A Case Series of Elizabethkingia Spp. Bacteremia in the Pediatric Population

Abstract

Elizabethkingia species are multi-drug resistant, Gram-negative bacteria that can adapt to different environmental conditions and rarely cause infections in humans but can be fatal among immunocompromised populations. We report our first experience of managing 2 pediatric patients infected with Elizabethkingia species. Over 12-months, 2 pediatric patients were infected with Elizabethkingia species in our hospital. They were both immunocompromised and were initially covered with broad spectrum antibiotics. Their conditions deteriorated and further investigations revealed the growth of Elizabethkingia species from the blood culture. Change of antibiotics was commenced and marked improvement was shown along the course of treatment. Both eventually completed the treatments and recovered remarkably well with no complications from the infections. However, colonization of the Elizabethkingia species was not identified on our environmental surveillance. Timely and appropriate anti-infectives and supportive management have shown marked improvement and disease curability in our patients who suffered from bacteremia and multiple liver abscesses.

Introduction

Elizabethkingia species are Gram-negative, rod-shaped bacteria widely available in nature. ¹ Humans can be exposed to Elizabethkingia species through contaminated medical equipment and water supplies. They commonly affect immunocompromised individuals and premature newborns and can even cause outbreaks in the hospital.^2,3 Common diagnoses associated with Elizabethkingia species include pneumonia, urinary tract infections, meningitis, bacteremia, with other unusual presentations such as septic arthritis, peritonitis, and abscess.^4,5 Elizabethkingia infection, has an estimated 50% mortality rate among the pediatric population, but survivors of the infection may face complications such as hydrocephalus, motor deficits, seizures, and hearing loss. ⁵

Elizabethkingia species, especially the virulent strains such as E. meningoseptica and E. anopheles, are not easily killed by antimicrobials. They possess extended spectrum β-lactamases, which make them resistant to most empirical antibiotics such as aminoglycosides, cephalosporins, and carbapenems. ² They were mostly reported to be susceptible to piperacillin, and fluoroquinolones and have variable sensitivity toward vancomycin, trimethoprim-sulfamethoxazole, and rifampicin. ⁶ The multi-drug resistance nature of the bacteria and the exceptionally high mortality rate possess a treatment quandary to the clinicians if not detected and treated timely.

In this case series, we report 2 pediatric cases involving Elizabethkingia bacteremia in immunocompromised patients in a district multi-specialty hospital in Malaysia.

Ethical Approval and Informed Consent

Written informed consents were obtained from the patients’ caretaker for the publication of this case series.

Case 1

A 2-and-a-half-year-old native girl was referred to us with 3 days history of fever, diarrhea, and passing out worms in her stools. According to the World Health Organization growth chart, she was identified as severely malnourished with both height and weight-for-age below third centile, corresponding to the 50th percentile of a 6-month-old child. She had no known chronic medical illness or allergy and had received all immunizations as per the national schedule. However, the child is living with only basic amenities and lacks access to safe tap water or basic sanitation.

