The History of Cystic Fibrosis by Dr James Littlewood OBE

Edited and produced by Daniel Peckham

 

 

* Some of these references do not appear in the main text

1980 Boxerbaum B. isolation of rapidly growing mycobacteria in patients with cystic fibrosis. J Pediatr 1980; 96:689-691.[PubMed]

Apparently the first reference to non tuberculous mycobacteris in cystic fibrosis patients.

1984 Efthimiou J, Smith MJ, Hodson ME, Batten JC. Fatal pulmonary infection Mycobacterium fortuitum in cystic fibrosis. Br J Dis Chest 1984; 78:299-302. [PubMed]
An early report of an atypical Mycobacterium infection in a young adult with cystic fibrosis. The organism was resistant to all antibiotics and the patient died.

Atypical mycobacteria were to become an increasing problem in people with CF. In a subsequent paper from Royal Brompton Smith MJ et al (1984 below) made a search to determine the prevalence of atypical mycobacteria in their CF patients – presumably as a result of experience with this patient. (see also Boxerbaum B. Isolation of rapidly growing mycobacteria in patients with cystic fibrosis. J Pediatr 1980; 96:689-691.[PubMed]).

 

1984 Smith MJ, Efthimiou J, Hodson ME, Batten JC. Mycobacterial isolations in young adults with cystic fibrosis. Thorax 1984; 39:369-375. [PubMed]
Seven of 223 patients with CF admitted to the Brompton Hospital over a six year period had Mycobacteria in their sputum. The organisms isolated were Mycobacterium tuberculosis in three patients, M. chelonei in one, M. fortuitum in one, and unidentified Mycobacteria in two. The diagnosis was not suspected on clinical grounds in any of these patients; in one patient, however, night sweats were a prominent feature before diagnosis. In four of the patients direct sputum smear examination did not reveal the organism, which was grown subsequently in culture.

These were early days for appreciating the role of atypical Mycobacteria in CF and the organisms were present in the sputa of patients with cystic fibrosis more often than previously recognised. Therefore the authors recommended that sputum examination and culture for Mycobacteria should be performed periodically in these patients. Subsequently problems with these organisms would become more widely recognised and occur as a problem sometimes after lung transplantation when the patients were on immunosuppressive therapy.


Probably as there were few adults at that time and so few CF centres for adults, there were no further reports until one from Dublin in 1990 (Mulherin D, et al. Respir Med 1990; 84:273-276. [PubMed]) where the frequency of positive skin reactions was found to be similar as in a control population. One of the 43 patients grew an atypical mycobacterium from the sputum.

 

1990 Hjelt L, Petrini B, Kallenius G Strandvik B, Prospective study of mycobacterial infections in patients with cystic fibrosis. Thorax 1990; 45:397-400. [PubMed]

Fifty four patients with cystic fibrosis, aged 3-67 years, were studied prospectively for pulmonary mycobacterial infection. Sputum smears and cultures were carried out and intradermal skin tests performed. Mycobacteria were cultured from six patients in association with clinical deterioration; four patients had positive direct smears. Mycobacterium tuberculosis, M. avium intracellulare, M. kansasii, and M. gordonae were isolated. There were no deaths and all improved with chemotherapy. A third of the other 48 patients had positive skin test responses (greater than 6 mm) to purified protein derivative (PPD) tuberculin and 21 to one or more antigens prepared from non-tuberculous mycobacteria. Sensitisation increased with age; before the age of 11 only one patient had a positive response to PPD tuberculin and none to any other antigen. This was less than in healthy control subjects of similar age. After age 11 the reactions in sensitised patients were stronger than in positive healthy control subjects.

