Objective: To understand the risk factors and antibiotics-resistant patterns of invasive Acinetobacter baumannii infection in Children. Methods: This retrospective study was conducted in 6 tertiary hospitals from January 2016 to December 2018. The basic information, clinical data and the results of antimicrobial susceptibility testing were collected from the 98 pediatric inpatients with Acinetobacter baumannii isolated from blood or cerebrospinal fluid and analyzed. According to the susceptibility of the infected strains to carbapenems, they were divided into carbapenem-sensitive Acinetobacter baumannii (CSAB) group and carbapenem-resistant Acinetobacter baumannii (CRAB) group. According to the possible sources of infection, they were divided into nosocomial infection group and community infection group. Chi-square test or Fisher exact test were used to analyze categorical variables and rank sum test were used to analyze continuous variables. The risk factors of invasive CRAB infection in children were analyzed by Logistic regression. Result: There were 56 males and 42 females in 98 cases. The onset age of patients was 8 (2, 24) months. There were 62 cases (63%) from rural area. A total of 87 cases (89%) were confirmed with bloodstream infection, and 12 cases (12%) confirmed with meningitis (1 case was accompanied with bloodstream infection). In these patients, 66 cases (67%) received invasive medical procedures or surgery, 54 cases (55%) received carbapenems-containing therapy. Twenty-four cases were infected with CRAB, and 74 cases with CSAB. The onset age of cases in CRAB group was lower than that in CSAB group (4 (1, 9) vs. 10 (4, 24) months, Z=-2.16, P=0.031). The proportions of hospitalization in intensive care unit, carbapenem antibiotics using, pneumonia and adverse prognosis in CRAB group were higher than those in CSAB group (6 cases (25%) vs. 4 cases (5%), 18 cases (75%) vs. 36 cases (49%), 17 cases (71%) vs. 17 cases (23%), 6 cases (25%) vs. 4 cases (5%), χ²=5.61, 5.09, 18.32, 5.61, all P<0.05). Seventy-seven cases were nosocomial infection and 21 cases were hospital-acquired infection. The proportion of children hospitalized in high-risk wards for nosocomial infections, length of hospitalization, number of antimicrobial therapy received and duration of antimicrobial therapy were higher in the hospital associated infection group than those in the community acquired infection group (all P<0.05). Logistic regression analysis showed that children from rural area (OR=8.42, 95%CI 1.45-48.88), prior mechanical ventilation (OR=12.62, 95%CI 1.31-121.76), and prior antibiotic therapy (OR=4.90, 95%CI 1.35-17.72) were independent risk factors for CRAB infection. The resistance percentage of CSAB isolates to many classes of antibiotics was <6% except to gentamicin, which was as high as 20% (13/65). All CRAB isolates of resistant to ampicillin-sulbactam (20/20), cefepime (23/23), piperacillin (17/17), meropenem (23/23) and imipenem (24/24) were 100%. The resistance percentage to other antibiotics were up to 42%-96%. Conclusions: Most of invasive Acinetobacter baumannii infection in children in China are hospital-acquired. The outcome of invasive CRAB infection was poorer than that of CSAB infection. The drug resistance rate of CRAB strains isolated is high. Living in rural area, prior invasive mechanical ventilation and prior antibiotic therapy were independent risk factors for invasive CRAB infection. The prevention and control of nosocomial infection and appropriate use of antibiotics to reduce Acinetobacter baumannii infection.
Acinetobacter Infections/epidemiology* ; Acinetobacter baumannii ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/therapeutic use* ; Child ; Cross Infection/epidemiology* ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Retrospective Studies ; Risk Factors ; Sepsis

