Extensive Drug-resistant Acinetobacter Baumannii Research Articles

Comparison Between the Combination Therapy in Terms of Therapeutic Effectiveness and Anti-Microbial Efficacy in Extensive Drug-Resistant Acinetobacter Baumannii Infections

Objective: To compare the clinical and antimicrobial efficacy of a triple-antibiotic regimen (Colistin, Cefoperazone/Sulbactam, and Tigecycline) with a double-antibiotic regimen (Colistin and Minocycline) for treating drug-resistant Acinetobacter baumannii infections in critically ill patients.Study Design: A comparative cross-sectional study design.Place and Duration of Study: The study was conducted at the Medical Intensive Care Unit (ICU) of Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan from April 2022 to October 2022.Materials and Methods: A total of 38 patients aged 18-70 years admitted to the Medical Intensive Care Unit (ICU) of the Pakistan Institute of Medical Sciences, Islamabad gave consent to participate in the study. Any patient having a culture-proven polymicrobial infection was excluded. A total of 20 patients were allocated to Group A (triple-antibiotic regimen) and 18 patients to Group B (double-antibiotic regimen). Vital statistics were recorded daily, while laboratory-based biochemical markers (leucocyte count, CRP, lactate, procalcitonin) were recorded every 48 hours for ten days. Antimicrobial efficacy was assessed by a culture analysis on the 10th day.Results: There were 20 patients in Group A and 18 in Group B. There were 32 patients with Ventilator-Associated Pneumonia (VAP), and six with bloodstream infection. No significant difference in the vitals and lab markers were found between the two groups. The only exception was serum lactate levels, which were significantly higher Group A (34.03 + 28.37 mg/dL), compared to Group B (16.11 + 15.63 mg/dL; p = 0.024). Group A therapy was also found to have significantly improved antimicrobial efficacy in terms of positive-culture results (n=4, 20%) compared to Group B (n=10, 55.6%; p = 0.023).Conclusion: The triple-antibiotic regimen had better antimicrobial efficacy than the double-antibiotic regimen for treating Acinetobacter baumannii-related infections.

Analysis of Efflux Pump System and Other Drug Resistance Related Gene Mutations in Tigecycline-Resistant Acinetobacter baumannii.

The isolation of tigecycline-resistant Acinetobacter baumannii in recent years has brought great difficulties to clinical prevention and treatment. To explore the effect of efflux pump system and other resistance related gene mutations on tigecycline resistance in Acinetobacter baumannii. Fluorescence quantitative PCR was used to detect the expression levels of major efflux pump genes (adeB, adeJ, and adeG) in extensive drug-resistant Acinetobacter baumannii. The minimum inhibitory concentration (MIC) of tigecycline was detected by the broth microdilution testing and efflux pump inhibition experiment to assess the role of efflux pump in tigecycline resistance of Acinetobacter baumannii. Efflux pump regulatory genes (adeR and adeS) and tigecycline resistance related genes (rpsJ, trm, and plsC) were amplified by PCR and sequenced. By sequence alignment, tigecycline sensitive and tigecycline-insensitive Acinetobacter baumannii were compared with standard strains to analyze the presence of mutations in these genes. The relative expression of adeB in the tigecycline-insensitive Acinetobacter baumannii was significantly higher than that in the tigecycline sensitive Acinetobacter baumannii (114.70 (89.53-157.43) vs 86.12 (27.23-129.34), P = 0.025). When efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was added, the percentage of tigecycline-insensitive Acinetobacter baumannii with tigecycline MIC decreased was significantly higher than that of tigecycline-sensitive Acinetobacter baumannii (10/13 (76.9%) vs 26/59 (44.1%)), P = 0.032); the relative expression of adeB in the MIC decreased group was significantly higher than that in the MIC unchanged group (110.29 (63.62-147.15) vs 50.06 (26.10-122.59), P = 0.02); The relative expression levels of efflux pumps adeG and adeJ did not increase significantly, and there was no significant difference between these groups. One adeR point mutation (Gly232Ala) and eight adeS point mutations (Ala97Thr, Leu105Phe, Leu172Pro, Arg195Gln, Gln203Leu, Tyr303Phe, Lys315Asn, Gly319Ser) were newly detected. Consistent mutations in trm and plsC genes were detected in both tigecycline-insensitive and tigecycline-sensitive Acinetobacter baumannii, but no mutation in rpsJ gene was detected in them. Tigecycline-insensitive Acinetobacter baumannii efflux pump adeABC overexpression was an important mechanism for tigecycline resistance, and the mutations of efflux pump regulator genes (adeR and adeS) are responsible for adeABC overexpression. The effect of trm, plsC, and rpsJ gene mutations on the development of tigecycline resistance in Acinetobacter baumannii remains controversial.

