Multiple Drug-resistant Acinetobacter Baumannii Research Articles

Molecular Characterization of Class A-ESBLs, Class B-MBLs, Class C-AmpC, and Class D-OXA Carbapenemases in MDR Acinetobacter baumannii Clinical Isolates in a Tertiary Care Hospital, West Bengal, India.

Background Acinetobacter calcoaceticus baumannii (ACB) complex has become a major concern nowadays because of its increasing involvement in several severe infections associated with catheter-related bloodstream and urinary tract infections, ventilator-associated pneumonia, cerebrospinal shunt-related meningitis, and wound infections. Multiple drug-resistant (MDR) ACB cases have been described with an increasing trend where at least it is resistant to a minimum of three antimicrobial groups. The mortality rate associated with A. baumannii is significantly higher than all Acinetobacterspp. isolates with the most prevalence seen in India and Thailand. The rapid spread of high resistance to most potent antimicrobial drugs is due to its ability to incorporate resistance determinants despite multifactorial reasons such as alteration in permeability of cell membrane by either losing expression of outer membrane porins or excess production of efflux pumps. This study aims to characterize resistance determinants responsible for MDR at the genetic level and emphasizes the use of genotyping in routine diagnosis as genotype analysis is reliable and valid. Methodology A total of 289 ACB complex clinical isolates were included in this study. The study for species-level identification of A. baumannii was conducted at the Department of Microbiology, IQ City Medical College Hospital, Durgapur, West Bengal. In addition, the detection of encoded genes associated with class A-extended spectrum beta-lactamases (i.e., CTX-M, KPC, SHV, and TEM genes), class B-metallo-β-lactamases (i.e., IMP, NDM, and VIM genes), Class C-AmpC cephalosporinase, and classD-OXA carbapenemases (i.e., blaOXA-10/11, blaOXA-24, blaOXA-48, blaOXA-58, blaOXA-143, and blaOXA-235was done using real-time polymerase chain reaction. Results All 289 non-repetitive ACB complex clinical isolates were confirmed as A. baumannii, of which 277 (96%) isolates were MDR. There were no findings of blaCTX-M, blaKPC, blaSHV, blaTEM, blaIMP, blaVIM, blaAmpC, blaOXA-10/11, blaOXA-24, blaOXA-48, blaOXA-58, blaOXA-143, and blaOXA-235 genes in our study. However, there were four (1.44%) positive findings of the blaNDM gene. All MDR isolates (n = 277) were positive for the blaOXA-51 gene. In addition, blaOXA-23 was positive in 269 (97.12%) isolates. Conclusions The oxacillinase production corresponding to blaOXA-23 and blaOXA-51 were the most prevalent antibiotic resistance determinants among MDR A. baumanniiin our study. Four (1.44%) isolates had the multiple genes blaOXA-51, blaOXA-23, and blaNDM that shows the coexistence of diverse genetic elements involved in MDR A. baumannii, resulting in total resistance except for a few potent drugs such as colistin and tigecycline. Genotyping is helpful in determining the contribution of the isolates in understanding their association with encoded genes, which, in turn, helps in designing effective surveillance and control strategies in the management of such MDR isolates.

Phage Digestion of a Bacterial Capsule Imparts Resistance to Two Antibiotic Agents.

Bacteriophages are viruses that infect bacteria, replicating and multiplying using host resources. For specific infections, bacteriophages have developed extraordinary proteins for recognizing and degrading their host. Inspired by the remarkable development of viral proteins, we used the tail fiber protein to treat multiple drug-resistant Acinetobacter baumannii. The tail fiber protein exhibits polysaccharide depolymerases activity which specifically degrades exopolysaccharide (EPS) during the phage–host interaction. However, EPS-degraded cells are observed altering host susceptibility to bacterial lysis peptide, the endolysin-derived peptide. Notably, endolysin is necessary in the process of progeny liberation by breaking the bacterial cell wall. Surprisingly, peeling the EPS animated host to resist colistin, the last-resort antibiotic used in multidrug-resistant Gram-negative bacteria infection. Tail fiber-modified cell wall reduces colistin attachment, causing temporary antibiotic-resistance and possibly raising clinical risks in treating multiple drug-resistant A. baumannii.