infections (IAIs).METHODS: This multicenter study was conducted at 6 university-affiliated hospitals in Korea between 2016 and 2018. All patients with microbiologically proven IAIs were retrospectively included, while patients with spontaneous bacterial peritonitis or continuous ambulatory peritoneal dialysis peritonitis were excluded. Identification and antimicrobial susceptibility testing were performed using automated microbiology systems.RESULTS: A total of 2,114 non-duplicated clinical isolates were collected from 1,571 patients. Among these pathogens, 510 (24.1%) were isolated from nosocomial infections, and 848 isolates (40.1%) were associated with complicated IAIs. The distribution of the microorganisms included aerobic gram-negative (62.6% of isolates), aerobic gram-positive (33.7%), anaerobic (0.9%), and fungal (2.8%) pathogens. The most common pathogens were Escherichia coli (23.8%), followed by Enterococcus spp. (23.1%) and Klebsiella spp. (19.8%). The susceptibility rates of E. coli and Klebsiella spp. to major antibiotics were as follows: amoxicillin/clavulanate (62.5%, 83.0%), cefotaxime (61.4%, 80.7%), ceftazidime (63.7%, 83.1%), cefepime (65.3%, 84.3%), ciprofloxacin (56.4%, 86.3%), piperacillin/tazobactam (99.0%, 84.8%), amikacin (97.4%, 98.3%), and imipenem (99.8%, 98.8%). The susceptibility rates of Enterococcus spp. to ampicillin were 61.0%, amoxicillin/clavulanate, 63.6%; ciprofloxacin, 49.7%; imipenem, 65.2%; and vancomycin, 78.2%. The susceptibility rates of Pseudomonas aeruginosa and Acinetobacter spp. to imipenem were 77.4% and 36.7%, respectively.CONCLUSION: Enterococcus spp. with susceptibility to limited antibiotics was one of the main pathogens in Korean IAIs, along with E. coli and Klebsiella spp., which were highly susceptible to imipenem, amikacin, and piperacillin/tazobactam. Meanwhile, the low susceptibilities of E. coli or Klebsiella spp. to amoxicillin/clavulanate, advanced-generation cephalosporins, and ciprofloxacin should be considered when determining empirical antibiotic therapy in clinical practice.]]>
Acinetobacter ; Amikacin ; Ampicillin ; Anti-Bacterial Agents ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Ciprofloxacin ; Cross Infection ; Enterococcus ; Epidemiology ; Escherichia coli ; Humans ; Imipenem ; Intraabdominal Infections ; Klebsiella ; Korea ; Peritoneal Dialysis, Continuous Ambulatory ; Peritonitis ; Pseudomonas aeruginosa ; Retrospective Studies ; Vancomycin

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.
Acinetobacter baumannii ; drug effects ; pathogenicity ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Ciprofloxacin ; pharmacokinetics ; pharmacology ; Female ; Gram-Negative Bacteria ; drug effects ; pathogenicity ; Humans ; Male ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; pathogenicity ; Respiratory Tract Infections ; drug therapy ; metabolism ; microbiology

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with high mortality. One of the strategies to reduce the mortality in patients with CRAB infections is to use intravenous colistin early but the effect of this strategy has not been proven. Therefore, we investigated the association of early colistin therapy with 28-day mortality in patients with CRAB bacteremia. METHODS: This retrospective multicenter propensity score-matching analysis was conducted in the Korea by reviewing the medical records of adult patients with CRAB bacteremia between January 2012 and March 2015. Early colistin therapy was defined as intravenous colistin administration for > 48 hours within five days after the blood culture collection. To identify the risk factors associated with the 28-day mortality in CRAB bacteremia, the clinical variables of the surviving patients were compared to those of the deceased patients. RESULTS: Of 303 enrolled patients, seventy-six (25.1%) patients received early colistin therapy. The 28-day mortality was 61.4% (186/303). Fatal or rapidly-fatal McCabe classifications, intensive care unit admission, Sequential Organ Failure Assessment scores ≥ 8, vasopressor use, and acute kidney injury were statistically independent poor prognostic factors. Catheter-related infection and early colistin therapy (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.21–0.94) were independent favorable prognostic factors associated with 28-day mortality in patients with CRAB bacteremia. Early colistin therapy was still significantly associated with lower 28-day mortality in the propensity score-matching analysis (aOR, 0.31; 95% CI, 0.11–0.88). CONCLUSION: This study suggests that early colistin therapy might help reduce the mortality of patients with CRAB bacteremia.
Acinetobacter ; Acinetobacter baumannii ; Acute Kidney Injury ; Adult ; Bacteremia ; Catheter-Related Infections ; Classification ; Colistin ; Humans ; Intensive Care Units ; Korea ; Medical Records ; Mortality ; Odds Ratio ; Organ Dysfunction Scores ; Retrospective Studies ; Risk Factors

