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To describe some clinical and subclinical characteristics in patients with sepsis caused by S. maltophilia and identify antibiotic resistance status in S. maltophilia strain was isolated.
Jourrnal of military pharmaco-medicine n09-2019 RESEARCH ON CLINICAL AND SUBCLINICAL CHARACTERISTICS IN PATIENTS WITH SEPSIS CAUSED BY STENOTROPHOMONAS MALTOPHILIA TREATED AT 103 MILITARY HOSPITAL AND 108 MILITARY CENTRAL HOSPITAL (FROM JANUARY 2014 TO OCTOBER 2018) Nguyen Hoang Thanh1; Hoang Vu Hung1 SUMMARY Objectives: To describe some clinical and subclinical characteristics in patients with sepsis caused by S maltophilia and identify antibiotic resistance status in S maltophilia strain was isolated Subjects and methods: Retrospective combined prospective, descriptive cases in 63 patients with sepsis caused by S maltophilia treated at 103 Military Hospital and 108 Central Military Hospital Results: 61.9% of patients > 60 years old; men: 77.8%; 85.7% pathological background; 76.2% identified the primary infection source; 99.4% fever in which suddenly of fever 51.6%, fluctuating of fever 64.5%, hot fever 41.9% Sepsis caused by S maltophilia damaged most organs: 42.9% consciousness disorders; heart rate > 90 cycles/minute: 60.4%; hypotension: 11.1%; pneumonia: 71.2%; abdominal pain: 18.8%; painful urination: 5.9%; WBC > 10 G/L: 67.7%; hemoglobin < 120 g/L: 68.4%; platelets < 150 GLl: 19.3%; urea > 7.5 mmol/L: 23.5%; ALT > 80 U/L: 11.8%; 22.7% of patients had total bilirubine > 17 µmol/L; 17.5% of patients had prothrombine ratio < 70%; 22% of patients had PCT > 10 ng/mL S maltophilia strain isolated were resistant to cefotaxime: 95.7%, ceftriaxone: 95%; imipenem: 100%, meropenem: 100%; ampicillin resistance: 100%; aminoglycosid antibiotics resistance: 70 - 80% Mortality rate was 17/63 patients (27%) Conclusion: Sepsis caused by S maltophilia was common in elderly people; the mortality rate was relatively high S maltophilia strain isolated was multi antibiotic resistance * Keywords: Sepsis; Stenotrophomonas maltophilia; Clinical and subclinical characteristics INTRODUCTION Sepsis caused by S maltophilia is rare, mainly diagnosed in patients with cancer, lung cystic fibrosis, immunodeficiency 103 Military Hospital and 108 Military Central Hospital are equipped with modern equipment such as Batec blood culture system, identifier and antimicrobial Vitek automatic… This has contributed positively to the diagnosis of rare pathogens, including S maltophilia In order to contribute to the diagnosis and timely treatment, selecting appropriate antibiotics, shortening hospital time, reducing costs for patients and reduce mortality rate in patients with sepsis caused by S maltophilia, we carried out this thesis with aims: 103 Military Hospital Corresponding author: Nguyen Hoang Thanh (hoangthanh27081991hvqy@gmail.com) Date received: 25/09/2019 Date accepted: 19/11/2019 255 Jourrnal of military pharmaco-medicine n09-2019 - Survey the number of characteristics in clinical, subclinical in patients with sepsis caused by S maltophilia - Determination of antibiotic resistance of isolated S maltophilia strains SUBJECTS AND METHODS Subjects 63 patients with sepsis caused by S maltophilia: 40 patients were hospitalized and treated at 103 Military Hospital and 23 patients were hospitalized and treated at 108 Military Central Hospital from January 2014 to November 2018 * Criteria for selecting patients: Patients were diagnosed with sepsis based on consent of the International Conference on Sepsis (2001) [6]: - Having systemic inflammatory response syndrome: At least of the following criteria (including a compulsory standard for abnormalities in body temperature or white blood cell counts) + Body temperature > 38ºC or < 36ºC + Heart rate > 90 cycles/minute + Frequency of breathing > 20 cycles/minute or PaCO2 < 32 mmHg + White blood cell counts > 12,000 or < 4,000/mm3, or young white blood cell count > 10% - Blood cultures were isolated S maltophilia bacteria - Patients over 18 years of age * Exclusion criteria: - The patient refused to participate in the study - The patient had a positive blood culture (+) with at least ≥ pathogens 256 Methods Cross-sectional combined with retrospective and prospective study for enough qualifies cases - Retrospective cases of sepsis caused by S maltophilia infection hospitalized and treated between 01 - 2014 and 10 - 2017 (55 patients) - Prospective cases of sepsis caused by S maltophilia infection hospitalized and treated between 11 - 2017 and 11 - 2018 (08 patients) Data collection through the store of medical records, all medical records were registered under unified form * Research content: - Distribution of patients according to age, gender, source of infection (hospital infections and community infections), pathological background, primary infections source - Shock and mortality rate - Clinical symptoms: Characteristics and properties of fever; skin and mucosa manifestations; consciousness disorder; damage to the circulatory system (pulse, blood pressure ); damage to the respiratory system (pneumonia, pleural effusion, respiratory failure ); damage to the digestive system (digestive disorders, hepatomegaly, splenomegaly, abdominal pain, jaundice ); damage to the urinary system (painful urination, oliguria, anuria ) - Learn about the clinical indicators: Number of red blood cells (T/L), hemoglobine (g/L); leukocyte count (G/L), percentage of neutrophil; platelets (G/L); prothrombine rate (%); enzymes AST, Jourrnal of military pharmaco-medicine n09-2019 ALT (U/L); total bilirubine (µmol/L); blood urea (mmol/L); blood creatinine (µmol/L); electrolytes; procalcitonine (ng/mL) automatically on the system identification Vitek - BIOMÉRIEUX or performed by Kirby - Bauer technique - Determine antibiotic resistance according to technical antimicrobial were performed The results collected were processed using SPSS software version 23.0 RESULTS Table 1: Epidemiological characteristics of patients Characteristics Number of patients (n = 63) The average age (years): - max Rate (%) 65.8 ± 17.7 (21 - 94) Group over 60 years old 39 61.9 Male 49 77.8 Hospital infection 33 52.4 Yes 54 85.7 Diabetes 22 34.9 Heart failure 10 15.9 Chronic renal failure 10 15.9 Respiratory tract 30 47.6 Gastrointestinal tract 14.3 Other 14.3 Pathological background Primary infections The group over 60 years old accounted for the largest proportion (61.9%) The proportion of male was 3.5 times higher than women Table 2: The clinical symptoms Symptom No patients Rate % Symptom No patients Rate (%) Suddenly 32/62 51.6 Abdominal pains 9/48 18.8 Fluctuating 40/62 64.5 Jaundice 4/48 8.3 Hot fever 26/62 41.9 Hepatomegaly 2/48 4.2 Pale of skin 39/63 61.9 Disorder of consciousness 27/63 42.9 Circuit > 90 cycles/min 32/53 60.4 Oliguria, anuria 3/51 5.9 Hypotension 7/63 11.1 Painful urination 3/51 5.9 Respiratory failure 12/59 20.3 Septic shock 11/63 17.5 Pneumonia 42/59 71.2 Mortality rate 17/63 27 Pleural effusion 17/59 28.8 Death due to septic shock 11/11 100 Fever Suddenly of fever and fluctuating of fever were occured in more than 50% of patients 257 Jourrnal of military pharmaco-medicine n09-2019 Table 3: Subclinical characteristics No patients Rate (%) No patients Rate (%) Hb < 120 g/L 39/57 68.4 CRP > 100 mg/L 21/41 51.2 WBC > 10 G/L 42/62 67.7 PCT > 10 ng/mL 11/50 22 Neutrophil > 70% 51/62 82.3 AST > 80U/L 7/51 13.7 Platelet < 150 G/L 11/57 19.3 ALT > 80 U/L 6/51 11.8 Glucose > 7.1 mmol/L 36/61 59 Bilirubine total > 17 µmol/L 10/44 22.7 Ure > 7.5 mmol/L 12/51 23.5 Albumin < 35 g/L 31/47 66 Creatinine > 120 µmol/L 3/51 5.9 Prothrombine < 70% 7/40 17.5 Subclinical index Subclinical index Table 4: Antibiotic resistance of S maltophilia strain were isolated Antibiotics Total Sensitive Intermediate Resistance n % n % n % Cefotaxime 23 4.3 0 22 95.7 Ceftriaxone 20 5.0 0 19 95.0 Ceftazidime 28 17.9 14.3 19 67.8 Cefepim 21 14.3 19.0 14 66.7 Gentamycin 21 14.3 14.3 15 71.4 Tobramycin 20 20.0 10.0 14 70.0 Amikacin 30 13.3 6.7 24 