationwide, rapid serotype replacement and increasing parapneumonic empyema, has been reported in Utah children. The effect of pediatric vaccination on adults in this population is unknown. We identified 117 adults with IPD from the Intermountain Healthcare Central Laboratory between November 2009 and October 2010. We serotyped 61 (52%) stored isolates. We compared the serotype distribution of adult IPD isolates with that of pediatric isolates collected in 2009-2010. PCV7 serotypes were rare in adults (3%) and children (3%). Emerging 13-valent PCV serotypes 3, 7F, and 19A caused the majority of IPD in adults (63%) and children (56%). Fifty-one (84%) adult isolates were serotypes included in 23-valent polysaccharide vaccine and 66% in PCV13. Adult and pediatric IPD serotypes are closely associated in Utah. PCV13 vaccination in Utah children is likely to significantly impact IPD in Utah adults.

Early Streptococcus pneumoniae serotype changes in Utah adults after the introduction of PCV13 in children

INTRODUCTION Pneumococcal conjugate vaccines (PCV) have indirect effects due to decreased Streptococcus pneumoniae colonization in vaccine recipients. We sought to determine whether the introduction of PCV13 in children led to changes in the epidemiology and clinical manifestations of invasive pneumococcal disease (IPD) in adults. METHODS We described demographics, comorbidities, clinical manifestations, and serotypes of IPD in Utah adults before (November 2009-February 2010) and after (March 2010-March 2012) the introduction of PCV13 in children. We also compare serotypes causing IPD in Utah adults and children. RESULTS After the introduction of PCV13 in the childhood vaccine program, the proportion of IPD due to PCV13 exclusive serotypes decreased significantly in Utah adults (64-40%, p=0.009), primarily due to a decline in serotype 7F (36-15%, p=0.008). There were non-significant increases in IPD due to Pneumococcal polysaccharide 23 (PPV23) unique serotypes and non-vaccine serotypes, most notably serotype 22F. Changes in the proportions of vaccine and non-vaccine serotypes were similar in adults and children. Meningitis was more commonly due to non-vaccine serotypes relative to non-meningitis cases (47% vs. 18%, p=0.007). When stratified by sex, decreases in PCV13 serotype IPD were only noted in men (76-33%, p=0.001). CONCLUSIONS Serotype epidemiology of IPD in adults closely follows that of children in the PCV13 era. Continued surveillance is needed to confirm whether replacement serotypes will lead to increases in pneumococcal meningitis and whether there are sex differences in the indirect effects of PCV vaccination in children.

Derivation and Multicenter Validation of the Drug Resistance in Pneumonia Clinical Prediction Score.

ABSTRACT The health care-associated pneumonia (HCAP) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. We aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of HCAP criteria. A derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. Risk factors for pneumonia due to drug-resistant pathogens were evaluated by logistic regression, and a novel prediction score (the drug resistance in pneumonia [DRIP] score) was derived. The score was then validated in a prospective, observational cohort of 200 microbiologically confirmed cases of pneumonia at four U.S. centers in 2013 and 2014. The DRIP score (area under the receiver operator curve [AUROC], 0.88 [95% confidence interval {CI}, 0.82 to 0.93]) performed significantly better (P = 0.02) than the HCAP criteria (AUROC, 0.72 [95% CI, 0.64 to 0.79]). At a threshold of ≥4 points, the DRIP score demonstrated a sensitivity of 0.82 (95% CI, 0.67 to 0.88), a specificity of 0.81 (95% CI, 0.73 to 0.87), a positive predictive value (PPV) of 0.68 (95% CI, 0.56 to 0.78), and a negative predictive value (NPV) of 0.90 (95% CI, 0.81 to 0.93). By comparison, the performance of HCAP criteria was less favorable: sensitivity was 0.79 (95% CI, 0.67 to 0.88), specificity was 0.65 (95% CI, 0.56 to 0.73), PPV was 0.53 (95% CI, 0.42 to 0.63), and NPV was 0.86 (95% CI, 0.77 to 0.92). The overall accuracy of the HCAP criteria was 69.5% (95% CI, 62.5 to 75.7%), whereas that of the DRIP score was 81.5% (95% CI, 74.2 to 85.6%) (P = 0.005). Unnecessary extended-spectrum antibiotics were recommended 46% less frequently by applying the DRIP score (25/200, 12.5%) than by use of HCAP criteria (47/200, 23.5%) (P = 0.004), without increasing the rate at which inadequate treatment recommendations were made. The DRIP score was more predictive of the risk of pneumonia due to drug-resistant pathogens than HCAP criteria and may have the potential to decrease antibiotic overutilization in patients with pneumonia. Validation in larger cohorts of patients with pneumonia due to all causes is necessary.

Predicting risk of drug-resistant organisms in pneumonia: Moving beyond the HCAP model

BACKGROUND Clinical management of community-acquired pneumonia (CAP) is increasingly complicated by antibiotic resistance. CAP due to pathogens resistant to guideline-recommended drugs (CAP-DRP) has increased. 2005 ATS/IDSA guidelines introduced a new category, healthcare-associated pneumonia (HCAP), and recommend extended-spectrum antibiotic treatment for patients meeting HCAP criteria. However, the predictive value of the HCAP model is limited and data suggest that outcomes are not improved using HCAP guideline-concordant therapy. Better methods to predict risk of CAP-DRP are needed. METHODS We reviewed currently published literature on the performance status of HCAP as a predictive tool and studies describing additional risk factors for CAP-DRP. We also summarize the performance characteristics of the currently published alternative clinical prediction scores and compare them to that of the HCAP model. RESULTS In addition to the five risk factors incorporated in HCAP, at least 13 other factors have been identified. The independent predictive value of any single factor is low, but accumulating factors results in increased risk of CAP-DRP. The performance characteristics of 9 clinical prediction scores are reviewed. Nearly all of the scores outperformed HCAP in their study populations. However, no single model has yet demonstrated adequate specificity to minimize unnecessary antibiotic use, while retaining sufficient sensitivity to prevent inadequate initial empiric antibiotic therapy when validated across a wide range of CAP-DRP prevalence. CONCLUSIONS Additional development and validation of prediction scores based upon more refined risk factors for CAP-DRP is needed. Once an accurate, adequately validated prediction score is available, an interventional trial will be needed to determine clinical impact.