The authors suggest that their study indicates that it is important to consider mycobacterial infection in patients with cystic fibrosis who deteriorate without obvious cause

 

1994 Hjelt K, Hojlyng N, Howitz P, Illum N, Munk E, Valerius NH, Hansen KN, Heltberg I, Koch C. The role of Mycobacteria Other Than Tuberculosis (MOTT) in patients with cystic fibrosis. Scand J Infect Dis 1994; 26:569-576. [PubMed]

The purpose of this study was to estimate the frequency of and evaluate the clinical impact of pulmonary mycobacterial infections among cystic fibrosis (CF) patients. 185 CF patients aged 2.2-38.5 years were screened by sputum samples and by intracutaneous skin tests against tuberculin and sensitins produced from Mycobacterium chelonae subsp. abscessus, M. avium, M. intracellulare and M. scrofulaceum (the MAIS complex). The skin tests towards the sensitins in BCG-vaccinated patients (n = 60) were significantly influenced by the vaccination.

26 of the remaining 125 non-vaccinated patients had one or more positive skin test (95% confidence limits 15-29%). The majority reacted against the MAIS complex. However, the reactions were similar to those of healthy siblings and an age-matched control group. Moreover, the lung function, growth and HbA1c were similar among skin test positive and negative patients.

Three patients had repeated positive sputum cultures, the point prevalence being 1.6% (M. intracellulare, n = 2 and M. chelonae subsp. abscessus, n = 1). During the subsequent 4 years, 4 additional patients with M. chelonae subsp. abscessus were identified. Based on clinical observations, 5 of the infected patients were considered asymptomatic, while 2 might have been symptomatic. In 1 patient, M. chelonae subsp. abscessus disappeared spontaneously.

Despite intensive treatment with new antibiotics against Mycobacteria Other Than Tuberculosis (MOTT) in 4 patients, the mycobacteria were not eradicated.

The authors concluded MOTT infection was rare and the clinical impact difficult to prove. Treatment should focus on clinical improvement in the individual patient suspected of suffering from significant symptomatic infection. Eradication of the bacteria should not be expected.

 

1996 Tomashefski JF Jr, Stern RC, Demko CA, Doershuk CF. Nontuberculous mycobacteria in cystic fibrosis. An autopsy study. Am J Resp Crit Care 1996;154:523-28.

[PubMed]

Lung and hilar lymph nodes were studied at autopsy in 18 patients with cystic fibrosis who had antemortem sputum cultures positive for nontuberculous mycobacteria (NTM). Histologic features were compared with those of 18 patients with CF who had negative antemortem cultures. The most frequent species isolated was M. chelonae group (10 patients). Multiple cultures were positive for NTM in six patients. Three patients were clinically considered to be infected, and two received antimycobacteria drugs. Necrotizing pulmonary granulomas associated with granulomatous organizing pneumonia were found at autopsy in two patients, each of whom had multiple positive sputum cultures and clinical evidence of infection. In one of these, mycobacterial infection was considered to be an important factor in her terminal illness. Neither necrotizing granulomas nor granulomatous organizing pneumonia were seen in the lung tissue of patients whose antemortem cultures were negative for mycobacteria. There was no difference in the prevalence of other granuloma-like lesions between those with and those without positive sputum cultures.

No mycobacteria-related granulomas occurred in hilar lymph nodes, although histoplasma granulomas involved hilar lymph nodes of three patients.

The authors concluded that granulomatous mycobacterial lung disease is present in a minority of patients (two of six patients in this study) who have multiple positive cultures. Histologic evidence of infection was not found in patients who had only one of multiple sputum cultures positive for NTM.

 

1998 Torrens JK, Dawkins P, Conway SP, Moya E. Non-tuberculous mycobacteria in cystic fibrosis. Thorax 1998 Mar;53(3):182-5. [PubMed]

A retrospective case-control study was performed to assess possible risk factors for non-tuberculous mycobacteria and its impact on clinical status in patients with cystic fibrosis. The records of all patients attending the Leeds cystic fibrosis clinics who were positive for non-tuberculous mycobacteria were examined. Each case was matched with two controls for sex, age, and respiratory function at the time of the first non-tuberculous mycobacteria isolate. Details of respiratory function, nutritional status, antibiotic and corticosteroid therapy, Shwachman-Kulczycki (S-K) score, Northern chest radiographic score, and the frequency of isolation of other bacteria and fungi were collected from two years before to two years after the first non-tuberculous mycobacteria isolate. The patients' genotype and the presence of diabetes mellitus were also recorded.

