Managing Multidrug-Resistant Stenotrophomonas Maltophilia Sepsis in a Child with Cerebral Palsy and Global Developmental Delay: A Complex Rare Case from a Resource-Limited Setting

Abstract

Stenotrophomonas maltophilia is a hospital-acquired, multidrug-resistant pathogen that poses significant therapeutic challenges, particularly in children with complex comorbidities. We report the case of a 5-year-old girl with cerebral palsy, global developmental delay, and epilepsy who developed S. maltophilia sepsis. She initially presented with fever and vomiting, followed by rapid clinical deterioration with pneumonia, septic shock, acute kidney injury, and new-onset seizures. Her course was further complicated by an underlying horseshoe kidney and suspected rectovaginal fistula. Despite empirical broad-spectrum antibiotic therapy, clinical improvement was not observed until blood culture identified S. maltophilia, resistant to most antibiotics but susceptible to trimethoprim–sulfamethoxazole, levofloxacin, and ciprofloxacin. Targeted antimicrobial therapy resulted in gradual recovery. Additional management included central line removal, re-initiation of antifungal therapy for persistent candiduria, and optimization of antiepileptic treatment. This case highlights the importance of early microbiological diagnosis, individualized pathogen-directed therapy, and vigilant monitoring when managing multidrug-resistant infections in resource-limited pediatric settings.

Introduction

Stenotrophomonas maltophilia, previously known as Pseudomonas maltophilia or Xanthomonas maltophilia, is a Gram-negative, non-fermenting bacillus that has become an increasingly recognized cause of serious hospital-acquired infections. It now stands alongside pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii as a challenging multidrug-resistant organism, particularly in vulnerable patient groups. Infections caused by this organism are often associated with considerable illness and death. ¹

This pathogen tends to affect immunocompromised individuals and is notorious for its role in nosocomial infections. While pneumonia remains its most frequently reported manifestation, S. maltophilia can also cause a variety of infections—ranging from bloodstream and urinary tract infections to those involving intra-abdominal sites, catheters, and implanted medical devices. On rare occasions, it may also be responsible for infections of the heart, bone, soft tissues, and nervous system.^2,3

Respiratory tract infections, including pneumonia and acute worsening of chronic obstructive pulmonary disease (COPD), are commonly linked to S. maltophilia. In patients with COPD or signs of respiratory infection, the presence of this organism should not be disregarded. ⁴

Several risk factors have been identified for S. maltophilia infection. These include immunosuppression, the presence of central venous catheters, extended hospital stays, and prior use of broad-spectrum antibiotics especially carbapenems. ⁵ Treating these infections is especially difficult due to the pathogen’s broad resistance profile. It exhibits both innate and acquired resistance to multiple antibiotic classes, including tetracyclines, quinolones, aminoglycosides, and beta-lactams. ⁶ Its resistance strategies include decreased outer membrane permeability, active drug efflux pumps, and the production of beta-lactamases, carbapenemases, and enzymes that modify aminoglycosides. ⁷

Hospital-acquired infections due to S. maltophilia are associated with high mortality rates, which have been reported to range from 14% to 69%, with attributable mortality as high as 37.5%.^8,9 In pediatric populations, particularly those in intensive care or with weakened immune systems, S. maltophilia bacteremia has emerged as a potentially fatal condition. Mortality rates among children with this infection range between 21% and 69%, with an attributable mortality of up to 26.7%. Common risk factors include central venous access, prolonged hospital stays, prior antibiotic exposure especially to meropenem, and underlying malignancy. One study found that nearly all affected patients (97%) had central lines, and the vast majority (88.2%) of bloodstream infections were catheter-related. ¹⁰

Following the CARE guidelines for case reporting, ¹¹ we present the case of a 5-year-old girl with cerebral palsy, global developmental delay, and epilepsy who developed severe sepsis due to multidrug-resistant Stenotrophomonas maltophilia. Her condition was further complicated by multiple comorbidities, and she was managed in a setting with limited healthcare resources. This case highlights the complexity of diagnosing and treating MDR infections in vulnerable pediatric patients, especially in low-resource environments.

Case Presentation

A 5-year-old girl with a background of cerebral palsy, global developmental delay, and epilepsy who was brought to our hospital with a 3-week history of on and off fever and 3 days of continuous vomiting. The fever would temporarily go down with medications but kept returning. Her vomiting was non-bilious, not forceful, and was not associated with diarrhea. She had received antibiotics at a local healthcare center without improvement, leading to her referral to our facility.