Intraventricular administration of antibiotics by ommaya reservoir for patients with multidrug-resistant Acinetobacter baumannii central nervous system infection

Aim To investigate whether the Ommaya reservoir can be used to treat multiple drug-resistant Acinetobacter baumannii (MDR-AB) infections in the central nervous system (CNS). Methods Retrospectively analyzed the clinical records and data of 15 MDR-AB CNS infection patients who were treated in our neuro-ICU. Four patients with MDR-AB CNS infection were involved in this study. Results We report the successful treatment of MDR-AB CNS infection by Ommaya reservoirs and intraventricular antibiotic (IVA) administration. Ommaya reservoirs allow serial CSF sampling and IVA injection. Furthermore, debridement can be performed during the operation to insert the Ommaya. Conclusion Ommaya reservoirs can be used as an effective treatment approach of MDR-AB or other multidrug-resistant Gram-negative bacteria CNS infections.

Polyamine acetylation and substrate-induced oligomeric states in histone acetyltransferase of multiple drug resistant Acinetobacter baumannii

Histone acetyltransferase (Hpa2) is an unusual acetyltransferase, with a wide range of substrates; including histones, polyamines and aminoglycosides antibiotic. Hpa2 belongs to GNAT superfamily and GNATs are well known for the formation of homo-oligomers. However, the reason behind their oligomerization remained unexplored. Here, oligomeric states of Hpa2 were explored, to understand the functional significance of oligomerization. Biochemical analysis suggests that Hpa2 exists as dimer in solution and self-assembles into tetramer in the spermine, spermidine and kanamycin bound form. Stability analysis with denaturants concludes that homo-oligomerization of Hpa2 relies on bound substrate and not on experimental conditions. Homo-oligomerization in Hpa2 depicts direct correlation with its polyamine acetylating capacity. This correlation and in silico model structures suggest that oligomerization of Hpa2 is associated with the hastening of acetylation process. Interestingly, polyamine acetylation down regulates biofilms formation in E. coli BL21/Hpa2-transformants cells. Therefore, we propose that Hpa2 manipulates survival strategies of the bacterium via polyamines and antibiotics acetylation.

Investigation of Association Between adeA, adeB ,adeI Genes and Phenotypic Activity of Efflux Pump in Multiple Drug Resistant Acinetobacter baumannii Isolates

Investigation of Association Between adeA, adeB ,adeI Genes and Phenotypic Activity of Efflux Pump in Multiple Drug Resistant Acinetobacter baumannii Isolates

Role of Acinetobacter baumannii thioredoxin in pulmonary bacterial dissemination following LPS induced lung injury

Abstract Despite medical advances, sepsis remains an increasing and major cause of death in hospitalized patients in the United States. Multiple-drug resistant Acinetobacter baumannii has emerged as an important hospital-acquired pathogen in both pulmonary infections and sepsis. Previously, our lab has shown the importance of bacterial thioredoxin during infection. A TrxA-null mutant (ΔTrxA) generated from A. baumannii Clinical isolate 79 (Ci79) showed a 100-fold decrease in virulence during systemic challenge. To further define the role of thioredoxin, our lab has created a pulmonary model of infection that leads to sepsis and death in C57BL/6 mice. This model is dependent on the induction of acute lung injury through E. coli lipopolysaccharide (LPS) injection. Lungs were analyzed for increased permeability using FITC-labeled dextran. Mice receiving the LPS showed significantly higher FITC-dextran particles in their serum compared to those that did not. Additionally, histopathology and cytokine production indicated limited immune response to the dose of LPS used. Using this model, mice showed significantly increased WT organ burdens in the lungs, liver, kidneys, cervical lymph nodes, and spleen compared to the mutant. Concurrently, mortality was significantly greater in the WT compared to ΔTrxA (~85%). Histopathological assessment showed increased cellular infiltrates and pulmonary inflammation during WT vs ΔTrxA infection. Finally, when the WT was treated with a thioredoxin blocker (PX-12) before challenge, mice survival improved from ~15% to ~75% with treatment. Together, this data demonstrates that thioredoxin plays a vital role in dissemination and virulence and could be a potential target to attenuate sepsis.