Non-tuberculous mycobacteria were isolated from 14 patients out of a cystic fibrosis population of 372 (prevalence = 3.8%). No significant effect of non-tuberculous mycobacteria was seen on respiratory function, nutritional status, or S-K score. There was a significant association with the number of intravenous antibiotic courses received before the first isolate with cases receiving, on average, twice as many courses as controls (cases 6.64, controls 2.86, 95% CI for difference 1.7 to 5.9). No significant difference was seen between cases and controls for Northern scores, previous steroid therapy, or the incidence of diabetes mellitus. Non-tuberculous mycobacteria infection in patients with cystic fibrosis is uncommon and its clinical impact appears to be minimal over a two year period. Frequent intravenous antibiotic usage is a possible risk factor for colonisation with non-tuberculous mycobacteria.

 

*2003 Olivier KN, Weber DJ, Wallace RJ Jr, Faiz AR, Lee JH et al. Nontuberculous Mycobacteria in Cystic Fibrosis Study group. Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis. Am J Respir Crit Care 2003; 167:828-834.[PubMed]

Nontuberculous mycobacteria (NTM) are potential respiratory pathogens in cystic fibrosis (CF). To assess the species-specific prevalence and risk factors for acquisition, we conducted a prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Almost 10% of patients with CF who were 10 years or older were included (n = 986).

The overall prevalence of NTM in sputum was 13.0% (range by center, 7-24%). Mycobacterium avium complex (72%) and Mycobacterium abscessus (16%) were the most common species. When compared with patients with CF without NTM, culture-positive subjects were older (26 vs. 22 years, p < 0.001), had a higher FEV1 (60 vs. 54%, p < 0.01), higher frequency of Staphylococcus aureus (43 vs. 31%, p < 0.01), and lower frequency of Pseudomonas aeruginosa (71 vs. 82%, p < 0.01). Molecular typing revealed that almost all patients within each center had unique NTM strains.

The group showed that NTM are common in patients with CF, but neither person-to-person nor nosocomial acquisition explained the high prevalence. Older age was the most significant predictor for isolation of NTM. The clinical significance of NTM in CF is incompletely defined, but patients with these organisms should be monitored with repeat cultures.

 

*2003  Olivier KN, Weber DJ, Lee JH, Handler A, Tudor G, Molina PL et al; Nontunberculous Mycobacteria Study Group. Nontuberculous mycobacteria. II: nested-cohort study of impact on cystic fibrosis lung disease. Am J Respir Crit Care 2003; 167:835-840. 12433669[PubMed]

The prevalence of nontuberculous mycobacteria (NTM) is high (approximately 13%) in sputum of patients with cystic fibrosis (CF), but the impact on lung disease is unknown. We followed 60 incident NTM-positive and 99 culture-negative patients with CF for 15 months and assessed clinical impact of NTM by FEV1 and high-resolution computed tomography (HRCT) of the chest. Mycobacterium avium complex was seen in 75% of NTM-positive subjects. The annual rate of decline in FEV1 was not different among control versus NTM-positive subjects who did not, or did, meet American Thoracic Society microbiologic criteria for NTM disease (3 +/- 1, 3 +/- 2, and 5 +/- 2%, respectively). More subjects with three or more positive cultures for NTM had two or more characteristic findings on entry HRCT (60%, 9/15) as compared with subjects with two positive cultures or less (32%) or negative cultures (19%; p < 0.02). All subjects with three or more positive cultures and exit HRCTs (n = 6) showed progression of HRCT findings, whereas only 17% of subjects with two positive cultures or less had progression (p = 0.0006).

