Gram-Negative Bacteria Holding Together in a Biofilm: The Acinetobacter baumannii Way

Bacterial biofilms are a serious public-health problem worldwide. In recent years, the rates of antibiotic-resistant Gram-negative bacteria associated with biofilm-forming activity have increased worrisomely, particularly among healthcare-associated pathogens. Acinetobacter baumannii is a critically opportunistic pathogen, due to the high rates of antibiotic resistant strains causing healthcare-acquired infections (HAIs). The clinical isolates of A. baumannii can form biofilms on both biotic and abiotic surfaces; hospital settings and medical devices are the ideal environments for A. baumannii biofilms, thereby representing the main source of patient infections. However, the paucity of therapeutic options poses major concerns for human health infections caused by A. baumannii strains. The increasing number of multidrug-resistant A. baumannii biofilm-forming isolates in association with the limited number of biofilm-eradicating treatments intensify the need for effective antibiofilm approaches. This review discusses the mechanisms used by this opportunistic pathogen to form biofilms, describes their clinical impact, and summarizes the current and emerging treatment options available, both to prevent their formation and to disrupt preformed A. baumannii biofilms.

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OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

Scientific Reports ◽

10.1038/s41598-021-86155-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shira Mandel ◽

Janna Michaeli ◽

Noa Nur ◽

Isabelle Erbetti ◽

Jonathan Zazoun ◽

...

Keyword(s):

Mechanism Of Action ◽

Antimicrobial Agents ◽

Cyclic Peptide ◽

Safety Margin ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Antibiotic Resistant ◽

Gram Negative ◽

Development Of Resistance ◽

Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

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Current Pattern and Clinico-Bacteriological Profile of Healthcare Associated Infections (HAI) in an ICU Setting: An Observational Study

10.21203/rs.3.rs-874099/v1 ◽

2021 ◽

Author(s):

Mradul Kumar Daga ◽

Govind Mawari ◽

Saman Wasi ◽

Naresh Kumar ◽

Udbhav Sharma ◽

...

Keyword(s):

Age Groups ◽

Healthcare Facility ◽

Central Line ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Healthcare Associated Infections ◽

Acinetobacter Species ◽

Gram Negative ◽

Causative Agents ◽

Healthcare Associated

Abstract Objective To understand the pattern and types of healthcare associated infections (HAI) at our healthcare facility, and to determine the common causative agents and their antibiotic susceptibility profile. Methods One hundred consecutive patients diagnosed with HAI were enrolled and monitored; the causative organisms isolated on culture were recorded and their sensitivity profile was generated. Results Of the 100 patients diagnosed with HAI (mean age ± SD being 42 ± 17 years), there were a total of 110 hospital acquired infections with 10 patients having two infections each. Out of 100 patients with HAI, 69 patients had ventilator associated pneumonia (VAP), 21 patients had catheter associated urinary tract infection (CAUTI) patients, and 20 patients had central line associated bloodstream infection (CLABSI). There were 10 patients with both VAP and CAUTI. All of the HAIs were device associated. A total of 76 pathogens were isolated on culture. No organism was isolated in 40 HAI. Majority (94.7%) of the organisms isolated from HAIs were gram-negative bacteria and all were multidrug resistant. Seventy-seven of the enrolled patients expired while 23 were discharged from the hospital Conclusions Our study demonstrated that HAIs occur in patients of all age groups; younger patients are not spared. Majority of the HAIs were caused by multidrug resistant gram-negative bacteria and were associated with high patient mortality. Acinetobacter species was the most common organism associated with HAI.

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Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00059-20 ◽

2020 ◽

Vol 64 (4) ◽

Cited By ~ 4

Author(s):

Ryan K. Shields

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Salvage Therapy ◽

Randomized Clinical Trials ◽

Treatment Options ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Potential Utility ◽

Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

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Transposition of Tn125encoding the NDM-1 carbapenemase inAcinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01755-16 ◽

2016 ◽

pp. AAC.01755-16 ◽

Cited By ~ 13

Author(s):

Séverine Bontron ◽

Patrice Nordmann ◽

Laurent Poirel

Keyword(s):