PGN-021 - Infections caused by extensive drug resistant (XDR) Acinetobacter baumannii: An experience of a tertiary care hospital

PGN-021 - Infections caused by extensive drug resistant (XDR) Acinetobacter baumannii: An experience of a tertiary care hospital

Whole Genome Analysis of Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates in Thailand.

Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen causing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase the understanding of resistant mechanisms, the emergence of novel resistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial- resistant genes-ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 β-lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminoglycoside-resistant genes (armA, aph(3')-Ia, aph(3")-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfonamide- resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under international clone II with different STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimicrobial agents. Inactivation of antimicrobials and target modification by enzymes and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

Multi- and Extensive-Drug Resistant Acinetobacter baumannii in ICUs: Risk Factors, Antimicrobial Resistance Profiles and co-harboring of gyrA and parC mutations

Background: Acinetobacter baumannii is a gram-negative organism that is implicated in hospital acquired infections. It confers high resistance to many classes of antibiotics. Objectives: To assess the prevalence of multi and extensive drug-resistant (MDR & XDR) Acinetobacter baumannii, their risk factors, antimicrobial resistance patterns and the presence of gyrA and parC gene mutations of quinolone resistance. Methodology: The study included 106 ICU patients (56 males & 50 females), samples were collected according to sites of infections, Acinetobacter baumannii was identified by morphology, biochemical reactions &API 20NE. Antimicrobial susceptibility testing was performed by disc diffusion method. The E-test was used to detect MIC of Ciprofloxacin & Levofloxacin, then a polymerase chain reaction- restriction fragment length polymorphism was performed to detect the occurence of gyrA and parC gene mutations of Quinolone resistance. Results: Thirty isolates were identified as Acinetobacter baumannii, most of which from respiratory infections (P=0.005) prolonged hospitalization, antibiotic use, urinary catheters & ventilator supports were found to be risk factors of infections. Acinetobacter baumannii isolates showed high resistance to most of the tested antibiotics (29 MDR & 28 XDR). All isolates were resistant to Ciprofloxacin & Levofloxacin with the co-presence of gyrA and parC mutations in all isolates (P<0.001). Conclusions: There is an increased prevalence of MDR & XDR Acinetobacter baumannii among ICU infections. The co-occurrence of gyrA and parC mutations is associated with high resistance to Quinolones.

Extensively-drug resistant Acinetobacter baumannii bacteremia in neonates: effective treatment with the combination of colistin and ampicillin/sulbactam

Acinetobacter baumannii has evolved as a major pathogen of outbreaks in the healthcare setting with increased morbidity and mortality. In neonates, treatment can be quite challenging due to the resistance profile of A. baumannii as well as limited data on pharmakokinetics and pharmakodynamics of antibiotics in this age group. We present an outbreak of eight cases of extensively-drug resistant (XDR) A. baumannii bacteremias successfully managed with the combination of colistin with high dose ampicillin/sulbactam.

Sulbactam enhances the in vitro activity of sitafloxacin against extensively-drug resistant Acinetobacter baumannii.

