A Case of Pan-resistant Burkholderia cepacia Complex Sepsis ... : The Pediatric Infectious Disease Journal (2024)

To the Editors:

B urkholderia cepacia is a Gram-negative, catalase-producing, glucose-nonfermenting, obligately aerobic bacillus distributed widely in water, soil, fruits and vegetables.¹ In recent years, B. cepacia has emerged as an important opportunistic pathogen especially in patients with cystic fibrosis, lung transplantation or immunosupression.² It rarely causes sepsis in neonates in the absence of predisposing factors and can lead to life-threatening infections. Treating B. cepacia poses a challenge due to its intrinsic resistance to aminoglycosides and colistin and becomes even more so when pan resistance develops.³ In this report, we present a case of pan-resistant B. cepacia complex sepsis in a newborn successfully treated with a combination therapy. To the best of our knowledge, this is the first case of a newborn with pan-resistant B. cepacia sepsis that was successfully treated.

The female newborn was referred to our neonatal intensive care unit due to necrotizing enterocolitis (NEC) on the 22nd postnatal day. The newborn was born as a twin via in vitro fertilization during the first pregnancy of a 38-year-old mother, weighed 1240 g at birth and was delivered via cesarean section at 32 weeks. Vital signs were normal at the time of admission. The general condition of the patient was moderate to poor, she appeared icteric. Her capillary refill time was prolonged and her abdomen appeared distended. Given the agents of nosocomial sepsis and NEC, the treatment regimen was maintained with vancomycin and meropenem, and fluconazole was incorporated. Because of cholestasis, meropenem treatment was switched to ceftazidime and amikacin. On the 7th day of hospitalization, her overall condition worsened, accompanied by episodes of low oxygen saturation and apnea attacks. The patient was intubated. B. cepacia was grown in the blood culture. Because the B. cepacia strain exhibited pan resistance, ceftazidime treatment was administered via 3-hour infusion, with the addition of trimethoprim-sulfamethoxazole and ciprofloxacin to the regimen (Table 1). Pan-resistant B. cepacia continued to grow in the blood culture taken at the 72nd hour of treatment. The patient developed thrombocytopenia. Since the patient had NEC and suspicion of a fungal infection, micafungin was commenced. He underwent surgery for NEC and ostomy was performed. Owing to the worsening clinical condition, persistent growth of pan-resistant Burkholderia in the blood culture and regression of cholestasis, ceftazidime was halted, and meropenem infusion was commenced as per the treatment protocol. The patient’s blood culture was sterile on the 7th day of antibiotic therapy. Consequently, meropenem treatment was concluded after a 21-day course, along with ciprofloxacin and trimethoprim-sulfamethoxazole. The patient responded well to this combination therapy. The patient, with stable vitals, maintained normal temperature, achieved successful feeding and weight gain, was discharged on the 41st day of hospitalization.

Antimicrobial resistance remains a significant challenge in nosocomial infections. The emergence of pan-resistant microorganisms over time significantly complicates treatment options, posing formidable challenges for effective management. In this article, we present a case of a newborn infected with pan-resistant B. cepacia, which posed challenges in treatment.

B. cepacia is an opportunistic infectious agent commonly found in individuals with cystic fibrosis and chronic granulomatous disease and those who have undergone organ transplantation.²B. cepacia is an uncommon cause of sepsis in newborns. However, it may lead to infection in newborns, particularly in the presence of underlying risk factors such as prematurity, surgical interventions and instrumentation. The immature immune system due to prematurity and abdominal surgery for NEC in this patient are considered major factors contributing to the development of B. cepacia bacteremia.⁴

B. cepacia is a microorganism that poses significant challenges in treatment, due to its intrinsic resistance to aminoglycosides and colistin, which can be a potential problem to effective therapy.³ In a study conducted in India, 12 newborns with Burkholderia bloodstream infections were reported. All isolates were sensitive to meropenem and neonates were treated with piperacillin-tazobactam, ciprofloxacin and cotrimoxazole either singly or in combination.⁴ Studies indicate that Burkholderia can exhibit resistance to every antibiotic by up to 50%. This suggests a high prevalence of multidrug resistance among Burkholderia strains.^3,5 In a pediatric study from Turkey, B. cepacia exhibited resistance rates of over 90% to aminoglycosides, 78.2% to piperacillin-tazobactam, 70.8% to meropenem and 84.3% to ciprofloxacin. Additionally, 62.9% of this species was susceptible to trimetoprim-sulfamethoxazole (TMP-SMX), and 75% seemed to be susceptible to levofloxacin.⁶ In the report by Kim et al,⁷B. cepacia was 71.4% susceptible to TMP-SMX, 64.3% to ceftazidime, 50% to levofloxacin and 78.6% to meropenem. The Centers for Disease Control and Prevention recommends that treatment decisions should be made on a case-by-case basis, relying on in vitro antibiotic susceptibility data and clinical response. Antibiotic options generally recommended for the treatment of B. cepacia include singly or in combinations containing TMP-SMX, ciprofloxacin, carbapenem or ceftazidime.⁸ However, no recommendation could be found in the literature regarding the treatment of pan-resistant B. cepacia sepsis. Studies have demonstrated that combination antibiotic therapy with prolonged infusion is effective in eradicating bacteria and reducing mortality rates.⁹ It is reasonable to employ combination regimens with prolonged infusions to capitalize on antibiotic synergy in severe extensively drug-resistant and pan-drug-resistant infections.¹⁰ Therefore, we opted for a combination treatment consisting of meropenem administered via 3-hour infusion, along with ciprofloxacin and TMP-SMX. We achieved a successful response by the end of the treatment. This case represents the first instance in the literature where a newborn with pan-resistant B. cepacia sepsis was successfully treated.

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