Acinetobacter Baumannii ◽

Direct Evidence ◽

Opportunistic Pathogen ◽

Target Site ◽

Gram Negative Bacteria ◽

Transposition Frequency ◽

Gram Negative ◽

Temperature Changes ◽

Site Consensus ◽

Almost All

TheblaNDM-1gene encodes a carbapenemase that confers resistance to almost all β-lactams, including latest resort carbapenems. It is increasingly reported worldwide in nosocomial and community-acquired Gram-negative bacteria.Acinetobacter baumanniiis an important opportunistic pathogen considered as an intermediate reservoir for theblaNDM-1gene. In this species, theblaNDM-1gene is located within the Tn125composite transposon. The mechanism driving the mobility of Tn125has not yet been elucidated. Here we experimentally demonstrated transposition of Tn125inA. baumannii. Systematic 3-bp duplication of the target site, being signature of transposition, was evidenced. The target site consensus for Tn125transposition was found to be GC-enriched at the duplicated 3 bp and AT-rich in the vicinity. Transposition frequency was not influenced by temperature changes or by exposure to sub-inhibitory concentrations of various antibiotics. This work is the first direct evidence of the functionality of a composite transposon inA. baumannii. It provides a mechanistic clue for the dissemination of theblaNDM-1gene inAcinetobacterspp. and subsequently among Enterobacteriaceae.

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Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

Antibiotics ◽

10.3390/antibiotics10091117 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1117

Author(s):

Anne Davin-Regli ◽

Jean-Marie Pages ◽

Aurélie Ferrand

Keyword(s):

Clinical Status ◽

Efflux Pumps ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Gram Negative Bacteria ◽

Easy Method ◽

Gram Negative ◽

Healthcare Associated ◽

Rational Use Of Antibiotics ◽

Antibiotic Efflux

Antibiotic efflux is a mechanism that is well-documented in the phenotype of multidrug resistance in bacteria. Efflux is considered as an early facilitating mechanism in the bacterial adaptation face to the concentration of antibiotics at the infectious site, which is involved in the acquirement of complementary efficient mechanisms, such as enzymatic resistance or target mutation. Various efflux pumps have been described in the Gram-negative bacteria most often encountered in infectious diseases and, in healthcare-associated infections. Some are more often involved than others and expel virtually all families of antibiotics and antibacterials. Numerous studies report the contribution of these pumps in resistant strains previously identified from their phenotypes. The authors characterize the pumps involved, the facilitating antibiotics and those mainly concerned by the efflux. However, today no study describes a process for the real-time quantification of efflux in resistant clinical strains. It is currently necessary to have at hospital level a reliable and easy method to quantify the efflux in routine and contribute to a rational choice of antibiotics. This review provides a recent overview of the prevalence of the main efflux pumps observed in clinical practice and provides an idea of the prevalence of this mechanism in the multidrug resistant Gram-negative bacteria. The development of a routine diagnostic tool is now an emergency need for the proper application of current recommendations regarding a rational use of antibiotics.

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Assessment of Ceftazidime-Avibactam 30/20-μg Disk, Etest versus Broth Microdilution Results When Tested against Enterobacterales Clinical Isolates

Microbiology Spectrum ◽

10.1128/spectrum.01092-21 ◽

2022 ◽

Author(s):

Renru Han ◽

Xuelin Yang ◽

Yang Yang ◽

Yan Guo ◽

Dandan Yin ◽

...

Keyword(s):

Treatment Options ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Gram Negative Bacteria ◽

Broth Microdilution ◽

Gram Negative ◽

Extended Spectrum ◽

The World ◽

Multidrug Resistant Pathogens ◽

Combinational Therapies

Multidrug-resistant Gram-negative bacteria, especially for extended-spectrum β-lactamases-producing and carbapenemase-producing Enterobacterales , are disseminating rapidly around the world. Treatment options for these infections are limited, which prompt the development of novel or combinational therapies to combat the infections caused by multidrug-resistant pathogens.

