Tuesday, October 21, 2014

A Simple Community-Acquired Pneumonia? -- Appropriate Antibiotic Choice in the Era of Strep Pneumo Resistance

Clinical Scenario:  

You are taking care of a middle-aged female who presents to the ER from home with fevers/chills, shortness of breath, and cough that has gotten progressively worse over the last two days. She has not been in the hospital within the last 3 months and does not have other HCAP risk factors. You decide to get a CXR which identifies a patchy left lower lobe airspace opacity and tiny left pleural effusion consistent with pneumonia. 

Clinical Question: 

With the increasing resistance of Strep pneumo to macrolides, should we consider changing outpatient CAP empiric treatment to a fluoroquinolone? Keep in mind, that here in Saint Louis, Strep pneumo is sensitive to erythromycin 54% of the time at BJH and 43% of the time at SLCH according to current antibiogram data.

Literature Review:  
In 2007, the Infectious Disease Society of America (IDSA) and the American Thoracic Society (ATS) convened a joint committee to develop a unified stance community acquired pneumonia (CAP) treatment. Their recommendations follow:

1.     Patients that are previously healthy with no risk factors for Drug Resistant Strep pneumo (DRSP) pneumonia can be treated with:
a.     A macrolide (azithromycin, clarithromycin, or erythromycin) (strong recommendation; level I evidence)
b.     Doxycycline (weak recommendation; level III evidence)
2.     HOWEVER, in regions with a high rate (greater than 25%) of infection with high-level (MIC, >16 mg/mL) macrolide-resistant S. pneumoniae, one should consider the use of alternative agents for any patient, including those without comorbidities. (Moderate recommendation; level III evidence.)
3.     Presence of comorbidities (including, chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; use of antimicrobials within the previous 3 months [in which case an alternative from a different class should be selected]; or other risks for DRSP infection) should prompt the selection of a regimen listed below
a.     A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]) (strong recommendation; level I evidence)
b.     A b-lactam plus a macrolide (strong recommendation; level I evidence) (High-dose amoxicillin [e.g., 1 g 3 times daily] or amoxicillin-clavulanate [2 g 2 times daily] is preferred; alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg 2 times daily]; doxycycline [level II evidence] is an alternative to the macrolide.) 

So did these recommendations affect clinical practice? A retrospective cohort study of adult outpatients treated for CAP in an urban, academic ED from May 2009 to October 2009 (after guidelines published) aimed to assess prevalence of Drug Resistant Strep Pneumo (DRSP) factors and how this affected antibiotic prescriptions written. A total of 175 cases were included that met eligibility criteria. Of the 175, at least one DRSP risk factor was present in 90 patients (51%). Common risk factors included asthma (16%), alcohol abuse (14%), diabetes mellitus (10%), chronic obstructive pulmonary disease (9%), age greater than 65 years (9%), and use of antibiotics within 3 months (9%). In other words, a little more than half of the patients had at least a single risk factor that suggests a Rx other than macrolide monotherapy should have been given.
However, when the types of antibiotics prescribed were tallied, appropriate therapy (concordant with IDSA/ATS guideline) was prescribed only 9% of the time in the DRSP risk factor group versus 87% of the time in the no DRSP risk factor group. This was statistically different with a p < 0.0001. This means that 91% of patients with risk factors for DRSP were not being treated with suggested antibiotic regimens. 
Clinical Takehome

- When selecting an outpatient antibiotic regimen for Community Acquired Pneumonia (CAP), one must take into account DRSP risk factors AND regional Strep pneumo sensitivities. 

- Macrolide monotherapy is not sufficient CAP treatment for a subset of patients. 

- Unfortunately, respiratory fluroquinolones are much more expensive than the traditional Z-pak. However, an acceptable alternative is azithromycin with amoxicillin.

1) Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72.
2) Jenkins TC, Sakai J, Knepper BC, Swartwood CJ, Haukoos JS, Long JA, Price CS, Burman WJ. Risk factors for drug-resistant Streptococcus pneumoniae and antibiotic prescribing practices in outpatient community-acquired pneumonia. Acad Emerg Med. 2012 Jun;19(6):703-6.

Contributed by Daniel Kolinsky, PGY-2

Faculty Reviewed by Dr. Stephen Liang 

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