Clinical Epidemiology of Stenotrophomonas maltophilia Colonization and Infection

Abstract

Introduction There is general concern regarding the widespread resistance to antibiotics and the increasing prevalence of nosocomial infections caused by multiresistant pathogens (22), such as methicillin-resistant Staphylococcus aureus, glycopeptide-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacteriaceae, and multiresistant nonfermenting Gram-negative bacilli (8). While therapeutic options for managing these infections are limited, deeper knowledge of their epidemiology may provide valuable information for the establishment of preventive and control strategies. Stenotrophomonas maltophilia is a nonfermentative Gram-negative bacillus that may cause nosocomial infections, mainly in debilitated, immunocompromised patients (11,42,54). Although considered a low-virulence pathogen, infections caused by this organism are difficult to treat due to its intrinsic resistance to multiple antimicrobial agents, including carbapenems. During the last decade, it has emerged as a relevant nosocomial pathogen and it is being isolated with increased frequency from clinical samples (42,46,52). Several nosocomial outbreaks caused by this organism have been described (1,10,20,26,33,39,40,62,70,71,74). Potential risk factors for the acquisition of S. maltophilia have been suggested by several descriptive series. Some underlying conditions, such as malignancy or chronic respiratory diseases, long hospital stay, stay in an intensive care unit (ICU), previous antimicrobial treatment, and indwelling devices are frequent among patients infected or colonized with this organism (14,15,26,30,32,35,36,40,46,47,64,68,71). However, data from case-control or cohort studies are scarce and should be interpreted in the light of the epidemiologic setting in which they were performed. We conducted this study to describe the clinical epidemiology of S. maltophilia in the endemic setting and to analyze the risk factors associated with the nosocomial acquisition of this organism beyond a concrete epidemiologic situation, that is, in patients with diverse underlying diseases from different services and hospitals. Methods Location Six hospitals from 3 cities located in Andalucía, Spain, participated in the study. The hospitals range from 532 to 1,700 beds (Table 1). All the hospitals are public, have ICUs and oncology/ hematology services, and attend medical and surgical patients (adults and pediatrics). Five are teaching hospitals. None had apparent outbreaks caused by S. maltophilia during the year before the study period.TABLE 1: Features of participating hospitalsDesign All hospitalized patients from which S. maltophilia was isolated from clinical samples between 1 February 1998 and 30 June 1999 were included prospectively (cases). Cases were detected through daily revision of microbiology reports. For each case, 2 controls were included. Controls were randomly chosen among patients from whom a similar sample had been obtained that was negative for S. maltophilia. Frequency matching for hospital and unit of admittance was used. The following data were collected: demographic characteristics, type and severity of underlying diseases (classified as nonfatal, ultimately fatal, or rapidly fatal according to McCabe criteria) (44), antimicrobial use, immunosuppressive drugs including corticosteroids (prednisone >10 mg qod or equivalent during more than 3 weeks), neutropenia (less than 500 neutrophils per mm3), invasive procedures (surgical procedures, intravascular catheters, urinary catheters, mechanical ventilation), parenteral nutrition, previous ICU stay, length of hospital stay, and hospitalization within the previous 3 months. Differentiation between nosocomial and community-acquired isolates, and between colonization and infection were assessed according to Centers for Disease Control and Prevention (CDC) criteria (21,29) by the investigator in each hospital. Chronic underlying disease must have been evident before hospital admission; the diseases were defined as follows: Chronic liver disease: biopsy-proven cirrhosis or documented portal hypertension, episodes of past upper gastrointestinal bleeding attributed to portal hypertension, prior episodes of hepatic failure or encephalopathy. Cardiac insufficiency: class IV of New York Heart Association. Chronic respiratory disease: chronic restrictive, obstructive, or vascular disease resulting in severe exercise restriction (unable to perform household duties) or documented chronic hypoxia, hypercapnia, secondary polycythemia, or severe pulmonary hypertension (>40 mmHg). Renal insufficiency: renal disease requiring chronic dialysis. Immunocompromising disease: primary immunodeficiency, leukemia, lymphoma, or acquired immunodeficiency syndrome (AIDS). Microbiologic studies Samples were processed in each hospital using standard protocols. Laboratory identification of S. maltophilia was performed by the Vitek 2 System (bioMérieux-Vitek, Hazelwood, MO) or the AutoScan Walk-Away (Dade-Behring, Sacramento, CA) identification system. Antibiotic susceptibility testing of the first isolate from each patient was performed by microdilution. Organisms