Treatment Outcomes of Stenotrophomonas maltophilia Bacteremia in Critically Ill Children: A Multicenter Experience.

OBJECTIVES: Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse. DESIGN: A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017. SETTING: Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly. PATIENTS: A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed. MEASUREMENTS AND MAIN RESULTS: The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01). CONCLUSIONS: The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

Risk analysis of antimicrobial resistance in outpatient urinary tract infections of young healthy adults.

Objectives: Most studies addressing community-acquired urinary tract infections (UTIs) pertain to mixed cohorts, in which young healthy adults are under-represented. We aimed to dissect the intricate interrelation between exposures and subsequent antimicrobial resistance (AMR) patterns in a unique setting of young healthy adults, allowing further guidance in this group. Methods: We carried out a retrospective cross-sectional study of all Enterobacteriaceae-associated outpatient UTIs during 2014-16 in soldiers, representing the young fit population in Israel. Electronic medical records were reviewed for demographic and clinical data, antimicrobial exposures and prescriptions. Risk factors for AMR were analysed by multivariate logistic regression. Results: Of 1207 cases, 1144 (94.8%) were females, with a median age of 20.2 years. Escherichia coli was the predominant species (83.2%). Only 686 (56.8%) isolates were fully susceptible. AMR rates were as follows: trimethoprim/sulfamethoxazole, 19.6%; oral cephalosporins, 9.7%-16.7%; amoxicillin/clavulanate, 12.1%; ciprofloxacin, 11.1%; and nitrofurantoin, 12.6%. Predictors of AMR were recurrent UTIs, past-year hospitalization, male gender and non E. coli strains. Antimicrobials prescribed >6 months preceding the culprit infection were not related to AMR. Fluoroquinolone and cephalosporin exposures were highly predictive of further AMR, yet nitrofurantoin and, to a lesser extent, amoxicillin/clavulanate had fewer associations with AMR induction and resistance to these antimicrobials was less associated with any exposure. Conclusions: This nationwide study of community-related UTIs shows significant AMR rates for commonly used oral antimicrobials even in young fit adults. Nitrofurantoin proved once more to be an adequate empirical choice regardless of previous exposures, having a less detrimental effect on future AMR. Conversely, both resistance to fluoroquinolones following previous exposures and the associated heavy ecological burden should deter their common use as first-line agents for UTIs.

Management of Stenotrophomonas maltophilia Infections in Critically Ill Children.

BACKGROUND: Stenotrophomonas maltophilia is a life-threatening nosocomial pathogen with profound multidrug-resistant attributes. It is associated with high mortality, particularly in immunocompromised patients. Data on therapy for S. maltophilia infections are scarce, especially in children hospitalized in intensive care settings (pediatric intensive care unit). METHODS: A retrospective chart review of pediatric patients with isolates of S. maltophilia hospitalized over a 5-year period in 2 pediatric intensive care units. RESULTS: Thirty-one patients and 91 isolates from blood, respiratory secretions and soft tissues were identified and reviewed. The overall incidence of S. maltophilia infections increased during the study period (P = 0.003). The all-cause crude mortality was 61%, and the attributed mortality was approximately 16%. Risk factors associated with mortality included longer hospitalization before infection (P = 0.002), septic shock (P = 0.003), mechanical ventilation (P = 0.004), an indwelling central vein catheter (P = 0.03) and prior use of steroids (P = 0.04) and carbapenems (P = 0.004). On multivariate analysis, mortality was associated with mechanical ventilation (P = 0.02) and preinfection hospitalization days (P = 0.01). Combination treatment of trimethoprim and sulfamethoxazole, ciprofloxacin and/or minocycline significantly extended survival time (P < 0.001). The method of treatment did not significantly affect the interval between S. maltophilia isolation to resolution of infection (P = 0.200). CONCLUSIONS: Combinations of trimethoprim and sulfamethoxazole, ciprofloxacin and minocycline are proposed for pediatric intensive care unit patients harboring S. maltophilia. Meticulous evaluation of central vascular access and prior treatment with carbapenems are indicated, especially for mechanically ventilated and septic children.

Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection.

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Effect of benzathine penicillin treatment on antibiotic susceptibility of viridans streptococci in oral flora of patients receiving secondary prophylaxis after rheumatic fever.

OBJECTIVE: To assess the level of antibiotic resistance of viridans streptococci in the oral flora of children with a history of rheumatic fever, receiving long-term monthly intramuscular benzathine penicillin G prophylaxis. PATIENTS AND METHODS: Oral swabs from patients receiving monthly penicillin G prophylaxis for rheumatic fever were cultured and tested for viridans streptococci. The E-test was used to test susceptibility to penicillin G, clindamycin, clarithromycin and rifampin. Findings were compared with samples from healthy children who had not been exposed to antibiotic treatment for at least 2 months. RESULTS: Twenty-six patients and 20 control children were included in the study. Duration of intramuscular antibiotic treatment ranged from 5 months to 13.5 years. Sixty isolates of viridans streptococci species were obtained, with a similar distribution in the two groups. Intermediate resistance to penicillin (MIC 0.25-2 mg/L) was documented in 10 of the 32 isolates (31.2%) in the study group, and high resistance in none, compared to seven of 28 isolates (25%) with intermediate or high resistance in the control group (p=NS). All isolates in the study group and all but one in the control group were susceptible to clindamycin, and all isolates from both groups were susceptible to rifampin. One isolate (3.1%) in the study group and two (7.1%) in the control group were resistant to clarithromycin. CONCLUSION: Monthly Intramuscular penicillin prophylaxis has no effect on the antibiotic susceptibility of viridans streptococci in oral flora in children with a history of rheumatic fever, receiving secondary prophylaxis after rheumatic fever, regardless of the duration of treatment.