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Letters to the Editor

Treatment of Post-Influenza Pneumonia in Health Care Workers

Raymond, Lawrence W. MD, ScM; Leach, Laura MLIS

Author Information
Journal of Occupational and Environmental Medicine: November 2007 - Volume 49 - Issue 11 - p 1181-1183
doi: 10.1097/JOM.0b013e318158a49c
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To the Editor: Recent recommendations1–3 remind us that health care workers (HCW) and others who wish to avoid influenza should obtain either the trivalent, inactivated influenza vaccine or the live, attenuated form each year. Despite the efficacy of such immunizations, HCW often fail to receive them, sometimes with important consequences such as increased mortality from pneumonia and all causes in elderly patients under their care. However, the efficacy of such immunization of HCW is limited unless their patients are immunized, too.4 In the relatively mild 2001 to 2002 flu season in North Carolina, one extended care facility was forced to suspend new admissions for 2 weeks when one-third of the staff were unable to work because of flu symptoms (Raymond LW, unpublished observation, 2002). Most had not received the inactivated vaccine offered on-site at no cost, 10 weeks earlier.

The clinical diagnosis of influenza has changed little since its viral etiology was first suggested in the British epidemic of 1933 by Smith, Andrews, and Laidlaw.5 That is, an abrupt prostrating fever is attended by shivering (without rigors), headache, cough, sore throat, weakness with generalized aching, and malaise. The diagnosis can be confirmed by point-of-care antigen tests, which though limited in sensitivity (50% to 70%) have specificity near 100%.3 Pneumonia is the most common complication of influenza. In the event of an epidemic or pandemic, it may occur in HCW as readily as in other persons in communities so affected.6 Pre-emptive treatment of influenza with oral oseltamivir (75 mg twice daily for 5 days) or inhaled zanamivir might reduce the likelihood of post-influenza pneumonia (PIP) under such circumstances.7–9 Next to patients hospitalized with influenza, HCW in direct contact with patients have been designated as having the highest priority for this anti-viral treatment, during any pandemic.10

PIP occurs in two main forms. First is the rare primary viral pneumonia, usually affecting the elderly and those with cardiovascular or pulmonary diseases, but also occurring in pregnant or otherwise healthy persons.11 The illness may be fulminant with fever of 39°C, tachypnea, tachycardia, hypotension, hypoxemia, and radiographic changes of Adult Respiratory Distress Syndrome, as early as the first day. It is uncertain whether this form of PIP can effectively be treated with amantadane tricyclic protein inhibitors such as amantadine or rimantadine, or by neurominidase inhibitors such as oseltamivir or zanamavir. However, the use of amantadanes is not recommended because of the emergence of resistant strains of influenza virus. Such antiviral agents, as well as corticosteroids, have been used in small observational series of patients with PIP12,13 but no randomized, controlled trials (RCTs) have been published.

More commonly, PIP is a secondary process, which follows an initial period of recovery and is usually due to a single bacterial strain.14 Occasionally, mixed viral and bacterial pathogens may be isolated. One study found higher temperatures, heart rates, and C-reactive protein levels, and more severe disease by radiographic and other criteria in 15 patients with such dual infections, than the levels in 28 patients whose pneumonia was of bacterial etiology alone.15 In another study, early use of oseltamivir reduced the incidence of PIP resulting in antibiotic use by 55%.16 Oseltamivir also reduced all-cause hospitalizations by 59%. As is true of viral PIP, however, no RCTs of antimicrobial or other agents have been reported for treating secondary bacterial or mixed PIP. While Streptococcus pneumoniae was the most common bacterial pathogen isolated in most PIP series, Staphylococcus aureus predominated in other reports. In one textbook, Staph. aureus PIP was described as both rare17 and common (25% or higher during epidemics).18Staph. aureus was isolated from post-mortem lungs in 49% of 312 fatal cases of PIP in Camp Jackson, SC during the 1918 pandemic,19 and from 62% of cases in the 1957 Asian influenza epidemic in the United Kingdom.20 It is noteworthy that four of Oliveira’s five recent cases of Staph. aureus PIP were due to methicillin-resistant (MRSA) strains.21 Some more recent cases of PIP due to MRSA strains elaborated the Panton Valentine leukocidin (PVL), associated with necrotizing pneumonia.22–24

In the absence of RCTs to guide the choice of antimicrobial agents, oseltamivir should be given immediately to treat PIP. Agents aimed at S. pneumoniae and Staph. aureus should also be administered using local patterns of microbial prevalence and sensitivity, especially in epidemics. Gram stain and culture of good-quality specimens of expectorated sputum can provide strong evidence against Staph. aureus if negative, while urinary pneumococcal antigen testing (specificity >90%) can give strong support for the suspicion of S. pneumoniae.3 Site-of-care decisions, eg, outpatient versus hospital ward versus intensive care unit, should be based on objective criteria such as the CURB-65 score (ie, one point for each of the following: Confusion; Urea nitrogen >20 mg/dL; Respirations ≥30/min, Blood pressure <90/60 mm Hg; age ≥65 years), patients with scores of 0 to 1 usually being treated as outpatients.25 A simplified version termed CRB-65 does not require blood urea nitrogen concentration for its calculation, thus facilitating decision-making in the office or urgent-care setting.25 This approach should be tempered by the physician’s clinical judgment and consideration of the patient’s safe and reliable use of oral medications, and of supportive home circumstances. Other algorithms such as the Pneumonia Severity Index (PSI) can add prognostic information, but the calculation of the PSI requires 20 variables, which may limit its application in decision-making for out-patients.

Once the decision is made to treat a health care worker with PIP as an outpatient, and after appropriate sputum and blood specimens are obtained—including testing for H5N1 infection, if such exposure is likely—antimicrobial treatment should be started without delay. Oseltamivir should be given as above. A respiratory fluoroquinolone such as levofloxacin (750 mg/d) is also recommended. Alternatively, a macrolide such as azithromycin (500 mg daily for 3 days) plus a beta-lactam such as amoxicillin-clavulanate (2 gm twice daily) should be prescribed. MRSA coverage should strongly be considered and linezolid (600 mg twice daily) added if appropriate, pending results of cultures.3,21 Fluoroquinolone (or amoxicillin-clavulanate) treatment should be continued for at least 5 days and the patient should be afebrile for 3 days and otherwise clinically stable.

While the above decisions on antimicrobial administration and site-of-care are obvious priorities in PIP, other major treatment issues include adequate oxygenation, prevention of thromboembolic disease, and appropriate ventilatory support. Treatment of patients with PIP who are immunocompromised or require hospitalization is beyond the scope of this note, but is well described by the recently updated guidelines of the Infectious Disease Society of American and American Thoracic Society.3 Before considering treatment of PIP to be completed in either out-patients or hospitalized patients, immunization (if needed) against influenza and pneumococci, counseling on tobacco cessation, and any needed follow-up care should be optimized.

Adequately powered RCTs are needed to identify the optimal treatment of PIP, not only for HCW but also for community members in general.

Lawrence W. Raymond, MD, ScM

Department of Family Medicine

Carolinas Medical Center

Charlotte, NC

Laura Leach, MLIS

Information Resource Center

Area Health Education Center

Carolinas Medical Center

Charlotte, NC

References

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2. Occupational Safety and Health Administration. Pandemic Influenza Preparedness and Response Guidance for Healthcare Workers and Healthcare Employers. OSHA 3328-05. 2007. Available at www.osha.gov/Publications/OSHA_pandemic_health.pdf. Accessed July 12, 2007.
3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27–S72.
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©2007The American College of Occupational and Environmental Medicine