On arrival, a chest X-ray showed patchy changes in the right lung, suggesting pneumonia. Due to difficulty obtaining good intravenous access and her need for close observation, she was admitted to the Pediatric Intensive Care Unit (PICU), where a central line was inserted. Shortly after admission, she developed acute kidney injury (AKI) and high blood pressure. An ultrasound revealed she had a congenital abnormality called a horseshoe kidney. As her kidney function worsened, we adjusted her fluid intake, reduced medication doses, and treated low potassium levels. Her anti-seizure medications zonisamide and clobazam were paused during this time but restarted once her urine output improved.

Her medical history was complex. As a newborn, she experienced low blood sugar and sepsis caused by Staphylococcus aureus. She also had early-onset seizures with abnormal startle responses and had been hospitalized multiple times in the past for pneumonia, urinary tract infections (UTIs), seizures, and a possible rectovaginal fistula. Her most recent admission had been 5 months prior for pharyngitis.

Lab tests showed signs of ongoing infection and inflammation, including a high white blood cell count (21 700/mm³), elevated platelet count (530 000/mm³), and markedly raised C-reactive protein (CRP). Her liver function was normal, but her albumin level was low. Urinalysis showed white blood cells and numerous yeast cells, suggesting a possible fungal UTI, so fluconazole was started.

Despite initial treatment with piperacillin-tazobactam, her condition deteriorated. On the third day of admission, her antibiotics were changed to meropenem, vancomycin, and clindamycin. She developed septic shock by the second day in the PICU and needed support with noradrenaline, which was tapered off after 3 days. Vancomycin was stopped due to concerns about kidney toxicity. She eventually required mechanical ventilation. A blood transfusion was given for anemia (hemoglobin 8.5 g/dL), after which she developed a facial rash, which was managed with antihistamines and steroids.

Since the fever continued and her breathing worsened, teicoplanin was added to cover gram-positive bacteria. On day 17, she spiked another fever. Levofloxacin was started, the central line was removed, and fluconazole was restarted due to persistent yeast in the urine.

Blood cultures were sent from both central line catheter and peripheral sites. Report from central line was obtained 6 hours earlier than peripheral site which showed presence of S. maltophilia, a resistant hospital-acquired bacteria. Later it was confirmed by culture report from peripheral site. The isolate was resistant to most antibiotics but remained sensitive to levofloxacin, ciprofloxacin, and cotrimoxazole. Levofloxacin was continued as targeted therapy, and her fever subsided within 40 hours, along with overall clinical improvement.

From the eighth day of admission, she began having new focal seizures, seen as eye fluttering, lip smacking, and jerking of the right limbs. These were managed by adding levetiracetam, increasing her sodium valproate dose, and restarting clobazam.

Her mother also reported occasional passage of stool from the vagina. Although a proctoscopy did not reveal any abnormalities, a contrast study was planned after discharge to further evaluate for a possible rectovaginal fistula.

By the time of discharge, the child was afebrile and clinically stable. She was receiving low-flow oxygen and was being fed through a nasogastric tube, as her caregivers were concerned about oral feeding. Given her complex medical background and involvement of multiple organ systems, she was referred to a tertiary center for neurological and genetic evaluation.

This case is unusual due to the combination of a rare bloodstream infection caused by multidrug-resistant S. maltophilia, a congenital kidney anomaly (horseshoe kidney), and a suspected rectovaginal fistula in a child with cerebral palsy and epilepsy. To the best of our knowledge, this constellation of findings has not been previously reported. The case highlights the need for careful clinical judgment, coordinated multidisciplinary care, and individualized diagnostic strategies, especially when managing children with multiple medical issues in resource-limited settings. The referral aimed to explore a possible unifying genetic or syndromic diagnosis behind her complex condition.

Discussion

Stenotrophomonas maltophilia is an emerging multidrug-resistant gram-negative bacillus commonly associated with hospital-acquired infections, particularly in patients who are immunocompromised or have experienced prolonged hospitalization, indwelling devices, or prior broad-spectrum antibiotic exposure. ¹ This organism can cause a diverse range of infections including respiratory tract infections, bloodstream infections, and less frequently skin and soft tissue, bone and joint, biliary tract, urinary tract infections, as well as more severe conditions like endophthalmitis, endocarditis, and meningitis. ¹²

Infections with S. maltophilia are often linked to specific risk factors such as immunosuppression, co-morbidities, chronic respiratory disease, indwelling catheters, and previous antibiotic use. The widespread use of broad-spectrum antibiotics, especially extended-spectrum agents used to treat polymicrobial infections, may contribute to the selection and proliferation of multidrug-resistant strains, complicating treatment efforts. ¹³