On admission, intravenous fluid therapy was initiated for mild dehydration. She was also empirically started on intravenous ampicillin and metronidazole for her enterocolitis. Oral albendazole was given for deworming. Her stool, urine, and blood cultures had no growth of pathogens. On the seventh day of hospitalization, she developed a high-grade fever with massive, tender hepatomegaly but had no cardiorespiratory instability. Her white cell counts (38 × 10³/µL), eosinophil counts (6 × 10³/µL), and C-reactive proteins (80 mg/L) were markedly raised. An urgent abdominal ultrasound showed the presence of multiple hypoechoic lesions with internal echoes suggestive of non-liquefied abscesses at segment VIII and segment V of the liver as shown in Figure 1. There was also disseminated worm infestation within the bowel, liver, and biliary system. Her repeated peripheral blood culture grew Elizabethkingia meningoseptica, which was identified by the Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The disk diffusion method revealed that the bacteria is sensitive to vancomycin, trimethoprim-sulfamethoxazole, rifampicin, ciprofloxacin, and erythromycin. Antibiotics were escalated to intravenous imipenem/cilastatin in suspicion of possible disseminated melioidosis which was highly endemic in the area and intravenous trimethoprim-sulfamethoxazole was also added for treatment of her Elizabethkingia meningoseptica bacteremia. After 72 hours following this combination of antibiotic therapy, her blood culture showed clearance of the organism and there was also an improvement in her septic parameters: white cell counts (26 × 10³/µL), eosinophil counts (6 × 10³/µL), and C-reactive proteins (18 mg/L) with lower temperature spikes. A repeated ultrasound of the liver after a week of antibiotics showed liver abscesses at segment VIII and segment V which were liquefied. After consultation with the pediatric surgical team, percutaneous drainage of the liver abscesses with pigtail insertion was done under ultrasound guidance by the interventional radiologist. However, only minimal pus was drained during the procedure and the pigtail was removed after 72 hours. She remained afebrile after surgical drainage. The pus culture had no growth of any organism. She was treated with 6 weeks of intravenous imipenem/cilastatin. On the other hand, intravenous trimethoprim-sulfamethoxazole was changed to oral therapy after a week to continue for 2 months.

Figure 1.

Ultrasound abdomen of case 1 suggestive of non-liquefied liver abscess at segment VII and VIII.

She was followed up at our pediatric clinic after completion of antibiotics. She remained well with good weight gain. Her weight had improved to achieve 10th centile for her age. Her repeated ultrasound abdomen showed resolving liver lesions with calcifications as shown in Figure 2. Mycobacterium tuberculosis culture of the pus and serum melioidosis serology were otherwise negative.

Figure 2.

Ultrasound abdomen of case 1 with improved liver collections and resolving liver lesions.

Case 2

A newborn premature baby girl was born by spontaneous vaginal delivery at the post-conceptional age of 27 weeks 1 day, with an extremely low body weight of 870 g. She was apneic and bradycardic at birth, rendering her to be intubated at 5 minutes of life due to poor respiratory effort. Subsequently, she was admitted to the neonatal intensive care unit. She had severe respiratory distress syndrome requiring ventilation with high-frequency oscillatory ventilation and received 2 doses of intratracheal beractant. Her umbilical artery and vein were cannulated at birth. She was also empirically covered with intravenous benzylpenicillin and gentamicin for presumed neonatal sepsis. Total parenteral nutrition was also commenced at 2 hours of life via the umbilical vein catheter.

On her fourth day of life, she developed nosocomial pneumonia evidenced by frequent desaturation with worsening alveolar infiltrates on her chest X-ray. The antibiotics were escalated to intravenous ceftazidime and amikacin. Despite this, she continued to develop leukocytosis with a white blood cell count of 42 × 10³/µL and thrombocytopenia with a platelet count of 45 × 10³/µL on the sixth day of life. Her C-reactive protein was raised at 17 mg/dL. Peripheral blood culture isolated a Gram-negative bacteria identified as Elizabethkingia anopheles by MALDI-TOF MS, which was sensitive to vancomycin, trimethoprim-sulfamethoxazole, rifampicin, and ciprofloxacin based on the disk diffusion method. The cerebrospinal fluid analysis was not suggestive of meningitis and culture was negative. Bedside cranial ultrasound showed left grade 1 intraventricular hemorrhage without any ventriculomegaly. She was commenced on a combination of intravenous vancomycin and ciprofloxacin.

Peripheral blood culture was repeated after 48 hours of treatment. However, there was persistent growth of the same organism with no improvement in her blood counts. Hence, the decision was made to withhold her total parenteral nutrition and remove both umbilical catheters. A pediatric infectious disease specialist was consulted, and the antibiotics were revised to a combination of intravenous vancomycin and oral rifampicin. Subsequent blood culture at 72 hours after removing the umbilical catheters was sterile, normalizing her platelet and white cell counts. Her c-reactive protein had also reduced to 3 mg/dL. Both intravenous vancomycin and oral rifampicin were continued for a total of 2 weeks.

