This retrospective study aimed to determine the clinical characteristics and outcomes of patients with pneumonia caused by Stenotrophomonas maltophilia. This validates previously published data regarding the clinical characteristics of patients with S. maltophilia (SM) pneumonia: the majority of affected patients have comorbidities, are hospitalized for an extended period of time, and are on mechanical ventilation.
The gender distribution of S. maltophilia patients included in this study was nearly equal. This finding contrasted with other studies in which the majority of patients with S. maltophilia infections were males.6,7 A meta-analysis of eight studies, however, found no link between gender and the development of S. maltophilia pneumonia.8
The median age of patients with SM pneumonia in this study was 59 years and 48.7% of cases were more than 60 years. This was slightly lower than those cited in the literature in which the median age of SM pneumonia patients ranged from 60.2 to 67.3 years.9,10,11 In a study that evaluated the risk factors for S. maltophilia pneumonia, the median age was significantly lower in the SM pneumonia group than in the non-SM pneumonia group (63.4 years vs 73.1 years).12
It is noteworthy that the majority of patients who developed S. maltophilia pneumonia were admitted to the service wards. This is in contrast with other studies which showed that S. maltophilia was mostly isolated from the respiratory specimens of ICU patients.13 This discrepancy could be explained by the fact that in our institution, there are limited beds in the intensive care unit and some of the intubated critical patients who are supposedly for ICU admission stay in the wards. In a study that investigated the microbiologic pattern of non-ICU-acquired pneumonia in Korea, the most common pathogens were P. aeruginosa, A. baumannii, and K. pneumoniae. S. maltophilia was an uncommon cause of non-ICU HAP and was listed among “other bacteria” along with M. catarrhalis, B. cepacia, L. monocytogenes, and so forth.14
Most of the subjects had at least one comorbid condition. Hypertension, diabetes mellitus, and malignancy were the most common. These findings were not novel and were similar to previous studies. In a 10-year retrospective study in Turkey, all patients with S. maltophilia pneumonia had comorbidity.9 A meta-analysis that included a sample size of 2,320 cases showed that among the pre-existing medical conditions, COPD and malignancy were significant risk factors for S. maltophilia pneumonia in ICU. There was no apparent correlation between S. maltophilia pneumonia and other comorbidities including diabetes, cardiovascular disease, renal insufficiency, and immunodeficiency disease.8 The high frequency of hypertension in this study could be explained by the fact that it is one of the leading illnesses in the Philippines.
The majority of cases were ventilator-associated pneumonia (VAP), which is consistent with previous studies that have shown that S. maltophilia is a common cause of VAP in critically ill patients.3 In this study, there were three cases of SM pneumonia which were classified as community-acquired. Among these patients, two patients had co-morbidities. One patient had gastric adenocarcinoma and the other patient had hypertension, tuberculosis and COPD. The former had recent hospitalizations and prior intravenous antibiotic use, and thus, had risk factors for developing a multi-drug resistant infection such as S. maltophilia. Only one patient had no co-morbidities at all. The results of this study run parallel with the results of a systematic review of 26 patients with community-acquired S. maltophilia infections which found that most affected individuals had significant health care exposure or underlying comorbidities.15
Most cases of S. maltophilia pneumonia were monomicrobial, with only 35.5% of cases being polymicrobial. The most commonly isolated organisms along with S. maltophilia were Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. These mirror the most common respiratory isolates based on the UP-PGH antibiogram. In a retrospective study that included 89 patients with a first episode of SM-VAP in ICU, prevalence of polymicrobial infection in patients infected with SM was 43.8%, with the most common co-infecting microorganism being P. aeruginosa.16
Secondary bacteremia from S. maltophilia pneumonia was rarely observed in this study when compared to previous studies' findings. It was seen in 7.1% of patients with S. maltophilia hospital-acquired pneumonia in a retrospective study in 25 French mixed intensive care units.7 Associated empyema thoracis was likewise uncommon which confirms the findings of previous studies. The incidence of S. maltophilia pleural infections ranged from 2.66 to 12.44 per 100,000 patient-days which were most commonly the result of surgical procedures, thoracostomy, and underlying fistulas. Pneumonia was the cause in only 5% (2/40) of cases in that study.17S. maltophilia pneumonia-related septic shock was identified in 41.5% of cases in our study. This finding was consistent with other published studies. For example, in a study of 282 patients with S. maltophilia pneumonia in ICU, septic shock was present in 43.6% of patients.7 The median interval between admission and acquiring pneumonia was 13 days (IQR: 7–22 days) in this study. This was similar to the findings of the prior studies in which the interval between admission to the development of SM pneumonia ranged from 12 to 16 days.3,7 This was longer compared to hospital acquired pneumonia caused by P. aeruginosa and other organisms in which the median intervals were 10 and 9 days respectively.3 The difference could be explained by the low virulence characteristic of S. maltophilia compared to P. aeruginosa and other organisms.