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.

Analysis of the characteristics of multi-drug resistant acinetobacter baumannii infection in elderly patients with severe respiratory

Objective To investigate the clinical characteristics of multiple drug resistant Acinetobacter baumannii infection in respiratory elderly patients. Methods A total of 102 elderly patients infected with multidrug-resistant Acinetobacter baumannii were enrolled in our hospital from January 2014 to December 2015. At the same time, no multiple drug-resistant Acinetobacter baumannii infection elderly patients was selected as a control group.The gender, age, antimicrobial use, white blood cell count, mechanical ventilation time and other differences between the two groups of elderly patients were compared. Results There were significant differences in the days of hospitalization〔(18.7±7.5) d vs.(10.0±2.7)d〕, the time of application of invasive ventilator〔(24.6±10.3) d vs.(11.6±6.9)d〕 and the time of application of antimicrobial agents〔(26.2±13.1) d vs.(8.0±2.6)d〕 (t=19.463、15.436、26.905, all P 0.05). Conclusions Reasonable scientific application of antimicrobial agents, reducing invasive mechanical ventilation time and improving patient immunity can help to reduce the risk of respiratory infection in elderly patients with multiple drug resistance to Acinetobacter baumannii. Key words: Gram-negative bacterial infections; Ventilators, mechanical

Investigation on nurse of knowledge and protection adherence of multiple drug-resistant Acinetobacter baumannii in a medical intensive care unit in central Taiwan

Investigation on nurse of knowledge and protection adherence of multiple drug-resistant Acinetobacter baumannii in a medical intensive care unit in central Taiwan

Extremely high prevalence of antiseptic resistant Quaternary Ammonium Compound E gene among clinical isolates of multiple drug resistant Acinetobacter baumannii in Malaysia.

BackgroundAntiseptics are commonly used for the management of MDR (multiple drug resistance) pathogens in hospitals. They play crucial roles in the infection control practices. Antiseptics are often used for skin antisepsis, gauze dressing, preparation of anatomical sites for surgical procedure, hand sterilization before in contact with an infected person, before an invasive procedure and as surgical scrub.MethodsWe screened 122 multiple drug resistant Acinetobacter baumannii (MDRAB) isolated from admitted patients in one of the tertiary care hospital in Malaysia for the presence of antiseptic resistant genes qacA and qacE (Quaternary Ammonium Compound) and susceptibility towards chlorhexidine (CLX), benzalkonium (BZK) and benzethonium (BZT).ResultsEighty-nine (73%) isolates harboured qacE gene, while none were positive for qacA. The MIC ranged from 0.2 to 0.6 for CLX, 0.02 to 0.2 for BZK and 0.04 to 0.2 μg/mL for BZT. The highest number of qacE positive isolates were obtained from surgery (n = 24; 27%; p < 0.05), followed by medical ward (n = 23; 25.8%) and ICU (n = 21; 23.6%). Majority of the isolates from wound swabs (n = 33; 37%), T/aspirate (n = 16; 18%) and tissue (n = 10; 11.2%) harboured the qacE genes.ConclusionThe present investigation showed high prevalence of qacE gene among the studied isolates. Antiseptics are important components of infection control, continuous monitoring of antiseptics use in the hospital is cautioned.

Control of hospital endemicity of multiple-drug-resistant Acinetobacter baumannii ST457 with directly observed hand hygiene.

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9%) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.

