The current retrospective study aimed to identify the differences of demographic and clinical characteristics, microbiological findings and the final mortality outcomes of patients with nosocomial primary bacteremia and pneumonia caused by
S. maltophilia. These infections are the most frequently reported infection types in the nosocomial setting, but no studies compared the clinical characteristics and outcomes of these two infections caused by
S. maltophilia in the literature.
Stenotrophomonas maltophilia pneumonia-associated mortality was previously reported as 23% - 44%. (
4,
13-
15).
Stenotrophomonas maltophilia bacteremia was reported as 21% - 51% (
8, 16-20). Lai et al. (
21) found that while
S. maltophilia bacteremia originating from respiratory tract was associated with higher mortality, CVC-related bacteremia was inversely associated with mortality. Another study found that secondary bacteremia was associated with a worse prognosis than catheter related bacteremia (
22).
The current study data exhibited a slight elevation in mortality in patients with
S. maltophilia pneumonia, but the difference was not statistically significant. Compared with patients with
S.maltophilia bacteremia, patients with
S. maltophilia pneumonia were older and used more inappropriate antibiotics. Patients with pneumonia staying in ICU were significantly more likely to have more severe illnesses as determined by APACHE II score and SOFA score. And also the polymicrobial infection rate was significantly higher such patients had. Previous studies frequently observed polymicrobial infection in nosocomial
S. maltophilia infection, if polymicrobial infection increases the mortality is controversial (
4, 21). The 14-day mortality rate was not statistically different due to the small number of cases in the two groups. However, the above mentioned findings may explain that the slight increase on mortality in patients with pneumonia was thought.
Stenotrophomonas maltophilia is an environmental microorganism, is isolated from various sources in a hospital setting (
15, 23,
24).
Stenotrophomonas maltophilia is naturally resistant to many antibiotics, including broad spectrum antimicrobials such as carbapenems, third and fourth generations of cephalosporins. These drugs are used extensively in healthcare setting to treat nosocomial infections and that leads to colonization of in-dwelling devices with resistant and environmental microorganism like
S. maltophilia. Colonization of in-dwelling devices is a key requirement for developing infection (
25, 26). Primary bacteremia due to
S. maltophilia usually occurs after the CVC colonization; similarly, pneumonia occurs after the colonization of respiratory tract (
22, 26). CVC usage was more common in bacteremia group and almost all of the primary bacteremia was associated with CVC use in the study.
Most of the subjects had at least one co-morbid disease, however, chronic obstructive pulmonary disease was more common in pneumonia group and that could explain why the rate of polymicrobial infection was higher in pneumonia group. Patients with such infections are often forced to use antibiotics repetitively, which causes more than one multi drug resistant bacteria colonization of respiratory tract. Prior hospitalization and prior antibiotic use were slightly more common in pneumonia group, but the differences were not significant, that also supported the higher polymicrobial infection in this group. In addition, it was found that
S. maltophilia strains, isolated from patients with pneumonia, were more resistant to ceftazidim and slightly more resistant to piperacillin-tazobactam and levofloxacin. The current study expected that these factors may also explain why the
S. maltophilia strains isolated from patients with pneumonia tended to be more resistant to antibiotics. However, no resistance was determined to trimethoprim-sulfamethoxazole in these strains and that can be explained by repeated antibiotic use in patients with chronic obstructive pulmonary disease that usually includes beta-lactams and quinolones, and not trimethoprim-sulfamethoxazole. These antibiotics lead to the development of resistance to many antibiotics especially in Gram-negative bacilli (
27, 28).
Prolonged hospitalization, staying in ICU, and mechanical ventilation are reported as precipitating risk factors for
S. maltophilia infections (
22, 26,
29-
31). Time of acquiring infection after hospitalization (median; min-max values were presented in
Table 1) was not different in the two groups, and more than half of the patients in the groups were in ICU. Also, clinical presentation and laboratory findings were not different.
Stenotrophomonas maltophilia is naturally resistant to many antibiotics such as beta-lactams and aminoglycosides, and these agents are widely used in empirical treatment of nosocomial bacteremia and pneumonia. Very few antibiotics such as trimethoprim-sulfamethoxazole and levofloxacin were effective on
S. maltophilia and used to treat
S. maltophilia infections, and the national committee for clinical laboratory standards recommended only antimicrobial susceptibility testing for minocycline, levofloxacin and trimethoprim-sulfamethoxazole (
4,
6). However these antibiotics are usually not used for initial empirical treatment of nosocomial infections such as bacteremia and pneumonia (
4, 5,
32,
33). Current antimicrobial treatment recommendation for
S. maltophilia infections are based on case series, case reports and in vitro susceptibility tests, and levofloxacin and trimethoprim-sulfamethoxazole are the most commonly used agents to treat these infections (
4).
Antimicrobial susceptibility tests were applied to all the strains in the study, and levofloxacin or trimethoprim-sulfamethoxazole, according to susceptibility tests, was selected. High crude mortality rate was reported for
S. maltophilia bacteremia and pneumonia (
5, 30,
34). In accordance to the literature, total mortality was 31.0% in the study. It seems to be relatively associated with initiation of treatment according to culture result, and also the fact that these infections occurred in immuncompromised and debilitated patients, and those undergoing invasive procedures. Advanced age, staying in ICU, septic shock, severe sepsis, invasive procedures such as mechanical ventilation, Foley catheter and nasogastric catheter, and also thrombocytopenia and increased blood urine nitrogen were risk factors for the 14-day mortality by univariate analysis and they were consistent with the literature (
21). But, it was important that all of the patients who died were in the group that used antibiotics inappropriately (63.6% versus 0%, P < 0.001,
Table 2). Inappropriate antimicrobial treatment was associated with mortality in a lot of studies (
16, 34) and the current study confirmed it too (
Table 3).
There were some limitations; although a long period was viewed, there were a relatively small number of cases in each group due to evaluation of a single institution’s data. In addition retrospective design hampered to manage some aspects of the study and explained some controversial issues such as selection of antibiotic or combined antimicrobial therapy (
2, 10). In the current study, no antibiotic combination was tested on
S. maltophilia infections, and the potential influences of the selected antibiotics were not evaluated. Also removal of the infected CVC is controversial and the therapeutic benefit of removal of infected CVC additional to antibiotic therapy in CVC related bacteremia was not examined in the current study. Polymicrobial infection was another problematic issue, the patients with polymicrobial growth were not excluded; all bacteria in the study were treated by adequate antibiotic. However, it was the first study comparing two most frequently observed infection types caused by
S. maltophilia in hospital setting that did not find differences in mortality rate but demonstrated the importance of appropriate antimicrobial therapy.
In conclusion, although there was no significant difference, a slightly higher mortality was observed in patients with pneumonia, which was strived to explain by advanced age, higher APACHE II and SOFA score, and also higher inappropriate use of antibiotics. All patients were analyzed for the 14-day mortality by multivariate analyses and results indicated that the inappropriate use of antibiotics was critically important for mortality. Mortality rates between the two groups were not statistically different. However, as mentioned above, a relatively small number of subjects was an obvious limitation of the study. Therefore, multicenter retrospective or prospective studies including huge number of patients should be designed to confirm the current study findings.