Counter Clinical Prognoses of Patients With Bloodstream Infections Between Causative Acinetobacter baumannii Clones ST191 and ST451 Belonging to the International Clonal Lineage II

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.

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In VitroandIn VivoAntimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01519-12 ◽

2012 ◽

Vol 56 (11) ◽

pp. 5961-5970 ◽

Cited By ~ 72

Author(s):

Luísa C. S. Antunes ◽

Francesco Imperi ◽

Fabrizia Minandri ◽

Paolo Visca

Keyword(s):

Human Serum ◽

Acinetobacter Baumannii ◽

Galleria Mellonella ◽

Therapeutic Potential ◽

Survival Rates ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Gallium Nitrate ◽

Content Type ◽

Bacterial Physiology

ABSTRACTMultidrug-resistantAcinetobacter baumanniiposes a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumanniichemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO3)3, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58A. baumanniistrains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO3)3delayed the entry ofA. baumanniiinto the exponential phase and drastically reduced bacterial growth rates. Ga(NO3)3activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO3)3also protectedGalleria mellonellalarvae from lethalA. baumanniiinfection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO3)3inhibited the growth in human serum of 76% of the multidrug-resistantA. baumanniiisolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment ofA. baumanniibloodstream infections. Ga(NO3)3also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistantA. baumannii.

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Growth Retardation, Reduced Invasiveness, and Impaired Colistin-Mediated Cell Death Associated with Colistin Resistance Development in Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01439-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 828-832 ◽

Cited By ~ 54

Author(s):

Spyros Pournaras ◽

Aggeliki Poulou ◽

Konstantina Dafopoulou ◽

Yassine Nait Chabane ◽

Ioulia Kristo ◽

...

Keyword(s):

Cell Death ◽

Acinetobacter Baumannii ◽

Biofilm Formation ◽

Bloodstream Infections ◽

Single Amino Acid ◽

Colistin Resistance ◽

Resistance Development ◽

Content Type ◽

Alkyl Hydroperoxide ◽

Severe Soft Tissue

ABSTRACTTwo colistin-susceptible/colistin-resistant (Cols/Colr) pairs ofAcinetobacter baumanniistrains assigned to international clone 2, which is prevalent worldwide, were sequentially recovered from two patients after prolonged colistin administration. Compared with the respective Colsisolates (Ab248 and Ab299, both having a colistin MIC of 0.5 μg/ml), both Colrisolates (Ab249 and Ab347, with colistin MICs of 128 and 32 μg/ml, respectively) significantly overexpressedpmrCABgenes, had single-amino-acid shifts in the PmrB protein, and exhibited significantly slower growth. The Colrisolate Ab347, tested by proteomic analysis in comparison with its Colscounterpart Ab299, underexpressed the proteins CsuA/B and C from thecsuoperon (which is necessary for biofilm formation). This isolate also underexpressed aconitase B and different enzymes involved in the oxidative stress response (KatE catalase, superoxide dismutase, and alkyl hydroperoxide reductase), suggesting a reduced response to reactive oxygen species (ROS) and, consequently, impaired colistin-mediated cell death through hydroxyl radical production. Colsisolates that were indistinguishable by macrorestriction analysis from Ab299 caused six sequential bloodstream infections, and isolates indistinguishable from Ab248 caused severe soft tissue infection, while Colrisolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Colsisolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Colrisolates. These observations indicate considerably lower invasiveness ofA. baumanniiclinical isolates following the development of colistin resistance.

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Development and Clinical Validation of a Droplet Digital PCR Method for Detection of Acinetobacter baumannii and Klebsiella pneumonia in Patients with Suspected Bloodstream Infections

10.22541/au.162337143.35366523/v1 ◽

2021 ◽

Author(s):

Yang Zheng ◽

Jun Jin ◽

Ziqiang Shao ◽

Jingquan Liu ◽

Run Zhang ◽

...

Keyword(s):

Blood Culture ◽

Acinetobacter Baumannii ◽

Limit Of Detection ◽

Early Stage ◽

Bloodstream Infections ◽

Digital Pcr ◽

Droplet Digital Pcr ◽

Klebsiella Pneumonia ◽

Clinical Validation ◽

Blood Samples

The relatively long turnaround time and low sensitivity of traditional blood culture may delay the effective antibiotic therapy in patients with bloodstream infection (BSI). To reduce the morbidity and mortality of BSI, a rapid and sensitive pathogen detection method is urgently required. Acinetobacter baumannii and Klebsiella pneumonia are two major microorganisms responsible for BSI. Here we reported a novel droplet digital PCR (ddPCR) method that can detect A. baumannii and K. pneumonia in whole blood samples within 4 h, with a specificity of 100% for each strain and limit of detection at 0.93 copies/microliter for A. baumannii and 0.27 copies/microliter for K. pneumonia. Clinical validation in 170 patients with suspected BSIs showed that, compared with blood culture that reported 4 (2.4%) A. baumannii cases and 7 (4.1%) K. pneumonia cases, ddPCR detected 23 (13.5%) A. baumannii cases, 26 (15.3%) K. pneumonia cases, and 4 (2.4%) dual infection cases, including the 11 positive patients reported by blood culture. In addition, the positive patients reported by ddPCR alone (n = 42) had significantly lower serum concentrations of procalcitonin and lactate, SOFA and APACHE II scores, and 28-day mortality than those reported by both blood culture and ddPCR (n = 11), suggesting that patients with less severe manifestations can potentially benefit from the guidance of ddPCR results. In conclusion, our study suggests that ddPCR represents a sensitive and rapid method to identify causal pathogens in blood samples and to guide the treatment decisions in the early stage of BSI.

