Friday, September 29, 2017

Literature Update in Pneumonia

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Authors: David Bostick, MD MPH; Phil Magidson, MD MPH; Carina Sorenson, MD; Neil Christopher, MD; Kami M. Hu, MD; David Wacker, MD PhD
Editors: Michael C. Bond, MD FAAEM; Jay Khadpe, MD FAAEM
Originally Published: Common Sense March/April 2015

Patients with community-acquired pneumonia (CAP) are frequently seen in the emergency department (ED). According to the National Hospital Ambulatory Medical Care Survey (NHAMCS), pneumonia is the third most common principal ED discharge diagnosis in the United States.[1] In this literature update, we examine: use of point-of-care ultrasound to diagnose pneumonia, obtaining routine blood cultures, risk factors for multi-drug resistant organisms and the efficacy of antibiotic monotherapy versus combination therapy in moderately severe pneumonia.

Prospective evaluation of point of care ultrasonography for the diagnosis of pneumonia in children and young adults. Shah VP, et al. JAMA Pediatr. 2013 Feb;167(2):119-25.

Lung ultrasound for the diagnosis of pneumonia in adults: A systematic review and meta-analysis. Chavez MA, et al. Respir Res. 2014 Apr 23;15:50.

A prospective observational study by Shah et al., examined the use of ED lung ultrasound (LUS) for the diagnosis of pneumonia in 200 patients. Patient age ranged from birth to 21 years. LUS, performed by ED physicians with various amounts of experience and training, demonstrated an overall sensitivity of 86% and specificity of 89% for diagnosis of pneumonia. Mean time to exam completion was seven minutes. Of the 13 patients with positive LUS and negative chest radiograph (CXR), the majority had lung consolidations less than 1cm in diameter and had a clinical picture consistent with pneumonia. Of the five false negatives (i.e., negative LUS but positive CXR), two were due to operator error and three were true misses (no sign of pneumonia on ultrasound review). There was no statistically significant difference in diagnostic accuracy between physicians who had performed more than 25 scans to those who performed less than 25 scans.

With regards to adult patients, a meta-analysis by Chavez et al., examined the use LUS to diagnose ED, ICU, and floor patients age >18 with pneumonia. Ten articles met the inclusion criteria and were used for analysis. Overall, LUS was 94% sensitive and 96% specific for the diagnosis of pneumonia in adults. When comparing LUS to clinical criteria and chest imaging, either CXR or computed tomography (CT), the pooled sensitivity and specificity were 95% and 94%, respectively. When compared specifically to CT, LUS was 94% sensitive and 99% specific in diagnosing pneumonia.

Point-of-care LUS is a powerful diagnostic tool that complements the history and physical exam. LUS performs well as both a rule-in and rule-out test for pneumonia in the adult and pediatric population, even with less-experienced ultrasound operators. The added benefits of decreased cost, radiation exposure and speed of diagnosis make it an attractive choice for ED patients.

Can we predict which patients with community-acquired pneumonia are likely to have positive blood cultures? Campbell SG, et al. World J Emerg Med. 2011;2(4):272-8.

Blood culture use in the emergency department in patients hospitalized for community-acquired pneumonia. Makam AN, et al. JAMA Intern Med. 2014 May;174(5):803-6.

A 2011 retrospective chart review by Campbell et al., attempted to identify ED patients with pneumonia who were more likely to have positive blood cultures (BCs). Variables associated with increased likelihood of a positive BC were:

  1. Leukopenia (white blood cell < 4.5 x109/L), LR=7.75
  2. Serum creatinine >1.2 mg/dL, LR=3.15
  3. Serum glucose <110 mg/dL, LR=2.46
  4. Fever (temperature >38°C), LR=2.25
Patients with all four findings had a LR of 135.53 for a positive BC.

Identifying the causative pathogen in pneumonia is most important in patients who: are elderly, are immunocompromised, have severe disease, or are likely to be infected with atypical or resistant pathogens. As patients with the above findings have a greater incidence of a positive BC, it is reasonable to obtain BCs in this subset of patients with pneumonia.

Additionally, a recent retrospective review by Makam et al., further explored the patterns of obtaining BCs in adult ED patients with CAP. Investigators found that the rate of obtaining BCs for CAP admissions increased from 29.4% (95% CI, 21.9-38.3%) in 2002 to 51.1% (95% CI, 41.8-60.3%) in 2010. This represents a 70% relative increase (p=0.03). For comparison, over the same period, the rate of obtaining BCs for urinary tract infection admissions remained stable (p=.47). Further analysis suggested that collection of BCs was not related to disease severity, as a higher CURB-65 score or intensive care unit (ICU) admission was actually associated with lower odds of obtaining BCs. Of note, BCs were obtained significantly more often in privately-owned hospitals and in cases where antibiotic therapy was initiated in the ED. This final finding suggests that changes in EP practices could significantly decrease unnecessary testing and costs.