Catheter-related bloodstream infections (CRBSIs) and central-line-associated bloodstream infections (CLABSIs) are the 2 primary definitions used to identify central line-associated infections ¹⁴ CLABSI is defined based on a temporal association between a bloodstream infection of unknown origin and the presence of a central venous catheter. This definition is commonly used for surveillance purposes due to its simplicity. ¹⁴

In contrast, CRBSI requires more specific microbiological evidence, including the isolation of the same microorganism from both the catheter tip and peripheral blood cultures, with a higher microbial load found at the catheter site. ¹⁴

Many CRBSIs are caused by Gram-positive organisms; therefore, empiric antibiotic therapy should include coverage for these pathogens, commonly with vancomycin. ¹⁵

In cases where the same organism is isolated from multiple blood cultures drawn from different sites, the likelihood of a true bloodstream infection increases. ¹⁵ Although there are limited studies to guide the exact duration of therapy, extended courses of antibiotics are generally recommended for complicated CRBSIs, as was relevant in our case. ¹⁵

Diagnostic confirmation traditionally relies on culturing clinical specimens on selective media, where S. maltophilia forms characteristic non-fermentative colonies. Biochemical testing and molecular methods, including PCR assays targeting bacterial 16S rRNA sequences, have enhanced identification accuracy. Recent advances in real-time PCR have demonstrated superior sensitivity and specificity compared to culture, particularly in detecting S. maltophilia in polymicrobial samples.^16,17

Treatment of infections caused by S. maltophilia remains challenging due to its intrinsic resistance to many antibiotics. According to SENTRY antimicrobial surveillance data and other literature reviews of bacteremia, S. maltophilia remains largely susceptible to trimethoprim–sulfamethoxazole (TMP/SMX) and levofloxacin, whereas agents such as ceftazidime and ciprofloxacin demonstrate only low to moderate activity. Other antibiotics, including minocycline and tigecycline, have also exhibited encouraging in-vitro efficacy, with several studies reporting near-universal susceptibility to minocycline. Infectious Diseases Society of America recommends TMP/SMX as the cornerstone of therapy for S. maltophilia infections, either as monotherapy or, ideally, in combination with another active agent rather than levofloxacin alone.^18,19 Early and appropriate targeted therapy is crucial, as empirical broad-spectrum antibiotics often prove ineffective against this pathogen. ³

Although vancomycin has historically been regarded as a potentially nephrotoxic agent, contemporary evidence suggests that chromatographically purified vancomycin, particularly when not administered concomitantly with aminoglycosides, is associated with a significantly lower risk of nephrotoxicity, as highlighted in Cunha’s Antibiotic Essentials. ²⁰ The case also highlights how excessive reliance on broad-spectrum antibiotics promotes multidrug-resistant S. maltophilia, emphasizing the importance of stronger antibiotic stewardship practices, particularly in resource-limited clinical settings to guide safer patient care practice.

The patient’s initial deterioration despite broad empirical antibiotic coverage highlights the importance of considering atypical and multidrug-resistant organisms like S. maltophilia in high-risk populations when there is poor clinical response. Treatment failure rates remain high in S. maltophilia infections, with reported 30-day mortality rates approaching 50%. Poor outcomes are often associated with factors including advanced age, hypoalbuminemia, severity of illness, mechanical ventilation, and septic shock. Although no statistically significant difference between monotherapy and combination therapy has been demonstrated, current clinical guidelines support a potential role for combination regimens in achieving more favorable outcomes. ¹⁹

Overall, this case emphasizes the need for heightened clinical suspicion, rapid and accurate diagnostic methods, and timely initiation of targeted antimicrobial therapy in managing S. maltophilia infections. Additionally, careful consideration of antibiotic nephrotoxicity is vital in patients with pre-existing renal conditions to minimize further complications.

Conclusion

This case underscores the importance of recognizing S. maltophilia as a potential cause of CLABSI/CRBSI, particularly in children with multiple comorbidities and prolonged hospital stays. Clinicians should keep S. maltophilia in mind when a hospitalized child develops fever, pneumonia, or other infections that do not respond to usual treatments. When the bacteria is sensitive, Levofloxacin can be an effective treatment option along with TMP-SMX alone or in combination. Early microbiological confirmation and targeted therapy are critical. In settings with limited resources, it’s important to refer patients to specialized centers to investigate possible underlying genetic or syndromic causes behind their complex health issues after the evaluation and initial management.