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

In the paper

“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”

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

“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”

In the paper

“While studies were generally representative of the targeted population, most studies did not report the percentage of patients that agreed to participate.”

In the paper

“Among the individual studies, the proportion of bacterial coinfection ranged from 2% (newborns born in USA) to 65% (immunocompetent adults in France) (Figure 3).”

In the paper

“Egger's test of asymmetry was also significant for bias (P = 0·0004).”

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

“Of those 27, only eight studies, with 334 patients, provided the numbers or percentages of each bacterial coinfecting pathogen.28, 32, 33, 34, 38, 43, 46, 47”

In the paper

“Severity of illness varied among studies, but all were focused on hospitalized patients, suggesting a greater than average severity.”

In the paper

“High statistical heterogeneity of the included studies (I 2 = 95%) removed confidence in reporting an estimate of the pooled mean proportion of bacterial coinfection through meta‐analysis.”

In the paper

“We found 27 studies covering 3215 patients.”

In the paper

“Streptococcus pneumoniae and Staphylococccus aureus were the most common pathogens accounting for 35% (95% CI, 14%–56%) and 28% (95% CI, 16%–40%) of identified coinfecting bacteria, respectively (Figure 4).”

In the paper

“A multivariate analysis also found no significant correlation between any of the variables and overall rates of coinfection.”

In the paper

“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.”

In the paper

“Severity of illness however was not a factor that could be standardized among the studies.”

In the paper

“The largest study contributed greatly to the heterogeneity of the results; however, study size did not significantly contribute to the heterogeneity in the results (P = 0·06 with the largest study, while P = 0·41 excluding this study).”

In the paper

“The results from these studies were highly variable, ranging from 2% to 65%.”

In the paper

“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.”

In the paper

“Streptococcus pneumoniae and Staphylococccus aureus were the most common pathogens accounting for 35% (95% CI, 14%–56%) and 28% (95% CI, 16%–40%) of identified coinfecting bacteria, respectively (Figure 4).”

In the paper

“Although the majority of studies ranged between 11% and 35%, no specific characteristics of the studies were associated with variability in coinfection frequency.”

In the paper

“Streptococcus pneumoniae and Staphylococccus aureus were the most common pathogens accounting for 35% (95% CI, 14%–56%) and 28% (95% CI, 16%–40%) of identified coinfecting bacteria, respectively (Figure 4).”

In the paper

“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.”

In the paper

“Subanalyses and meta‐regression of age, setting, year of enrollment, study type, study size, and bacterial collection method were unable to determine the main sources of heterogeneity.”

In the paper

“No significant trend was seen when stratifying the studies by mean or median age (Figure S1).”

In the paper

“The proportion of bacterial coinfection among the remaining 20 studies, representing 64% of all patients, was between 11% and 35% (I 2 = 37%).”

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

“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.”

In the paper

“Although the majority of studies ranged between 11% and 35%, no specific characteristics of the studies were associated with variability in coinfection frequency.”

In the paper

“A number of other pathogens were also identified as causing coinfections: Pseudomonas aeruginosa, Streptococcus pyogenes, Haemophilus influenzae, Klebsiella pneumoniae, and Mycoplasma pneumoniae.”

In the paper

“However, although there have been significant increases in the incidence of MRSA infections in the last decade, particularly community‐associated MRSA (CA‐MRSA),64 there was not enough data to draw any inferences regarding temporal changes in the etiology of coinfecting pathogens.”

What the sources say

• Not checked yetcites [64] Klein EY, Sun L, Smith DL, Laximarayan R. The changing epidemiology of methicillin‐resistant Staphylococcus aureus in the United States: A national observational study. Am J Epidemiol 2013; 177: 666– 674. 23449778 source

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.”

• Also stated in: § Conclusion · plain

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

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

“It was not accounted for by differences in patient age, year, study enrollment setting, study design, study size, or method of bacterial sample collection or detection.”

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”

In the paper

“Finally, we were unable to explain the significant heterogeneity among studies.”

In the paper

“An additional six studies reported on participant antibiotic use at the time of enrollment and found that 12–50% of patients had preceding antibiotic treatment which may have led to an underestimation of the true frequency of bacterial coinfection in their sample population.30, 33, 40, 45, 47, 52”

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
• Not checked yetcites [33] Cordero E, Perez‐Romero P, Moreno A et al Pandemic influenza A(H1N1) virus infection in solid organ transplant recipients: impact of viral and non‐viral co‐infection. Clin Microbiol Infect 2012; 18: 67– 73. 21790857 PMC7129435 source
• Not checked yetcites [40] Johansson N, Kalin M, Annika TL, Giske CG, Hedlund J. Etiology of Community‐Acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 2010; 50: 202– 209. 20014950 PMC7107844 source

In the paper

“Coinfecting bacterial pathogens are a major cause of that morbidity and mortality and are associated with both pandemic and seasonal influenza virus illness.2”

What the sources say

• Not checked yetcites [2] Metersky ML, Masterton RG, Lode H, File TM Jr, Babinchak T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis 2012; 16: e321– e331. 22387143 source

In the paper

“Coinfecting bacterial pathogens are a major cause of that morbidity and mortality and are associated with both pandemic and seasonal influenza virus illness.2”

What the sources say

• Not checked yetcites [2] Metersky ML, Masterton RG, Lode H, File TM Jr, Babinchak T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis 2012; 16: e321– e331. 22387143 source

In the paper

“While prior studies have examined the frequency of select bacterial species in influenza cases,13, 14 particularly the presence of methicillin‐resistant S. aureus (MRSA),15, 16, 17, 18 the frequency of overall coinfection in influenza patients is still poorly characterized.”

