H1N1 Influenza Center

From the Publishers of the New England Journal of Medicine

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

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 1 qualitatively outlines some of the factors that would make one consider a bacterial component to H1N1 influenza illness.

NEJMopv0910749t1

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.

13 Responses »

  1. Very useful information. It addresses a very important question and provides a general guidance for primary care physicians who often struggle with the question of when antibiotics should be initiated. There is enough data supporting the fact that most patients with severe respiratory illnesses have severe viral pneumonia and ARDS. The differentiating features outlined by the authors seem to be a reasonable approach for now although it needs to be verified in larger group of patients.

  2. There is an unnecessary scare and unjustified hurry to start antiviral drugs in those who are tested positive for H1N1; those who are seriously ill are those with underlying cardio-respiratory diosrders or elderly, or immunocompromised or even more commonly malnourisehd. As suggested in the article, in all these individuals it is the associated secondary bacterial infection which could be more fatal than the H1N1 itself; but the stress is on antiviral drugs and the testing for the virus and the vaccination; this unfortuntaely is not the correct apppraoch as it is diverting the attention and magnifying the scare and even diverting the resources which are meager in the underprevileged areas and people. The root cause of all infections, including H1N1, is malnutrition which is ignored or goes undetected ,esepcially when it is micronutirent deficiency alone like VitD deficinecy . The next important cause is lack of hygiene(personal, respiratory and environmental) and unsafe drinking water; all these problems are ignored and we waste our effort and resources only to satisfy the market forces or out of unresoanable scare. After all uncertainty is the only certainty in life, let us accept that and concentrate on basic issues which are negelected but easily identified by studying the cohort of patients for their lifestyle, diet and environment rather than H1N1 screening for everyone with Flu like symptoms which has become a practice now. Of course antibiotic treatment may be more rational than antiviral drugs in certain patients to pull them out of the crisis
    Dr.P.K.Sasidharan, Professor of Medicine, Calicut, Kerala, India

  3. We agree with Dr. Wright et al. about the importance of secondary bacterial pneumonia in the novel swine-origin Influenza A infection and especially about Staphylococcus aureus secondary infection. Community-associated Staphylococcus aureus (CA-SA) can produce a severe necrotizing pneumonia that typically has been associated with seasonal influenza virus infection. The Centers for Disease Control and Prevention (CDC) has issued warnings of fatal infections in children with seasonal influenza co-infected with MRSA following reports of severe cases of pneumonia.

    With the outbreak of novel swine-origin influenza A (H1N1) an increase of severe secondary staphylococcal necrotizing pneumonia is being detected. The aggressiveness of this pneumonia has been related not to the methicillin resistance but to the presence of the gene encoding for the Panton-Valentine leukocidin (PVL), a cytotoxin that lyses leucocytes and a major determinant virulence factor.

    We believe that treatment for the child admitted to an intensive care unit in respiratory distress or with severe pneumonia will need not only coverage for MRSA but coverage for PVL therefore the combination of antibiotics should include at least one molecule active against PVL production like clindamycin or linezolid.

    Pablo Rojo M:D.
    Marta Barrios M.D.
    Alba Palacios M. D.
    Pediatric Immunodeficiencies Unit
    Department of Pediatrics
    Hospital 12 de Octubre
    Madrid, Spain

  4. Absolutely useful information .This gives us overall guidance in regards to when to start antibiotics.I feel antivirals are being overused in treatment and prophylaxis,as most healthy adults would get better anyway.

  5. I totally agree with Dr. Sasidharan comments. In developing countries such as India, mortality in Influenza infection is often due to secondary bacterial pneumonia. Physicians should be alert in ruling out secondary bacterial pneumonia in patients who have severe symptoms, especially when they present late. Appropriate antibiotics will be life saving in such settings.

  6. thank very important issue
    we observe on our area that ,hini positive majorty assosciated with atypical pneumonia like mycoplasma,legionella and treated with adding azithromax for 10 days give very good recover

    DR:YOUSEF EL NEMRAWI

    CHEIFOF INTERNAL MEDICINE DEPARTMENT
    AL HAMMADI HOSPITAL -KSA

  7. Very useful information. We have a problem in collection of lower respiratory specimens for Gram stain from young children. Any suggestions?

  8. the secondary bacterial infection following influenza by streptococci and other gram positive bacteria including haemophilus is interesting, thus azothromycin and pentids will give definite releif and spontaneous recovery of the patient is possible

  9. Until now, little is known about secondary infections associated with Pandemic influenza A H1N1 2009. Thus, this study should be useful information especially for least developed countries, where diagnostic tools are not frequently available to detect secondary respiratory tract infection. Although this study did not show atypical pneumonia associated with H1N1, atypical pneumonia could be possibly associated with H1N1, as YOUSEF EL NEMRAWI(Riyadh) did observe, especially in developing countries settings. Information on secondary infection of respiratory infection is essential from developing countries to reach an adequate decision prior to initiating antibiotics.

    Dr.Sher Bahadur Pun
    Everest International Clinic and Research Center
    Kathmadu, Nepal

  10. Tks: In uncertainty times we need evidence because the empiricism of face a new challenge bring it in most cases difficult decisions. In my hospital in Mexico city we use in hospitalized patients with influenza pneumonia suspect cephalosporin third generation and clarithromycin but always with doubt about of possible bacterial ressistence induction. Was 2 months ago when i listen from a infectology physician in the Respiratory Diseases National Institute about the not need of athypical coverage in this patients.
    Although, always are grateful about the evidence leads beyond expert reviews….

  11. Very useful information. In most instances, we diagnose pneumonia without knowing the exact pathogen, since the proof of lower respitatroy secretion detection for virus is lacking. Early use of broad spectrum antibiotics may result in secondary resistant bacterial infection. Serum CRP and PCT may not give correct guidance for starting antibiotic therapy.

  12. 1) Can you comment on Tamiflu dosing in Critically ill patients with Renal Failure “especially with the new expert opinion of 150mg q 12 hours in the following situations:

    a) Normal Cr Clearance: Would Tamiflu 150 mg q 12 be ok?

    b) Cr Clearance 10-30: Would 75 mg po q 24 be ok or should we go 75 mg q 12?

    c) Intermittent dialysis: Should we go Tamilfu 75 mg q 24hours or Tamiflu 75 mg q12? The data of 30 mg every other session is limited data that even Roche does not adopt based on even phone calls with them…. this is left open or ” up in the air issue”

    2) Some experts recommend to extend the Tamiflu longer than 5 days to prevent cytokine release which exacerbates ARDS in critically ill patients. Is 10 days enough time or should it be longer and if longer how long?

    3) Regarding to the use of steroids in ARDS management…… to prevent replication of the virus:= How many days should you use the steroids after the illness??? Is 10 days a good number of days?

    4) Have you seen the transaminitis phenomenon with H1Tamilfu and multisystem organ failure?

    5) Do we need IRB approval from our Hospital to get Premavir Since its invetigational drug ? onr can we just request it online if so any kind of consent/ protection that the manufacturor or FDA provides?

    6) How common are Strokes/ Visual loss/ Deafness/ Seizures/ Neurological sequalae after H1N1 as I have heard of several cases in the country with strokes, deafness, aphasia?

    7) When when would the CDC consider the Loeb study published in JAMA to allow us use Surgical masks instead of the N95 masks especially with the national shortage and its cost?

    Thanks

    Those questions are concerning many colleagues across this country and Europe. We appreciate your reply?

    Mike

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