Streptococcus pneumoniae and chronic endobronchial infections in childhood

Abstract

Streptococcus pneumoniae (pneumococcus) is the main cause of bacterial pneumonia worldwide and has been studied extensively in this context. However, its role in chronic endobronchial infections and accompanying lower airway neutrophilic infiltration has received little attention. Severe and recurrent pneumonia are risk factors for chronic suppurative lung disease (CSLD) and bronchiectasis; the latter causes considerable morbidity and, in some populations, premature death in children and adults. Protracted bacterial bronchitis (PBB) is another chronic endobronchial infection associated with substantial morbidity. In some children, PBB may progress to bronchiectasis. Although nontypeable Haemophilus influenzae is the main pathogen in PBB, CSLD and bronchiectasis, pneumococci are isolated commonly from the lower airways of children with these diagnoses. Here we review what is known currently about pneumococci in PBB, CSLD and bronchiectasis, including the importance of pneumococcal nasopharyngeal colonization and how persistence in the lower airways may contribute to the pathogenesis of these chronic pulmonary disorders. Antibiotic treatments, particularly long-term azithromycin therapy, are discussed together with antibiotic resistance and the impact of pneumococcal conjugate vaccines. Important areas requiring further investigation are identified, including immune responses associated with pneumococcal lower airway infection, alone and in combination with other respiratory pathogens, and microarray serotyping to improve detection of carriage and infection by multiple serotypes. Genome wide association studies of pneumococci from the upper and lower airways will help identify virulence and resistance determinants, including potential therapeutic targets and vaccine antigens to treat and prevent endobronchial infections. Much work is needed, but the benefits will be substantial.

Antibiotic-tolerant persisters are pervasive among clinical Streptococcus pneumoniae isolates and show strong condition-dependence

“…pneumoniae causes, to a lesser extent, also recurrent and chronic infections (41,42,45,65). After mathematical analyses of the killing data of S. pneumoniae D39, we detected a biphasic killing pattern, which indicates the presence of persister cells.…”

“…S. pneumoniae is well-known to cause acute infections while antibiotic tolerance and persistence are mostly connected with recurrent and chronic infections (2, 7). Nonetheless, we expected to find persister cells as persistence is identified in many, if not all, bacterial species that were studied and S. pneumoniae causes, to a lesser extent, also recurrent and chronic infections (41, 42, 45, 65). After mathematical analyses of the killing data of S. pneumoniae D39, we detected a biphasic killing pattern, which indicates the presence of persister cells.…”

“…Antibiotic-tolerant persisters are mostly connected with recurrent and chronic infections and the role of persisters in acute infections is not clear (7,18). Nonetheless, S. pneumoniae is also, albeit to a lesser extent, the causative agent of chronic diseases, like chronic endobronchial infections in children (40)(41)(42) and it can reside in biofilms in the middle ear of children causing recurrent and chronic otitis media (43)(44)(45)(46). The role of persister cells, both in acute and chronic pneumococcal infections, needs to be elucidated in order to gain a better understanding in how S. pneumoniae evades elimination by antibiotic treatment (7,18,47).…”

Antimicrobial Resistance in Common Respiratory Pathogens of Chronic Bronchiectasis Patients: A Literature Review

“…Other gram-negative organisms isolated from patients with bronchiectasis include: Stenotrophomonas maltophilia [48], Klebsiella pneumonia [49], Moraxella catarrhalis [50], Achromobacter [51], Serratia marcescens [52], and Escherichia coli [53]. Instead, Staphylococcus aureus [54] and Streptococcus pneumoniae are gram-positive organisms most frequently seen in bronchiectasis patients [52,55,56].…”

Pediatric Pulmonology year in review 2017: Part 3

“…When the wet cough does not improve following 4 weeks of antibiotic treatment, there is moderate‐quality evidence that further investigations should be considered to look for an underlying disease. In a State of the Art review, Hare et al pointed out that while non‐typeable Haemophilus influenzae is the most common bacterial pathogen in children with chronic suppurative lung diseases (including non‐CF bronchiectasis and PBB), Streptococcus pneumoniae and M. catarrhalis are also common. For S. pneumoniae , azithromycin‐resistant strains are becoming more common; the relationship between vaccination against S. pneumoniae and risk for chronic lower respiratory disease needs further investigation.…”