were classified as susceptible, moderately resistant, or resistant according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria (48). Statistical analysis Univariate comparison between cases and controls was performed using the Student t test for continuous variables and the chi-squared test for categorical variables. Odds ratios and their 95% confidence intervals (CI) were calculated. Multivariate analysis of potential risk factors, including potential interactions, was performed by means of logistic regression analysis. Selection of variables was performed by a stepwise backward method, in which the less significantly associated variable was eliminated in each step. The variables “hospital” and “service” were kept in the models obtained as they were used for frequency matching. Results Incidence During the 17 months of the study, S. maltophilia was isolated from 129 hospitalized patients in the 6 participating hospitals (cases). The pooled-incidence was 5.73 per 10,000 admissions, ranging in the different centers from 3.4 to 12.1 per 10,000 admissions (see Table 1). There was no relation between incidence and the size or general features of the hospitals. Clusters of cases were not apparent throughout the study period in any hospital. Description of the cases Among the 129 cases, 7 were neonates (5%), 1 was 6 years old, and the rest were adults (94%). Neonates had a mean age of 33 days, and adults of 56 years (range, 19–90 yr). Eighty-six cases (67%) were male. When S. maltophilia was isolated, 41 patients (32%) were in an ICU, 24 (18%) in surgical services, 14 (11%) in oncology/hematology services, and 50 (39%) in other medical services. Seventeen patients (13%) had previously been in the ICU during the present admission. Overall, 102 patients (79%) had a chronic underlying disease; among them, chronic pulmonary disease was the most frequent (25% of cases), followed by neoplastic diseases (21%), diabetes (19%), and chronic renal insufficiency (11%). The underlying disease was considered nonfatal in 35% of the patients, ultimately fatal in 52%, and rapidly fatal in 13%. The median duration of hospitalization before the isolation of S. maltophilia was 17 days (range, 0–180 d). Thirty percent had been admitted to the hospital within the 3 months before the present admission. In 12 patients (9%), the sample was taken when the patient had been 2 or fewer days in the hospital (6 of them had been recently hospitalized). Forty-one percent of the patients had undergone surgery during the present admission, abdominal surgery being the most frequent (30%), followed by orthopaedic (17%), cardiac (11%), and cranial surgery (11%). Thirty percent had received immunosuppressive drugs, and 7% were neutropenic. Regarding devices, 48% had a urinary catheter (median days, 12.5), and 92% vascular catheters (43% of them being central venous catheters). The median duration of vascular catheterization was 14 days. Thirty-six percent of cases had been on mechanical ventilation during the preceding week for a median of 8 days, and 12% had received parenteral nutrition. Overall, 88% had received systemic antimicrobial therapy during the present admission. Among these patients, the mean number of antimicrobials received by each was 2.7 (range, 1–7), and the median duration of antimicrobial therapy was 11 days. The antimicrobials most frequently administered were third-generation cephalosporins (43%), aminoglycosides (29%), carbapenems (28%), glycopeptides (25%), and quinolones (23%). Clinical microbiology S. maltophilia was isolated from respiratory tract samples (52% of isolates), wounds (18%), urine (9%), blood (9%), catheter-tip (5%), intraabdominal fluid (4%), and other samples (3%). The distribution of samples was not homogeneous among the different services. Thus, respiratory samples were the most frequent in internal medicine (57%), pneumology (72%), ICU (67%) and neonatology units (85%); blood cultures predominated in hematology/oncology wards (35%); urine in nephrology (35%); and wounds in surgical services (58%). The organism was isolated from more than 1 sample in 21% of patients. In 26% of the samples, it was isolated together with 1 or more other microorganisms (the most frequent being Enterobacteriaceae, Enterococcus spp., other nonfermentative Gram-negative bacilli, and staphylococci). In 56% of cases, S. maltophilia was considered to be the cause of infection, while in the rest of the cases patients were considered colonized only. All patients with blood cultures and intraabdominal fluid yielding S. maltophilia were infected. The proportion of infected patients among those with urine, respiratory, and wound samples was 50%, 46%, and 43%, respectively. Respiratory tract infections were the most frequent, followed by surgical site infections, urinary tract infections, and intraabdominal infections (Table 2). Pneumonia occurred in 8 of 32 patients in other medical services and in 15 of 16 in ICUs. Twelve patients were bacteremic; sources of bacteremia were respiratory tract (3 patients), vascular catheter (3 patients), urinary tract (1 patient), and unknown (5 patients). For patients admitted to hematology/oncology services, primary bacteremia