CF patients are afflicted by a vicious cycle of infection and inflammation of the airway due to decreased airway surface liquid volume and impaired mucociliary clearance . A small group of bacterial species colonizes the airway in CF, causing chronic infection . Understanding the prevalence and antimicrobial susceptibility pattern of these colonizing bacteria in the context of the country is important for the appropriate management of infection in CF patients. We aimed to study this pattern in the case of children with CF in Bangladesh.
Our study revealed that Pseudomonas aeruginosa is the predominant isolate from respiratory pathogens, and nearly three-quarters of children with CF were infected with a single microorganism. Among all the antimicrobial agents tested, levofloxacin was the most sensitive, and amoxicillin, erythromycin, and rifampicin were the most resistant. There was no association of outcome with species of bacteria isolated from the respiratory specimens.
We isolated P. aeruginosa and S. aureus in 36% and 16% of specimens, respectively. Our findings corroborate those of Kabir et al. , who conducted a large-scale clinico-epidemiologic study of CF children in Bangladesh and found a high prevalence of P. aeruginosa (27%). Nobandegani et al.  found a predominance of S. aureus isolates in 54% of specimens and found P. aeruginosa in 30% of specimens. Likewise, Valenza et al.  found a high prevalence of S. aureus (63.3%) and P. aerugisona (50%) in their participants. However, the latter two studies included both children and adults, and Santos et al.  previously found that P. aeruginosa and S. aureus were the most frequently found organisms in these two groups of patients. The use of antimicrobials might also affect the distribution of causative microbes in children with CF. Hauser et al.  noted that during the early half of the twentieth century in children with CF, when potent antistaphylococcal drugs were not available, S. aureus was the predominant isolate from respiratory pathogens and was subsequently replaced by P. aeruginosa with the development of potent antistaphylococcals.
Another noticeable observation in this study was the presence of K. pneumoniae, a gram-negative bacterium, in the respiratory specimens of our participants, which is usually associated with healthcare-acquired pneumonia and is not a typical pathogen of CF . However, the genetic flexibility of K. pneumoniae enables it to evade host immunity and colonize respiratory epithelia, which might have been the reason behind such a high prevalence in our study participants.
Antimicrobial sensitivity pattern analysis in the present study showed that some of the first-generation antimicrobials, such as amoxicillin, erythromycin, and rifampicin, were nearly completely resistant against different microorganisms isolated from children with CF. Alarmingly, the emergence of carbapenem resistance was evident from our analysis, and none of the imipenem and meropenem isolates were 100% sensitive against any organisms. A northern European study  among cystic fibrosis patients found the development of high resistance rates of P. aeruginosa against different antimicrobials, including carbapenems. Another study in Germany noted carbapenem resistance in both mucoid and nonmucoid P. aeruginosa . Frequent use of carbapenems as a broad-spectrum antibiotic in the hospital setting might lead to the development of high resistance rates to these drugs in children with CF. This is of concern, as the options of broad-spectrum antimicrobials are becoming narrower daily.
We noted high methicillin resistance among the staphylococcal isolates in our study, which conforms to the findings of previous studies . Even vancomycin was found to be highly resistant (87.5%) against S. aureus. Only fluoroquinolones such as levofloxacin, ciprofloxacin, and fourth-generation cephalosporine (cefepime) were found to be effective against these strains. All beta-lactam antibiotics were resistant to E. coli. Only levofloxacin and linezolid were effective against it.
Levofloxacin was the only drug found to be 100% sensitive against all species of bacteria found in respiratory specimens of children with CF. This, although good news for clinicians, necessitates judicial and cautious use of antibiotics in cystic fibrosis patients.
The present study did not find any association between bacterial species and the outcome of cystic fibrosis patients. However, studies  concerning microbial species and clinical outcome in cystic fibrosis are limited by the fact that any association, if found, does not imply causation, it is impossible to find a comparison group without microbial infection, and there is lack of antimicrobial specification because of polymicrobial infection of the patients.
Excessive use of antibiotics along with lack of patient compliance leads to rapid development of resistant strains, some of which are resistant to multiple drugs. Therefore, antibiotic guidelines should be updated regularly in light of continuously updated research findings for the context of a country. Here, we found that levofloxacin is the most sensitive drug that should be preserved for the most resistant cases. Additionally, specific antibiotics should be chosen for a specific set of bacteria according to the culture and sensitivity results of respiratory specimens in children with CF.
The limitations of our study include that it was a single-center study with a small number of patients. However, the strength of the study was to present the ongoing microbial diversity and antimicrobial sensitivity pattern in children with cystic fibrosis in Bangladesh.