Gram-negative bacteria as causative agents of ventilator-associated pneumonia and their respective resistance mechanisms

Bandić-Pavlović, Daniela; Zah-Bogović, Tajana; Žižek, Marta; Bielen, Luka; Bratić, Vesna; Hrabač, Pero; Slaćanac, Domagoj; Mihaljević, Slobodan; Bedenić, Branka

doi:10.1080/1120009x.2020.1793594

Cited by 17 publications

(16 citation statements)

References 49 publications

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“…The enzyme lactamase is formed in the periplasmic space, which inactivates the antibiotic after penetration into the bacterial organism and breaks the amide bond of the four-membered beta-lactam ring, deactivating the molecule’s antimicrobially active molecules through hydrolysis. The highly drug-resistant P. aeruginosa , A. baumannii, and K. pneumoniae in HAP and VAP patients encodes plasmid-mediated AmpC b-lactamases on their chromosomes that hydrolyze cephalosporins, monobactams, and cephamycins, as well as the expression of class A KPC b-lactamases, confer resistance to carbapenems [ 97 ]. Moreover, the loss of OprD associated with resistance to carbapenems such as imipenem and meropenem in P. aeruginosa and i ncreased production of drug efflux pump systems ( mex ), as part of either an acquired or intrinsic resistance repertoire, is capable of exporting various substrates from the periplasm of GNB to the surrounding environment before the action of the drug [ 98 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns

Assefa

2022

Pneumonia

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Bacterial pneumonia is one of the most serious public health issues owing to its medical and economic costs, which result in increased morbidity and mortality in people of all ages around the world. Furthermore, antimicrobial resistance has risen over time, and the advent of multi-drug resistance in GNB complicates therapy and has a detrimental impact on patient outcomes. The current review aimed to summarize bacterial pneumonia with an emphasis on gram-negative etiology, pathogenesis, risk factors, resistance mechanisms, treatment updates, and vaccine concerns to tackle the problem before it causes a serious consequence. In conclusion, the global prevalence of GNB in CAP was reported 49.7% to 83.1%, whereas in VAP patients ranged between 76.13% to 95.3%. The most commonly reported MDR-GNB causes of pneumonia were A. baumannii, K. pneumoniae, and P. aeruginosa, with A. baumannii isolated particularly in VAP patients and the elderly. In most studies, ampicillin, tetracyclines, amoxicillin-clavulanic acid, cephalosporins, and carbapenems were shown to be highly resistant. Prior MDR-GNB infection, older age, previous use of broad-spectrum antibiotics, high frequency of local antibiotic resistance, prolonged hospital stays, ICU admission, mechanical ventilation, and immunosuppression are associated with the MDR-GNB colonization. S. maltophilia was reported as a severe cause of HAP/VAP in patients with mechanically ventilated and having hematologic malignancy due to its ability of biofilm formation, site adhesion in respiratory devices, and its intrinsic and acquired drug resistance mechanisms. Effective combination therapies targeting PDR strains and drug-resistant genes, antibiofilm agents, gene-based vaccinations, and pathogen-specific lymphocytes should be developed in the future.

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Section: Introductionmentioning

confidence: 99%

Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns

Assefa

2022

Pneumonia

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“…Colistin resistance was not detected in our study’s antibiogram samples of K. pneumoniae . In Bandic-Pavlovic’s investigation, the rate of ciprofloxacin resistance was 55% [ 16 ]. In Phuc H.L.’s study, ciprofloxacin resistance was 69.6%, levofloxacin resistance was 56.5%, and colistin resistance was 30.8% [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…P. aeruginosa was resistant to all β-lactam antibiotics tested in our study (piperacillin/tazobactam, aztreonam, ceftazidime, cefepime, imipenem, and meropenem). According to Bandic-Pavlovic’s research, P. aeruginosa was resistant to piperacillin/tazobactam at 68%, imipenem at 74%, and meropenem at 68% [ 16 ]. Resistance to piperacillin/tazobactam was 58.8%, ceftazidime was 64.7%, cefepime was 64.7%, imipenem was 64.7%, and meropenem was 70.6%, according to Phuc H.L.’s research [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Ventilator-Associated Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Vietnam: Antibiotic Resistance, Treatment Outcomes, and Colistin-Associated Adverse Effects