A new strategy for healthcare-associated pneumonia: A 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Maruyama T, et al. Clin Infect Dis. 2013 Nov;57(10):1373-83.

The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines state that all patients with healthcare-associated pneumonia (HCAP) be treated empirically with multiple antibiotics directed against multi-drug resistant (MDR) pathogens.[2] Patients considered to have HCAP include those who: reside in a nursing home or other long-term care facility, attend a hemodialysis clinic, or have received IV antibiotics, chemotherapy or wound care within the last 30 days. Some argue that not all HCAP patients are at equal risk of acquiring an MDR pathogen; therefore, they may not all require broad-spectrum empiric antibiotics.

This prospective multicenter cohort study utilized a previously-described algorithm to guide therapy for 445 patients with pneumonia requiring admission for either CAP or HCAP.[3] The algorithm stratified HCAP patients as low or high-risk based on the severity of illness and the presence of other risk factors for MDR pathogens, then assigned them to either standard CAP therapy or guideline-recommended hospital-acquired pneumonia (HAP) therapy consisting of two or three antibiotics: an antipseudomonal beta-lactam, a quinolone or aminoglycoside, and optional linezolid or vancomycin.

Among HCAP patients, both the 30-day mortality and presence of MDR pathogens was significantly lower in patients with 0-1 MDR risk factors as compared to those with ≥2 risk factors (mortality: 8.6% vs 18.2%, p=.012, MDR pathogen identified: 2% vs. 27.2%, p<.001). In total, 299 HCAP patients were treated according to the therapy algorithm, with 50.5% receiving CAP therapy. Of these, only 3.2% received inappropriate therapy which interestingly was not independently associated with increased mortality. This study shows that not all HCAP patients require antibiotics for MDR organisms and that some can be treated with typical CAP antibiotics.

β-lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community acquired pneumonia: A randomized noninferiority trial. Garin N, et al. JAMA Intern Med. 2014 Dec 1;174(12):1894-901.

Optimal antibiotic coverage for CAP covers both Streptococcus pneumoniae and atypical pathogens (e.g., Legionella, Mycoplasma, and Chlamydia), usually with the combination of a beta-lactam and a macrolide. Current studies have not provided significant data to show that combination therapy is essential. Furthermore, while macrolides may add anti-inflammatory effects, they can also lead to increased cardiovascular risk as well as antibiotic resistance. Thus, the authors of this study compared the efficacy of standard combination therapy using beta-lactam antibiotics plus a macrolide to that of beta-lactam antibiotics alone.

This multicenter, non-inferiority trial included 580 adult patients with moderately severe CAP. All patients received cefuroxime or amoxicillin/clavulanic acid. Patients randomized to the combination therapy arm also received clarithromycin. The primary outcome was time to clinical stability as defined by vital signs at day seven and secondary outcomes included 30 and 90-day mortality.

For the primary outcome, 41.2% of monotherapy patients and 33.6% of combination therapy patients were not clinically stable at day seven (p=0.07), which did not fall within the predefined CI boundary to demonstrate non-inferiority. There was also no overall difference in survival or time to clinical stability, but there was a trend towards better outcomes in the combination therapy arm for patients with higher Pneumonia Severity Index (PSI) or CURB65 scores.[4,5] There was a statistically significant increase in readmissions and a trend towards more severe events in the monotherapy arm. Ultimately, these findings support the current practice of combination therapy.

For patients presenting to the ED with suspicion of pneumonia, consider use of point of care ultrasound. Consider the necessity of blood cultures for CAP and the requirement for MDR organism coverage. Finally for patients with CAP admitted to the hospital, combination therapy may be the most appropriate antibiotic option to ensure rapid improvement and a good outcome.

1. CDC. (2010). National Hospital Ambulatory Medical Care Survey: 2010 Emergency Department Summary Tables. Retrieved online at on November 26th, 2014

2. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(14):388-416.

3. Brito V, Niederman MS. Healthcare-associated pneumonia is a heterogeneous disease, and all patients do not need the same broad-spectrum antibiotic therapy as complex nosocomial pneumonia. Curr Opin Infect Dis. 2009;22:316-25.

4. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A predication rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997 Jan 23;336(4):243-50.

5. Lim W, van der Eerden MM, Laing R, Boersma W, Karalus N, Town G, Lewis S, Macfarlane J. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003 May;58(5):377–382.

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