In this study, 23% of S. maltophilia isolates were resistant to TMP-SMX, 4.8% to minocycline, and 4.2% to levofloxacin. A meta-analysis of 184 studies on the frequency of antibiotic resistance showed that 14.4% of patients were resistant to levofloxacin, 9.2% to TMP-SMX, and 1.4% to minocycline. The same study looked at 39 case reports and case series studies and found that the most common types of antibiotic resistance were to TMP-SMX (36.84%), levofloxacin (19.29%), and minocycline (1.75%).18 In a local retrospective study conducted in 2012 at the University of Santo Tomas Hospital, the resistance rates of S. maltophilia isolates to TMP-SMX and levofloxacin were 16.7% and 15.4% respectively.19 Given the rising resistance to TMP-SMX, patients' drug regimens should be closely monitored to prevent the emergence of multidrug-resistant S. maltophilia isolates.
Trimethoprim-sulfamethoxazole (TMP-SMX) has the most reliable in vitro activity against S. maltophilia. It is still the drug of choice and is the cornerstone of treatment for Stenotrophomonas infections. The TMP component is typically administered at a dose of 15–20 mg/kg/day in divided doses.20 Tetracycline derivatives such as minocycline and tigecycline, and fluoroquinolone levofloxacin are favored for infections for which TMP-SMX is not an option or for combination therapy with TMP-SMX.21
The overall mortality of patients who had S. maltophilia pneumonia in this study was 45.3%. The frequency of death attributable to S. maltophilia infection was 60.8%. This is similar to other studies which showed crude mortality rates associated with S. maltophilia infections ranged from 21–69%.6 In contrast, locally, the reported mortality rate directly attributable to S. maltophilia infection was only 4.5% (3/66) in a private hospital in Manila.19 These poor outcomes could be attributed at least partially to the provision of inadequate empiric antibiotic therapy. The empiric antibiotic regimen for hospital-acquired pneumonia in our institution includes meropenem and amikacin, both of which have no activity against S. maltophilia.
In terms of directed antimicrobial therapy, TMP-SMX was the most commonly prescribed overall and as monotherapy, while TMP-SMX plus levofloxacin as combination therapy. The Infectious Diseases Society of America (IDSA) suggests monotherapy of either TMP-SMX or minocycline as the preferred agent for mild S. maltophilia infections. For moderate to severe infections, one of three approaches is recommended: (1) combination therapy with TMP-SMX and minocycline, (2) TMP-SMX alone with the addition of a second agent (minocycline [preferred], tigecycline, levofloxacin, or cefiderocol) if there is a delay in clinical improvement with TMP-SMX monotherapy, or (3) the combination of ceftazidime-avibactam and aztreonam when intolerance occurs.22 In our institution, levofloxacin was more commonly prescribed than minocycline because the former is more readily available in the hospital pharmacy since the latter is not included in the national formulary.
One particular strength of our study is that it has a relatively larger sample size compared to a previous study done in the local setting.19 Our study has several limitations. First, it was a single-center study, and findings may not be generalizable to other settings. Second, because of the retrospective descriptive design, there is lack of rigorous control of confounding factors. Numerous variables can influence the outcomes of S. maltophilia pneumonia, such as comorbidities, concomitant treatments, or underlying immunosuppression. Without controlling for these factors, it becomes challenging to attribute the observed effects solely to S. maltophilia pneumonia. A well-designed, multi-center prospective observational cohort study can therefore be carried out. Such a study has the advantage of being tailored to identify specific risk factors and determinants of clinical outcomes.23 Lastly, this study only presents the phenotypic characteristics of S. maltophilia isolates, whereas some studies have already explored their genotypic profile that could potentially confer resistance to antibiotics, examples of which are overexpression of smeD efflux system for cotrimoxazole resistance24 and Smqnr for resistance to quinolones and tetracyclines.25 Future studies may help to elucidate the concordance between the phenotypic and genotypic characteristics among S. maltophilia isolates.