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Cited by 574Influenza Virus Research StudiesPneumonia and Respiratory InfectionsRespiratory viral infections research

The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis.

Open access
Klein, Eili Y., Monteforte, Bradley, Gupta, Alisha, Jiang, Wendi, May, Larissa, Hsieh, Yu‐Hsiang, Dugas, Andrea·2016·Influenza and Other Respiratory Viruses
DOI 10.1111/irv.12398PMC PMC4947938
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Abstract

Aim: Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients. Method: A systematic search of Me SH , Cochrane Library, Web of Science, SCOPUS , EMBASE , and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria. Results: Twenty‐seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results ( I 2 = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta‐regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus , which accounted for 35% (95% CI , 14%–56%) and 28% (95% CI , 16%–40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small‐study publications may have biased the results. Conclusions: The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large‐scale studies are needed to better understand the etiology of influenza bacterial coinfection.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis found that bacterial coinfection in laboratory-confirmed influenza patients was highly variable across studies, with reported rates from 2% to 65%. Streptococcus pneumoniae and Staphylococcus aureus were the most common coinfecting pathogens, but heterogeneity was too high to support a single pooled coinfection estimate.

Key findings

  • Twenty-seven studies including 3215 participants met inclusion criteria; reported bacterial coinfection ranged from 2% to 65%, with high heterogeneity (I² = 95%).
  • Among eight studies with species-level data (334 patients), S. pneumoniae accounted for 35% (95% CI, 14%–56%) and S. aureus for 28% (95% CI, 16%–40%) of identified coinfecting bacteria.
  • After excluding seven studies that contributed more than 50% of heterogeneity, the remaining 20 studies representing 64% of patients had coinfection proportions between 11% and 35% (I² = 37%).
  • No study characteristic examined—age, setting, enrollment year, study design, study size, or bacterial collection/detection method—was significantly associated with coinfection frequency.

Methods

  • Systematic review and meta-analysis reported per PRISMA, searching MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed in August 2014; inclusion required human studies with all individuals having laboratory-confirmed influenza and all tested for common bacterial species.
  • Data from 27 observational studies (13 prospective, 14 retrospective) were extracted; most enrolled hospitalized patients, with 11 studies focused on ICU patients, 10 on non-ICU hospitalized patients, 3 on ED patients, and 2 on mixed inpatient/outpatient settings.
  • Coinfection frequency was analyzed using the DerSimonian-Laird method in R’s metafor package; heterogeneity was quantified with I², and meta-regression, leave-one-out analysis, and Cook’s distances were used to explore heterogeneity.

Limitations

  • The paper states that the sample of 27 studies and >3000 patients is small relative to annual influenza-related hospitalizations; studies included only hospitalized patients with moderate to severe influenza, so outpatients and asymptomatic patients are not represented.
  • The paper states that bacterial detection methods varied in sensitivity and sampling site, potentially underdiagnosing difficult-to-detect bacteria; antibiotic use before or at enrollment was not systematically assessed and may have led to underestimation.
  • The paper states that significant heterogeneity could not be explained by measured study characteristics; evident from the text, all included studies were observational and most were small cohort studies, with selection bias and data-collection reliability concerns noted in the quality assessment.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/irv.12398

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 44 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Twenty-seven studies including 3215 participants met all inclusion criteria and were included in the final analysis.

    “A total of 27 articles encompassing 3215 patients met all the inclusion criteria and were included in the final analysis.28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Coinfection was assumed to be any acute bacterial infection identified in respiratory secretions, sputum, or sterile site (e.g., bacteremia).
  • Findingown data

    All 27 included studies were observational.

    “All 27 included studies were observational, of which 13 (1218 patients) were prospective studies,30, 32, 33, 36, 40, 41, 43, 44, 48, 49, 50, 51, 52 and 14 (1997 patients) were retrospective analyses (Table 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Seven studies contributed more than 50% of the heterogeneity.

    “Using Cook's distances to identify studies that most greatly affected the heterogeneity and results, we found that seven studies contributed more than 50% of the heterogeneity.29, 31, 34, 39, 40, 45, 46”
    Quote in the paperNot a substantial claim
  • Findingown data

    Most studies did not report the percentage of patients that agreed to participate.