In summary, no significant short-term effect on FEV1 was detected in patients with multiple positive NTM cultures, but an abnormal HRCT was predictive of progression. Patients with CF and multiple positive NTM cultures, characteristic HRCT findings, and progression of HRCT changes should be monitored closely and considered for antimycobacterial therapy.

 

2009 Radhakrishnan DK, Yau Y, Corey M, Richardson S, Chedore P, Jamieson F, Dell SD. Non-tuberculous mycobacteria in children with cystic fibrosis: isolation, prevalence, and predictors. Pediatr Pulmonol 2009; 44:1100-1106. [PubMed]
Screening for non-tuberculous mycobacteria (NTM) is recommended for adults with cystic fibrosis. The relevance of this organism in North American pediatric CF patients is unclear as there is limited NTM prevalence data for children. 6.1% of 98 children at the hospital for Sick Children Toronto were positive for NTM - 2 M. abscessus and 4 M. avium - one with M. abscessus required treatment. As the NTM prevalence rate in children with CF is within the range previously reported in adults and there are no reliable clinical predictors for isolation, annual sputum screening is needed to identify NTM in children. The authors considered further research was needed to determine the best sputum decontamination method for NTM culture in pediatric patients.

This is a useful study from Toronto detailing the prevalence of NTM in their paediatric CF population - which they found to be similar to that in adults.

 

2009 van Ingen J, de Zwaan R, Dekhuijzen RP, Boeree MJ, van Soolingen D. Clinical relevance of Mycobacterium chelonae-abscessus group isolation in 95 patients. J Infect 2009; 59:324-331. [PubMed]

To determine the clinical relevance of Mycobacterium chelonae-abscessus group isolation from clinical samples the authors retrospectively reviewed medical files of all patients from whom these mycobacteria were isolated between January 1999 and January 2005. They applied the American Thoracic Society (ATS) diagnostic criteria to establish clinical relevance. Ninety-five patients were traced (56 M. chelonae, 25 Mycobacterium abscessus, 8 Mycobacterium massiliense, 6 Mycobacterium bolletii). Most isolates were cultured from pulmonary samples in patients with pre-existing pulmonary disease. Among patients with pulmonary isolates, 27% (20/74) meets ATS criteria; M. abscessus is most relevant (50%; 9/18), followed by M. massiliense (29%; 2/7), M. bolletii (20%; 1/5) and M. chelonae (18%; 8/44). Extrapulmonary disease presented as disseminated skin disease, eye disease specific for M. chelonae and otomastoiditis for M. abscessus. Treatment, especially for pulmonary M. abscessus disease, yielded limited results. One-fourth of the patients with pulmonary M. chelonae-abscessus group isolates met the ATS criteria; this percentage differs by species. Species distribution and clinical relevance differ from other regions.

M. abscessus isolation in cystic fibrosis patients warrants special attention. Current ATS criteria might be too lenient to diagnose M. chelonae-abscessus group disease.

There is increasing interest in NTM in CF. This survey gives an idea of the general prevalence of the various NTMs.

 

2009 Roux AL, Catherinot E, Ripoll F, Soismier N, Macheras E, Ravilly S, Bellis G, Vibet MA, Le Roux E, Lemonnier L, Gutierrez C, Vincent V, Fauroux B, Rottman M, Guillemot D, Gaillard JL, Jean-Louis Herrmann for the OMA Group. Multicenter study of prevalence of nontuberculous mycobacteria in patients with cystic fibrosis in France. J Clin Microbiol 2009; 47:4124-4128. [PubMed]
A multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%).

A useful large survey of NTM in France showing an overall prevalence of 6.6%.- very similar to previous reports.