was the most frequent type of infection (4 of 9 infected patients). Among the 10 patients with surgical site infections, 3 had undergone orthopaedic procedures, 2 amputations, 2 intraabdominal surgery, 2 thoracostomy, and 1 drainage of fascitis. In of these cases, the infection was of the 10 patients with surgical site infection had previously received 2 site infections were the most among surgical patients (6 of of infections due to Stenotrophomonas were no between patients with S. maltophilia infection and colonization with to characteristics, underlying diseases, or antimicrobial not for the following infected patients were less frequently 95% had been less frequently on mechanical ventilation 95% and had received for a mean period of 95% The antimicrobial susceptibility of S. maltophilia is in Table The most in was of were or followed by were and percent of were resistant to was more frequent among patients with or isolates, and that 95% previous was more frequent among patients with 95% There was no between susceptibility to other antimicrobial and previous use, or unit of not susceptibility of S. maltophilia study The 129 cases were with controls with to risk In 8 cases, 1 control was of the of potential risk factors and the isolation of S. maltophilia from the clinical are in and Cases and controls were similar in age and rapidly fatal chronic underlying disease and chronic renal insufficiency were significantly more frequent among the There was no in any other underlying including liver or pulmonary immunodeficiency infection, or other immunosuppressive in previous ICU stay, or hospital. had been in cases than in Cases had more frequently undergone surgery during present (the being in and received immunosuppressive drugs, was no in the frequency of The of patients with urinary vascular mechanical or parenteral was similar between cases and the duration of mechanical ventilation and urinary or vascular catheterization was significantly among analysis of the of categorical variables and the isolation of S. maltophilia in clinical analysis of the of continuous variables and the isolation of S. maltophilia in clinical antimicrobial was more frequent among Cases received more antimicrobial and for a period of to cases received significantly more and The duration of of these antimicrobials and of was significantly in Multivariate analysis was performed to those variables associated with an increased risk of S. maltophilia. All variables were 2 different In the first (the antibiotics and invasive procedures were considered variables or and the variable of was (Table In the (the antibiotics and invasive procedures were considered continuous of and the variable of was not (Table between procedures and underlying diseases with antimicrobials were were not to be In the the variables associated with S. maltophilia colonization or infection were duration of mechanical and previous of or In the the variables were days of use, days of carbapenems use, days of quinolones use, and days of mechanical was similar for models Multivariate analysis of risk factors for the isolation of S. maltophilia in clinical Multivariate analysis of risk factors for the isolation of S. maltophilia in clinical The of together with other extended-spectrum has increased in years as a of the of Gram-negative bacilli, such as extended-spectrum Enterobacteriaceae, or of or a be a for the of a of S. maltophilia maltophilia or has during the last as a relevant nosocomial pathogen from several centers have in the incidence of the isolation and bacteremia due to this organism during the and the Incidence of S. maltophilia isolation from different hospitals colonized and infected from to cases per 10,000 or cases per of those were performed in the The incidence from the hospitals participating in study is ranging from 3.4 to 12.1 cases per 10,000 with no apparent of in the incidence among the participating hospitals are to in antimicrobial or other factors be with data a in which may be more similar to present incidence in most the clinical epidemiology of S. maltophilia has been performed in the of outbreaks or in studies mainly ICU patients patients or patients We may not be to from those studies to other epidemiologic or other of hospitalized patients. study the hospitalized from 6 a more of the epidemiology of this organism be Some have S. maltophilia to be acquired in of hospitalized cases, and have that colonization not be hospitals In study, of cases were considered and of these patients had been recently that S. maltophilia as a nosocomial pathogen, in with the of other in the epidemiology of the organism have not been and the among S. maltophilia has been isolated from a of in mainly from sources in sources in to be the most of nosocomial In several nosocomial outbreaks have been to of S. maltophilia has been in neonatology units to and with it not to be as as with other multiresistant ICU and neonatology units are the hospital S. maltophilia is isolated most frequently as with other nosocomial In study, of patients were or had recently been in the The incidence of S. maltophilia isolation in these in to the of in any the of antibiotics within ICUs. However, more than of