Acinetobacter baumannii is a Gram-negative opportunistic pathogen widely distributed in hospital settings. It can survive for a long time and cause a variety of infections, including pneumonia, septicemia, urinary tract infections, and meningitis. The bacterium demonstrates extensive resistance, particularly to critical antibiotics like carbapenems and polymyxins, posing a serious threat to the recovery of severely ill patients. Carbapenem-resistant A. baumannii has been designated as a pathogen of critical priority on the World Health Organization (WHO) Bacterial Pathogen Priority List, requiring urgent development of new therapeutic agents. Phages, as a novel biological control approach, exhibit substantial potential in combating A. baumannii infections due to their specific ability to infect and lyse bacteria. This review highlights the application and potential of phages and phage-derived enzymes against multidrug-resistant A. baumannii, considering the epidemiological trends of A. baumannii in China, with the aim of providing innovative insights and strategies for phage therapy of drug-resistant bacterial infections.
Acinetobacter baumannii/drug effects* ; Drug Resistance, Multiple, Bacterial ; Phage Therapy/methods* ; Acinetobacter Infections/microbiology* ; Humans ; Bacteriophages/physiology* ; Anti-Bacterial Agents/pharmacology*

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

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

BACKGROUND/AIMS: Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. METHODS: Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital-onset MDR A. baumannii among patients in the ICUs. RESULTS: The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 +/- 82.26 defined daily doses per 1,000 patient-days to 94.85 +/- 50.98 defined daily doses per 1,000 patient-days (p = 0.016). CONCLUSIONS: Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year.
Acinetobacter Infections/epidemiology/microbiology/*prevention & control/transmission ; Acinetobacter baumannii/*drug effects/pathogenicity ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Carbapenems/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cross Infection/epidemiology/microbiology/*prevention & control/transmission ; Disinfection ; *Drug Resistance, Multiple, Bacterial ; *Endemic Diseases ; Hand Disinfection ; Humans ; Incidence ; Infection Control/*methods ; Microbial Sensitivity Tests ; Odds Ratio ; Patient Isolation ; Program Evaluation ; Republic of Korea/epidemiology ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome

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

BACKGROUND: We investigated the whole genome sequence (WGS) of a carbapenem-resistant Acinetobacter baumannii isolate belonging to the global clone 2 (GC2) and predicted resistance islands using a software tool. METHODS: A. baumannii strain YU-R612 was isolated from the sputum of a 61-yr-old man with sepsis. The WGS of the YU-R612 strain was obtained by using the PacBio RS II Sequencing System (Pacific Biosciences Inc., USA). Antimicrobial resistance genes and resistance islands were analyzed by using ResFinder and Genomic Island Prediction software (GIPSy), respectively. RESULTS: The YU-R612 genome consisted of a circular chromosome (ca. 4,075 kb) and two plasmids (ca. 74 kb and 5 kb). Its sequence type (ST) under the Oxford scheme was ST191, consistent with assignment to GC2. ResFinder analysis showed that YU-R612 possessed the following resistance genes: four β-lactamase genes bla(ADC-30), bla(OXA-66), bla(OXA-23), and bla(TEM-1); armA, aadA1, and aacA4 as aminoglycoside resistance-encoding genes; aac(6')Ib-cr for fluoroquinolone resistance; msr(E) for macrolide, lincosamide, and streptogramin B resistance; catB8 for phenicol resistance; and sul1 for sulfonamide resistance. By GIPSy analysis, six putative resistant islands (PRIs) were determined on the YU-R612 chromosome. Among them, PRI1 possessed two copies of Tn2009 carrying bla(OXA-23), and PRI5 carried two copies of a class I integron carrying sul1 and armA genes. CONCLUSIONS: By prediction of resistance islands in the carbapenem-resistant A. baumannii YU-R612 GC2 strain isolated in Korea, PRIs were detected on the chromosome that possessed Tn2009 and class I integrons. The prediction of resistance islands using software tools was useful for analysis of the WGS.
Acinetobacter Infections/*drug therapy/microbiology ; Acinetobacter baumannii/drug effects/*genetics/isolation & purification ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/*therapeutic use ; DNA, Bacterial/chemistry/*genetics/metabolism ; Drug Resistance, Bacterial ; Genomic Islands/genetics ; Humans ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Plasmids/genetics/metabolism ; Polymerase Chain Reaction ; Sequence Analysis, DNA