 

2011 Renna M, Schaffner C, Brown K, Shang S, Tamayo MH, Hegyi K, Grimsey NJ, Cusens D, Coulter S, Cooper J, Bowden AR, Newton SM, Kampmann B, Helm J, Jones A, Haworth CS, Basaraba RJ, DeGroote MA, Ordway DJ, Rubinsztein DC, Floto RA. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. J Clin Invest 2011; 121:3554-63. [PubMed]
A recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). This study confirms that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identifies an underlying mechanism. In primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. The findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.

Autophagy = "the segregation of part of the cell's own protoplasmic material within an membrane and its digestion after fusion of the segregated vacuole with a lysosome". As many people with CF now receive long term azithromycin treatment further information on this association will be awaited with interest.

 

Subsequent information from the CF Patient Registry did not confirm a relationship between chronic azithromycin use and nontuberculous mycobacterial infection (Binder Am et al. Am J Resp Crit Car 2013 188:807-812.[PubMed]).

 

2012 Catherinot E, Roux AL, Vibet MA, Bellis G, Ravilly S, Lemonnier L, Le Roux E, Bernede-Bauduin C, Le Bourgeois M, Herrmann JL, Guillemot D, Gaillard JL, for the OMA group.  Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations.J Cyst Fibros 2012 Jul 31. [PubMed]

Clinical observations suggest that Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) may affect cystic fibrosis(CF)patients with different characteristics and risk factors, but this has never been demonstrated within a single prospective cohort. The authors studied 50 MABSC-positive and 23 MAC-positive patients from a French prevalence study of non-tuberculous mycobacteria (NTM) in CF. Risk factors specifically associated with MABSC and MAC were analyzed by nested case-control studies, with two NTM-negative controls matched by age, sex and center for each case.

MAC-positive patients were significantly older than MABSC-positive patients (mean [SD] age, 23.1 [10.2] vs 17.4 [8.3] years, p=0.013), and were also older at CF diagnosis (mean [SD] age, 12.9 [16.1] vs 3.1 [7.7] years, p=0.015); they tended to be less frequent of the ΔF508/ΔF508 genotype (33.3 vs 61.1%, p=0.17) and to use pancreatic extracts less frequently (82.4 vs 97.6%, p=0.07). Risk factors identified by multivariate analysis were: i) in the MAC case-control study, an older age at CF diagnosis (p=0.004); ii) in the MABSC case-control study, at least one course of intravenous antibiotics (p=0.01) and more frequent isolation of Aspergillus (p=0.03).MAC affects adult patients with a mild form of CF, whereas MABSC affects younger patients with more severe CF and more frequent intravenous antimicrobial treatment.

 

2012 Hill UG, Floto RA, Haworth CS. Non-tuberculous mycobacteria in cystic fibrosis. J R Soc Med 2012;105 (Suppl 2):S14-8. [PubMed]

An up to date review of the subject by Charlie Haworth of Papworth Hospital Cambridge. Overall rates of recovery were 3.7% to 24% depending on location and patient population - in USA overall prevalence 13% (7 - 24%) and in France 6.6% (3.7 - 9.6%).  M. avium complex and M. abscessus complex most frequently isolated. ATS guidelines were published in 2007 but were not specific for CF. (free download available from ATS website)

There follows a detailed review of diagnosis and treatment.

 

2015 Andres Floto R, Haworth CS. The growing threat of non-tuberculous mycobacteria in CF. J Cyst Fibros 2015; 14(1):1-2. Editorial. [PubMed]
The authors note the recent growing awareness of the threat of non-tuberculous mycobacteria (NTM) to individuals with cystic fibrosis (CF) and an increasing appreciation of the difficulties in screening, diagnosing and treating NTM-pulmonary infection in the context of CF lung disease. They provide a useful summary of the present situation.
There are two main groups of NTM that cause the majority of infections in individuals with CF: the Mycobacterium avium complex (MAC) consisting of M. avium, M. intracellulare and M. chimaera; and the M. abscessus complex (MABSC) made up of three subspecies, M. abscessus spp. abscessus, M. abscessus. spp. massiliense and M. abscessus spp. bolettii. While MAC is the more common infection in the US [PubMed], studies have suggested that MABSC is more frequent in Europe [PubMed] and elsewhere [PubMed]. Moreover, the rates of MABSC infection appear to be rising across the world [PubMed]; CFF Registry 2010]; a positive sputum culture for MABSC is more likely to indicate the presence of NTM-mediated lung damage (termed ‘NTM pulmonary disease’) rather than asymptomatic colonisation [PubMed]; and treatment of MABSC remains extremely difficult.
 

