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Point/Counterpoint Editorials |

Point: Does the Risk of Cross Infection Warrant Exclusion of Adults With Cystic Fibrosis From Cystic Fibrosis Foundation Events? YesRisk of Cystic Fibrosis Cross Infection? Yes FREE TO VIEW

Manu Jain, MD; Lisa M. Saiman, MD, MPH; Kathy Sabadosa, MPH; John J. LiPuma, MD
Author and Funding Information

From the Department of Medicine and Pediatrics (Dr Jain), Feinberg School of Medicine, Northwestern University; Department of Pediatrics (Dr Saiman), Columbia University Medical Center; Department of Infection Prevention and Control (Dr Saiman), New York-Presbyterian Hospital; Dartmouth Institute for Health Policy & Clinical Practice (Ms Sabadosa), Geisel School of Medicine; and the Department of Pediatrics and Communicable Disease (Dr LiPuma), University of Michigan Medical School.

Correspondence to: Manu Jain, MD, Northwestern University, 240 E Huron M-332, Chicago, IL 60611; e-mail: m-jain@northwestern.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Saiman receives funding from the CF Foundation to provide expertise in infectious diseases and microbiology. Ms Sabadosa is a full-time, 10-year employee of the Cystic Fibrosis Foundation. Drs Jain and LiPuma have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(4):678-680. doi:10.1378/chest.13-2404
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In 1990, LiPuma and colleagues1 described person-to-person transmission of Pseudomonas cepacia (now Burkholderia cepacia) between young adults with cystic fibrosis (CF) attending an educational program. One of the newly infected individuals had been previously in good health, but deteriorated rapidly and died within several months. This tragic case highlights the potential for catastrophic consequences from person-to-person transmission of bacterial pathogens in CF. This report and others from around the world that also described person-to-person transmission of B cepacia associated with acceleration of pulmonary disease and death led to the recommendation that people infected with B cepacia not attend Cystic Fibrosis Foundation (CF Foundation)-sponsored events. Reports describing person-to-person transmission of other more prevalent CF pathogens, most notably Pseudomonas aeruginosa, soon followed. In response, the CF Foundation published recommendations for infection prevention and control in 2003.2 Over the last 10 years, accumulating evidence has described further instances of person-to-person transmission of CF pathogens as well as poor clinical outcomes associated with transmission of certain strains of P aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Burkholderia.3 In response, the CF Foundation commissioned an update of the guidelines and invited public comment on a draft version. The period for public comment is now closed.

The updated recommendation that has generated the greatest controversy is that only one person with CF attend an indoor CF Foundation-sponsored or CF center-sponsored event. We make the case that this recommendation is the most prudent course of action to protect the health of an individual with CF and for the CF community as a whole.

To support the recommendation that only one person with CF should attend an indoor event, we believe the following three questions can be answered in the affirmative: (1) Can cross infection occur between people with CF? (2) Can acquisition of microorganisms through person-to-person transmission lead to clinical deterioration and possibly death? (3) Can limiting exposure of individuals with CF to each other reduce the risk of cross infection?

Person-to-person transmission of species in the B cepacia complex, including Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia dolosa has been well documented.3 However, at most CF centers, Burkholderia species are detected in a small number of patients, in contrast to P aeruginosa, which chronically infects as many as 80% of adults with CF. Although historically it was believed that P aeruginosa was almost exclusively acquired from the environment, person-to-person transmission has been increasingly described. The earliest reports of cross infection involved CF camps. In one study, investigators described new P aeruginosa infection in eight of 10 individuals. A mucoid P aeruginosa strain was recovered from three of the newly infected individuals, suggesting cross infection from a chronically infected person.4 Another report described the acquisition of P aeruginosa in five previously uninfected individuals attending a week-long camp, and molecular analysis confirmed that these strains matched the P aeruginosa strain isolated from an attendee known to be chronically infected with P aeruginosa.5 Subsequently, investigators from the United Kingdom described recovery of the same strain of P aeruginosa in 55 children cared for at the Liverpool CF center.6 Infection with this strain, now referred to as the Liverpool Epidemic Strain, has been detected in many other centers in the United Kingdom and described in adults with CF in Ontario, Canada.7 We emphasize that shared strains of P aeruginosa can only be reliably identified by molecular testing.

With respect to other CF pathogens, epidemiologic studies have shown that individuals with CF can share S aureus strains, including MRSA.8 Most recently, two reports have described person-to-person transmission of nontuberculous mycobacteria at CF centers.9,10 Although it remains difficult to precisely quantify the risk of person-to-person transmission, it is clear that the answer to the question “Can cross infection occur between people with CF?” is an unequivocal yes.

