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Antibiotics
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Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia
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Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 34892

Special Issue Editor

Prof. Dr. Demosthènes A. Makris

E-Mail Website
Guest Editor
Intensive Care Unit, University Hospital of Larissa, University of Thessaly, 41110 Biopolis Larissa, Greece
Interests: pneumonia; intensive care; MDR infections; antibiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nosocomial infections, such as ventilator-associated pneumonia (VAP), cause serious morbidity in critical care patients [1-3]. Patients with no previous respiratory problems otherwise may be at increased risk to present with respiratory infections [1, 4-6]. Moreover, recent exposure to either antibiotics or healthcare settings can predispose a patient to multidrug-resistant (MDR) infections, which are associated with adverse outcomes in the intensive care unit (ICU) [4, 7]. Several strategies have been suggested to prevent or manage MDR infections in the ICU [8-11]. Some of these interventions were associated with reduced pneumonia rates or improvements in the clinical course of infections [9, 10, 11]. However, other studies have reported an increased incidence of MDR following strategies for the prevention of pneumonia [12]. Hence, there is skepticism concerning the role of preventive strategies using antibiotics, topically applied in the bronchial tree, to prevent VAP.

In the present Special Issue, we point out strategies for the prevention or therapy of pneumonia caused by MDR, based on the use of antibiotics, either topically applied or used by a systemic route.

References

  1. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165:867–903.
  2. Rello J, Ollendorf DA, Oster G, et al. VAP Outcomes Scientific Advisory Group: Epidemiology and Outcomes of Ventilator-Associated Pneumonia in a Large US Database. Chest 2002; 122:2115-2121.
  3. Bercault N and Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: A prospective case-control study. Crit Care Med 2001; 29:2303–2309.
  4. ATS: Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia. Am J Respir Crit Care Med 2005: 171:388–416.
  5. Bouderka MA, Fakhir B, Bouaggad A, et al. Early Tracheostomy versus Prolonged Endotracheal Intubation in Head Injury. J Trauma 2004; 57:251–254.
  6. Karvouniaris M, Makris D, Manoulakas E, et al. Ventilator-Associated Tracheobronchitis Increases the Length of Intensive Care Unit Stay. Infect Control Hosp Epidemiol 2013; 34(8): 800-808.
  7. Nseir S, Blazejewski C, Lubret R, et al. Risk of acquiring multidrug resistant Gram-negative bacilli from prior room occupants in the intensive care unit. Clin Microbiol Infect 2011; 17: 1201–1208.
  8. Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the ICU. Crit Care Med 2008; 36: 2008-13.
  9. Karvouniaris M, Makris D, Zygoulis P, Triantaris A, Xitsas S, Mantzarlis K, Petinaki E, Zakynthinos E. Nebulised colistin for ventilator-associated pneumonia prevention. Eur Respir J. 2015 Dec;46(6):1732-9.
  10. Klick JM, du Moulin GC, Hedley-Whyte J, et al. Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. J Clin Invest 1975; 55(3): 514–519.
  11. Tsolaki V , Mantzarlis K , Mpakalis, et al. Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients Antimicrob Agents Chemothepy 2020 Feb 21;64(3):e02320-19.
  12. Feeley TW, Du Moulin GC, Hedley-Whyte J, et al. Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med 1975; 293:471-475.

Prof. Dr. Demosthènes A. Makris
Guest Editor

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Published Papers (8 papers)

