Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease among people of European heritage [30]. In the United States, about 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, about 4000 people have CF [31]. Around 1 in 25 people of European descent, and one in 30 of Caucasian Americans [32], is a carrier of a CF mutation. Although CF is less common in these groups, roughly one in 46 Hispanics, one in 65 Africans, and one in 90 Asians carry at least one abnormal CFTR gene [33, 34]. Ireland has the world’s highest prevalence of CF, at one in 1353 [35].
CF is a common genetic disease. Due to this condition, mucosal secretions in the lung can cause recurrence and persistent respiratory infections. A number of opportunistic pathogens settle in these patients. In most cases, in chronic infections, Pseudomonas, Burkholderia, as well as Pandoraea spp. have been isolated from the lung of CF patients, which play role in emerging pathogenesis. Pandoraea spp. are considered emerging pathogens in the context of CF and are difficult to identify by conventional biochemical methods. Most Pandoraea spp. are present in the lung of CF patients, lung infections, and oral and dental infections. According to the studies conducted to data on patients with CF and lung infection diseases, opportunistic pathogens that have been involved in causing diseases including Pseudomonas, Burkholderia and Pandoraea species, have been isolated and identified [29, 36,37,38].
One group of bacteria currently considered to be emerging CF pathogens belongs to the genus Pandoraea. The genus Pandoraea was described by Coenye et al. (2000) to differentiate them from other already well-known CF pathogens, including Pseudomonas and two closely related Gram-negative rods, Burkholderia and Ralstonia species. In fact, phenotypic methods used by many microbiology laboratories commonly lead to the misidentification of Pandoraea species as either Burkholderia or Ralstonia species [2, 4].
Pandoraea infection led to the production of high levels of antibodies, and to a worsened CF lung disease [4, 10, 39]. After first colonization, Pandoraea spp. were able to chronically colonize the CF respiratory tract (CFRT) [10, 40,41,42], were transmissible between patients [4, 37] and can produce severe lung diseases and bacteremia [12, 43]. The pathogenicity appears mainly supported by a pro-inflammatory response induction significantly greater than with P. aeruginosa [19, 44] and the treatment may be complicated by multidrug resistance conferred by carbapenem hydrolyzing oxacillinases [19]. The potential involvement of Pandoraea in complex interactions between microorganisms within the CF airways was also suggested [44].
In current study from 31 samples of bronchoalveolar lavage and sputum, by culture method eight Pandoraea bacteria were isolated and identified. These bacteria were isolated and purified using conventional diagnostic methods such as culture and biochemical tests. But finally by PCR assay just 4 isolates confirmed as Pandoraea. Also, in addition to Pandoraea spp. other bacteria including Staphylococcus, Pseudomonas, Neisseria flavorans, Delftia acidovorans and Klebsiella were also isolated.
In 2001, Coenye et al. identified and investigated species of Pandoraea bacteria. In this study, from 123 samples, Pandoraea (69), Burkholderia (30), Ralstonia (9) and Pseudomonas aeruginosa (5) were isolated and identified. For the first time, PCR testing was performed to identify the member of genus Pandoraea, which were able to detect P. apista, P. pnomenusa, P. sputorum, P. pulmonicola and P. norimbergensis [26].
Daneshvar and colleagues in 2001 examined the cellular effects of Pandoraea spp. on lung cells in CF patients. The study also found that it was possible to isolate the Pandoraea from the cultures of patient’s blood who did not have cystic fibrosis [2].
In the study of Spreet et al., conducted in Canada in 2002, from a total of 447 CF patients in 8 provinces included 5 Pandoraea (1.1%), 412 Burkholderia (92.6%) and 5 Ralstonia (1.1%) bacteria, using culture techniques, biochemical tests and molecular techniques including PFGE, RAPD and RFLP were identified and isolated [45].
In 2003, Jorgensen et al., examined the epidemic of P. apista in patients with cystic fibrosis. According to the results of this study, it has been shown that P. apista should be added to the ever increasing list of pathogens that can cause chronic lung infections in CF patients [43].
In 2008, Karher et al. examined the pathogenic and genetic characteristics of Pandoraea species in lung epithelial cells. In this study, 17 Pandoraea bacteria were isolated including 5 species: P. apista, P. pnomenusa, P. sputorum, P. pulmonicola and P. norimbergensis [38].
In a study conducted by Panickar and David (2015) from October 2012 to September 2014 on outpatient, and lavage samples from 182 CF children treated at the Royal Manchester Hospital, 5(3%) were Burkholderia, 17(19%) Exophiala, 32(18) Achromobacter and 32 (18%) Rhodotorula, 18 (10%) Achromobacter, 1 Ralstonia and 6 (3%) Pandoraea were identified. This study showed that the number of Pandoraea and Achromobacter bacteria in CF children is increasing [39].
Antibiotic treatment of infections caused by Pandoraea species is difficult because it has been demonstrated resistant against a wide range of antibiotics such as ampicillin, cefazolin, piperacillin, azithroman, broad- spectrum cephalosporins and aminoglycosides, and show a different response to quinolones, trimethoprim-sulfumethoxazole, colistin and carbapenems. Pandoraea species are resistant to most antibiotics, including beta-lactams and aminoglycosides. The bacteria in the subjects evaluated moderate sensitivity to imipenem, doxycycline and ceftriaxone, and an unusual antibiotic susceptibility pattern to carbapenem was also found in Pandoraea bacteria and resistance to meropenem and sensitivity to imipenem has been reported.
The result shows that for antibiotic treatment of Pandoraea infection, antibiogram test for each person has been done individually. Then if a person is allergic to imipenem they can use carbapenem. All Pandoraea species except P. apista, G9278 are resistant to amikacin and cefazolin antibiotics, most of which are resistant to broad-spectrum cephalosporins, azithroman and piperacillin. Also, these organisms are resistant to aminoglycosides such as gentamicin, tobramycin and amikacin, but their susceptibility to fluroquinolones is different [40].
Puges et al. (2015), reported that P. sputorum was susceptible to imipenem and resistant to meropenem. This discrepancy has already been described by several authors and is because of meropenem-hydrolyzing β-lactamases. Some strains are resistant to both imipenem and meropenem, and an imipenem-hydrolyzing oxacillinase named OXA-62 has been identified in P. pnomenusa [45].
In this study susceptibility to antibiotics was detected using 5 antibiotics including amikacin, ciprofloxacin, trimethoprim-sulfumethoxazole, gentamicin and piperacillin. Antibiotic susceptibility test were indicated all isolates were resistant to gentamicin, imipenem and amikacin and susceptible to ciprofloxacin, trimethoprim-sulfumethoxazole, tetracycline and piperacillin.
Biofilms are microbial society encased in extracellular polymeric substances (EPS) [18]. Biofilm formation symbolizes a protective mode of growth that allows microorganisms to survive in hostile environments [46]. Biofilm is responsible for persistent in chronic infections, due to their inherent resistance to antimicrobial agents. Biofilms are shown as being resistant to killing by a broad range of antimicrobial agents [47]. Some bacteria such as P. aeruginosa secrete the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease [48]. Biofilm production has been considered to be an important determinant of pathogenicity in most infections. In this study all 3 evaluated isolates showed strong biofilm formation ability.