The present study aimed to determine the in vitro activities of sulbactam and sitafloxacin against extensively-drug resistant Acinetobacter baumannii (XDR-A. baumannii). A total of 50 strains of XDR-A. baumannii were isolated from clinical specimens. Broth microdilution assay was applied to determine the minimum inhibitory concentration (MIC) for sulbactam and sitafloxacin. Microdilution checkerboard method was used to determine the in vitro activity of this antimicrobial combination. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated. Time-kill study was also carried out for four strains with different susceptibilities to determine the bactericidal activities of individual or combined use of sitafloxacin and sulbactam. Isolates with MICs of sitafloxacin ≤2 mg/l were considered to be susceptible to sitafloxacin. The susceptibility rate for sitafloxacin was 92% originally. When combined with sulbactam, this rate increased to 96%. Microdilution checkerboard results indicated that, when tested in combination, sulbactam/sitafloxacin exhibited marked synergistic and partial synergistic effects on 16 and 50% of the 50 strains, respectively. Time-kill assay suggested that sulbactam enhanced the bactericidal activity of sitafloxacin and the combination induced a synergistic effect. For strains that were not susceptible to sitafloxacin, the bactericidal activities of the combination of sitafloxacin and sulbactam at a sub-MIC concentration were impaired. However, this impairment could be overcome with the increase of the concentration to 1X MIC. The present study demonstrated that sulbactam enhanced the in vitro antimicrobial activity of sitafloxacin against XDR-A. baumannii.

Efficacy of extended-infusion of carbapenem plus sulbactam for ventilator-associated pneumonia caused by extensive drug-resistant Acinetobacter baumannii

Objective: To evaluate the efficacy of extended-infusion of carbapenem plus sulbactam for ventilator-associated pneumonia caused by extensive drug-resistant Acinetobacter baumannii (XDRAB). Methods: Clinical data of patients with ventilator-associated pneumonia caused by XDRAB who were treated with extended-infusion carbapenem plus sulbactam or tigecycline-based therapy in Peking University First Hospital from January 2015 to December 2016 were collected and reviewed in this retrospective study. Twenty-one patients were treated with extended-infusion carbapenem plus sulbactam, and 20 other patients received tigecycline combined with other antibiotics. The general status of the patient, microbiological eradication rate, superinfection rate, new microorganism colonization rate, clinical resolution rate on the third day, clinical cure rate and mortality during treatment were compared between the two groups. Results: The two groups shared similar characteristics except that patients in the carbapenem group were younger. Microbiological eradication was not observed. Superinfections occurred in 1 patients (4.8%) in the carbapenem group and 0 patients in the tigecycline group (P=1.000), the occurrences of new microorganisms colonization were 14.3% and 25.0% respectively (P=0.638). Clinical cure were achieved in 57.1% of the patients in the carbapenem group and 50.0% of the patients in the tigecycline group (P=0.647), the clinical resolution rates on the third day were 52.4% and 45.0% respectively (P=0.636). The mortality during treatment was 9.5% in carbapenem group, and 20.0% in tigecycline group (P=0.612). No serious adverse drug reactions occurred. Conclusions: Ventilator-associated pneumonia caused by XDRAB treated with either extended-infusion carbapenem plus sulbactam or tigecycline-based therapy has a similar clinical outcome.

Pneumonia caused by extensive drug-resistant Acinetobacter baumannii among hospitalized patients: genetic relationships, risk factors and mortality