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Exploring a phage-based real-time PCR assay for diagnosing Acinetobacter baumannii bloodstream infections with high sensitivity

Analytica Chimica Acta ◽

10.1016/j.aca.2018.09.038 ◽

2018 ◽

Vol 1044 ◽

pp. 147-153 ◽

Cited By ~ 5

Author(s):

Jun Luo ◽

Mengwei Jiang ◽

Jin Xiong ◽

Junhua Li ◽

Xiaoxu Zhang ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Real Time ◽

Real Time Pcr ◽

Bloodstream Infections ◽

High Sensitivity ◽

Pcr Assay

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Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace

Biomolecules ◽

10.3390/biom10050720 ◽

2020 ◽

Vol 10 (5) ◽

pp. 720 ◽

Cited By ~ 10

Author(s):

Maria Soledad Ramirez ◽

Robert A. Bonomo ◽

Marcelo E. Tolmasky

Keyword(s):

Acinetobacter Baumannii ◽

Nosocomial Infections ◽

Acquired Resistance ◽

Clinical Manifestations ◽

High Capacity ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Drug Resistant ◽

Wound Infections ◽

Extensively Drug Resistant

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of A. baumannii nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. A. baumannii has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among A. baumannii strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.

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Bacteraemia in Intensive Care Unit: Clinical, Bacteriological, and Prognostic Prospective Study

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2017/4082938 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Zineb Lachhab ◽

Mohammed Frikh ◽

Adil Maleb ◽

Jalal Kasouati ◽

Nouafal Doghmi ◽

...

Keyword(s):

Intensive Care ◽

Acinetobacter Baumannii ◽

Intensive Care Units ◽

Bloodstream Infections ◽

Blood Cultures ◽

Common Source ◽

Gram Negative ◽

Extended Spectrum Beta Lactamases ◽

Gram Negative Organisms ◽

One Year

Objectives.We conducted a one-year observational study from December 2012 to November 2013 to describe the epidemiology of bacteraemia in intensive care units (ICU) of Mohammed V Military Teaching Hospital of Rabat (Morocco).Methods.The study consisted of monitoring all blood cultures coming from intensive care units and studying the bacteriological profile of positive blood cultures as well as their clinical significance.Results.During this period, a total of 46 episodes of bacteraemia occurred, which corresponds to a rate of 15,4/1000 patients. The rate of nosocomial infections was 97% versus 3% for community infections. The most common source of bacteraemia was the lungs in 33%, but no source was identified in 52% of the episodes. Gram negative organisms were isolated in 83,6% of the cases withAcinetobacter baumanniibeing the most frequent. Antibiotic resistance was very high with 42,5% of extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae and 100% of carbapenemase inAcinetobacter baumannii. The antibiotherapy introduced in the first 24 hours was adequate in 72% of the cases.Conclusions.Bloodstream infections in ICU occur most often in patients over 55 years, with hypertension and diabetes. The bacteria involved are mainly Gram negative bacteria multiresistant to antibiotics. Early administration of antibiotics significantly reduces patients mortality.

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Impact of early appropriate antimicrobial therapy on survival in Acinetobacter baumannii bloodstream infections

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2009.07.006 ◽

2009 ◽

Vol 34 (6) ◽

pp. 575-579 ◽

Cited By ~ 65

Author(s):

Ayşe Erbay ◽

Aysun İdil ◽

M. Gökhan Gözel ◽

İpek Mumcuoğlu ◽

Neriman Balaban

Keyword(s):

Acinetobacter Baumannii ◽

Antimicrobial Therapy ◽

Bloodstream Infections

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Impact of Carbapenem Resistance and Receipt of Active Antimicrobial Therapy on Clinical Outcomes of Acinetobacter baumannii Bloodstream Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01728-10 ◽

2011 ◽

Vol 55 (10) ◽

pp. 4844-4849 ◽

Cited By ~ 55

Author(s):

John S. Esterly ◽

Milena Griffith ◽

Chao Qi ◽

Michael Malczynski ◽

Michael J. Postelnick ◽

...

Keyword(s):

Hospital Mortality ◽

Acinetobacter Baumannii ◽

Antimicrobial Therapy ◽

Active Agent ◽

Carbapenem Resistance ◽

Bloodstream Infections ◽

Chronically Ill ◽

Cox Proportional Hazards Model ◽

Bivariate Analysis ◽

Content Type

ABSTRACTNosocomialAcinetobacter baumanniibloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance inA. baumanniiand patient outcomes remains unclear. A retrospective cohort study was conducted on patients withA. baumanniibacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistantA. baumannii(CNRAB) and carbapenem-resistantA. baumannii(CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P< 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P= 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5;P< 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%;P= 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P= 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.

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