Dinh

Phan

et al. 2022

Healthcare

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Background: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) gram-negative bacteria (GNB) presents a serious clinical scenario, and there is disagreement regarding the role of colistin in treatment. This study aimed to characterize the antibiotic resistance of MDR GNB and evaluate the treatment outcomes and side effects of colistin in VAP patients caused by MDR GNB, particularly in Vietnam. Methods: A prospective cohort research was undertaken. We enrolled 136 intubated patients diagnosed with VAP according to the Centers for Disease Control and Prevention (CDC) 2019. Sixty-six individuals with an isolated gram-negative bacterium (Acinetobacter baumannii, Klebsiella pneumoniae, or Pseudomonas aeruginosa) satisfied the European Centre for Disease Prevention and Control (ECDC)’s criteria for multi-antibiotic resistance. Results: GNB resistance was categorized as 10.6% MDR, 63.6% XDR, and 25.8% PDR. GNB were resistant to β-lactams 80–100%, aminoglycosides 50–86.7%, fluoroquinolones 100% and colistin 2.8–20%. The 28-day mortality rate was 54.5%, and acute kidney injury occurred at 12.1%. There was no statistically significant difference in mortality rate between groups receiving regimens with or without colistin (58.3% and 73.3%, respectively; OR = 1.964; 95%CI 0.483–7.989). Neither was there a statistically significant difference in acute renal damage rate between groups receiving regimens with or without colistin (14.3% and 9.7%, respectively; OR = 1.556; 95%CI 0.34–7.121). Conclusions: GNB had a high rate of antibiotic resistance to most antibiotics. The addition of colistin to the medication did not show significant differences in renal toxicity or mortality, while colistin resistance was relatively low; larger studies need to be conducted.

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“…The trial enrolled over 1300 patients, making it a relatively large trial for cUTI. The overall response rate was 59% with tebipenem and 62% with ertapenem, with a resulting noninferiority margin that fell below the 12.5% upper boundary [1]. Analyses restricted to patients with ESBL-producing pathogens generally revealed similar efficacy between oral tebipenem and intravenous ertapenem.…”

Section: Tebipenemmentioning

confidence: 94%

Novel agents in development for multidrug-resistant Gram-negative infections: potential new options facing multiple challenges

Arya

Goldner

Shorr

2022

Current Opinion in Infectious Diseases

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Purpose of reviewTo review novel antiinfective agents in development for multidrug-resistant (MDR) Gram-negative bacterial infections. Recent findingsFour novel agents are in various phases of development (tebipenem, durlobactam-sulbactam, cefepimetaniborbactam, and xeruborbactam). Tebpipenem is an oral carbapenem with a recently completed phase III trial for complicated urinary tract infections while durlobactam-sulbactam represents a potential alternative for drug-resistant Acinetobacter baumannii. Cefepime-taniborbactam possesses in-vitro potency against a range of troubling pathogens and we await further information on a recently completed study on complicated urinary tract infection. Finally, xeruborbactam is an ultrabroad beta-lactamase inhibitor that can be paired with a range of intravenous and oral agents. It exhibits enhanced in-vitro activity against many MDR pathogens, including those resistant to newer, broader spectrum options. Data in humans with xeruborbactam are limited.

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Gram-negative bacteria as causative agents of ventilator-associated pneumonia and their respective resistance mechanisms

Cited by 17 publications

References 49 publications

Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns

Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns

Ventilator-Associated Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Vietnam: Antibiotic Resistance, Treatment Outcomes, and Colistin-Associated Adverse Effects

Novel agents in development for multidrug-resistant Gram-negative infections: potential new options facing multiple challenges

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