Recent trends in late-onset neonatal sepsis have revealed an increase in Gram-negative organisms as causative agents. Ochrobactrum anthropi is an emerging human pathogen that has been reported primarily in immunocompromised hosts, especially those with indwelling catheters or other medical devices. We report the occurrence of late-onset urosepsis secondary to O. anthropi in a preterm neonate with posterior urethral valves and review the salient features of the pathogen and its management.
Late-onset neonatal sepsis is an important cause of morbidity and mortality in hospitalized newborns, and ongoing observation for epidemiological trends and emerging pathogens is warranted.1, 2, 3, 4 Ochrobactrum anthropi infections have been reported primarily in patients with immunosuppressive conditions: most notably as bacteremia associated with indwelling central venous or dialysis catheters, but also as endocarditis, osteomyelitis, wound infections, necrotizing fasciitis, endophthalmitis, peritonitis and pelvic abscess and meningitis.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15
Neonatal infections have been reported rarely and include one case of meningitis occurring as an episode of late-onset neonatal sepsis in a former 28-week premature female infant, and one of the bacteremia following placement of a peritoneal lavage catheter for meconium peritonitis.16, 17 We describe the first reported case of O. anthropi urosepsis in a preterm male infant with congenital urinary tract abnormalities and review the strategies for management of this emerging pathogen.
A male infant born at 30 3/7 weeks via cesarean delivery, secondary to a decreased amniotic fluid index, presented at birth for management of suspected posterior urethral valves. He was diagnosed with bladder and abdominal distention in utero, and bladder shunts were placed three times during gestation. Postnatal evaluation revealed ‘prune belly’ syndrome, right-sided hydronephrosis, bilateral hydroureter, bilateral vesicoureteral reflux (Grade V) with a large fluid-filled bladder and evolving respiratory distress syndrome and mild pulmonary hypoplasia requiring mechanical ventilation. His resuscitative course included intubation with surfactant delivery and was complicated by bilateral pneumothoraces ultimately requiring multiple chest tubes bilaterally. On neonatal intensive care unit admission, umbilical arterial and venous catheters were placed, blood and urine cultures were obtained, Foley catheter was placed and he started empirical intravenous ampicillin and cefotaxime. Third-generation cephalosporin was initiated rather than gentamicin, with consideration of existing renal abnormalities and potential for aminoglycoside nephrotoxicity, increased risk of Gram-negative infection with continuous indwelling Foley catheter and possible multifocal pneumonia with bilateral chest tubes in situ. High-frequency oscillatory ventilation and intermittent dopamine infusion for blood pressure support were required between days of life 3 and 7. Although blood and urine cultures were ultimately negative, antibiotics were given for 10 days for culture-negative sepsis with bilateral pneumonia.
Serial renal ultrasounds showed bilateral renal papillary necrosis and ureterectasis. Renal function was closely monitored; the patient's creatinine peaked at 1.47 mg dl−1 on day of life 6, but normalized over the next several days. The infant was weaned from the ventilator to room air on day of life 12. After completion of the intravenous antibiotic course, he began enteral amoxicillin for urinary tract infection prophylaxis.
On day of life 21, he developed episodes of apnea and bradycardia, a peripheral white blood cell count of 20.92 × 103 μl−1 with left shift and an elevated C-reactive protein of 6.2 mg dl−1. Blood and Foley catheter urine cultures were drawn, and he was empirically treated with IV vancomycin and cefotaxime. The following day, Gram-negative rods were isolated in both the blood and urine cultures. Vancomycin was discontinued and pipercillin–tazobactam was started empirically. Repeat catheterized urine culture obtained after 48 h of therapy was also positive for the Gram-negative organism. Cerebrospinal fluid studies and repeat blood cultures showed no growth, nor evidence of meningitis.
The organism was preliminarily identified from the blood culture by DNA sequencing as Ochrobactrum species. With species identification and antimicrobial susceptibility pending, but with persistently positive urine cultures, gentamicin was given with cefotaxime IV and pipercillin–tazobactam discontinued. Urine cultures also demonstrated Ochrobactrum species and remained positive until six days after initiation of antimicrobial therapy.
Throughout the ensuing week, the patient’s temperature was intermittently elevated, with fever of 100.7 °F recorded on two occasions. The bloodstream bacterial isolate was confirmed as O. anthropi by the Centers for Disease Control and Prevention, and on day of life 34 (antibiotic treatment day 13) antibiotic susceptibilities returned. The organism was fully susceptible only to amikacin, levofloxacin and meropenem, intermediately susceptible to gentamicin and resistant to all beta-lactams. The antibiotic regimen was accordingly changed to IV amikacin and meropenem.