BackgroundThe clonal spread of multiple drug-resistant Acinetobacter baumannii is an emerging problem in China. We analysed the molecular epidemiology of Acinetobacter baumanni isolates at three teaching hospitals and investigated the risk factors, clinical features, and outcomes of hospital-acquired pneumonia caused by extensive drug-resistant Acinetobacter baumannii (XDRAB) infection in Guangzhou, China.MethodsFifty-two A. baumannii isolates were collected. Multilocus sequence typing (MLST) was used to assess the genetic relationships among the isolates. The blaOXA-51-like gene was amplified using polymerase chain reaction (PCR) and sequencing. The resistance phenotypes were determined using the disc diffusion method. A retrospective case-control study was performed to determine factors associated with XDRAB pneumonia.ResultsMost of the 52 A. baumannii isolates (N = 37, 71.2%) were collected from intensive care units (ICUs). The respiratory system was the most common bodily site from which A. baumannii was recovered (N = 45, 86.5%). Disc diffusion classified the isolates into 17 multidrug-resistant (MDR) and 35 extensively drug-resistant (XDR) strains. MLST grouped the A. baumannii isolates into 5 existing sequence types (STs) and 7 new STs. ST195 and ST208 accounted for 69.2% (36/52) of the isolates. The clonal relationship analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. According to the sequence-based typing (SBT) of the blaOXA-51-like gene, 51 A. baumannii isolates carried OXA-66 and the rest carried OXA-199. There were no significant differences with respect to the resistance phenotype between the CC92 and non-CC92 strains (P = 0.767). The multivariate analysis showed that the APACHE II score, chronic obstructive pulmonary disease (COPD) and cardiac disease were independent risk factors for XDRAB pneumonia (P < 0.05). The mortality rate of XDRAB pneumonia was high (up to 42.8%), but pneumonia caused by XDRAB was not associated with in-hospital mortality (P = 0.582).ConclusionsST195 may be the most common ST in Guangzhou, China, and may serve as a severe epidemic marker. SBT of blaOXA-51-like gene variants may not result in sufficient dissimilarities to type isolates in a small-scale, geographically restricted study of a single region. XDRAB pneumonia was strongly related to systemic illnesses and the APACHE II score but was not associated with in-hospital mortality.

Whole-Genome Analysis of an Extensive Drug-Resistant Acinetobacter Baumannii ST195 Isolate from a Recipient After DCD Renal Transplantation in China

Background/Aims: Infection with Acinetobacter baumannii was emerging as one of the leading causes of mortality after donation after cardiac death transpalantion. Methods: We reported a case of a recipient who underwent DCD renal transplantation and later got infected by A.baumannii. Etests were done to verify the susceptibility test results in clinic. Whole-genome analysis was applied to investigate the resistant mechanism at gene level. Results: The pathogen was isolated from his draining liquid the day after the surgery, and susceptibility test reavealed that it was sensitive to tigecycline. However, the isolate obtained from the draining liquid became tigecycline-resistant after fifteen-day administration of tigecycline. The Susceptibility tests showed that the pathogen recovered from tigecycline resistance and became intermediated to tigecycline. Whole-Genome analysis revealed the genetic level change leading to tigecycline resistance and we identified the location of mutation by comparing the whole genome sequence of the isolates. Three loci were figured out which may contribute to drug resistance, including genes encoding HTH domain protein, MFS transporter and AdeS. Conclusion: Understanding the genetic characteristics associated with drug resistance mechanism and antimicrobial profiles of pathogen is important in controlling infection outbreak and preventing serious complications and gives a new insight into the development of antimicrobial agents.

Colistin monotherapy versus colistin-based combination therapy in the treatment of extensive drug-resistant Acinetobacter baumannii infections: A retrospective cohort study

Introduction: Acinetobacter baumannii is a Gram-negative Coccobacillus and is a frequent cause of hospital-acquired infections. Because some strains of A. baumannii are resistant to many antibiotics (i.e., extensively drug-resistant A. baumannii, or XDRAB), selecting antibiotics to treat infected patients is challenging. Clinical outcomes in critically ill patients with XDRAB infections are poor. In this study, we evaluated the clinical effectiveness of colistin as monotherapy and in combination with other antibiotics. Patients and Methods: A retrospective cohort study was performed on 94 critically ill patients (age ≥18 years) to assess the clinical effectiveness of treating XDRAB infections with colistin, either in monotherapy or combination with tigecycline, meropenem, or both. Clinical and microbiological data were obtained from patient records. We included patients suffering from XDRAB ventilation-associated pneumonia (VAP), or ventilator-associated tracheobronchitis (VAT), or VAT with bacteremia. Results: The mean age of the patients was 53.3 years (±23.7 years), and the mean Acute Physiology and Chronic Health Evaluation II score was 22.7 (standard deviation = 7.1). VAP and VAT with bacteremia were found in 84% and 16% of patients, respectively. Half (51%) of patients achieved microbiological clearance. The median Intensive Care Unit (ICU) stay was 29 days (interquartile range [IQR]: 17, 55) and the median mechanical ventilation (MV) duration was 21 days (IQR: 12, 42). MV duration and ICU length of stay were lower in the group of patients treated with colistin and meropenem than in those treated with colistin alone. Mortality was significantly lower in patients who received (colistin and tigecycline 30%) than in those who were treated with monotherapy (75%) with an odd ratio 0.03 (95% confidence interval: 0.00, 0.32; P

Tigecycline combination for ventilator-associated pneumonia caused by extensive drug-resistant Acinetobacter baumannii.