cases were not and occurred in internal and general surgery services. Although infections due to S. maltophilia have been described in previously patients in most of the cases the organism patients with 1 or several underlying diseases, have indwelling devices, invasive procedures, and immunosuppressive drugs, as a nosocomial In study of patients had a chronic underlying which was considered ultimately or rapidly fatal in The underlying diseases most frequently in different studies are in Table The of study not to study the of those underlying diseases that are in 1 unit as chronic pulmonary disease or with the acquisition of S. as used the unit of for frequency matching. Thus, on the descriptive data obtained from Chronic underlying diseases of patients colonized or infected with S. previous and present most frequent underlying disease was chronic pulmonary disease (25%), most chronic pulmonary There are other studies in which pulmonary disease is describe as the most frequent in patients infected or colonized with S. maltophilia is not for patients to be by this organism However, 1 in study from the that included hospitalized patients. and neoplastic diseases have been described frequently in patients with S. maltophilia mainly in bacteremia In study, of patients had an underlying Chronic renal insufficiency to be frequent underlying disease in patients with S. of patients chronic or dialysis. underlying disease was less frequent in previous studies of S. of patients in a study by were on and of colonized or infected patients had renal failure in a study by infection and infection in patients on due to S. maltophilia have been The acquisition of S. maltophilia in patients with chronic renal failure may be to other of other central venous catheterization and vascular and of has been considered a potential disease in studies of patients had However, the frequency of diabetes was not significantly different among cases and S. maltophilia was most frequently isolated from respiratory samples in study, followed by urine, and blood The respiratory samples were the most frequent for S. maltophilia in other of samples The distribution of samples in study and on the units patients are and in relation to the underlying Thus, respiratory samples are more frequent among medical patients or blood cultures among or patients and wound in surgical patients. with other low-virulence colonization from infection is is for respiratory tract and wound samples, or when cultures are in a study performed between and considered that 6 of S. maltophilia were the cause of of infection, ranging from to of these used criteria for the of In study, of the patients were considered to be infected. considered of S. maltophilia to an infection in ICU patients. that ICU patients were more frequently infected than patients in We no in the of infection between ICU and patients, due to the of different Although it is difficult to the from these it that S. maltophilia is to cause nosocomial infections in a proportion of colonized patients. However, must be of the to clinical and criteria for the isolation of S. maltophilia in clinical of clinical has been attributed to S. maltophilia a number of patients (Table Respiratory tract infections are the most described and colonization are difficult to in the of respiratory 33 of patients with a respiratory sample were considered to have a respiratory tract infection in study. due to S. maltophilia has been associated frequently with mechanical ventilation of patients with in of respiratory tract previous antimicrobial in and chronic respiratory disease in has been in patients with due to this organism of infections caused by S. previous and present is frequent in patients of the episodes are primary of these infections in vascular catheters Thus, infections should be considered in patients no other of infection is In study, 12 patients of infected were and 8 of them had primary is not for S. maltophilia to be isolated from wounds and in and on the organism to be a The in which the sample was obtained as as the clinical data should be considered before a wound infection to S. maltophilia. However, it is this bacillus is not considered an cause of infections, 10 patients with a surgical site have similar (see Table this organism should be considered a potential cause of surgical site infection in patients had previously received several of antimicrobial susceptibility of S. maltophilia in study was similar to that previously in All were resistant to antimicrobial was the most in from 24 patients were resistant to in study. most isolates, is considered the of for the of S. maltophilia infections that resistance to was more frequent in and the and of S. maltophilia isolates, than in or The resistance to in the 12 years The attributed this to the that was no being used as a in patients. In Spain, a in the incidence of resistance in Among the and were the most in study. have described a range of susceptibility from to an between previous and resistance was in study. are of in previously colonized patients or of previously resistant However, these data are to be considered as the number of patients previously with this antimicrobial was and