Several studies have shown that acquisition of shared strains of Burkholderia can be devastating.11,12 There is also substantial evidence that transmissible strains of Pseudomonas are associated with clinically significant deterioration. Reports from Australia describe acquisition of mucoid, multidrug-resistant P aeruginosa by young children who attended CF clinic on the same day as older patients infected with the same strain.13 These children died before 7 years of age. Individuals with CF infected with the Liverpool Epidemic Strain are hospitalized more frequently, lose lung function at a greater rate, and are more likely to die or require lung transplantation than those infected with unique strains.7 During, the last several years, multiple studies have found that MRSA infection is associated with faster decline in lung function and increased risk of death.14,15 Further, in a recent outbreak of Mycobacteria abscessus subspecies massiliense at a CF center in Seattle, Washington, two of four patients who had identical isolates by molecular typing to the index case died within months of acquiring the organism.10 These data suggest that microorganisms acquired from another individual with CF may be more virulent than those acquired from the environment, and could accelerate decline in lung function, hasten lung transplantation, and/or increase the risk of death. Thus, the answer to the question “Can acquisition of microorganisms through person-to-person transmission lead to clinical deterioration and possibly death?” is yes.

Finally, can the risk of cross infection be reduced if individuals with CF limit exposure to one another? While not advocated by the CF Foundation, many centers practice cohort segregation whereby only people infected with the same pathogens, such as MRSA or specific epidemic strains of P aeruginosa, attend the same clinic session.16 This strategy, which was supplemented by other interventions such as alternative waiting rooms and discouraging socialization between individuals with CF, has proven successful in limiting the spread of epidemic P aeruginosa strains and Burkholderia species.17-19 Similarly, interventions that limit exposure of individuals with CF to each other in clinic (eg, no shared waiting room and faster throughput of patients) have been associated with a reduced prevalence of chronic P aeruginosa infection.20 In addition, not attending CF camps is associated with a much lower risk of acquiring B cepacia infection,21 and discontinuing CF camps is associated with lower risk of cross infection with P aeruginosa.4 Two decades of compelling evidence supports the premise that limiting exposure between people with CF significantly decreases the risk of pathogen transmission. Thus, the answer to the question “Can limiting exposure of individuals with CF to each other reduce the risk of cross-infection?” is yes.

In summary, (1) pathogen transmission can occur between people with CF; (2) such transmission may involve especially virulent strains, worsening clinical outcomes and resulting in premature death; and (3) infection prevention and control measures have proven effective in halting the transmission of specific pathogens. While it seems intuitive that the risk of transmission is likely greater with closer contact between individuals with CF, the precise risk cannot be quantified. More importantly, it is impossible to exclude with confidence which individuals may be harboring virulent, transmissible strains since acquisition of new pathogens is most often “silent” (ie, not initially marked by obvious clinical signs or symptoms) and new potentially virulent pathogens continually emerge. For the safety and well-being of all individuals with CF, the most prudent course of action to reduce the risk of person-to-person transmission is to limit exposure. It is unfortunate that this recommendation adds to the burden of disease as the value of the psychosocial support provided by participation in CF community activities cannot be overstated. Adults with CF are particularly affected as their contact with one another in camps and educational retreats has ended and in clinical settings has become more and more restricted. These previous actions reflected growing knowledge of the routes and risks of transmission, and in the updated guidelines, new knowledge has led to the current recommendation to restrict attendance at indoor events. To enable individuals with CF to connect with each other and the community, we urge the CF Foundation and centers to use readily available online and video communication technologies. We also emphasize that other recommendations regarding the potential risks associated with leisure activities in the updated guidelines are intended to help individuals with CF make informed choices. We believe that as a community, we need to continue to be extremely mindful of how to live safely with CF, for ourselves, for family members, and for everyone around us who share in the hope that one day there will be a cure.

Abbreviations

CF

cystic fibrosis

MRSA

methicillin-resistant Staphylococcus aureus

LiPuma JJ, Dasen SE, Nielson DW, Stern RC, Stull TL. Person-to-person transmission ofPseudomonas cepaciabetween patients with cystic fibrosis. Lancet. 1990;336(8723):1094-1096. [CrossRef]
 
Saiman L, Siegel J; Cystic Fibrosis Foundation Consensus Conference on Infection Control Participants. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission. Am J Infect Control. 2003;31(suppl_3):S6-52. [CrossRef]
 
LiPuma JJ. The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev. 2010;23(2):299-323. [CrossRef]
 
Tümmler B, Koopmann U, Grothues D, Weissbrodt H, Steinkamp G, von der Hardt H. Nosocomial acquisition ofPseudomonas aeruginosaby cystic fibrosis patients. J Clin Microbiol. 1991;29(6):1265-1267.
 