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Dissemination of Carbapenem-resistance and Plasmids-encoding Carbapenemases in Gram-negative Bacteria Isolated from India

10.1101/2020.05.18.102434 ◽

2020 ◽

Author(s):

Prasanth Manohar ◽

Sebastian Leptihn ◽

Bruno S. Lopes ◽

Nachimuthu Ramesh

Keyword(s):

Tamil Nadu ◽

Treatment Options ◽

Public Health Problem ◽

Carbapenem Resistance ◽

Gram Negative Bacteria ◽

Gram Negative ◽

E Coli ◽

Diagnostic Center ◽

Lactamase Gene

AbstractCarbapenem resistance in Gram-negative bacteria is an ongoing public-health problem of global dimensions leaving very few treatment options for severely infected patients. This study focuses on the dissemination of plasmid-borne carbapenemase genes in Gram-negative bacteria in Tamil Nadu, India. A total of 151 non-repetitive isolates belonging to 11 genera were collected from a diagnostic center in Tamil Nadu. E. coli (n=57) isolates were classified as, Enteropathogenic (n=12), Enteroaggregative (n=9), Enterohemorrhagic (n=8), Enterotoxigenic (n=3), Enteroinvasive (n=1) and unclassified E. coli (n=24). Of the 45 Klebsiella species, 14 were K1 whereas 11 were K2 serotype and in 20 Klebsiella serotype could not be determined. Other isolates (n=49) consisted of P. aeruginosa, S. typhi, E. cloacae, A. baumannii, S. marcescens, A. xylosoxidans, P. mirabilis and E. meningoseptica. Of the 151 isolates, 71% (n=107) and 68% (n=103) were found to be resistant to meropenem and imipenem respectively. The most prevalent beta-lactamase gene was blaNDM-1 (21%, 12/57) followed by blaOXA-181 (16%, 9/57), blaGES-9 (n=8), blaOXA-23 (n=7), blaIMP-1 (n=3), blaGES-1 (n=11) and blaOXA-51 (n=9). The unusual presence of blaOXA-23 was seen in E. coli (n=4), and blaOXA-23 and blaOXA-51 (IncA/C) in K. pneumoniae (n=3). Plasmid incompatibility (inc/rep) typing results showed that the plasmids carrying resistance genes (n=11) belonged to IncX, IncA/C, IncFIA-FIB and IncFIIA groups. E. coli and K. pneumoniae were able to transfer plasmid-borne carbapenemase via conjugation. This study highlights the prevalence of carbapenem resistance and the acquisition of plasmid-borne carbapenemase genes in Gram-negative bacteria highlighting the role of plasmid transfer in disseminating resistance.

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Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria

Revista Española de Quimioterapia ◽

10.37201/req/s01.12.2021 ◽

2021 ◽

Vol 34 (Suppl 1) ◽

pp. 41-43

Author(s):

José Tiago Silva ◽

Francisco López-Medrano

Keyword(s):

Bacterial Pneumonia ◽

Treatment Options ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Phase Iii ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Tract Infections ◽

Transport Channels ◽

Hospital Acquired

Cefiderocol is a novel catechol-substituted siderophore cephalosporin that binds to the extracellular free iron, and uses the bacterial active iron transport channels to penetrate in the periplasmic space of Gram-negative bacteria (GNB). Cefiderocol overcomes many resistance mechanisms of these bacteria. Cefiderocol is approved for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in the case of adults with limited treatment options, based on the clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In the CREDIBLE-CR trial, a higher all-cause mortality was observed in the group of patients who received cefiderocol, especially those with severe infections due to Acinetobacter spp. Further phase III clinical studies are necessary in order to evaluate cefiderocol´s efficacy in the treatment of serious infections.

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Characteristics of Microbial Factors of Healthcare-Associated Infections Including Multidrug-Resistant Pathogens and Antibiotic Consumption at the University Intensive Care Unit in Poland in the Years 2011–2018

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17196943 ◽

2020 ◽

Vol 17 (19) ◽

pp. 6943

Author(s):