Clinical Course and Computed Tomography Abnormalities Associated without and with Concomitant Infection in Patients with Pandemic Influenza A (H1N1) 2009 Virus Infection

The goal was to evaluate the imaging findings in patients infected primarily with the pandemic influenza A (H1N1) 2009 virus and secondarily with a bacterium.Between October 2009 and March 2010, thirteen patients were included in this study. Five patients had H1N1 pneumonia without evidence of co-infection and their CT images showed diffuse or patchy areas of ground glass opacities and/or consolidations, lower lung zone predominant, without cyst/cavity lesion or newly developing pleural effusion. Another eight patients had H1N1 pneumonia with co-infections. The following organisms were identified: Oxacillin-resistant Staphylococcus aureus (2), Pneumocystis jiroveci (1), Haemophilus parainfluenzae (3), Klebsiella pneumoniae (1), Streptococcus pneumoniae (2), and multiple-drug resistant Acinetobacter baumannii (1), Their CT scans showed diffuse or patchy areas of ground-glass attenuation mixed with consolidation but also revealed cyst/cavity lesions (3), centrilobular nodules (3), tree-in-bud opacity (4), mediastinal lymphadenopathy (6), and pleural effusion (4), These CT changes are definitely different from H1N1 monoinfection. The secondary infectious process may cause additional CT abnormalities.The possibility of H1N1 pneumonia with co-infections should be considered if there are CT findings other than pure H1N1 pneumonia.

A multiple drug resistant Acinetobacter baumannii outbreak in a burn center: Trying to stop the unstoppable?

A multiple drug resistant Acinetobacter baumannii outbreak in a burn center: Trying to stop the unstoppable?

Outbreak of Acinetobacter Infection in Extremely Low Birth Weight Neonates

We describe the first outbreak of multiple drug-resistant Acinetobacter baumannii (MDR-Ab) in a neonatal intensive care unit in the United States. MDR-Ab was identified in the blood of a 24-week gestation, 7-day-old extremely low birth weight neonate. Multiple samplings of surveillance surface cultures were performed on exposed and nonexposed neonates. Enhanced infection control measures were implemented. Pulsed-field gel electrophoresis was performed to determine the genetic relatedness of the MDR-Ab isolates. Medical records were reviewed for all exposed patients. MDR-Ab was recovered from 6 additional neonates. Of these 7 MDR-Ab (index + 6) neonates, 4 died, 3 of whom had positive blood cultures. All affected neonates were born between 23 to 26 weeks gestational age, and were <7 days postnatal age and <750 g (430-720) at the time of exposure. All were housed within the same room as the index case. None of the other 5 exposed neonates older than postnatal day 7 or weighing >750 g at birth were affected. No additional cases occurred outside the original room. Pulsed-field gel electrophoresis was consistent with a clonal origin, identical to MDR-Ab recovered from the referring hospital. This MDR-Ab outbreak was rapidly controlled with enhanced infection control measures and was novel in that it affected only <750 g neonates, at < or =26 weeks gestational age, and < or =7 days postnatal age at the time of exposure, suggesting that invasive Ab has a special affinity for damaged or nonkeratinized immature skin in developmentally immature immunologic hosts.

Refractory Post-Herpetic Neuralgia As An Initial Presentation Of Olfactory Neuroblastoma-Related Ectopic ACTH Syndrome

We report a woman aged 64 years with ectopic adrenocorticotropic hormone (ACTH) syndrome caused by olfactory neuroblastoma as an initial presentation of refractory post-herpetic neuralgia. The manifestations such as cushingoid appearance and endocrine abnormalities are compatible with Cushing's syndrome. Brain computed tomography revealed a sellar mass. A biopsy revealed olfactory neuroblastoma. Immunohistochemical staining further defined the tumor as an ACTH-secreting neuroblastoma. Subsequent opportunistic infections by Candida glabrata fungemia and multiple drug-resistant Acinetobacter baumannii pneumonia occurred during hospitalization as a complication of severe hypercortisolism. Before any therapy for Cushing's syndrome and neuroblastoma could be initiated, the patient died from sepsis and multiorgan failure. We propose that Cushing's syndrome is more complex than what clinicians thought, and that meticulous cerebral imaging studies are crucial.

