Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients

Abstract

Pseudomonas aeruginosa and Staphylococcus aureus are thought to cause the majority of lung infections in patients with cystic fibrosis (CF). However, other bacterial pathogens may contribute to the pathophysiology of lung disease. Here, obligate anaerobes were identified in a cross-sectional study, and cell numbers and antibiotic susceptibilities of facultative and obligate anaerobes from 114 sputum samples from nine children and 36 adults with CF were determined. Furthermore, in 12 CF patients, we investigated whether conventional intravenous antibiotic therapy, administered during acute exacerbations, would affect the numbers of obligate anaerobes. Fifteen genera of obligate anaerobes were identified in 91% of the CF patients. Cell numbers (mean: 2.2 x 10(7) +/- standard deviation 6.9 x 10(7) CFU/mL of sputum sample) were comparable to those of P. aeruginosa and S. aureus. Staphylococcus saccharolyticus and Peptostreptococcus prevotii were most prevalent. Infection with P. aeruginosa did not increase the likelihood that obligate anaerobes are present in sputum specimens. Single obligate anaerobic species persisted for up to 11 months in sputum plugs in vivo. Patients with and without obligate anaerobes in sputum specimens did not differ in lung function. Intravenous therapy directed against P. aeruginosa during acute exacerbations increased lung function, but did not reduce the numbers of obligate anaerobes. Obligate anaerobic species differed widely in their patterns of resistance against meropenem, piperacillin-tazobactam, clindamycin, metronidazole and ceftazidime. In 58% of patients with acute exacerbations, obligate anaerobes were detected that were resistant to the antibiotics used for treatment. Antibiotic therapy, optimized to target anaerobes in addition to P. aeruginosa, may improve the management of CF lung disease.

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

“…However, fermentative signals observed from CF samples were not likely from saliva contamination, because the characteristic gas bubble formation was only present during exacerbation and never at times of stability even though sampling procedures were identical. Oral bacteria have been detected before in the upper airways and sputum of CF patients (Tunney et al, 2008;Worlitzsch et al, 2009;Goddard et al, 2012;Willner et al, 2012), and our results indicate that they colonize lung mucus and may contribute significantly to exacerbations. However, it cannot be known whether these bacteria drive exacerbation onset or whether their growth is favored during the conditions of an exacerbating CF lung.…”

“…This treatment strategy is inherently biased towards aerobic microbes that grow on media selected by clinical microbiologists (Burns and Rolain, 2014). There is growing evidence that CF microbes survive in a low oxygen environment and many grow anaerobically deep in the mucus plugs of CF lungs (Worlitzsch et al, 2002(Worlitzsch et al, , 2009Bjarnsholt et al, 2009;Lipuma, 2010). Thus conventional culture on microbiological media misses important components of the CF microbial community that may contribute to exacerbations and provides antibiotic resistance profiles from microbes not grown in a state in which they cause disease.…”

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth

“…Many typical cystic fibrosis pathogens, including Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa, are facultative anaerobes [3]. Recent advances in metagenomic analysis of the lung microbiome have further revealed a major presence of obligate anaerobic species in cystic fibrosis airways [4,5], but the clinical relevance of these species in cystic fibrosis lung disease is still unclear.…”

The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway

“…Studies exploring the role of anaerobes have failed to show a direct impact on airway function in CF (7,8). However, more recent studies have associated decreasing CF airway microbial diversity, to which anaerobic bacteria contribute, with poorer lung function (9)(10)(11).…”

“…Anaerobic bacteria are present in the airways of 66-91% people with CF (PWCF) (7,8) in numbers equal to those of P. aeruginosa, a well-established pathogen in the CF airways (3,7). Studies exploring the role of anaerobes have failed to show a direct impact on airway function in CF (7,8).…”