Acinetobacter baumannii (A. Baumannii) is an emerging opportunistic pathogen responsible for hospital-acquired infections, and which now constitutes a sufficiently serious threat to public health to necessitate the development of an effective vaccine. In this study, a recombinant fused protein named OmpK/Omp22 and two individual proteins OmpK and Omp22 were obtained using recombinant expression and Ni-affinity purification. Groups of BALB/c mice were immunized with these proteins and challenged with a clinically isolated strain of A. baumannii. The bacterial load in the blood, pathological changes in the lung tissue and survival rates after challenge were evaluated. Mice immunized with OmpK/Omp22 fused protein provided significantly greater protection against A. baumannii challenge than those immunized with either of the two proteins individually. The results provide novel clues for future design of vaccines against A. baumannii.
Acinetobacter Infections ; pathology ; prevention & control ; Acinetobacter baumannii ; genetics ; immunology ; Animals ; Antibodies, Bacterial ; blood ; Bacterial Load ; Bacterial Outer Membrane Proteins ; genetics ; immunology ; Bacterial Vaccines ; immunology ; Disease Models, Animal ; Female ; Mice, Inbred BALB C ; Pneumonia, Bacterial ; pathology ; prevention & control ; Recombinant Fusion Proteins ; genetics ; immunology

BACKGROUNDThe accuracy of nasopharyngeal aspirate (NPA) specimens in detecting lower respiratory pathogens remains controversial. The objective of this study was to evaluate the diagnostic accuracy of aspirates (NPAs) specimen in lower respiratory tract infections (LRTIs) in children.

METHODSThe prospective study was designed to collect the data of paired NPAs and bronchoalveolar lavage fluids from children with acute LRTIs from January 2013 to December 2015. All specimens were subjected to pathogen detection: bacterial detection by culture, Mycoplasma pneumoniae (Mp) detection by polymerase chain reaction assay and virus (influenza A and B viruses, parainfluenza virus [PIV] Types 1 and 3, respiratory syncytial virus, and adenovirus) detection by immunofluorescence assay. The diagnostic accuracy analysis of NPAs was stratified by age ≤3 years (n = 194) and >3 years (n = 294).

RESULTSWe collected paired specimens from 488 children. The positive rate of pathogen was 61.6%. For Streptococcus pneumoniae, NPA culture had the specificity of 89.9% and negative predictive value of 100% in age ≤3 years, the specificity of 97.2% and negative predictive value of 98.9% in age >3 years. For Mp, the positive predictive values of NPA was 77.4% in children ≤3 years, and 89.1% in children >3 years. For PIV III, NPA specimen had the specificity of 99.8% and negative predictive value of 96.5% in children ≤3 years. For adenovirus, NPA had the specificity of 97.8% and negative predictive value of 98.4% in age ≤3 years, the specificity of 98.9% and negative predictive value of 99.3% in age >3 years.

CONCLUSIONSNPAs are less invasive diagnostic respiratory specimens, a negative NPA result is helpful in "rule out" lower airway infection; however, a positive result does not reliably "rule in" the presence of pathogens.

Acinetobacter baumannii ; isolation & purification ; pathogenicity ; Adolescent ; Child ; Child, Preschool ; Clinical Laboratory Techniques ; methods ; Enterobacter aerogenes ; isolation & purification ; pathogenicity ; Escherichia coli ; isolation & purification ; pathogenicity ; Female ; Haemophilus influenzae ; isolation & purification ; pathogenicity ; Humans ; Infant ; Male ; Nasopharynx ; microbiology ; Prospective Studies ; Pseudomonas aeruginosa ; isolation & purification ; pathogenicity ; Respiratory Tract Infections ; diagnosis ; microbiology ; Sensitivity and Specificity ; Staphylococcus aureus ; isolation & purification ; pathogenicity ; Streptococcus pneumoniae ; isolation & purification ; pathogenicity