2015 Bar-On O; Mussaffi H; Mei-Zahav M; Prais D; Steuer G; Stafler P; Hananya S; Blau H.  Increasing nontuberculous mycobacteria infection in cystic fibrosis.   J Cyst Fibros 2015; 14(1):53-62.  [PubMed]
Patient records, 2002-2011, were reviewed for NTM infection. FEV1, pancreatic function, sputum microbiology, and serum cytokines were compared in patients with and without NTM infection.
The incidence of NTM infection increased from nil in 2002 to 8.7% in 2011 (p<0.001). NTM infection prevalence increased 3-fold from 5% (4/79) in 2003 to 14.5% (16/110) in 2011 (p=0.05).  NTM incidence and prevalence have increased dramatically in the CF clinic in the Graub CF Center in Israel, associated with a severe CF genotype and phenotype. M. abscessus, the most prevalent NTM, caused prolonged infection despite therapy. There has been some decrease in the prevalence of NTM lung disease since 2009.

 

- A useful record of longitudinal experience from a major clinic in Israel documenting the increasing problem of nontuberculous mycobacterial infection.

 


2015 Roux AL, Catherinot E, Soismier N, Heym B, Bellis G, Lemonnier L, Chiron R, Fauroux B, Le Bourgeois M, Munck A, Pin I, Sermet I, Gutierrez C, Véziris N, Jarlier V, Cambau E, Herrmann JL, Guillemot D, Gaillard JL; OMA group.  Comparing Mycobacterium massiliense and Mycobacterium abscessus lung infections in cystic fibrosis patients. J Cyst Fibros. 2015; 14(1):63-9. doi: 10.1016/j.jcf.2014.07.004. Epub 2014 Jul 30. [PubMed]

This data from a national French survey, show a particular link between M. massiliense and malnutrition specifically in CF patients. Unlike M. abscessus, the bacteriological response of M. massiliense to combination antibiotic therapies containing clarithromycin was excellent. Distinguishing between M. massiliense and M. abscessus has major clinical implications for CF patients.
Longitudinal registry study of 432 patients with cystic fibrosis contributing 53,771 lung function measures between 1974 and 2014. Infections with a significant impact on rate of decline in % FEV1 were Mycobacterium abscessus complex with -2.22% points per year (95% CI -3.21 to -1.23), Burkholderia cepacia complex -1.95% (95% CI -2.51 to -1.39), Achromobacter xylosoxidans -1.55% (95% CI -2.21 to -0.90), and Pseudomonas aeruginosa -0.95% (95% CI -1.24 to -0.66). Clearing M. abscessus complex was associated with a change to a slower decline, similar in magnitude to the pre-infection slope.
 


2015 Qvist T, Taylor-Robinson D, Waldmann E, Olesen HV, Hansen CR, Mathiesen IH, Høiby N, Katzenstein TL, Smyth RL, Diggle PJ, Pressler T.  Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis. J Cyst Fibros. 2015 Oct 5. pii: S1569-1993(15)00215-5. doi: 10.1016/j.jcf.2015.09.007. [Epub ahead of print]   [PubMed]

Longitudinal registry study of 432 patients with cystic fibrosis contributing 53,771 lung function measures between 1974 and 2014. Infections with a significant impact on rate of decline in % FEV1 were Mycobacterium abscessus complex with -2.22% points per year (95% CI -3.21 to -1.23), Burkholderia cepacia complex -1.95% (95% CI -2.51 to -1.39), Achromobacter xylosoxidans -1.55% (95% CI -2.21 to -0.90), and Pseudomonas aeruginosa -0.95% (95% CI -1.24 to -0.66). Clearing M. abscessus complex was associated with a change to a slower decline, similar in magnitude to the pre-infection slope.