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/AIMS: Whether the causative organism influences the clinical course of pneumonia in the intensive care unit (ICU) is controversial. We assessed the clinical manifestations and prognosis of pneumonia according to the causative pathogens in patients in a medical ICU. METHODS: A retrospective observational study was performed in a medical ICU. Among 242 patients who were admitted to the ICU, 103 who were treated for pneumonia were analyzed. RESULTS: The causative pathogen was identified in 50 patients (49.0%); 22 patients (21.6%) had multidrug-resistant (MDR) pathogens. The distribution of causative micro-organisms was Staphylococcus aureus (20%), Pseudomonas species (16%), Klebsiella pneumoniae (14%), and Acinetobacter baumannii (12%). No significant difference in ICU mortality rate, duration of ICU stay, duration of mechanical ventilation, or frequencies of re-intubation and tracheostomy were detected based on the identification of any pathogen. In sub-analyses according to the pneumonia classification, the number of pathogens identified did not differ between pneumonia types, and a higher incidence of identified MDR pathogens was detected in the hospital-acquired pneumonia group than in the community-acquired or healthcare- acquired pneumonia groups. However, the clinical outcomes of pneumonia according to identification status and type of pathogen did not differ significantly between the groups. CONCLUSIONS: Neither the causative micro-organism nor the existence of MDR pathogens in critically ill patients with pneumonia was associated with the clinical outcome of pneumonia, including ICU mortality. This result was consistent regardless of the pneumonia classification.
Acinetobacter Infections/diagnosis/*microbiology/mortality/therapy ; Aged ; Anti-Bacterial Agents/therapeutic use ; Critical Illness ; Drug Resistance, Multiple, Bacterial ; Female ; Hospital Mortality ; Humans ; Intensive Care Units ; Klebsiella Infections/diagnosis/*microbiology/mortality/therapy ; Length of Stay ; Male ; Middle Aged ; Pneumonia, Bacterial/diagnosis/*microbiology/mortality/therapy ; Proportional Hazards Models ; Pseudomonas Infections/diagnosis/*microbiology/mortality/therapy ; Respiration, Artificial ; Retrospective Studies ; Risk Factors ; Staphylococcal Infections/diagnosis/*microbiology/mortality/therapy ; Time Factors ; Tracheostomy ; Treatment Outcome

PURPOSE: Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediated by a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC, and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumannii is not well understood. MATERIALS AND METHODS: We investigated the genotypic and phenotypic changes that underlie pan-drug resistance mechanisms by determining differences between the alterations in extensively drug-resistant (XDR) A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart (AB003) recovered from one patient before and after antibiotic treatment, respectively. RESULTS: All three clinical isolates shared an identical sequence type (ST138), belonging to the global epidemic clone, clonal complex 92, and all produced OXA-23 carbapenemase. The PDR AB003 showed two genetic differences, acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene, relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC, or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-time of flight analysis, the three isolates commonly showed two major peaks at 1728 m/z and 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detected only in the PDR A. baumannii AB003 isolate. CONCLUSION: Our results show that changes in lipid A structure via a mutation in the pmrB gene and acquisition of armA gene might confer resistance to colistin and aminoglycosides to XDR A. baumannii strains, resulting in appearance of a PDR A. baumannii strain of ST138.
Acinetobacter Infections/*drug therapy/microbiology ; Acinetobacter baumannii/*drug effects/*genetics/isolation & purification ; Aged ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Proteins/*genetics ; Colistin/*pharmacology/therapeutic use ; *Drug Resistance, Bacterial ; Electrophoresis, Gel, Pulsed-Field ; Genotype ; Humans ; Male ; Microbial Sensitivity Tests ; Molecular Typing ; Mutation ; Polymerase Chain Reaction ; Transcription Factors ; beta-Lactamases

No abstract available.
Acinetobacter baumannii/isolation & purification ; Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; C-Reactive Protein/analysis ; Community-Acquired Infections/*diagnosis/microbiology/pathology ; Female ; Humans ; Klebsiella pneumoniae/isolation & purification ; Leukocyte Count ; Male ; Middle Aged ; Neutrophils/*cytology ; Pneumonia/*diagnosis/microbiology/pathology ; ROC Curve ; Respiratory Tract Infections/*diagnosis/microbiology/pathology ; Severity of Illness Index ; Staphylococcus aureus/isolation & purification ; Streptococcus pneumoniae/isolation & purification