Brandon J. Webb

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.

Prediction of Bloodstream Infection Due to Vancomycin-Resistant Enterococcus in Patients Undergoing Leukemia Induction or Hematopoietic Stem-Cell Transplantation.

Background. Bloodstream infection (BSI) to due vancomycin-resistant Enterococcus (VRE) is an important complication of hematologic malignancy. Determining when to use empiric anti-VRE antibiotic therapy in this population remains a clinical challenge. Methods. A single-center cohort representing 664 admissions for induction or hematopoietic stem-cell transplant (HSCT) from 2006 to 2014 was selected. We derived a prediction score using risk factors for VRE BSI and evaluated the models predictive performance by calculating it for each of 16232 BSI at-risk inpatient days. Results. VRE BSI incidence was 6.5% of admissions (2.7 VRE BSI per 1000 BSI at-risk days). Adjusted 1-year mortality and length of stay were significantly higher in patients with VRE BSI. VRE colonization (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI] = 3.4-20.6; P < .0001), renal insufficiency (aOR = 2.4; 95% CI = 1.0-5.8; P = .046), aminoglycoside use (aOR = 4.7; 95% CI = 2.2-9.8; P < .0001), and antianaerobic antibiotic use (aOR = 2.8; 95% CI = 1.3-5.8; P = .007) correlated most closely with VRE BSI. A prediction model with optimal performance included these factors plus gastrointestinal disturbance, severe neutropenia, and prior beta-lactam antibiotic use. The score effectively risk-stratified patients (area under the receiver operating curve = 0.84; 95% CI = 0.79-0.89). At a threshold of ≥5 points, per day probability of VRE BSI was increased nearly 4-fold. Conclusions. This novel predictive score is based on risk factors reflecting a plausible pathophysiological model for VRE BSI in patients with hematological malignancy. Integrating VRE colonization status with risk factors for developing BSI is a promising method of guiding rational use of empiric anti-VRE antimicrobial therapy in patients with hematological malignancy. Validation of this novel predictive score is needed to confirm clinical utility.

Health Care–Associated Pneumonia is Mostly Dead. Long Live the Acronym PES?

Community-acquired pneumonia is most often caused by pneumococcus, Haemophilus influenzae, methicillinsensitive Staphylococcus aureus, Mycoplasma pneumoniae, Klebsiella species, and other bacteria sensitive to empirically prescribed antibiotics such as ceftriaxone and azithromycin. However, a few patients are infected with pathogens resistant to these antibiotics (1). Presuming that effective empiric antibiotic therapy would improve clinical outcomes, the 2005 American Thoracic Society/Infectious Disease Society of America nosocomial pneumonia guidelines recommended extended-spectrum antibiotic therapy for patients suspected of harboring a resistant organism (2). These patients were defined in the guideline using a limited set of risk factors as having health care–associated pneumonia (HCAP) (3). Since 2005, multiple investigators have further studied factors associated with resistant pathogens. Recent reviews highlight variable and mostly poor performance of the HCAP criteria in accurately identifying patients with resistant organisms (1, 4–6). Administering broadspectrum antibiotic therapy to patients at higher risk for resistant pathogens has not been shown to improve outcomes (4, 5). Consequently, use of the HCAP criteria to select patients for empiric, extendedspectrum antibiotics is mostly dead. In this issue of AnnalsATS, Prina and colleagues (pp. 153–160) identify clinical characteristics associated with drug-resistant pathogens among immunocompetent patients with pneumonia in a large, prospective, observational Spanish database (7). They propose a new acronym, PES, to signify the three prevalent groups of resistant organisms: Pseudomonas aeruginosa, Enterobacteriaceae producing extendedspectrum beta-lactamase, and methicillinresistant Staphylococcus aureus (MRSA). Previous authors have used the abbreviations MDR for multidrug-resistant pathogens or DRP for drug-resistant pathogens for resistant bacteria found in patients with pneumonia (1, 8). The 15year database in this study comprises 4,549 patients; a microbiological diagnosis was made in 1,597 cases. A PES organism was recovered in 94/4549 (2.1%) of all patients, representing 6% of the culture-positive subgroup. The authors identified seven independent PES predictors at the time of diagnosis: age>65 years, male sex, previous antibiotic use, chronic respiratory disease, chronic kidney disease, altered mental status, and temperature greater than 37.88C on arrival. Male sex, altered mental status, and fever have not been previously reported, nor would they seem conceptually associated with resistant pathogens. A probabilistic prediction score was derived based on weighted results from logistic regression, and a threshold of five points in individual patients was optimum for differentiating risk of pneumonia caused by PES pathogens. Using the denominator of 1,597, the area under the receiver operating curve (AUC-ROC) was 0.75 and the accuracy of classification was 71%. Although using this scoring threshold would have increased empiric administration of antibiotics with in vitro activity to 70% (66/94) of patients with resistant pathogens, 381 of the 1,597 patients (24%) would receive unnecessarily broad-spectrum antibiotics. Empirically prescribed antibiotics effective against PES organisms were not associated with improved survival. The test performance characteristics of PES are similar in predictive value to other previously published scores: sensitivity, specificity, and AUC-ROC in the 0.7 range (1, 4). Similar to other published scores, PES favors overtreatment. Considering that resistant organisms are more easily recovered and less likely causes of culture-negative pneumonia, additional overtreatment would result if the scoring model were applied to all patients presenting to the hospital with pneumonia (9, 10). A limitation of the study by Prina and colleagues is that 68% of identified pathogens were recovered only from expectorated sputum. Expectorated sputum passes through the oropharynx, where organisms capable of causing pneumonia are present as colonizers, not pathogens. Even when sputum collection and microbiology laboratory procedures are optimized as in this prospective study, bacteria recovered only in sputum are classified as “presumptive” rather than confirmed lung pathogens. Therefore, some of the 64 patients with PES on sputum culture alone would not have had a lower respiratory tract infection with a resistant pathogen. Selecting a small subset of patients with pneumonia with resistant pathogens at the time of presentation and treating them effectively is difficult. Although Prina and

