Abstract
Stenotrophomonas maltophilia, an environmentally ubiquitous microbe, is a challenging opportunistic pathogen in the hospital setting. Neonates are particularly vulnerable to infection with Stenotrophomonas but information on presentation, therapeutic response and outcome of such infection in this population is limited. To expand this knowledge, we report here a series of five cases. All the five neonates having S. maltophilia sepsis, were preterms (27–32 weeks), very low birth weight, with clinical presentation within three weeks of life, with respiratory involvement presenting as respiratory distress due to pulmonary haemorrhage, non-specific features like lethargy, altered blood sugar levels and haemodynamic instability. The microbe was sensitive to amikacin, ceftazidime, cotrimoxazole, gentamycin, levofloxacin and minocycline except in two cases showing levofloxacin resistance. All but one neonate survived with morbidities like retinopathy of prematurity, bronchopulmonary dysplasia and metabolic bone disease.
Keywords: Stenotrophomonas maltophilia, Neonatal infection, Neonatal sepsis
Introduction
Stenotrophomonas maltophilia, the sole member of its genus and previously in the Pseudomonas and Xanthomonas genera, is an opportunistic environmental pathogen1 of serious concern among the immunocompromised, including neonates, in whom a compromised cytokine response to the microbe leads to high mortality.2 To expand our limited knowledge on the presentation, therapeutic response, and outcome of this infection in neonates, we present a series of the five neonatal cases who were infected with Stenotrophomonas while in the neonatal intensive care unit (NICU) of an academic medical centre in year 2021 (Fig. 1).
Fig. 1.
Clinical timelines of the cases in the series. BPD, bronchopulmonary dysplasia; b/l, bilateral; CPAP, continuous positive airway pressure; CRP, C reactive protein; F, female; g, grams at birth; IVH, intra-ventricular haemorrhage; M, male; MBD, metabolic bone disease; PDA, patent ductus arteriosus; PLT, platelet count; ROP, retinopathy of prematurity; TLC, total leucocyte count; VAE, ventilator-associated event; w, weeks of gestation.
Case report
Case 1
A 28 weeks male baby, weighing 1085 g, born by caesarean, with no maternal risk factors for sepsis, had respiratory distress at birth and required mechanical ventilation, surfactant, and paracetamol for haemodynamically significant patent ductus arteriosus (hsPDA). His respiratory status worsened on day 3 with haemodynamic instability, pulmonary haemorrhage, and thrombocytopaenia. The baby was provided with colistin, meropenem, vasopressors, blood components, immunoglobulin and high-frequency ventilation. Blood culture grew levofloxacin-sensitive S. maltophilia and the antibiotic was administered. Grade III intraventricular haemorrhage (IVH), cerebellar haemorrhage and death occurred over the next three days.
Case 2
A 27 weeks male baby, weighing 1120 g, born by caesarean for placental disruption, required mechanical ventilation, surfactant and paracetamol for hsPDA. On day 5, he had worsening respiratory status, shock and pulmonary haemorrhage and was given colistin, meropenem, vasopressors, immunoglobulin and high-frequency ventilation. Levofloxacin was given in view of case 1's Stenotrophomonas diagnosis two days earlier. The baby responded to the management, and his blood culture grew Stenotrophomonas sensitive to ceftazidime, cotrimoxazole and levofloxacin. He subsequently developed bronchopulmonary dysplasia (BPD), hypophosphatemic metabolic bone disease (MBD) and retinopathy of prematurity (ROP). Despite anti-VEGF therapy and laser and surgical interventions, led to poor vision. The baby was accepting breastfeeds and was discharged.
Case 3
A 32 weeks female baby, weighing 975 g, was born vaginally, with no maternal history suggestive of sepsis, required non-invasive respiratory support, surfactant and paracetamol for hsPDA. On day 7, decreased activity with abdominal distension and feed intolerance were noticed. As respiratory status worsened and sepsis markers were positive, baby received colistin, meropenem and immunoglobulin besides supportive care. With blood culture positive for Stenotrophomonas sensitive to ceftazidime, cotrimoxazole and minocycline, but resistant to levofloxacin, she was given minocycline and ceftazidime. With persistent bacteraemia and no clinical improvement, intravenous cotrimoxazole was added. This led to bacterial clearance and improvement. She developed stage 1 ROP and BPD with pulmonary hypertension that required sildenafil. She had a humerus fracture attributed to hypophosphatemic MBD, which required splinting. The baby was accepting breastfeeds and was discharged.
Case 4
A 27 weeks, male baby, weighing 815 g, born vaginally spontaneously, was referred to this hospital after initial resuscitation. He required mechanical ventilation, surfactant and paracetamol for hsPDA. He had apnoea with hyperglycemia on day 7 followed by respiratory worsening and was stabilized with colistin, meropenem, vasopressors, immunoglobulin, blood components and mechanical ventilation. Blood culture grew levofloxacin-sensitive Stenotrophomonas and the antibiotic was administered. The baby improved and was weaned off support, but developed BPD, hypophosphatemic MBD and stage 2 ROP. The baby was accepting breastfeeds and was discharged.
Case 5
A 30 weeks, male baby, weighing 1265 g, born by caesarian, for maternal indication, required non-invasive respiratory support, surfactant and antibiotics at birth. On day 18, his respiratory distress worsened with infiltrates in chest radiograph. Blood culture grew Stenotrophomonas sensitive to amikacin and levofloxacin. Levofloxacin was started but amikacin was added in view of persistent bacteraemia. The baby improved and was weaned off support but developed BPD, hypophosphatemic MBD, and grade II IVH. The baby was accepting breastfeeds and was discharged (Fig. 1). All participants had given informed written consent regarding their participation.