Ojeniyi B, Frederiksen B, Hoiby N. Pseudomonas aeruginosacross-infection among patients with cystic fibrosis during a winter camp. Pediatr Pulmonol. 2000;29(3):177-181. [CrossRef]
 
Cheng K, Smyth RL, Govan JR, et al. Spread of beta-lactam-resistantPseudomonas aeruginosain a cystic fibrosis clinic. Lancet. 1996;348(9028):639-642. [CrossRef]
 
Aaron SD, Vandemheen KL, Ramotar K, et al. Infection with transmissible strains ofPseudomonas aeruginosaand clinical outcomes in adults with cystic fibrosis. JAMA. 2010;304(19):2145-2153. [CrossRef]
 
Elizur A, Orscheln RC, Ferkol TW, Dunne WM Jr, Storch GA, Cannon CL. Transmission of Panton-Valentine leukocidin-positiveStaphylococcus aureusbetween patients with cystic fibrosis. J Pediatr. 2007;151(1):90-92. [CrossRef]
 
Bryant JM, Grogono DM, Greaves D, et al. Whole-genome sequencing to identify transmission ofMycobacterium abscessusbetween patients with cystic fibrosis: a retrospective cohort study. Lancet. 2013;381(9877):1551-1560. [CrossRef]
 
Aitken ML, Limaye A, Pottinger P, et al. Respiratory outbreak ofMycobacterium abscessussubspecies massiliense in a lung transplant and cystic fibrosis center. Am J Respir Crit Care Med. 2012;185(2):231-232. [CrossRef]
 
Kalish LA, Waltz DA, Dovey M, et al. Impact ofBurkholderia dolosaon lung function and survival in cystic fibrosis. Am J Respir Crit Care Med. 2006;173(4):421-425. [CrossRef]
 
Mahenthiralingam E, Vandamme P, Campbell ME, et al. Infection withBurkholderia cepaciacomplex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replaceBurkholderia multivoransClin Infect Dis. 2001;33(9):1469-1475. [CrossRef]
 
Nixon GM, Armstrong DS, Carzino R, et al. Clinical outcome after earlyPseudomonas aeruginosainfection in cystic fibrosis. J Pediatr. 2001;138(5):699-704. [CrossRef]
 
Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. Association between respiratory tract methicillin-resistantStaphylococcus aureusand survival in cystic fibrosis. JAMA. 2010;303(23):2386-2392. [CrossRef]
 
Dasenbrook EC, Merlo CA, Diener-West M, Lechtzin N, Boyle MP. Persistent methicillin-resistantStaphylococcus aureusand rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med. 2008;178(8):814-821. [CrossRef]
 
Doe SJ, McSorley A, Isalska B, et al. Patient segregation and aggressive antibiotic eradication therapy can control methicillin-resistantStaphylococcus aureusat large cystic fibrosis centres. J Cyst Fibros. 2010;9(2):104-109. [CrossRef]
 
Razvi S, Quittell L, Sewall A, Quinton H, Marshall B, Saiman L. Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005. Chest. 2009;136(6):1554-1560. [CrossRef]
 
Chen JS, Witzmann KA, Spilker T, Fink RJ, LiPuma JJ. Endemicity and inter-city spread ofBurkholderia cepaciagenomovar III in cystic fibrosis. J Pediatr. 2001;139(5):643-649. [CrossRef]
 
Muhdi K, Edenborough FP, Gumery L, et al. Outcome for patients colonised withBurkholderia cepaciain a Birmingham adult cystic fibrosis clinic and the end of an epidemic. Thorax. 1996;51(4):374-377. [CrossRef]
 
Farrell PM, Shen G, Splaingard M, et al. Acquisition ofPseudomonas aeruginosain children with cystic fibrosis. Pediatrics. 1997;100(5):E2. [CrossRef]
 
Pegues DA, Carson LA, Tablan OC, et al. Acquisition ofPseudomonas cepaciaat summer camps for patients with cystic fibrosis. Summer Camp Study Group. J Pediatr. 1994;124(5 pt 1):694-702. [CrossRef]
 

Figures

Tables

References

LiPuma JJ, Dasen SE, Nielson DW, Stern RC, Stull TL. Person-to-person transmission ofPseudomonas cepaciabetween patients with cystic fibrosis. Lancet. 1990;336(8723):1094-1096. [CrossRef]
 
Saiman L, Siegel J; Cystic Fibrosis Foundation Consensus Conference on Infection Control Participants. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission. Am J Infect Control. 2003;31(suppl_3):S6-52. [CrossRef]
 
LiPuma JJ. The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev. 2010;23(2):299-323. [CrossRef]
 
Tümmler B, Koopmann U, Grothues D, Weissbrodt H, Steinkamp G, von der Hardt H. Nosocomial acquisition ofPseudomonas aeruginosaby cystic fibrosis patients. J Clin Microbiol. 1991;29(6):1265-1267.
 