Extensive drug-resistant Acinetobacter baumannii (XDR A. baumannii) has emerged as an important pathogen in patients with ventilator-associated pneumonia (VAP) worldwide. This study determined whether or not combination tigecycline (TGC) treatment improved the short-term outcome of patients with XDR A. baumannii-induced VAP. Methods: Fifty-eight patients admitted to our intensive care unit (ICU) with confirmed XDR A. baumannii VAP between January 2011 and June 2013 were retrospectively studied. Fourteen patients were excluded. The included subjects were classified into two groups depending on treatment regimens with or without TGC (TGC group, n=20; non-TGC group, n=24). Thirty-day mortality rates, and clinical and microbiologic responses were reviewed and compared in detail. Microbiological eradication was observed in 3 patients (15.0%) in the TGC group and 7 patients (29.2%) in the non-TGC group (P=0.264). The mean time-to-eradication of XDR A. baumannii was 5.3±2.1 versus 7.6±4.0 days (P=0.395). Ten of 20 (50%) patients developed resistance to TGC after initiation of TGC therapy in the TGC group. Clinical cure were achieved in 50.0% of the patients (10/20) in the TGC group and 45.8% of the patients (7/24) in the non-TGC group (P=1.000). No differences existed in the 30-day mortality, length of ICU stay, length of hospital stay (LOS), and length of invasive mechanical ventilation (MV) between the two groups. The occurrence of septic shock was significantly lower in the TGC group (20.0% vs. 54.2%; P=0.030). TGC combination therapy did not improve the clinical cure and microbiologic eradication in patients with XDR A. baumannii VAP. TGC combination therapy did not decrease all-cause mortality in patients with XDR A. baumannii VAP. TGC combination therapy reduced the incidence of septic shock in patients with XDR A. baumannii VAP, and might decrease the incidence of poly-microbial VAP. TGC combination therapy can only be recommended as an option when other optimized therapeutics, such as colistin, are unavailable.

Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections

The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were ‘time to any kidney injury’ (AKI stages 1–3) and ‘time to severe kidney injury’ (considering only AKI stages 2–3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4–6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither ‘any’ nor ‘severe AKI’ were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.

Characterization of bacteriophage vB_AbaP_PD-AB9 infecting Acinetobacter baumannii with broad host range

Objective To isolate bacteriophages against extensively-drug resistant Acinetobacter baumannii from hospital sewage and analyze their biological characteristics. Methods Extensively-drug resistant Acinetobacter baumannii isolated from several hospitals in Shanghai during December, 2013 to July, 2014 were used as host bacteria, adopting double-layer agar method to isolate bacteriophages from raw sewage of these hospitals. The phage with broad host range was selected for further study, including observation of electron microscopic morphology, examination of thermal stability, pH stability and the optimal MOI, drawing of the adsorption, one-step-growth and infection curves, as well as sequencing of the phage genome DNA. Results An extensively-drug resistant Acinetobacter baumannii bacteriophage vB_AbaP_PD-AB9 (PD-AB9 for short) with broad host range was isolated, and electron microscopy revealed it belonged to Podoviridae family. The optimal MOI of PD-AB9 was 0.001. PD-AB9 remained stable among 4 ℃ to 50 ℃ and pH 4 to 11. In the adsorption experiment, the adsorption rate of PD-AB9 reached above 95% within 5 min.PD-AB9 had a latent period of 4 min and a burst size of 213. PD-AB9 could obviously restrain the host growth, with faster effect at the higher MOIs (MOI=1, 0.1, 0.01) than at the lower ones (MOI=0.001, 0.000 1). Furthermore, genome of PD-AB9 proved to be a double-stranded linear DNA with size of 40 938 bp and GC content of 39.34%. Conclusions PD-AB9 exhibits good thermal stability, wide pH tolerance range, very fast adsorption, a short latent period, a large burst size and it could quickly cause effective host lysis after infection. Therefore, PD-AB9 is promised to act as a new antimicrobial agent to control drug-resistant Acinetobacter baumannii infections and its bio information remains to be further studied.(Chin J Lab Med, 2016, 39: 296-300) Key words: Bacteriophages; Acinetobacter baumannii; Drug resistance, bacterial; Biological assay; Genome components