Acinetobacter baumannii is a source of opportunistic infection in hospital and can cause central nervous system infection mainly by neurosurgical operation. Community acquired infection by Acinetobacter baumannii is very rare. A 58-year-old man was presented with fever, decreased consciousness and seizure. Acinetobacter baumannii was identified in the CSF culture, and colistin was administered intravenously. Patient's clinical symptoms improved after treatment. We report a case of successful treatment of Acinetobacter baumannii meningitis with colistin.
Acinetobacter baumannii* ; Acinetobacter* ; Central Nervous System Infections ; Cerebrospinal Fluid ; Colistin* ; Consciousness ; Fever ; Humans ; Meningitis* ; Middle Aged ; Opportunistic Infections ; Seizures

Animal models are essential to studies of infectious diseases. The use of mice to test bacterial infection has been extensively reported. However, methods applied to clinical isolates, particularly for carbapenem-resistant bacteria, must be tailored according to the infection models and bacteria used. In this study, we infected 6-week-old female BALB/c mice intraperitoneally with different strains of resistant bacteria plus 3% hog gastric mucin. This method was found to be efficient and readily applicable for investigation of carbapenem-resisant Gram-negative pathogens (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) detected in Korea.
Acinetobacter ; Animals ; Bacteria ; Bacterial Infections ; Communicable Diseases ; Escherichia coli ; Female ; Gastric Mucins* ; Gram-Negative Bacteria* ; Humans ; Klebsiella pneumoniae ; Korea ; Methods ; Mice ; Models, Animal ; Peritonitis* ; Pseudomonas aeruginosa

BACKGROUND: Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii. METHODS: Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 microg/mL, doripenem 8 microg/mL) and achievable tissue levels (tigecycline 2 microg/mL) for each antibiotic were used in this study. RESULTS: The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, thedoripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bacteri-cidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination. CONCLUSIONS: The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropri-ate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.
Acinetobacter Infections/drug therapy/microbiology ; Acinetobacter baumannii/*drug effects/genetics/isolation & purification ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/*pharmacology/therapeutic use ; Colistin/*pharmacology/therapeutic use ; Drug Resistance, Multiple, Bacterial/*drug effects ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Microbial Sensitivity Tests ; Minocycline/*analogs & derivatives/pharmacology/therapeutic use ; Multilocus Sequence Typing ; beta-Lactamases/genetics

BACKGROUND: Acinetobacter baumannii has a greater clinical impact and exhibits higher antimicrobial resistance rates than the non-baumannii Acinetobacter species. Therefore, the correct identification of Acinetobacter species is clinically important. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has recently become the method of choice for identifying bacterial species. The purpose of this study was to evaluate the ability of MALDI-TOF MS (Bruker Daltonics GmbH, Germany) in combination with an improved database to identify various Acinetobacter species. METHODS: A total of 729 Acinetobacter clinical isolates were investigated, including 447 A. baumannii, 146 A. nosocomialis, 78 A. pittii, 18 A. ursingii, 9 A. bereziniae, 9 A. soli, 4 A. johnsonii, 4 A. radioresistens, 3 A. gyllenbergii, 3 A. haemolyticus, 2 A. lwoffii, 2 A. junii, 2 A. venetianus, and 2 A. genomospecies 14TU. After 212 isolates were tested with the default Bruker database, the profiles of 63 additional Acinetobacter strains were added to the default database, and 517 isolates from 32 hospitals were assayed for validation. All strains in this study were confirmed by rpoB sequencing. RESULTS: The addition of the 63 Acinetobacter strains' profiles to the default Bruker database increased the overall concordance rate between MALDI-TOF MS and rpoB sequencing from 69.8% (148/212) to 100.0% (517/517). Moreover, after library modification, all previously mismatched 64 Acinetobacter strains were correctly identified. CONCLUSIONS: MALDI-TOF MS enables the prompt and accurate identification of clinically significant Acinetobacter species when used with the improved database.
Acinetobacter Infections/*microbiology/pathology ; Acinetobacter baumannii/*chemistry/classification/isolation & purification ; Bacterial Proteins/chemistry/genetics/metabolism ; Databases, Factual ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization