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

In the paper

“The majority (21) of studies were cohort studies, and the rest were case–control studies.”

In the paper

“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).”

In the paper

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

In the paper

“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”

In the paper

“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.”

In the paper

“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.”

In the paper

“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).”

In the paper

“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.”

In the paper

“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.”

In the paper

“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).”

In the paper

“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.”

In the paper

“In addition, other Staphylococcal pathogens such as S. epidermidis, and Gram‐negative bacteria, such as Escherichia coli and Moraxella catarrhalis, were also frequently found.”

In the paper

“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).”

In the paper

“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.”

In the paper

“Further, some studies only included severely immunocompromised patients who had concurrent malignancy or organ transplant,31, 33, 49 while others excluded immunocompromised patients.”

In the paper

“Only three studies excluded participants based on antibiotic use and reported coinfection rates of 12·2%, 26·7%, and 46·6%.28, 34, 36”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [62] McCullers JA. The co‐pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Micro 2014; 12: 252– 262. 24590244 source

In the paper

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

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [20] National Collaborating Centre for Methods and Tools. Quality Assessment Tool for Quantitative Studies. Vol (Updated 13 April. Hamilton. ON: McMaster University, 2010; 2008.

In the paper

“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).”

In the paper

“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.”

In the paper

“In seasonal epidemics, influenza bacterial coinfection is associated with increases in hospital admissions,4, 5 more severe symptoms,6 and increases in mortality.7”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“Two authors (BM, AG) extracted study data from all included publications independently, and results were then compared. Differences were resolved by consensus.”

In the paper

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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“Identification of coinfected patients and coinfecting pathogen enables clinicians to initiate appropriate antibiotic therapy and improve patient outcomes.12”

What the sources say

• Not checked yetcites [12] Van‐Tam J, Sellwood C. Pandemic Influenza. Boston: CABI, 2012. source

In the paper

“Funnel plots and calculation of Egger's test of asymmetry were also used to assess biases such as publication and small‐study effects.23”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

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

In the paper

“However, there was some suggestion that negative findings or low levels of bacterial coinfection were not published.”

In the paper

“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.”

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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).”

In the paper

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

In the paper

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

In the paper

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

In the paper

“One study found that previous antibiotic use made patients more likely to acquire atypical bacterial infections.50”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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