Successful treatment of Stenotrophomonas maltophilia with ceftazidime‐avibactam and aztreonam in an individual with cystic fibrosis: A case report

This is a case of a 10-year-old female who has pancreatic insufficient cystic fibrosis (CF). She is heterozygous for the R553X and 621 + 1 G > T variants. She is not eligible for CFTR modulator therapy based on genotype. She had a challenging course in early life which included chronic Pseudomonas aeruginosa airway infection by age three and MRSA by the age of four. She had a history of poor weight gain and required gastrostomy tube placement at age two. Her home respiratory regimen at the time of admission consisted of two or three respiratory treatments per day including albuterol, dornase alpha, and n-acetylcysteine 10% nebulized solution (used due to intolerance of sodium chloride 7% solution). Inhaled vancomycin was alternated every other month with inhaled tobramycin. Airway clearance therapies included high frequency chest wall oscillation and Aerobika® two or three times daily. In the previous 12 months, her respiratory cultures consistently grew MRSA, P. aeruginosa, and Stenotrophomonas maltophilia. During the same 12 months, she experienced three pulmonary exacerbations that required hospitalization; treatment included IV tobramycin, IV levofloxacin, and IV vancomycin for 19 to 24 days. During hospitalizations, she was noted to have slow improvements in precent predicted FEV1 (ppFEV1) and incomplete resolution of cough and sputum production. Her appetite did not improve, and her fatigue persisted throughout the admissions. Prednisolone 2 mg/kg/day orally for 5 days was prescribed during one of the hospitalizations; no benefit was noted. Her discharge ppFEV1 ranged from 80% to 87%, with a previous baseline of 90%. In December 2023, she developed a new pulmonary exacerbation. Symptoms included increased cough and sputum production, decreased appetite, and fatigue. No fever or upper respiratory symptoms were reported. Attempts at outpatient management included use of oral linezolid followed by oral minocycline. Despite this, a decrease in pulmonary function was noted. Her ppFEV1 was 75% compared to baseline of 90%. Based on limited improvement on the previous IV regimen, aztreonam 75 mg/kg/dose IV every 6 h (infused over 30 min), ceftazidime-avibactam 50 mg/kg/dose IV every 8 h (infused over 2 h), and vancomycin 21 mg/kg/dose IV every 6 h (infused over 2 h) were initiated. Airway clearance therapy was increased from her home regimen to four times daily and all other maintenance medications for management of CF were continued. Laboratory monitoring included biweekly complete blood counts, basic metabolic panel, and hepatic function panel. Vancomycin therapeutic drug monitoring was appropriate. No adverse effects were noted with this regimen except for mildly elevated transaminases (<2X ULN). A polymerase chain reaction (PCR) panel was not obtained due to lack of symptoms consistent with an upper respiratory infection. This treatment approach resulted in a more robust and timely improvement in cough and sputum production. Spirometry improved more rapidly compared to her previous three hospitalizations; by day 6 of hospitalization her ppFEV1 had improved to 94%. Duration of hospitalization was 9 days compared to previous mean hospital stays of 21 days. On the day of discharge, she was free of daily cough and sputum production. Fatigue and appetite were improved. A weight gain of 2.9 kg was documented. The Cystic Fibrosis Care Center at Children's Mercy Kansas City reports a case of successful treatment of a pulmonary exacerbation caused by multi-drug resistant organisms, including methicillin-resistant S. aureus (MRSA), P. aeruginosa, and Stenotrophomonas maltophilia with intravenous (IV) aztreonam and IV ceftazidime-avibactam. Informed consent was obtained. Institutional Review Board review was completed and determined to be exempt. People with cystic fibrosis (pwCF) have abnormal ion transport that leads to airway surface liquid depletion. This defect promotes a cycle of inflammation, obstruction, and infection by opportunistic pathogens.1 As lung disease progresses among pwCF, the airways become chronically infected with organisms, such as Staphylococcus aureus, Pseudomonas aeruginosa (P. aeruginosa), and atypical pathogens including Stenotrophomonas maltophilia (S. maltophilia), Achromobacter sp., and Burkholderia cepacia complex. S. maltophilia is an aerobic, gram-negative bacillus that is inherently resistant to antimicrobials due to several resistance genes carried by many isolates.2 Treatment of S. maltophilia among pwCF remains a challenge due to resistance mechanisms, lack of robust comparative effectiveness studies, and insufficient data to reliably determine antimicrobial susceptibility patterns. Studies comparing the effectiveness of commonly used antimicrobials for treating S. maltophilia are absent. The Infectious Diseases Society of America provided recommendations including two primary approaches for the treatment of S. maltophilia infection. The first is using a combination of two of the following agents: trimethoprim-sulfamethoxazole, minocycline/tigecycline, cefiderocol, and levofloxacin. The second is the combination of ceftazidime-avibactam and aztreonam, as it overcomes drug-resistant enzymes including two inducible β-lactamases, L1 and L2.3 L1 hydrolyzes carbapenems and other β -lactams with the exception of aztreonam. L2 confers resistance to extended-spectrum cephalosporins and aztreonam but can be inhibited by available β -lactamase inhibitors like avibactam. Aztreonam's ability to avoid hydrolysis by L1 and coadministration of the β -lactamase inhibitor, avibactam, allows this combination to overcome both the L1 and L2 β -lactamases leading to bactericidal activity against S. maltophilia.2 There are limited data published regarding the efficacy of this treatment strategy for S. maltophilia infection among people with CF.4 A case report describing an 11-year-old child with CF describes the use of aztreonam and ceftazidime-avibactam for the treatment of a pulmonary exacerbation caused by S. maltophilia. After 11 days of treatment, the child demonstrated clinical improvement in symptoms and better air movement on examination, but no improvement in ppFEV1.5 This case report describes the successful treatment of S. maltophilia infection in the context of a CF pulmonary exacerbation, adding to the limited data describing treatment options. Randomized clinical trials are required to determine optimum treatment strategies for CF pulmonary exacerbations caused by S. maltophila. Stephanie Duehlmeyer: Conceptualization; writing—original draft; writing—review and editing. Ellen Meier: Conceptualization; writing—original draft; writing—review and editing. Christopher Oermann: Writing—review and editing. The authors declare no conflict of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.