The patient underwent surgical urethral dilation and transurethral resection of the posterior urethral valves on day of life 34. His Foley catheter was removed post procedure, and he subsequently required intermittent straight catheterization three times daily. Repeat blood and urine cultures obtained on day of life 36 and 37, respectively, were negative. He completed a total of 10 days of amikacin and meropenem, and was discharged from the hospital on day of life 60 in good condition.
O. anthropi, formerly CDC biotype group Vd ‘Achromobacter,’ has been identified as a pathogen in several case reports since first appearing in the literature in the 1980s.18 It is a non-lactose-fermenting, non-pigment-producing, oxidase-positive, urease-positive, Gram-negative rod that grows well on MacConkey agar.5, 18 It is a naturally occurring environmental organism found in water and soil, and has similarities to Pseudomonas spp. in its motility and obligate-aerobic growth.5 It also possesses adherence properties similar to Staphylococcal spp., which allows for survival on surfaces of medical devices such as catheters and prostheses.5, 19 It has been previously isolated from wound, throat, blood, urine, vaginal and stool samples and has been proposed as a component of normal human intestinal flora.6 O. anthropi has been identified as a nosocomial pathogen, but has also been documented as an environmental contaminant resulting in pseudobacteremia traced to its ability to colonize blood collection tubes with likely inoculation and contamination of the blood culture media at the time of venipuncture.20 These factors and the organism’s apparent low virulence make careful consideration of clinical correlation necessary when a positive blood or other body fluid culture is identified.
Despite its low virulence as a human pathogen, O. anthropi is notoriously antibiotic resistant and beta-lactams, aztreonam and chloramphenicol are typically ineffective, leaving carbapenems, aminoglycosides, fluoroquinolones or trimethoprim/sulfamethoxazole as treatment options.5, 6, 15 However, there have been reports of resistance to each of these antimicrobials, and some have recommended combination therapy and removal of indwelling infected hardware, especially in critically ill patients.5, 6, 7, 8 The optimal antimicrobial regimen and duration of therapy are unclear, however, and there are reported patients who have recovered clinically without antibiotics or with inappropriate antimicrobials based on susceptibility patterns, especially in cases where indwelling hardware is removed. In our case, the patient appeared to improve initially on inadequate therapy (intermediately susceptible gentamicin). However, fever recurred, and removal of the indwelling Foley and a fully susceptible antimicrobial regimen were required to successfully eradicate the infection.
The importance of multi-drug-resistant pathogens causing late-onset sepsis has been increasingly reported, as has the association of increased risk of necrotizing enterocolitis and mortality in premature infants exposed to prolonged empirical antibiotic courses.21 Whether the early course of antibiotics our patient received for culture-negative sepsis, and subsequent antibiotic prophylaxis regimen, affected the resistance pattern of the organism is unknown, but this treatment course may have facilitated a host environment favorable for nosocomial infection with a low-virulence, but multi-drug-resistant, organism such as O. anthropi. Other risk factors in this neonate include a history of placement of bladder shunts in utero, long-term in-dwelling Foley catheterization, umbilical venous catheterization and chest tube placement.
To our knowledge, this is the first reported case of O. anthropi urosepsis in a premature infant. The accumulating data suggest that infections with O. anthropi are opportunistic, frequently nosocomial and perhaps have increasing pathogenicity. This case highlights the increasing importance of multi-drug-resistant Gram-negative organisms including O. anthropi as causative pathogens of late-onset neonatal sepsis, and supports the rationale for judicious empirical antimicrobial use in premature infants. Necessary interventions in premature infants, which breach the immature skin barrier and the placement of indwelling hardware (intravenous access, chest tubes and Foley catheterization), pose risks that were likely associated with this neonate’s infection. In addition, the importance of device removal for eradication of O. anthropi is underscored. This case also emphasizes the principle that careful attention to antibiotic selection, specifically including avoidance of beta-lactams, is warranted when infection with O. anthropi is suspected.
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The authors declare no conflict of interest.
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Qasimyar, H., Hoffman, M. & Simonsen, K. Late-onset Ochrobactrum anthropi sepsis in a preterm neonate with congenital urinary tract abnormalities. J Perinatol 34, 489–491 (2014). https://doi.org/10.1038/jp.2014.31
- Ochrobactrum anthropi
- late-onset neonatal sepsis
- Gram-negative bacterial infections
- antimicrobial therapy
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