Ojeniyi B, Frederiksen B, Hoiby N. Pseudomonas aeruginosacross-infection among patients with cystic fibrosis during a winter camp. Pediatr Pulmonol. 2000;29(3):177-181. [CrossRef]
 
Cheng K, Smyth RL, Govan JR, et al. Spread of beta-lactam-resistantPseudomonas aeruginosain a cystic fibrosis clinic. Lancet. 1996;348(9028):639-642. [CrossRef]
 
Aaron SD, Vandemheen KL, Ramotar K, et al. Infection with transmissible strains ofPseudomonas aeruginosaand clinical outcomes in adults with cystic fibrosis. JAMA. 2010;304(19):2145-2153. [CrossRef]
 
Elizur A, Orscheln RC, Ferkol TW, Dunne WM Jr, Storch GA, Cannon CL. Transmission of Panton-Valentine leukocidin-positiveStaphylococcus aureusbetween patients with cystic fibrosis. J Pediatr. 2007;151(1):90-92. [CrossRef]
 
Bryant JM, Grogono DM, Greaves D, et al. Whole-genome sequencing to identify transmission ofMycobacterium abscessusbetween patients with cystic fibrosis: a retrospective cohort study. Lancet. 2013;381(9877):1551-1560. [CrossRef]
 
Aitken ML, Limaye A, Pottinger P, et al. Respiratory outbreak ofMycobacterium abscessussubspecies massiliense in a lung transplant and cystic fibrosis center. Am J Respir Crit Care Med. 2012;185(2):231-232. [CrossRef]
 
Kalish LA, Waltz DA, Dovey M, et al. Impact ofBurkholderia dolosaon lung function and survival in cystic fibrosis. Am J Respir Crit Care Med. 2006;173(4):421-425. [CrossRef]
 
Mahenthiralingam E, Vandamme P, Campbell ME, et al. Infection withBurkholderia cepaciacomplex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replaceBurkholderia multivoransClin Infect Dis. 2001;33(9):1469-1475. [CrossRef]
 
Nixon GM, Armstrong DS, Carzino R, et al. Clinical outcome after earlyPseudomonas aeruginosainfection in cystic fibrosis. J Pediatr. 2001;138(5):699-704. [CrossRef]
 
Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. Association between respiratory tract methicillin-resistantStaphylococcus aureusand survival in cystic fibrosis. JAMA. 2010;303(23):2386-2392. [CrossRef]
 
Dasenbrook EC, Merlo CA, Diener-West M, Lechtzin N, Boyle MP. Persistent methicillin-resistantStaphylococcus aureusand rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med. 2008;178(8):814-821. [CrossRef]
 
Doe SJ, McSorley A, Isalska B, et al. Patient segregation and aggressive antibiotic eradication therapy can control methicillin-resistantStaphylococcus aureusat large cystic fibrosis centres. J Cyst Fibros. 2010;9(2):104-109. [CrossRef]
 
Razvi S, Quittell L, Sewall A, Quinton H, Marshall B, Saiman L. Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005. Chest. 2009;136(6):1554-1560. [CrossRef]
 
Chen JS, Witzmann KA, Spilker T, Fink RJ, LiPuma JJ. Endemicity and inter-city spread ofBurkholderia cepaciagenomovar III in cystic fibrosis. J Pediatr. 2001;139(5):643-649. [CrossRef]
 
Muhdi K, Edenborough FP, Gumery L, et al. Outcome for patients colonised withBurkholderia cepaciain a Birmingham adult cystic fibrosis clinic and the end of an epidemic. Thorax. 1996;51(4):374-377. [CrossRef]
 
Farrell PM, Shen G, Splaingard M, et al. Acquisition ofPseudomonas aeruginosain children with cystic fibrosis. Pediatrics. 1997;100(5):E2. [CrossRef]
 
Pegues DA, Carson LA, Tablan OC, et al. Acquisition ofPseudomonas cepaciaat summer camps for patients with cystic fibrosis. Summer Camp Study Group. J Pediatr. 1994;124(5 pt 1):694-702. [CrossRef]
 
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