    “While studies were generally representative of the targeted population, most studies did not report the percentage of patients that agreed to participate.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Among the individual studies, the proportion of bacterial coinfection ranged from 2% to 65%.

    “Among the individual studies, the proportion of bacterial coinfection ranged from 2% (newborns born in USA) to 65% (immunocompetent adults in France) (Figure 3).”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Coinfection was assumed to be any acute bacterial infection identified in respiratory secretions, sputum, or sterile site (e.g., bacteremia).
  • Classified as probably not a substantial claim. 20
  • May combine two claims. 33

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The majority (21) of included studies were cohort studies, and the rest were case-control studies.

    “The majority (21) of studies were cohort studies, and the rest were case–control studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The average quality of the included studies was moderate, with the most common quality issues being related to study design, selection biases, and data collection.

    “The average quality of the studies was moderate, with the most common quality issues being related to study design, selection biases, and data collection (Table S2).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Most included studies enrolled only adults, although lower age cutoffs varied.

    “Most studies enrolled only adults, although the lower age cutoffs varied (e.g., some studies considered adults older than 14 while others used 21).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Seven included studies (1214 patients) focused on young children or newborns, and two studies (504 patients) included both children and adults.

    “Only seven studies (1214 patients) focused on young children or newborns,29, 31, 38, 46, 49, 51, 54 and two studies (504 patients) included both children and adults.42, 53”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A funnel plot appeared asymmetrical, suggesting statistical heterogeneity; there seems to have been a lack of smaller studies with lower rates of bacterial coinfection.

    “A funnel plot appeared asymmetrical (Figure 2), suggesting statistical heterogeneity; in particular, there seems to have been a lack of smaller studies with lower rates of bacterial coinfection.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The median sample size was 51 (IQR, 18.5-101), and the mean was 119 (SD: 203).

    “The median sample size was 51 (IQR, 18·5–101), and the mean was 119 (SD: 203), which was driven by three large studies29, 44, 53 that contributed 1958 (61%) of the total number of patients included in this analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of the 27 included studies, 13 (1218 patients) were prospective and 14 (1997 patients) were retrospective.

    “All 27 included studies were observational, of which 13 (1218 patients) were prospective studies,30, 32, 33, 36, 40, 41, 43, 44, 48, 49, 50, 51, 52 and 14 (1997 patients) were retrospective analyses (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Fifteen included studies (1885 patients) began enrollment in 2009 or later, and of these, all but one focused on the 2009 H1N1 pandemic strain.

    “Fifteen of the studies (1885 patients) began enrollment in 2009 or later,28, 32, 33, 34, 35, 37, 39, 41, 42, 44, 46, 48, 49, 53, 54 and of these, all but one was specifically focused on the 2009 H1N1 pandemic strain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The largest potential source of bias was that all studies were observational and most were small cohort studies.

    “However, results from the bias assessment suggest that the largest potential source of bias was the fact that all the studies were observational studies, and most were small cohort studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Patients enrolled in the ICU had a slightly higher frequency of coinfection than patients enrolled elsewhere, although this was not statistically significant (P = 0.14).

    “Patients enrolled in the ICU had a slightly higher frequency of coinfection than patients enrolled elsewhere, although this was also not statistically significant (P = 0·14).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Study design (P = 0.47) and bacterial coinfection collection and detection methods (all P > 0.05) were not significant.

    “Finally, study design (P = 0·47) and bacterial coinfection collection and detection methods (each was tested independently and all P‐values were greater than 0·05) were also not significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Other Staphylococcal pathogens such as S. epidermidis, and Gram-negative bacteria such as Escherichia coli and Moraxella catarrhalis, were also frequently found.

    “In addition, other Staphylococcal pathogens such as S. epidermidis, and Gram‐negative bacteria, such as Escherichia coli and Moraxella catarrhalis, were also frequently found.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Although heterogeneity was greater in pediatric studies (I2 = 98%) than in adult studies (I2 = 89%), coinfection frequency was statistically the same (P = 0.47).