80.0 Minocyclin 9 100 0 0 Doxycillin 11 81.8 0 18.2 Levofloxacin 41 36 87.8 2.4 9.8 Ciprofloxacin 21 12 57.1 14.3 28.6 Colistin 20 16 80.0 10.0 10.0 Imipenem 37 0 0 37 100 Meropenem 40 0 0 40 100 Ertapenem 17 5.9 5.9 15 88.2 Aztreonam 19 0 0 19 100 Trimethoprim/sulfamethoxazol 44 40 90.9 0 9.1 Amoxicillin/clavunalic 21 4.8 0 20 95.2 Ampicillin 0 0 100 Ampicillin/sulbactam 11.1 0 88.9 Ticarcillin 18 0 5.6 17 94.4 Ticarcillin/clavunalic 18 33.3 0 12 66.7 258 Jourrnal of military pharmaco-medicine n09-2019 - Bacteria were highly sensitive with trimethoprim/sulfamethoxazole antibiotics (90.9%); antibiotics of cycline group: minocyclin (100%), doxycycllin (81.8%); colistin (80.0%); levofloxacin (87.8%) - S maltophilia most resistant to cephalosporin antibiotics: Cefotaxime (95.7%), ceftriaxone (95.0%); carbapenem antibiotics: imipenem (100%), meropenem (100%), ertapenem (88.2); aminoglycoside antibiotics: gentamycin (71.4%), tobramycin (70.0%), amikacin (80.0%) DISCUSSION In recent decades, sepsis caused by S maltophilia was a medical problem that needs attention due to the increasing incidence of morbidity and mortality According to the study by Chung-Hsu Lai (2004), 84 sepsis patients caused by S maltophilia had an average age of 62.3 ± 2.0 years old; male 75%; hospital sepsis 76%; primary infection from respiratory tract 33% and intravascular catheter 31%; septic shock 48%; mortality rate of 33%; antimicrobial results of S maltophilia strains were isolated 100% resistant to imipenem; some antibiotics susceptible including ciprofloxacin 39/47 (83.0%); trimethoprim/sulfamethoxazole 64/84 (76.0%); these results were similar to our study [4] Xi Chen, Wenjun Wu et al (2017) studied retrospectively 95 sepsis patients caused by S maltophilia in years (2009 2015) at Zhejiang University (China) Results: The mortality rate was higher than our study (37.9%); common background diseases were diabetes and blood cancer with the same rate (19%), COPD (13.7%) and chronic kidney failure (6.3%); 93.7% of patients with fever was higher than 38ºC, the average temperature was 39.2ºC; proportion of patients with leukocytosis was 29.5%; CRP concentration > 10 mg/L accounted for 88.4%; S maltophilia strains resistance to gentamycin (87.6%), amikacin (85.6%), and imipenem (97.8%) [9] Mustafa Gokhan Gozel (2015) studied at Turkey's Cumhuriyet Hospital on 35 patients with sepsis caused by S maltophilia, the average age of patients was 61.9 ± 18; proportion of male infected was 22/35 (62.9%); pathological background was similar to our research included: chronic obstructive bronchitis (37.1%), diabetes (31.4%), cancer (28.6%), heart failure (17.1%), chronic renal failure (11.4%); the proportion of patients with anemia (82.9%); 40% of patients increased the number of white blood cells; 37.1% of patients with reduced platelet count; 85.7% of patients increased CRP levels [7] According to research by Ya-Ting Chang (2012), 94 patients sepsis caused by S maltophilia had common pathological background included: cancer (41.5%), diabetes (33.0%), chronic kidney failure 25/94 (26.6%), chronic obstructive bronchopulmonary disease (8.5%); 61.4% of patients with hospital infections; primary infection detecting from intravascular catheter (20.2%), respiratory tract (14.9%), gastrointestinal tract (7.4%); bacteria sensitive to the antibiotic TMP/SMX (68.9%), levofloxacin (89.9%), minocycline (99.4%) [10] Research by Hirotaka Ebara (2015): average age of 44 patients with sepsis caused by S maltophilia was 48.9; male 63.6%; 4.5% of patients had damaged 259 Jourrnal of military pharmaco-medicine n09-2019 skin and soft tissue; primary infection from intravascular catheter 36.4%, gastrointestinal tract 11.4%, respiratory tract 4.5%, unknown infection source 43.2%; mortality proportion 38.9% [5] Sumida et al (2015) studied 30 sepsis patients caused by S maltophilia with an average age of 51; the proportion of male patients were 1.5 times higher than female; septic shock 20% [8] Recent domestic studies also reported S