 

- A helpful record of extensive experience over a considerable time from Copenhagen confirming the more serious consequences of M. abscessus.

 

2015 Qvist T, Gilljam M, Jönsson B, Taylor-Robinson D, Jensen-Fangel S, Wang M, Svahn A, Kötz K, Hansson L, Hollsing A, Hansen CR, Finstad PL, Pressler T, Høiby N, Katzenstein TL; Scandinavian Cystic Fibrosis Study Consortium (SCFSC).  Epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia.  J Cyst Fibros. 2015; 14(1):46-52. doi: 10.1016/j.jcf.2014.08.002. Epub 2014 Aug 30. [PubMed]
Data from Danish, Swedish and Norwegian CF centres between 2000 and 2012 identified 11% (157/1270) patients with at least one positive NTM culture during this period. Higher rates of NTM were detected in larger centres.

 



2015 Patil N, Marco A, Montales MT, Bhaskar N, Mittadodla P, Mukasa LN. Pulmonary Tuberculosis in a Patient with Cystic Fibrosis. N Am J Med Sci. 2015 May;7(5):233-5. doi: 10.4103/1947-2714.157494.  [PubMed]    Free PMC Article

A 24-year-old CF patient had fever, cough, hemoptysis, and weight loss of 1week duration prior to admission. Past sputum cultures grew methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The patient was treated with broad spectrum antibiotics based on previous culture data, but failed to improve. Chest radiograph and computed tomography (CT) chest revealed chronic collapse of the anterior sub segment of right upper lobe and multiple bilateral cavitary lesions which were worse compared to prior films. Mycobacterium tuberculosis (MTB) was suspected and was confirmed by positive acid-fast bacilli (AFB) smears and cultures. After receiving first-line anti-tuberculous drugs, the patient's condition markedly improved.
 
- MTB is an infrequent finding, but considered a potential pathogen in CF patients, and may lead to serious pulmonary complications if there is a delay in diagnosis and treatment. The same group from Arkansas report a 26 year old pregnant CF patient who had recurreent MTB infection (Marco A et al. Respir Med case Rep 2015; 16;57-9. [PubMed]).

 


Park IK; Olivier KN.  Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis. Respir Crit Care Med 2015; 36(2):217-24. 25826589  [PubMed]
Increasing numbers of CF and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two species of NTM account for up to 95% of the pulmonary NTM infections: Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). Diagnosis of pulmonary NTM infection is based on criteria specified in the 2007 American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines.
While many initial positive cultures do not progress to active NTM disease, even a single positive NTM sputum culture obtained from higher risk groups such as classic CF or older women with bronchiectasis and very low body mass index should be closely monitored for progressive disease.
Macrolides remain the most effective agents available against MAC and MABSC. Infection with MABSC may be associated with worse clinical outcomes, as more than half of MABSC isolates have inducible macrolide resistance conferred by an active erm(41) gene.
Of growing concern in CF is that MABSC is becoming more common than MAC, seems to target younger patients with classic CF, and is more difficult to manage, often requiring prolonged courses of intravenous antibiotics. Recurrence rates of NTM after initial successful treatment remain high, likely due to non-modifiable risk factors raising the question of whether secondary prophylaxis is feasible. More rapid and readily available methods for detecting inducible macrolide resistance and better in vitro susceptibility testing methods for other drugs that correlate with clinical responses are needed. This is crucial to identify more effective regimens of existing drugs and for development of novel drugs for NTM infection
 
- A timely article on an increasing problem in people with CF by experts in this area.