Discussion and conclusion
Diagnosis of Stenotrophomonas infection is confirmed by bacterial growth in cultures of body fluids such as blood, eye discharge and tracheal secretion. During The study of one-year period, blood cultures of 10% of blood samples from patients with suspected sepsis in this NICU grew S. maltophilia, similar to another study.2 None of these five cases were positive for the pathogen in cultures of cerebrospinal fluid, urine or tracheal secretion, though it is identifiable in tracheal secretions of 20% of ventilator-associated pneumonia (VAP) cases.3 All neonates are vulnerable to Stenotrophomonas, but premature ones are at a greater risk,4 as also seen in our series. Our cases also had exposure to broad spectrum antibiotics, central lines and parenteral nutrition, which, besides prolonged hospitalization and use of histamine H2 receptor blockers and steroids, increase the risk of Stenotrophomonas infection.2,4 The broad spectrum antibiotics usage was on the basis of antibiogram of the unit showing multidrug resistant gram negative bacteria.
Neonates with Stenotrophomonas infection can present with conjunctivitis, VAP, meningitis or sepsis.2,5 Our cases had respiratory involvement (two with pulmonary haemorrhage) and four had haemodynamic instability during the bacteraemia. Though all cases had respiratory involvement, we did not notice any unique presentation of S. maltophilia sepsis against the other cases of neonatal sepsis in our NICU during the study period. The cases received levofloxacin following diagnosis and testing of the Stenotrophomonas cultures that showed susceptibility to amikacin, cotrimoxazole, gentamycin, levofloxacin and/or minocycline (Table 1). One case had persistence of the pathogen in repeated blood cultures after five days of levofloxacin, and the addition of amikacin led to clinical improvement. In another case, the addition of cotrimoxazole led to improvement after two weeks, as documented by others.3,6 Early-onset Stenotrophomonas sepsis has higher mortality (66%) than late-onset sepsis in neonates.6,7 In our series too, the one case of early-onset sepsis did not survive. All but one surviving case had ROP, and all had BPD and MBD. These morbidities were associated with Stenotrophomonas infection and were primarily prematurity related.
Table 1.
Antibiogram of the Stenotrophomonas maltophilia isolated from blood and antimicrobials used.
| Case No | Antimicrobial | MIC | Interpretation | Antibiotics given |
|---|---|---|---|---|
| 1 | Levofloxacin | 1 | S | Levofloxacin |
| Minocycline | ≤0.5 | S | (10 mg/kg/dose; 12 hourly) | |
| Trimethoprim sulfamethoxazole | ≤20 | S | 14 days | |
| 2 | Levofloxacin | 1 | S | Levofloxacin |
| Minocycline | ≤0.5 | S | (10 mg/kg/dose; 12 hourly) | |
| Trimethoprim sulfamethoxazole | ≤20 | S | 14 days | |
| 3 | Levofloxacin | 1 | S | Levofloxacin |
| Minocycline | ≤0.5 | S | (10 mg/kg/dose; 12 hourly) | |
| Trimethoprim sulfamethoxazole | ≤20 | S | 14 days | |
| 4 | Trimethoprim sulfamethoxazole | ≤20 | S | Levofloxacin |
| Minocycline | ≤0.5 | S | (10 mg/kg/dose; 12 hourly) × 5 | |
| Amikacin | NA | S | days (till culture report) | |
| Levofloxacin | – | R | Amikacin | |
| Ceftazidime | – | R | (15 mg/kg/dose, 24 hourly) | |
| Chloramphenicol | – | R | 14 days | |
| 5 | D0 | |||
| Levofloxacin | – | R | Minocycline | |
| Minocycline | ≤0.5 | S | (4 mg/kg once, then 2 mg/kg/dose 12 hourly) | |
| Trimethoprim sulfamethoxazole | ≤20 | S | 10 days | |
| D4 | Amikacin | |||
| Gentamycin | NA | S | (15 mg/kg/dose, 24 hourly) | |
| Amikacin | NA | S | 6 days | |
| D7 | Trimethoprim | |||
| Trimethoprim sulfamethoxazole | ≤20 | S | Sulfamethoxazole | |
| D11 | (4 mg/kg/dose, 12 hourly) | |||
| Trimethoprim sulfamethoxazole | ≤20 | S | 14 days |
MIC: minimum inhibitory concentration; S: sensitive; R: resistant.
Neonatal Stenotrophomonas infection can be community-acquired or nosocomial, with source traceable to healthcare providers8 or other cases.9,10 In our series, the second case of infection occurred two days after the first. Environmental surveillance could not identify an infection source, though Stenotrophomonas was cultured from an ultrasound jelly sample a month later. The last three infection cases occurred six months after the first two and their source could not be identified, as all samples from equipment, water, ultrasound jelly, environment and hands of health care providers were sterile.
This case series highlights the significance of S. maltophilia as a cause of neonatal sepsis with adverse outcomes. Timely suspicion and recognition of the pathogen by clinicians and microbiologists to appropriately direct antimicrobial therapy and close monitoring for multiple morbidities like BPD and ROP associated with prematurity is necessary for its optimal management.
Patients/ Guardians/ Participants consent
Patients informed consent was obtained.
Ethical clearance
Not Applicable.
Source of support
Nil.
Disclosure of competing interest
The authors have none to declare.
Acknowledgements
None.
References
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