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Research

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15 pages, 3730 KiB  
Article
Bibliometric Analysis of Global Research Output on Antimicrobial Resistance among Pneumonia Pathogens (2013–2023)
by Nurgul Ablakimova, Gaziza A. Smagulova, Svetlana Rachina, Aigul Z. Mussina, Afshin Zare, Nadiar M. Mussin, Asset A. Kaliyev, Reza Shirazi, Nader Tanideh and Amin Tamadon
Antibiotics 2023, 12(9), 1411; https://doi.org/10.3390/antibiotics12091411 - 6 Sep 2023
Cited by 8 | Viewed by 2406
Abstract
Antimicrobial resistance (AMR) is a pressing global concern, posing significant challenges to the effective treatment of infections, including pneumonia. This bibliometric analysis aims to investigate the research output on AMR among pneumonia pathogens from 2013 to 2023. Data were extracted from the Web [...] Read more.
Antimicrobial resistance (AMR) is a pressing global concern, posing significant challenges to the effective treatment of infections, including pneumonia. This bibliometric analysis aims to investigate the research output on AMR among pneumonia pathogens from 2013 to 2023. Data were extracted from the Web of Science Core Collection (WOS-CC) using an inclusive search strategy. The analysis included 152 relevant studies published in 99 different sources, involving 988 authors and yielding an average of 16.33 citations per document over the past decade. The findings reveal a notable increase in research on AMR among pneumonia pathogens, indicating a growing awareness of this critical issue. Collaborative studies were prevalent, with the majority of authors engaging in joint research efforts. Bradford’s Law identified twelve core journals that were instrumental in disseminating research in this field, with “Medicine” emerging as the most prolific journal. The USA and China emerged as the leading contributors, while Germany displayed a strong inclination towards collaborative research. Intermountain Medical Center, Saitama Medical University, and Udice-French Research Universities were the most productive institutions, and Yayan J. and Rasche K. were the top authors. Furthermore, the analysis identified commonly encountered microorganisms such as Acinetobacter baumanii and Klebsiella pneumoniae in the context of AMR. Time-based analysis of keywords highlighted the significance of terms like “community-acquired pneumonia” and “ventilator-associated pneumonia”. Overall, this comprehensive study sheds light on the global research landscape of AMR among pneumonia pathogens. The insights gained from this analysis are essential for guiding future research priorities and collaborative efforts to combat AMR effectively and improve treatment outcomes for pneumonia and related infections. As the frequency of reports concerning resistance among pneumonia pathogens, notably A. baumannii and K. pneumoniae, continues to rise, there is an immediate requirement for pharmaceutical manufacturers and healthcare providers to respond proactively and ready themselves for the forthcoming implications of this matter. It also underscores the importance of knowledge dissemination and evidence-based interventions to address this growing public health challenge. However, the study acknowledges the limitations associated with using a single publication database and encourages the inclusion of data from other sources in future research. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
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13 pages, 3391 KiB  
Article
Critical-Illness: Combined Effects of Colistin and Vasoactive Drugs: A Pilot Study
by Rodopi Stamatiou, Anna Vasilaki, Dimitra Tzini, Vasiliki Tsolaki, Konstantina Zacharouli, Maria Ioannou, George Fotakopoulos, Markos Sgantzos and Demosthenes Makris
Antibiotics 2023, 12(6), 1057; https://doi.org/10.3390/antibiotics12061057 - 15 Jun 2023
Cited by 2 | Viewed by 1876
Abstract
Colistin is often used as a last resort for treating multidrug-resistant infections, particularly in critically ill patients in intensive care units. Nonetheless, its side effects, including myopathy, require careful monitoring. Vasoconstrictive drugs are also used in intensive care to increase blood pressure and [...] Read more.
Colistin is often used as a last resort for treating multidrug-resistant infections, particularly in critically ill patients in intensive care units. Nonetheless, its side effects, including myopathy, require careful monitoring. Vasoconstrictive drugs are also used in intensive care to increase blood pressure and improve blood flow to vital organs, which can be compromised in critically ill patients. The exact mechanism of colistin-induced muscle toxicity is of significant interest due to its potential intensive-care clinical implications. Colistin alone or in combination with vasoconstrictive agents was administrated in non-septic and LPS-induced septic animals for 10 days. Histopathological evaluation of the gastrocnemius muscle and dot-blot protein tissue analysis were performed. Increased intramuscular area, de-organization of the muscle fibers and signs of myopathy were observed in colistin-treated animals. This effect was ameliorated in the presence of vasoconstrictive drugs. Administration of colistin to septic animals resulted in a decrease of AMPK and cyclin-D1 levels, while it had no effect on caspase 3 levels. Vasoconstrictive drugs’ administration reversed the effects of colistin on AMPK and cyclin D1 levels. Colistin’s effects on muscle depend on septic state and vasoconstriction presence, highlighting the need to consider these factors when administering it in critically ill patients. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