    “Although heterogeneity was greater in the pediatric studies (I 2 = 98%) than in the adult studies (I 2 = 89%), coinfection frequency was statistically the same (P = 0·47).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Older age, higher APACHE II score, diabetes, and sepsis were risk factors for coinfection.

    “Only four studies explicitly measured and reported on comorbidities of patients with coinfection and found that older age,28, 44, 53 a higher APACHE II (Acute Physiology and Chronic Health Evaluation II) score,44, 53 diabetes,33 and sepsis33 were risk factors for coinfection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Some studies only included severely immunocompromised patients with concurrent malignancy or organ transplant, while others excluded immunocompromised patients.

    “Further, some studies only included severely immunocompromised patients who had concurrent malignancy or organ transplant,31, 33, 49 while others excluded immunocompromised patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Only three studies excluded participants based on antibiotic use and reported coinfection rates of 12.2%, 26.7%, and 46.6%.

    “Only three studies excluded participants based on antibiotic use and reported coinfection rates of 12·2%, 26·7%, and 46·6%.28, 34, 36”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [28] Ahn S, Kim WY, Kim SH et al Role of procalcitonin and C‐reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza Other Respi Viruses 2011; 5: 398– 403. PMC5780656 21668682 source

      Not checked in the free run.

    • cites [34] Cuquemelle E, Soulis F, Villers D et al Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med 2011; 37: 796– 800. 21369807 PMC7080069 source

      Not checked in the free run.

    • cites [36] Falsey AR, Becker KL, Swinburne AJ et al Bacterial complications of respiratory tract viral illness: a comprehensive evaluation. J Infect Dis 2013; 208: 432– 441. 23661797 PMC3699009 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The predominant coinfecting organism in the studies was S. pneumoniae followed by S. aureus, but many other organisms were also found to cause infections.

    “The predominant coinfecting organism in the studies was S. pneumoniae followed by S. aureus, but many other organisms were also found to cause infections.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Staphylococcus aureus and other bacterial coinfections were also quite common.

    “Consistent with the prior literature,55, 62 we found that S. pneumoniae was the most frequent bacterial coinfection; however, both S. aureus and other bacterial coinfections were also quite common.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [55] Brundage JF. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis 2006; 6: 303– 312. 16631551 PMC7106411 source

      Not checked in the free run.

    • cites [62] McCullers JA. The co‐pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Micro 2014; 12: 252– 262. 24590244 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Bacterial coinfection of hospitalized patients with influenza is often common, although results were highly heterogeneous.

    “We found that bacterial coinfection of hospitalized patients with influenza is often common, although results were highly heterogeneous.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lung tissue samples from the 1918 influenza pandemic suggest that the majority of the estimated 20-60 million deaths were from bacterial infections rather than from direct effects of the virus.

    “Lung tissue samples from the 1918 influenza pandemic suggest that the majority of the estimated 20–60 million deaths were from bacterial infections rather than from direct effects of the virus.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008; 198: 962– 970. 18710327 PMC2599911 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The potential bias of each study was assessed using the Quality Assessment Tool for Quantitative Studies.

    “The potential bias of each study was assessed using the Quality Assessment Tool for Quantitative Studies developed by the National Collaborating Centre for Methods and Tools.20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] National Collaborating Centre for Methods and Tools. Quality Assessment Tool for Quantitative Studies. Vol (Updated 13 April. Hamilton. ON: McMaster University, 2010; 2008.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Sources of data were carefully reviewed by BM, AG, EK, and studies reporting already included data were excluded.

    “Sources of data were carefully reviewed by BM, AG, EK, and studies reporting already included data were excluded (the study with the earlier publication date was considered the primary study, and all others excluded).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The full text of all studies meeting criteria and those for which a conclusion could not be made were reviewed independently by two authors, with disagreements resolved through consultation with a third party.

    “The full text of all studies meeting the criteria and those for which a conclusion could not be made were reviewed independently by the two authors. Disagreements were resolved through consultation with a third party.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In seasonal epidemics, influenza bacterial coinfection is associated with increases in hospital admissions, more severe symptoms, and increases in mortality.