What the sources say

• Not checked yetcites [13] Chertow DS, Memoli MJ. Bacterial coinfection in influenza: a grand rounds review. JAMA 2013; 309: 275– 282. 23321766 source
• Not checked yetcites [14] Wang X‐Y, Kilgore PE, Lim KA et al Influenza and bacterial pathogen coinfections in the 20th century. Interdiscip Perspect Infect Dis 2011; 2011: 146376. 21747847 PMC3124839 source
• Not checked yetcites [15] Centers for Disease Control Prevention. Severe methicillin‐resistant Staphylococcus aureus community‐acquired pneumonia associated with influenza–Louisiana and Georgia, December 2006‐January 2007. MMWR Morb Mortal Wkly Rep 2007; 56: 325– 329. 17431376
• Not checked yetcites [16] Centers for Disease Control Prevention. Severe coinfection with seasonal influenza A (H3N2) virus and Staphylococcus aureus–Maryland, February‐March 2012. MMWR Morb Mortal Wkly Rep 2012; 61: 289– 291. 22534762
• Not checked yetcites [17] Randolph AG, Vaughn F, Sullivan R et al Critically ill children during the 2009–2010 influenza pandemic in the United States. Pediatrics 2011; 128: e1450– e1458. 22065262 PMC3387899 source
• Not checked yetcites [18] Reed C, Kallen AJ, Patton M et al Infection with community‐onset Staphylococcus aureus and influenza virus in hospitalized children. Pediatr Infect Dis J 2009; 28: 572– 576. 19478685 source

In the paper

“High statistical heterogeneity of the included studies (I 2 = 95%) removed confidence in reporting an estimate of the pooled mean proportion of bacterial coinfection through meta‐analysis.”

In the paper

“Severity of illness varied among studies, but all were focused on hospitalized patients, suggesting a greater than average severity.”

In the paper

“This lack of detail did not allow us to eliminate the possibility of selection bias in the study cohorts.”

In the paper

“Despite the long historical understanding of the risk posed by bacterial coinfections in influenza patients,2 the extent of coinfection has not been systematically examined.55”

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

In the paper

“This diagnostic uncertainty has contributed to a widely recognized overuse of antibiotics in patients with viral illness.56, 57”

What the sources say

• Not checked yetcites [56] Gonzales R, Bartlett JG, Besser RE et al Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults: background, specific aims, and methods. Ann Emerg Med 2001; 37: 690– 697. 11385342 source
• Not checked yetcites [57] Metlay JP, Camargo CA, MacKenzie T et al Cluster‐randomized trial to improve antibiotic use for adults with acute respiratory infections treated in emergency departments. Ann Emerg Med 2007; 50: 221– 230. 17509729 source

In the paper

“This meta‐analysis increases understanding of the likelihood that patients hospitalized with influenza also have a bacterial coinfection; however, the variability in results suggests that physicians should ensure that appropriate cultures are taken to minimize the overuse of antibiotics.”

In the paper

“An assessment of bias suggested that lack of small‐study publications may have biased the results.”

In the paper

“However, as previous observational studies have shown, patients admitted to the hospital with influenza are more likely to receive antibiotics than antiviral medications.59, 60”

What the sources say

• Not checked yetcites [59] Dugas AF, Monteforte B, Puri A, Awad M, Hsieh Y‐H, Rothman R. ED compliance with influenza antiviral recommendations. Am J Emerg Med 2014; 32: 1550– 1552. 25445855 source
• Not checked yetcites [60] Dugas AF, Valsamakis A, Atreya MR et al Clinical diagnosis of influenza in the ED. Am J Emerg Med 2015; 33: 770– 775. 25827595 PMC4458223 source

In the paper

“Some difficult‐to‐detect bacteria may, therefore, be underdiagnosed.”

In the paper

“The study does not, therefore, represent the vast majority of influenza patients, including asymptomatic patients, who are not hospitalized.”

In the paper

“Third, studies included in this analysis detected bacterial pathogens in a number of different ways, which have varying sensitivity for different organisms and potential coinfecting sites (e.g., sputum versus blood).”

In the paper

“First of all, although our final sample size included 27 studies and more than 3000 patients, these are relatively small numbers compared to annual estimates of up to 200 000 influenza‐related hospitalizations.65”

What the sources say

• Not checked yetcites [65] Thompson WW, Shay DK, Weintraub E et al Influenza‐associated hospitalizations in the United States. JAMA 2004; 292: 1333– 1340. 15367555 source

In the paper

“This identifies a gap in the current literature as the frequency of bacterial coinfection in outpatients with confirmed influenza remains unknown.”

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 [64] Klein EY, Sun L, Smith DL, Laximarayan R. The changing epidemiology of methicillin‐resistant Staphylococcus aureus in the United States: A national observational study. Am J Epidemiol 2013; 177: 666– 674. 23449778 source

In the paper

“An additional six studies reported on participant antibiotic use at the time of enrollment and found that 12–50% of patients had preceding antibiotic treatment which may have led to an underestimation of the true frequency of bacterial coinfection in their sample population.30, 33, 40, 45, 47, 52”

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
• Not checked yetcites [33] Cordero E, Perez‐Romero P, Moreno A et al Pandemic influenza A(H1N1) virus infection in solid organ transplant recipients: impact of viral and non‐viral co‐infection. Clin Microbiol Infect 2012; 18: 67– 73. 21790857 PMC7129435 source
• Not checked yetcites [40] Johansson N, Kalin M, Annika TL, Giske CG, Hedlund J. Etiology of Community‐Acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 2010; 50: 202– 209. 20014950 PMC7107844 source