Decrease in Vancomycin-Resistant Enterococcus Colonization After Extensive Renovation of a Unit Dedicated to the Treatment of Hematologic Malignancies and Hematopoietic Stem-Cell Transplantation

OBJECTIVE While a direct relation between hospital construction and concomitant infection rates has been clearly established, few data are available regarding the environmental decontamination effects of renovation in which surfaces are replaced and regarding subsequent infection incidence. DESIGN Retrospective clinical study with vancomycin-resistant Enterococcus (VRE) molecular strain typing and environmental cultures. SETTING A regional referral center for acute leukemia and hematopoietic stem-cell transplantation. PATIENTS Overall, 536 consecutive hospital admissions for newly diagnosed acute leukemia or a first autologous or allogeneic stem-cell transplantation were reviewed. INTERVENTION During 2009-2010, our unit underwent complete remodeling including replacement of all surfaces. We assessed the effects of this construction on the incidence of hospital-acquired VRE colonization before, during, and after the renovation. RESULTS We observed a sharp decrease in VRE colonization rates (hazard ratio, <0.23; 95% confidence interval, 0.18-0.44; P<.0001) during the first year after the renovation, with a return to near baseline rates thereafter. The known risk factors for VRE colonization appeared to be stable over the study interval. Environmental cultures outside of patient rooms revealed several contaminated areas that are commonly touched by unit personnel. Multilocus sequence typing of VRE isolates that were cryopreserved over the study interval showed that dominant strains prior to construction disappeared and were replaced by other strains after the renovation. CONCLUSIONS Unit reconstruction interrupted endemic transmission of VRE, which resumed with novel strains upon reopening. Contamination of environmental surfaces and shared equipment may play an important role in endemic transmission of VRE. Infect Control Hosp Epidemiol 2017;38:1055-1061.

Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health Care–associated Pneumonia

Rationale: Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care‐associated pneumonia, especially where no microbiological diagnosis is made. Objectives: To compare outcomes between patients who were transitioned to broad‐ versus narrow‐spectrum oral antibiotics after initially receiving broad‐spectrum intravenous antibiotic coverage. Methods: We performed a secondary analysis of an existing database of adults with community‐onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology‐negative health care‐associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad‐spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad‐spectrum (fluoroquinolone) versus narrow‐spectrum (usually a &bgr;‐lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB‐65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy. Measurements and Main Results: Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30‐day readmission (11.9 vs. 21.4%; P = 0.26) and 30‐day all‐cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30‐day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06‐5.2; P = 0.61) or 30‐day all‐cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19‐1.6; P = 0.26) between narrow and broad oral antibiotic groups. Conclusions: On the basis of analysis of a limited number of patients observed retrospectively, our findings suggest that it may be safe to switch from broad‐spectrum intravenous antibiotic coverage to a narrow‐spectrum oral antibiotic once clinical stability is achieved for hospitalized patients with health care‐associated pneumonia when no microbiological diagnosis is made. A larger retrospective study with propensity matching or regression‐adjusted test of equivalence or ideally a prospective comparative effectiveness study will be necessary to confirm our observations.