两例疑似泛耐药鲍曼不动杆菌感染的临床处置和转归分析

两例疑似泛耐药鲍曼不动杆菌感染的临床处置和转归分析

Risk factors for extensive drug-resistance and mortality in geriatric inpatients with bacteremia caused by Acinetobacter baumannii

The aim of this study was to explore the risk factors for developing bacteremia caused by extensive drug-resistant (XDR) Acinetobacter baumannii and the associated mortality in geriatric inpatients. We conducted a retrospective study of 125 patients with A baumannii bacteremia between October 2008 and December 2013 at a medical center in China. The 30-day hospital mortality rate was 55.2%. XDR A baumannii was detected in 31.2% of all cases. A logistic regression analysis suggested that chronic obstructive pulmonary disease, a bedridden status, and central venous catheters were associated with bacteremia caused by XDR A baumannii, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of 2.59 (1.01-6.64), 4.08 (1.39-12.01), and 9.52 (1.90-47.56), respectively. Furthermore, intensive care unit (ICU) stay, bacteremia caused by XDR A baumannii, concurrent fungal infection, and age (70-80 years old and >80 years old) were associated with mortality, with aORs and 95% CIs of 3.16 (1.29-7.73), 4.01 (1.46-11.04), 3.20 (1.28-7.98), 4.31 (1.44-12.92), and 5.46 (1.94-15.35), respectively. Bacteremia is associated with a high 30-day hospital mortality rate in geriatric inpatients. Furthermore, ICU stay, bacteremia caused by XDR A baumannii, concurrent fungal infection, and age are associated with increased mortality in geriatric inpatients with A baumannii bacteremia.

Surveillance of catheter-related infections: the supplementary role of the microbiology laboratory.

BackgroundThe burden of catheter-related infections (CRIs) in developing countries is severe. In South Africa, a standardised surveillance definition does not exist and the collection of catheter days is challenging. The aim of the study was to provide baseline data on the prevalence of CRIs and to describe the epidemiology of CRI events within a tertiary academic hospital.MethodsSurveillance was laboratory-based and conducted for a six month period. A microbiologically confirmed CRBSI (MC-CRBSI) event was defined as the isolation of the same microorganism from the catheter and concomitant blood cultures (BCs), within 48 h of catheter removal, which were not related to an infection at another site.ResultsA total of 508 catheters, removed from 332 patients, were processed by the laboratory, of which only 50% (253/508 removed from 143/332 patients) of the catheters were accompanied by BCs within 48 h. Sixty-five episodes of MC-CRBSI in 57 patients were detected, involving 71 catheters and 195 microbial isolates. The institutional prevalence rate was 3.7 episodes per 1 000 admissions and 5.8 episodes per 10 000 in-patient days. Catheter day data was collected in only six wards of the hospital. The pooled laboratory incidence was 10.1 MC-CRBSI episodes per 1 000 catheter days, whereas the hospital-based central line-associated bloodstream infection (CLABSI) rate was pooled at 5.7 episodes per 1 000 catheter days. The majority of patients had an underlying gastro-intestinal condition (33%; 19/56) with a non-tunnelled, triple-lumen central venous catheter, placed in the subclavian vein (38%; 27/71). The most predominant pathogen was methicillin-resistant Staphylococcus epidermidis (28%; 55/195), followed by extensively-drug resistant Acinetobacter baumannii (18%; 35/195).ConclusionsCatheter-related infection prevention and control efforts require urgent attention, not only to keep patients safe from preventable harm, but to prevent the spread of multidrug resistant microorganisms.