    “In seasonal epidemics, influenza bacterial coinfection is associated with increases in hospital admissions,4, 5 more severe symptoms,6 and increases in mortality.7”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [4] Masiá M, Padilla S, Antequera P, Ramos JM, Ruiz M, Gutiérrez F. Predictors of pneumococcal co‐infection for patients with pandemic (H1N1) 2009. Emerg Infect Dis 2011; 17: 1475. 21801627 PMC3381536

      Not checked in the free run.

    • cites [5] Blyth CC, Webb SA, Kok J et al The impact of bacterial and viral co‐infection in severe influenza. Influenza Other Respir Viruses 2013; 7: 168– 176. 22487223 PMC5006004 source

      Not checked in the free run.

    • cites [6] Cillóniz C, Ewig S, Menéndez R et al Bacterial co‐infection with H1N1 infection in patients admitted with community acquired pneumonia. J Infect 2012; 65: 223– 230. 22543245 PMC7132402 source

      Not checked in the free run.

    • cites [7] Paddock CD, Liu L, Denison AM et al Myocardial injury and bacterial pneumonia contribute to the pathogenesis of fatal influenza B virus infection. J Infect Dis 2012; 205: 895– 905. 22291193 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Two authors independently extracted study data from all included publications, and results were compared, with differences resolved by consensus.

    “Two authors (BM, AG) extracted study data from all included publications independently, and results were then compared. Differences were resolved by consensus.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two authors independently screened the title and abstract of all search-returned publications to determine whether they met study criteria.

    “Two authors (BM, AG) independently screened the title and abstract of all the search‐returned publications to determine whether they met study criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The systematic review is reported in accordance with PRISMA guidelines.

    “We conducted a systematic review, which is reported in accordance with PRISMA guidelines,19 to determine the frequency of bacterial coinfection among individuals with laboratory confirmed influenza.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Liberati A, Altman DG, Tetzlaff J et al The PRISMA statement for reporting systematic reviews and meta‐analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339:b2700. doi: 10.1136/bmj.b2700. PMC2714672 19622552 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Inclusion was restricted to studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species.

    “Inclusion was restricted to studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Identification of coinfected patients and coinfecting pathogen enables clinicians to initiate appropriate antibiotic therapy and improve patient outcomes.

    “Identification of coinfected patients and coinfecting pathogen enables clinicians to initiate appropriate antibiotic therapy and improve patient outcomes.12”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Van‐Tam J, Sellwood C. Pandemic Influenza. Boston: CABI, 2012. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Funnel plots and Egger's test of asymmetry were used to assess biases such as publication and small-study effects.

    “Funnel plots and calculation of Egger's test of asymmetry were also used to assess biases such as publication and small‐study effects.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Egger M, Smith GD, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997; 315: 629– 34. 9310563 PMC2127453 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Studies were not fully clear on the reliability of the tools used for data collection, making it difficult to eliminate this as a potential source of bias in the strains detected.

    “Studies were also not fully clear on the reliability of the tools used for data collection, which made it difficult to eliminate this as a potential source of bias in the strains detected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Quality Assessment Tool for Quantitative Studies has shown good reliability and validity.

    “This tool was selected for its comprehensive ability to assess the methodological quality of non‐randomized studies and has shown good reliability and validity.21, 22”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Thomas BH, Ciliska D, Dobbins M, Micucci S. A process for systematically reviewing the literature: providing the research evidence for public health nursing interventions. Worldviews Evid Based Nurs 2004; 1: 176– 184. 179p. 17163895 source

      Not checked in the free run.

    • cites [22] Deeks J, Dinnes J, D'Amico R, Sowden A, Sakarovitch C. Evaluating non‐randomised intervention studies. Health Technol Assess 2003; 7: 186. 14499048 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Each study was independently evaluated by two authors, and discrepancies regarding bias assessment were resolved by consensus.

    “Each study was independently evaluated by two authors, and discrepancies regarding bias assessment were resolved by consensus.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    There was some suggestion that negative findings or low levels of bacterial coinfection were not published.

    “However, there was some suggestion that negative findings or low levels of bacterial coinfection were not published.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Antibiotic use at the time of or prior to enrollment may have contributed to significant heterogeneity but could not be systematically assessed.