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14 pages, 1482 KiB  
Article
Clinical Features and Outcomes of VAP Due to Multidrug-Resistant Klebsiella spp.: A Retrospective Study Comparing Monobacterial and Polybacterial Episodes
by Dalia Adukauskiene, Ausra Ciginskiene, Agne Adukauskaite, Despoina Koulenti and Jordi Rello
Antibiotics 2023, 12(6), 1056; https://doi.org/10.3390/antibiotics12061056 - 15 Jun 2023
Viewed by 1546
Abstract
VAP due to multidrug-resistant (MDR) bacteria is a frequent infection among patients in ICUs. Patient characteristics and mortality in mono- and polybacterial cases of VAP may differ. A single-centre, retrospective 3-year study was conducted in the four ICUs of a Lithuanian referral university [...] Read more.
VAP due to multidrug-resistant (MDR) bacteria is a frequent infection among patients in ICUs. Patient characteristics and mortality in mono- and polybacterial cases of VAP may differ. A single-centre, retrospective 3-year study was conducted in the four ICUs of a Lithuanian referral university hospital, aiming to compare both the clinical features and the 60-day ICU all-cause mortality of monobacterial and polybacterial MDR Klebsiella spp. VAP episodes. Of the 86 MDR Klebsiella spp. VAP episodes analyzed, 50 (58.1%) were polybacterial. The 60-day mortality was higher (p < 0.05) in polybacterial episodes: overall (50.0 vs. 27.8%), in the sub-group with less-severe disease (SOFA < 8) at VAP onset (45.5 vs. 15.0%), even with appropriate treatment (41.7 vs. 12.5%), and the sub-group of extended drug-resistant (XDR) Klebsiella spp. (46.4 vs. 17.6%). The ICU mortality (44.0 vs. 22.5%) was also higher in the polybacterial episodes. The monobacterial MDR Klebsiella spp. VAP was associated (p < 0.05) with prior hospitalization (61.1 vs. 40.0%), diabetes mellitus (30.6 vs. 5.8%), obesity (30.6 vs. 4.7%), prior antibiotic therapy (77.8 vs. 52.0%), prior treatment with cephalosporins (66.7 vs. 36.0%), and SOFA cardiovascular ≥ 3 (44.4 vs. 10.0%) at VAP onset. Patients with polybacterial VAP were more likely (p < 0.05) to be comatose (22.2 vs. 52.0%) and had a higher SAPS II score (median [IQR] 45.0 [35.25–51.1] vs. 50.0 [40.5–60.75]) at VAP onset. Polybacterial MDR Klebsiella spp. VAP had distinct demographic and clinical characteristics compared to monobacterial, and was associated with poorer outcomes. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
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10 pages, 868 KiB  
Article
Impact of Bacterial Infections on COVID-19 Patients: Is Timing Important?
by Christos Michailides, Themistoklis Paraskevas, Iosif Karalis, Ioanna Koniari, Charalampos Pierrakos, Vasilios Karamouzos, Markos Marangos and Dimitrios Velissaris
Antibiotics 2023, 12(2), 379; https://doi.org/10.3390/antibiotics12020379 - 12 Feb 2023
Cited by 5 | Viewed by 2545
Abstract
Background: Along with important factors that worsen the clinical outcome of COVID-19, it has been described that bacterial infections among patients positive for a SARS-CoV-2 infection can play a dramatic role in the disease process. Co-infections or community-acquired infections are recognized within the [...] Read more.
Background: Along with important factors that worsen the clinical outcome of COVID-19, it has been described that bacterial infections among patients positive for a SARS-CoV-2 infection can play a dramatic role in the disease process. Co-infections or community-acquired infections are recognized within the first 48 h after the admission of patients. Superinfections occur at least 48 h after admission and are considered to contribute to a worse prognosis. Microbiologic parameters differentiate infections that happen after the fifth day of hospitalization from those appearing earlier. Specifically, after the fifth day, the detection of resistant bacteria increases and difficult microorganisms emerge. Objectives: The aim of the study was to evaluate the impact of bacterial infections in patients with COVID-19 on the length of the hospital stay and mortality. Methods: A total of 177 patients hospitalized due to COVID-19 pneumonia were consecutively sampled during the third and fourth wave of the pandemic at a University Hospital in Greece. A confirmed bacterial infection was defined as positive blood, urinary, bronchoalveolar lavage (BAL) or any other infected body fluid. Patients with confirmed infections were further divided into subgroups according to the time from admission to the positive culture result. Results: When comparing the groups of patients, those with a confirmed infection had increased odds of death (odds ratio: 3.634; CI 95%: 1.795–7.358; p < 0.001) and a longer length of hospital stay (median 13 vs. 7 days). A late onset of infection was the most common finding in our cohort and was an independent risk factor for in-hospital death. Mortality and the length of hospital stay significantly differed between the subgroups. Conclusion: In this case series, microbial infections were an independent risk factor for a worse outcome among patients with COVID-19. Further, a correlation between the onset of infection and a negative outcome in terms of non-infected, community-acquired, early hospital-acquired and late hospital-acquired infections was identified. Late hospital-acquired infections increased the mortality of COVID-19 patients whilst superinfections were responsible for an extended length of hospital stay. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
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Review