maltophilia bacteria as an emerging cause of sepsis Research by Tran Van Si et al (2013) at Kiengiang General Hospital found that sepsis caused by S maltophilia accounted for 1.7% [2] Tran Thi Thanh Nga studied 8,665 strains of bacteria isolated from sepsis patients at Cho Ray Hospital for years showed that S maltophilia tend to increase in 2011 and 2012, 5.7% and 13.7%, respectively compared with 2009 was only 1% [1] The study by Le Xuan Truong (2009): 6/79 sepsis patients (7.6%) caused by S maltophilia had average PCT value of 36.2 ng/mL [3] CONCLUSION Sepsis caused by S maltophilia was common in elderly people (61.9%); 85.7% of patients had pathological background; 76.2% identified the primary infection (in which primary infection was common in respiratory tract 47.6%); fever 99.4% (in which suddenly fever 51.6%, fluctuating fever 64.5%, hot fever 41.9%) Sepsis caused by S maltophilia damaged most organs: 42.9% consciousness disorders; heart rate > 90 cycles/minute 60.4%; hypotension 11.1%; pneumonia 71.2%; abdominal pain 18.8%; painful urination 260 5.9%; white blood cells > 10 G/L (67.7%); Hb < 120 g/L (68.4%); platelets < 150 G/L (19.3%); ure > 7.5 mmol/L (23.5%); ALT > 80 U/L (11.8%); 22.7% of patients had total bilirubine > 17 µmol/L; 17.5% of patients had prothrombine rate < 70%; 22% patients with PCT > 10 ng/mL There were 17.5% of patients manifested septic shock; 27% mortality Strains of S maltophilia isolated multiple antibiotic resistance included: Cephalosporin antibiotic group: cefotaxime 95.7%, ceftriaxone 95%; carbapenem antibiotic group: imipenem 100%, meropenem 100%; 100% ampicillin resistance; aminoglycoside resistance 70 - 80% REFERENCES Tran Thi Thanh Nga Sepsis pathogens and tendency of resistance to antibiotics for years from 2008 - 2012 at Cho Ray Hospital Hochiminh City Medicine 2014, Vol 18, Supplement of number 2, pp.485-490 Tran Van Si, Tran Do Hung, Nguyen Ngoc Mai Survey on the situation causing sepsis at Kien Giang General Hospital Journal of Practical in Medicine 2013, N0 1, pp.12-19 Le Xuan Truong Diagnostic and prognostic value of serum Procalcitonin in the sepsis Hochiminh City Journal of Medicine 2009, (13), pp.213-241 Chung-Hsu Lai et al Clinical characteristics and prognostic factors of patients with Stenotrophomonasmaltophilia bacteremia J Microbiol Immunol Infect 2004, 37, pp.350-358 Hirotaka Ebara et al Clinical characteristics of Stenotrophomonas maltophilia bacteremia: Jourrnal of military pharmaco-medicine n09-2019 A regional report and a review of Japanese case series Intern Med 2015, 56, pp.137-142, A matched case-control study PLoS One 2015, 10 (7), p.0133731 Levy M, Fink M.P, Marshall J.C et al "SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conferenc Crit Care Med 2003 Xi Chen, Wenjun Wu et al Retrospective analysis of Stenotrophomonas maltophilia bacteremia: Clinical features, risk factors and therapeutic choices J Clin Exp Med 2017, 10 (8), pp.12268-12276 Mustafa Gokhan Gozel et al Stenotrophomonas maltophilia infections in adults: Primary bacteremia and pneumonia Jundishapur J Microbiol 2015, August, (8), e23569 Sumida K et al Risk factors associated with Stenotrophomonas maltophilia bacteremia: 10 Ya-Ting Chang, Chun-Yu Lin et al Stenotrophomonas maltophilia bloodstream infection: Comparison between community onset and hospital-acquired infections Journal of Microbiology, Immunology and Infection 2014 47, pp.28-35 261 ... of isolated S maltophilia strains SUBJECTS AND METHODS Subjects 63 patients with sepsis caused by S maltophilia: 40 patients were hospitalized and treated at 103 Military Hospital and 23 patients. ..Jourrnal of military pharmaco-medicine n09-2019 - Survey the number of characteristics in clinical, subclinical in patients with sepsis caused by S maltophilia - Determination of antibiotic... were hospitalized and treated at 108 Military Central Hospital from January 2014 to November 2018 * Criteria for selecting patients: Patients were diagnosed with sepsis based on consent of the International