    “Antibiotic use at the time of, or prior to enrollment, was another factor that may have contributed to significant heterogeneity, but could not be systematically assessed.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The diverse profile of coinfecting pathogens confirms current IDSA recommendations for broad-spectrum antibiotic coverage for influenza-related pneumonia.

    “This diverse profile of coinfecting pathogens confirms current Infectious Disease Society of America (IDSA) recommendations for broad‐spectrum antibiotic coverage for influenza‐related pneumonia.63”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Harper SA, Bradley JS, Englund JA et al Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 1003– 1032. 19281331 PMC7107965 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Our study supports IDSA recommendations for empiric coverage of CA-MRSA in influenza-related pneumonia patients.

    “Given that over 25% of identified isolates were S. aureus, and that approximately 50% of hospital S. aureus isolates are MRSA,64 our study supports IDSA recommendations for empiric coverage of CA‐MRSA in influenza‐related pneumonia patients.63”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Harper SA, Bradley JS, Englund JA et al Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 1003– 1032. 19281331 PMC7107965 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Patients hospitalized with moderate to severe influenza may be coinfected with both viral and bacterial pathogens, but many patients will likely not be coinfected.

    “Our findings suggest that while patients hospitalized with moderate to severe influenza may be coinfected with both viral and bacterial pathogens, many patients will likely not be coinfected.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The lack of statistically significant variability may be due to unrecorded differences in the studies, such as genetic differences in the populations, local differences in severity of viral or bacterial illness, unrecorded patient comorbidities, variation in treatment, or antibiotic use.

    “This lack of statistically significant variability may be due to unrecorded differences in the studies, such as genetic differences in the populations, local differences in either the severity of viral or bacterial illness, unrecorded patient comorbidities, variation in treatment, or as noted above, antibiotic use (either current or past).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Studies included only patients who were hospitalized for influenza and thus represent a population with moderate to severe influenza.

    “Second, studies included only patients who were hospitalized for influenza and thus represent a population with moderate to severe influenza.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    Although a few studies enrolled patients in the outpatient or ED setting, all required hospitalization.

    “Although a few studies enrolled patients in the outpatient or ED setting, all required hospitalization.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    These results may underrepresent the actual number of bacterial coinfections and the distribution of the pathogens of those coinfections.

    “Hence, these results may underrepresent the actual number of bacterial coinfections and the distribution of the pathogens of those coinfections.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One study found that previous antibiotic use made patients more likely to acquire atypical bacterial infections.

    “One study found that previous antibiotic use made patients more likely to acquire atypical bacterial infections.50”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Van Gageldonk‐Lafeber AB, Wever PC, Van DL et al The aetiology of community‐acquired pneumonia and implications for patient management. Neth J Med 2013; 71: 418– 425. 24127502

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bjarnason and colleagues found that none of the patients using antibiotics were in the coinfected group and when they excluded antibiotic users, the prevalence of coinfection increased from 14% to 45%.

    “For example, Bjarnason and colleagues found that none of the patients using antibiotics were in the coinfected group and when they excluded antibiotic users from the study, the prevalence of coinfection increased from 14% to 45%.30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Bjarnason A, Thorleifsdottir G, Love A et al Severity of influenza A 2009 (H1N1) pneumonia is underestimated by routine prediction rules. Results from a prospective, population‐based study. PLoS ONE 2012; 7: e46816. 23071646 PMC3469650 source

      Not checked in the free run.

44 of 44

  • The authors state this as an assumption.

    Coinfection was assumed to be any acute bacterial infection identified in respiratory secretions, sputum, or sterile site (e.g., bacteremia).

    “Coinfection was assumed to be any acute bacterial infection identified in respiratory secretions, sputum, or sterile site (e.g., bacteremia).”

  • The paper relies on this without support.

    Differentiating viral from bacterial infection remains a challenge for clinicians.

    “Differentiating viral from bacterial infection remains a challenge for clinicians.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The frequency of influenza and bacterial co-infection ranged from 2% to 65%.

    “The frequency of influenza and bacterial co-infection ranged from 2% to 65%.”