Agnieszka Litwin ◽

Olga Fedorowicz ◽

Wieslawa Duszynska

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Multidrug Resistant ◽

Defined Daily Dose ◽

Gram Negative Bacteria ◽

Healthcare Associated Infections ◽

Gram Negative ◽

Enterococcus Spp ◽

Healthcare Associated ◽

The University

Introduction: In recent years, an increase in healthcare-associated infections (HAIs) caused by resistant pathogens, which is a clinically troublesome trend, has been observed. The aim of the study was to analyze the microbial factors of HAIs and the drug resistance of microorganisms to selected antibiotics and their consumption. Material and Methods: The retrospective study included 3708 patients hospitalized in the intensive care unit (ICU) of the University Teaching Hospital in Wroclaw, who were diagnosed with 742 HAIs in the period from 1 January 2011 to 31 December 2018. The aim of the study was the analysis of microorganisms isolated in the respective clinical forms of HAIs, including the occurrence of “alert pathogens”, presence of multidrug-resistant (MDR) strains, and consumption of selected antibiotics. Findings: During the study period, 846 microorganisms were cultured in patients with HAIs, and among them, Acinetobacter baumannii MDR represented 31.8%; Klebsiella pneumoniae ESBLs, 11.3%; Pseudomonas aeruginosa MDR, 4.1% and MRSA, 2.2%; and Enterococcus spp. vancomycin-resistant enterococci (VRE), 1.3%. Among all the pathogens, Gram-negative bacteria (GNB) were dominant (71.6%). Gram-positive bacteria and fungi accounted for 21.6% and 7%, respectively. The total number of strains responsible for ventilator-associated pneumonia (VAP), urinary tract infection (UTI), and central line-associated blood stream infection (CLA-BSI) was as follows: 458 (54.1%), 274 (32.4%), and 114 (13.5%), respectively. Among the etiological factors of VAP, there was a prevalence of A. baumannii MDR (41.9%), as well as in the case of UTI (21.9%). With regards to CLA-BSI, MRCNS (29.8%) was the dominant pathogen. The “alert pathogens” accounted for 54.7% of all the analyzed strains. The MDR strains represented 72.6% and 9.7% among A. baumannii and P. aeruginosa, respectively. In the years 2011 vs. 2018, an increase in infections with MDR bacilli was observed, 34.6% vs. 61.0% (p = 0.0008), respectively, including A. baumannii MDR 16.54% vs. 34.56 % (p = 0.0009) and Enterobacterales ESBL+/AMPC 11.8% vs. 15.44 % (p = 0.3921). Resistance to methicillin was confirmed in 35.2% of S. aureus strains. Resistance to vancomycin was found among 30.9% of Enterococcus spp. The observed period was marked by an increase in the consumption of carbapenems: 197.7 vs. 235.9 defined daily dose (DDD)/1000 patients-days. Conclusions: Gram-negative bacteria were found to be dominant pathogens in healthcare-associated infections. The most frequently cultured pathogens were multidrug-resistant A. baumannii, K. pneumoniae ESBL(+), and P. aeruginosa. The study showed an increase in the incidence of “alert pathogens” and MDR bacilli, as well as the tendency of a growing resistance to antibiotics during the observed period. Microbiological analysis of HAIs and the consumption of antibiotics is the necessary element of the proper antibiotic policy in hospitals.

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A Review of Superbug: A Global Threat in Health Care System

Bangladesh Journal of Infectious Diseases ◽

10.3329/bjid.v4i1.37678 ◽

2018 ◽

Vol 4 (1) ◽

pp. 25-28 ◽

Cited By ~ 2

Author(s):

Bhuiyan Mohammad Mahtab Uddin ◽

Md Abdullah Yusuf ◽

Zubair Ahmed Ratan

Keyword(s):

Public Health ◽

Health Problem ◽

Antimicrobial Agents ◽

Public Health Problem ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Major Public Health Problem ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Hospital Acquired

The rapid spread and dissemination of the multidrug-resistant bacteria worldwide represents a major public health problem. The development of antibiotics decreased the mortality among the human and animals leading to a better life expectancy. But the injudicious use of antimicrobials and selection pressure the microbes have developed resistance which became more prominent during last few decades. With the evolution of Methicilin-resistant Staphylococcus aureus (MRSA), Hospital-acquired MRSA, Communityacquired MRSA and MDR TB (Multidrug resistant tuberculosis) challenge for the clinicians have increased to a greater extent. The global emergence and dissemination of acquired carbapenemases among gram negative bacteria are considered a major public health problem. Gram-negative bacteria, most notably Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most important causes of serious hospital-acquired and community-onset bacterial infections in humans, and resistance to antimicrobial agents in these bacteria has become an increasingly relevant problem. Recent development in nanotechnology based drug delivery system may prove to be solution for combating these resistant bacteria. However policies and regulations for antibiotic use should be formulated to control the further development of resistance among the microbes.Bangladesh Journal of Infectious Diseases 2017;4(1):25-28

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