She was successfully extubated on her 10th day of life but had moderate bronchopulmonary dysplasia. She had bilateral stage 1 retinopathy of prematurity and her cranial ultrasound prior to discharge was normal. She was discharged home on day 115 of life and continued to follow up at our pediatric clinic.

Case Discussion

Over the past few decades, 32 cases associated with Elizabethkingia species infections were reported in Malaysia, and E. meningoseptica was found to be the culprit of all these reports. ⁷ Despite the potential misidentification of the pathogens from earlier publications, ⁸ our findings indicate that this may be the first published E. anopheles human infection in Malaysia and the first Elizabethkingia bacteremia in pediatric patient complicated with liver abscess.

In clinical settings, these primarily opportunistic pathogens normally infect neonates and immunocompromised patients. ⁷ This is in line with our findings. The first patient is a native girl with severe malnutrition while the second patient is a premature baby girl with extremely low birth weight. Both were initially treated for diagnoses unlikely to be associated with Elizabethkingia infections, but their clinical presentations and septic parameters deteriorated after short-term hospital stays, suggestive of nosocomial infections.

We escalated the antimicrobial therapy to empirically cover common hospital-acquired infections using third generation cephalosporins and even carbapenem. However, despite the excellent coverage, our patients showed no significant clinical or biochemical improvement. The blood culture and sensitivity results elucidated the impediment to treatment success. E. meningoseptica and E. anopheles were isolated respectively, justifying the poor response to the aggressive antimicrobials.

In the first case, biliary stasis due to parasitic infection may lead to abscess formation from the hematogenous spread of Elizabethkingia. Although liver involvement is rare, cases of multi-organ abscesses and deep-seated infection were reported. ⁶ The negative melioidosis serology and failure to incubate Burkholderia species in the cultures negates the possibility of disseminated melioidosis.

The resistance pattern in our patients was reported to be almost similar to the published literature. ⁷ Although previously published cases mostly used piperacillin-tazobactam with fluoroquinolones to treat Elizabethkingia infections,^1,2 we decided to use trimethoprim-sulfamethoxazole and vancomycin as the mainstream treatment. This is because sensitivity toward piperacillin-tazobactam was not reported in both blood culture reports. Besides, fluoroquinolone use is inappropriate in our patients due to the correlation with the emergence of bacterial resistance and possible adverse musculoskeletal effects in the pediatric population. ⁹ Trimethoprim-sulfamethoxazole was not considered in the second patient due to the potential risk of myelosuppression, hyperbilirubinemia, and kernicterus among neonates. ¹⁰ Thus, we employed a combination of vancomycin with rifampicin as vancomycin alone was not recommended especially in complicated cases.^1,2

Apart from that, we took preventive measures including thorough disinfection of the wards, isolation of the patients, strict adherence to hand hygiene practice, and mandatory wearing of personal protective equipment before examination to prevent the outbreaks of Elizabethkingia infections.^8,11 Nevertheless, we were unable to identify the source of the nosocomial infection in both cases as the environmental surveillance returned negative.

Despite the reported high mortality of the infection, our patients with Elizabethkingia infections achieved complete eradication of bacteremia with no significant adverse events. They progressed well to full recovery and were still attending our outpatient clinic for follow-up. Primary immunodeficiency workup was not done for the native girl with this rare infection as this was her first hospitalization associated with infection and she responded well with the treatment and did not present with any recurrent infections. The success of treatment was attributed to the accurate and rapid identification of the causative pathogens, expeditious decisions to change the antibiotics to definitive treatment, and the removal of the source of infections through aspiration of pus and catheter removal.

Conclusion

Elizabethkingia species should be at suspicion of infection which fails to improve with usual broad-spectrum antibiotics in immunocompromised children. Definitive treatment with antibiotics such as vancomycin, trimethoprim-sulfamethoxazole, and rifampicin, and removal of source of infections are important to ensure success in the treatment of Elizabethkingia infection in children. Infection control measures are crucial to prevent the spread of the bacterium.