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When to Consider the Use of Antibiotics in the Treatment of 2009 H1N1 Influenza–Associated Pneumonia

Peter F. Wright, M.D., Kathryn B. Kirkland, M.D., and John F. Modlin, M.D.

N Engl J Med 2009; 361:e112December 10, 2009

Article

We are now facing a pandemic caused by an epidemiologically distinct, novel virus, the 2009 pandemic influenza A (H1N1) virus (swine flu), against which few persons born since 1970 have antibodies. The severity of illness in the individual varies, and our understanding of the role of bacterial infection in novel 2009 H1N1 infection is still evolving. A current summary of bacterial isolates from 53 fatal pediatric cases of novel H1N1 with adequate sampling of normally sterile sites showed that 17 (32%) had bacterial pathogens of which 8 were Staphylococcus aureus, and of these, 6 were methicillin-resistant S. aureus (MRSA) (http://www.cdc.gov/flu/weekly/).

Although data from fatal cases are not representative of the influenza illnesses commonly encountered by community-based practitioners, the fact that secondary bacterial pneumonia is occurring with the novel H1N1 strain highlights a challenge facing clinicians who make decisions about antibiotic treatment of their influenza patients with lower respiratory tract disease. Table 1Table 1Indications of the Etiology or Etiologies of Pneumonia in Patients with Influenza-Related Lower Respiratory Tract Disease. qualitatively outlines some of the factors that would make one consider a bacterial component to H1N1 influenza illness.

Three adolescent patients recently hospitalized at the Children's Hospital at Dartmouth brought this dilemma into focus for us. All three had underlying neuromuscular disease with prior respiratory compromise. One child presented within 24 hours after onset of symptoms, required intubation, and had hematologic and clinical and laboratory findings suggestive of viral pneumonia. The other two had onset of respiratory decline and recrudescence of fever after an influenza-like illness, and they also required intubation and ventilation. Each had novel H1N1 infection confirmed by polymerase chain reaction (PCR). Sputum specimens from the latter two patients grew in one case Moraxella catarrhalis and in the other methicillin-sensitive S. aureus. All three patients were empirically started on broad-spectrum antibiotics (vancomycin and piperacillin–tazobactam) by their pediatric critical care attending physician at the time of hospitalization. The clinical course in each child has been one of slow resolution, with narrowing of the antibiotic spectrum on the basis of the bacteriologic results.

For the child or adult admitted to a hospital intensive care unit in respiratory distress, we believe that empirical initial therapy with broad-spectrum antibiotics to include coverage for MRSA, as well as Streptococcus pneumoniae and other common respiratory pathogens, is appropriate. For the previously healthy child or adult with influenza who requires admission to a community hospital and has features that suggest a secondary pneumonia (Table 1), we would recommend empirical treatment with a drug such as intravenous second- or third-generation cephalosporin, after an effort has been made to prove the association with influenza and to get adequate lower respiratory tract specimens for Gram's stain and bacterial culture. If the Gram's stain suggests the presence of staphylococci or if there is a rapidly progressive or necrotizing pneumonia, an additional antimicrobial agent to cover MRSA is appropriate.

For outpatient treatment of most patients who have influenza–associated pneumonia with a suspected secondary bacterial infection, the bacterial component can be treated with appropriate oral antibiotics for age — amoxicillin–clavulanate or a second-generation cephalosporin for both children and adults. There is no evidence for synergistic coinfection of influenza with Mycoplasma pneumoniae or other agents of atypical pneumonia. We do not believe that initial coverage for MRSA is indicated in all patients who are thought to have secondary bacterial pneumonia. Moreover, given emerging epidemiologic and clinical data, we have a strong suspicion that much of the lower respiratory tract illness will turn out to be of viral origin and should not require antibacterial therapy.

Peter F. Wright, M.D.
Kathryn B. Kirkland, M.D.
John F. Modlin, M.D.
Section of Infectious Disease and International Health, Departments of Pediatrics and Medicine, Dartmouth Medical School, Hanover, NH

No potential conflict of interest relevant to this article was reported.

This article (10.1056/NEJMopv0910749) was published on November 25, 2009, at NEJM.org.

Citing Articles (9)

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   B. M. Davis, A. E. Aiello, S. Dawid, P. Rohani, S. Shrestha, B. Foxman. (2012) Influenza and Community-acquired Pneumonia Interactions: The Impact of Order and Time of Infection on Population Patterns. American Journal of Epidemiology
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   Shin Ahn, Won Young Kim, Sung-Han Kim, SangBum Hong, Chae-Man Lim, YounSuck Koh, Kyung Soo Lim, Won Kim. (2011) Role of procalcitonin and C-reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza and Other Respiratory Viruses 5:6, 398-403
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   S. Reyes, B. Montull, R. Martínez, J. Córdoba, J.M. Molina, V. Martí, A. Martínez, P. Ramírez, R. Menéndez. (2011) Risk factors of A/H1N1 etiology in pneumonia and its impact on mortality. Respiratory Medicine 105:9, 1404-1411
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   Min Hyok Jeon, Jin-Won Chung, Seong-Ho Choi, Tae Hyong Kim, Eun Jung Lee, Eun Ju Choo. (2011) Pneumonia risk factors and clinical features of hospitalized patients older than 15 years with pandemic influenza A (H1N1) in South Korea: a multicenter study. Diagnostic Microbiology and Infectious Disease 70:2, 230-235
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   Myung Jae Yun, Seong Tae Lee, Hye Jin Oh, Seung June Lee, Sook Hee Song, In Sohn, Jae Phil Choi, Su Hyun Kim. (2011) Clinical Features of Hospitalized Patients with Community Acquired Pneumonia during 2009 Influenza A (H1N1) Pandemic. The Korean Journal of Critical Care Medicine 26:3, 162
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   Nabihah Sachedina, Liam J Donaldson. (2010) Paediatric mortality related to pandemic influenza A H1N1 infection in England: an observational population-based study. The Lancet 376:9755, 1846-1852
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   Lewis Satterwhite, Ashish Mehta, Greg S. Martin. (2010) Novel findings from the second wave of adult PH1N1 in the United States. Critical Care Medicine1
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   Chang Hoon Han, Yu Kyung Hyun, Yu Ri Choi, Na Young Sung, Yoon Seon Park, Kkot Sil Lee, Jae Ho Chung. (2010) Clinical Features of Hospitalized Adult Patients with Pneumonia in Novel Influenza A (H1N1) Infection. Tuberculosis and Respiratory Diseases 69:1, 24
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   Shin Ahn, Won Young Kim, Ji Young Yoon, Chang Hwan Sohn, Dong Woo Seo, Sung Han Kim, Sang Bum Hong, Chae Man Lim, Youn Suck Koh, Won Kim. (2010) Procalcitonin in 2009 H1N1 Influenza Pneumonia: Role in Differentiating from Bacterial Pneumonia. Tuberculosis and Respiratory Diseases 68:4, 205
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