have have in S. maltophilia in studies The of a in the of severe infections is not as and (the by S. which resistance to most are Results from an study that therapy with and or be to in patients with antimicrobial that have variable in S. maltophilia in different studies are and in susceptibility to these antimicrobials have been due to the different and criteria used to susceptibility and to the number of included in of quinolones to be more than clinical with these is risk factors for the acquisition of S. maltophilia have been suggested by descriptive such as previous antimicrobial central venous to an ICU or neonatology mechanical and respiratory diseases Among them, previous use, and those antibiotics that for this multiresistant such as is the most frequently However, case-control or cohort studies performed to risk factors for S. maltophilia acquisition have been (Table of those studies included patient patients ICU patients and patients Thus, to is 1 other case-control study to and cohort studies on risk factors associated with S. maltophilia colonization infection, previous and present patients, that days, days of days of and chronic infection with other pathogens were associated with increased risk of S. maltophilia colonization or Multivariate analysis was not performed in that study. that several factors to antimicrobial therapy were the most variables for S. maltophilia in a similar using number of days on therapy and chronic of performed a case-control study in patients with infection to the factors associated with S. maltophilia that increased the risk of S. maltophilia were previous therapy with or other and central venous while previous therapy with was a In a cohort study, and that patients with were not risk for nosocomial acquisition of S. maltophilia than those with However, analysis was not and the study not control for several such as invasive In a respiratory ICU, performed a cohort study during an to the hospital by and of a number of antimicrobials were for S. maltophilia infection or antimicrobial was as a risk performed a case-control study to factors associated with the isolation of S. maltophilia. Controls were patients cultures other Gram-negative bacilli, that risk factors to the isolation of S. maltophilia of other Gram-negative performed 2 to be significantly associated with increased risk of S. maltophilia isolation in models were previous therapy with and chronic respiratory and were in 1 of the was not a risk in that study, the number of patients had received this antimicrobial was We were in the of antimicrobial as risk factors for the acquisition of S. maltophilia. epidemiologic in participating hospitals and units were in the of the study by frequency matching. a the of underlying diseases in a as risk factors was and not be and were by analysis. controls were patients not S. maltophilia. Thus, the risk factors to the risk of S. maltophilia isolation per The variables associated with increased risk in the 2 models performed were previous of or and mechanical as categorical and continuous variables. The of and quinolones as risk factors may be by their be that the patients have acquired the organism before being admitted to the or more during their hospital stay, mainly from with those antimicrobials for S. maltophilia of its intrinsic resistance to most colonization to with clinical cultures and the of infection in patients in relation to invasive have several S. maltophilia should be considered a potential cause of nosocomial infections in patients previously received a of a or a of these antimicrobials to and control the of S. maltophilia in hospitals. study has The first is that not to detected as colonized by means of clinical samples a proportion of the colonized However, the information by data may be for is that the study is a study. The identification of the organism and the study of antimicrobial susceptibility were performed in the in each of the participating in of them standard by the was used. not perform of the of cases were not of have However, several studies have in the endemic acquired of S. maltophilia are study the incidence and risk factors for colonization and infection by Stenotrophomonas performed a case-control study in 6 hospitals during a All hospitalized patients had S. maltophilia isolated from clinical samples were included (cases). Controls were chosen among patients from whom a similar sample was negative for this During the study 129 cases were included 7 and 1 The incidence of S. maltophilia colonization or infection was cases per 10,000 of the patients were in the intensive care In of cases, the organism was considered S. maltophilia was isolated more frequently from respiratory samples was the most antimicrobial in followed by and while of were resistant to the patients were considered to be infected. Pneumonia was the most frequent type of infection of them were followed by other respiratory tract infections surgical site infections and primary bacteremia (11%). the following risk factors for colonization or infection with S. maltophilia were in the 2 models previous of or and mechanical We the from hospitals for their in cases and controls and for the susceptibility