Hydrophilic/hydrophobic characters of antimicrobial peptides derived from animals and their effects on multidrug resistant clinical isolates.

Multidrug resistant (MDR) pathogen infections are serious threats to hospitalized patients because of the limited therapeutic options. A novel group of antibiotic candidates, antimicrobial peptides (AMPs), have recently shown powerful activities against both Gram-negative and Gram-positive bacteria. Unfortunately, the viability of using these AMPs in clinical settings remains to be seen, since most still need to be evaluated prior to clinical trials and not all of AMPs are potent against MDR clinical isolates. To find a connection between the characteristics of several of these AMPs and their effects against MDR pathogens, we selected 14 AMPs of animal origin with typical structures and evaluated their in vitro activities against clinical strains of extensive drug-resistant Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, extended spectrum β-lactamase-producing Pseudomonas aeruginosa and extended spectrum β-lactamase-producing Escherichia coli. Our results showed that these peptides' hydrophilic/hydrophobic characteristics, rather than their secondary structures, may explain their antibacterial effects on these clinical isolates. Peptides that are amphipathic along the longitudinal direction seemed to be effective against Gram-negative pathogens, while peptides with hydrophilic terminals separated by a hydrophobic intermediate section appeared to be effective against both Gram-negative and Gram-positive pathogens. Among these, cathelicidin-BF was found to inhibit all of the Gram-negative pathogens tested at dosages of no more than 16 mg/L, killing a pandrug-resistant A. baumannii strain within 2 h at 4×MICs and 4 h at 2×MICs. Tachyplesin III was also found capable of inhibiting all Gram-negative and Gram-positive pathogens tested at no more than 16 mg/L, and similarly killed the same A. baumannii strain within 4 h at 4×MICs and 2×MICs. These results suggest that both cathelicidin-BF and tachyplesin III are likely viable targets for the development of AMPs for clinical uses.

Synergistic effects of ethnomedicinal plants of Apocynaceae family and antibiotics against clinical isolates of Acinetobacter baumannii

ObjectiveTo investigate the efficacy of 17 ethnomedicinal plants belonging to Apocynaceae family used in combination with 16 conventional antibiotics against non-multidrug resistant-, multidrug resistant (MDR)-, and extensive drug resistant (XDR) Acinetobacter baumannii (A. baumannii). MethodsAntibacterial activity and resistance modifying ability of 272 combinations were determined by growth inhibition assays and further confirmed by time-kill assay. ResultsAmong the combinations of the antibiotics with Apocynaceae ethanol extracts on this pathogen, 15 (5%) had synergistic effects, 23 (8%) had partial synergistic effects and 234 (86%) had no effects. Synergistic activity was observed mostly when the Apocynaceae extracts were combined with rifampicin or cefazolin. Interestingly, 10 out of 17 combinations between the extracts and rifampicin displayed synergistic or partial synergistic behaviors. Holarrhena antidysenterica extract was additionally tested to restore rifampicin activity against clinical isolates of MDR and XDR A. baumannii. With respect to total or partial synergy, 70% was XDR A. baumannii isolates and 66% was MDR A. baumannii isolates. ConclusionsHolarrhena antidysenterica extract clearly demonstrated the ability to restore rifampicin activity against both A. baumannii ATCC19606 and clinically isolated A. baumannii. Additional studies examining its active principles as well as mechanisms of actions such as the effects on efflux pumps and outer membrane permeability alterations are recommended.

Ventilator-associated pneumonia due to extensive drug-resistant Acinetobacter baumannii: Risk factors, clinical features, and outcomes

Acinetobacter baumannii is characterized by a rapid development of resistance to the commonly used antimicrobial agents. We investigated the risk factors, clinical features, and outcomes in ventilator-associated pneumonia (VAP) caused by extensive drug-resistant Acinetobacter baumannii (XDRAB). Clinical parameters and overall in-hospital mortality rates were compared between the VAP with and without XDRAB infection groups. This study showed that VAP caused by XDRAB was not associated with in-hospital mortality. However, it was related to high Simplified Acute Physiology Score II scores and increasing durations of hospital stays.