    From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Klein et al., 2016

  • Streptococcus pneumoniae and Staphylococcus aureus accounted for 35% and 28% of influenza bacterial infections.

    “Among them, Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% and 28% of infections (Klein et al., 2016).”

    From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Klein et al., 2016

  • The bacteria most commonly associated with influenza infection are those which commonly colonise the nasopharynx, such as Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes, with secondary infection usually occurring in the first 6 days of influenza.

    “The bacteria most commonly associated with influenza infection have been reported to be those which commonly colonise the nasopharynx, such as Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes, with secondary infection usually occurring in the first 6 days of influenza.43, 44, 45”

    From Co-infections in people with COVID-19: a systematic review and meta-analysis. (2020) · cites this paper as [45]

  • In laboratory-confirmed influenza, bacterial co/secondary infection has been reported in up to 65% of cases, although a meta-analysis found that in most included studies the figure ranged between 11 and 35%.

    “Studies have shown that up to 65% of laboratory confirmed cases of influenza infection exhibited bacterial co/secondary infection, although Klein et al. (2016) state that in the majority of the research included in their meta-analysis this figure ranged between 11 and 35%.”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Klein et al., 2016

  • M. catarrhalis has been highlighted as a frequent source of co-infection for influenza since the early 1980s.

    “M. catarrhalis has been highlighted as a frequent source of co-infection for influenza since the early 1980’s (Klein et al., 2016).”

    From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Klein et al., 2016

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Mixed-setting total includes an uncounted third study

    Minor

    The two cited mixed-setting studies have 833 and 160 patients, totaling 993 rather than 1100. Table 1 lists a third mixed-setting study, Carr et al. (107 patients), which brings the total to 1100.

    Reported 1100 · recomputed 993

1 of 1

Cites

Flagged first, then by citations

1 of the 66 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. National Collaborating Centre for Methods and Tools. Quality Assessment Tool for Quantitative Studies. Vol (Updated 13 April, 2010, Hamilton, 2008
  2. Dave BM, 2014, Clinical data of h1n1 infected patients, 2012–2013, Indian J Crit Care Med, 18, S25
  3. Guervilly C, 2010, High levels of procalcitonin and (greater‐than or equal to) reactive protein during H1N1 illness, Intensive Care Med, 36, S138
  4. Yan XX, 2011, Influenza a (H1n1) virus complicated with bacteria infection, Respirology, 16, 60

Cited by

Sorted by citations

Related

Authors
Klein, E. Y., Monteforte, B., Gupta, A., Jiang, W., May, L., Hsieh, Y., & Dugas, A.
Affiliations
  • Center for Disease Dynamics, Economics & Policy (US)
  • Eastern Virginia Medical School (US)
  • Allegheny General Hospital (US)
  • George Washington University (US)
  • Johns Hopkins University (US)
Corresponding author
Klein, Eili Y.
ORCID
Venue
Influenza and Other Respiratory Viruses
Publisher
Wiley
Published
2016-06-24
Volume
10
Issue
5
Pages
394-403
ISSN
  • 1750-2640 (ISSN-L)
  • 1750-2659
DOI
10.1111/irv.12398
PMC
PMC4947938
OpenAlex
W2402456610
Semantic Scholar
210ca1b97c01c947b269aac6fab9f37485337e22
Cited by
574
References
66
Citations by year
2026: 29 · 2025: 46 · 2024: 51 · 2023: 96 · 2022: 104 · 2021: 112 · 2020: 58 · 2019: 20 · 2018: 24 · 2017: 15 · 2016: 5
FWCI
2.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Influenza and Other Respiratory Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
U.S. Department of Health and Human Services (IDSEP130014‐01‐00)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Keywords
influenza, bacterial co-infection, Streptococcus pneumoniae, Staphylococcus aureus, hospitalized influenza patients, pathogenic bacteria
MeSH terms
Adolescent, Adult, Child, Child, Preschool, Female, Hospitalization, Humans, Infant, Infant, Newborn, Influenza, Human, Male, Middle Aged, Pneumococcal Infections, Staphylococcal Infections, Streptococcus pneumoniae, Drug Resistance, Bacterial, Methicillin-Resistant Staphylococcus aureus, Young Adult, Coinfection

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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