The Experience of a Novel Glycylcycline Antibiotic for a Patient with Infection Caused by Multiple Drug-Resistant Pathogens: What is the Benefit?

We report a 75-year-old man with septic shock induced by ventilator-associated pneumonia caused by multiple drug-resistant Acinetobacter baumannii and catheter-related infection by vancomycin-resistant enterococci. He failed to respond to the initial management, including antibiotics (linezolid, imipenem, sulbactam and colistin) and hemodynamic-guided fluid challenge. However, his condition improved dramatically after the antibiotic regimen was changed to tigecycline and ceftazidime. In addition to the superiority of the antibacterial effect of tigecycline, fluid control can be achieved more easily while using a single antibiotic instead of multiple drugs, which is also important for care of a critically ill elderly man with compromised cardiorespiratory or renal function. Here, we present a patient infected with multiple drug-resistant pathogens, who improved clinically after being treated with tigecycline, to demonstrate the benefits of this antibiotic.

Emergence and spread of carbapenem-resistant Acinetobacter baumannii in a tertiary care hospital in Turkey

An intensive care unit (ICU)-based OXA-23-producing multiple-drug resistant Acinetobacter baumannii (MDRAB) outbreak was detected between October 2005 and October 2006. A total of 47 patients were infected/colonized with the outbreak strain. Clinical data were available from 37 patients. The all-cause mortality rate among the patients exposed to the epidemic strain was 35% (13/37). The outbreak strain and the resistance determinants were characterized both by microbiological methods and by molecular techniques. Cloning and sequencing experiments identified ISAbaI-associated bla(oxa-23) on the chromosome. Screening of imipenem-resistant Acinetobacter isolated from the ICU during the outbreak period with PCR identified 97 isolates as positive for the ISAbaI-bla(oxa-23) structure. Pulsed-field gel electrophoresis and plasmid analyses with selected nonrepetitive isolates revealed the clonality. Disk diffusion on cloxacillin-supplemented agar media and the real-time PCR experiments showed that outbreak isolates are overexpressing the ampC enzyme. This study highlights the occurrence of OXA-23-producing and ampC-overexpressing MDRAB in ICUs.

Effects of Aerosol Colistin Treatment of Pneumonia Caused by Multi-drug Resistant Acinetobacter baumannii

Background: Acinetobacter infections are difficult to treat as they often exhibit multiple resistance to the antibiotics that are currently available for the treatment of pneumonia. Colistin is active against gram-negative bacteria, including the multiple drug resistant (MDR) Acinetobacter species. However, intravenous administration of colistin was abandoned because of its nephrotoxicity and neurotoxicity. The aims of this study were to examine the efficacy and safety of colistin administered by aerosol in the treatment of pneumonia caused by MDR Acinetobacter baumannii. Methods: We retrospectively reviewed the medical records of patients admitted to the intensive care unit (ICU) from Dec. 2006 to Aug. 2007 who had been diagnosed as suffering from pneumonia due to MDR Acinetobacter baumannii and had been treated with nebulized colistin. Results: 31 patients received aerosolized colistin. The average duration of the treatment was days and the daily dose of ranged from 225 mg to 300 mg. All patients received concomitant intravenous antimicrobial agents. The average length of the stay in the ICU was days and in the hospital days. The overall microbiological eradication was observed in 25 patients (80.6%). 14 of these (56%) were cured, and 11 (44%) were infected with other microorganisms. The overall crude mortality of the ICU was 48%. Nephrotoxicity and significant bronchial constriction did not occur in any patient during neublized colistin treatment. Conclusion: Nebulized colistin may be a safe and effective option in the treatment of pneumonia due to MDR Acinetobacter baumannii. Its role in therapy warrants further investigation in comparative studies.