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15 pages, 324 KiB  
Review
Treatment Strategies of Colistin Resistance Acinetobacter baumannii Infections
by Andria Papazachariou, Renatos-Nikolaos Tziolos, Stamatis Karakonstantis, Petros Ioannou, George Samonis and Diamantis P. Kofteridis
Antibiotics 2024, 13(5), 423; https://doi.org/10.3390/antibiotics13050423 - 6 May 2024
Cited by 3 | Viewed by 4219
Abstract
Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing [...] Read more.
Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing to this resistance, such as modifications to lipopolysaccharide or lipid A structures, alterations in outer membrane permeability via porins and heteroresistance. In light of this escalating threat, the review also evaluates available treatment options. The development of new antibiotics (cefiderocol, sulbactam/durlobactam) although not available everywhere, and the use of various combinations and synergistic drug combinations (including two or more of the following: a polymyxin, ampicillin/sulbactam, carbapenems, fosfomycin, tigecycline/minocycline, a rifamycin, and aminoglycosides) are discussed in the context of overcoming colistin resistance of A. baumannii infections. Although most studied combinations are polymyxin-based combinations, non-polymyxin-based combinations have been emerging as promising options. However, clinical data remain limited and continued investigation is essential to determine optimal therapeutic strategies against colistin-resistant A. baumannii. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
15 pages, 297 KiB  
Review
Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review
by Pavlos Myrianthefs, George E. Zakynthinos, Vasiliki Tsolaki and Demosthenes Makris
Antibiotics 2023, 12(5), 801; https://doi.org/10.3390/antibiotics12050801 - 23 Apr 2023
Cited by 4 | Viewed by 3267
Abstract
Background: Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with [...] Read more.
Background: Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. Aim: The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? Results: There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. Conclusion: Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
12 pages, 662 KiB  
Review
Ventilator-Associated Pneumonia in Immunosuppressed Patients
by Louis Kreitmann, Alexandre Gaudet and Saad Nseir
Antibiotics 2023, 12(2), 413; https://doi.org/10.3390/antibiotics12020413 - 20 Feb 2023
Cited by 7 | Viewed by 3884
Abstract
Immunocompromised patients—including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases—account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and [...] Read more.
Immunocompromised patients—including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases—account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and intensive care unit (ICU)-acquired infections. The most frequent of these are ventilator-associated lower respiratory tract infections (VA-LTRI), which include ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT). Recent studies have shed light on some of the specific features of VAP and VAT in immunocompromised patients, which is the subject of this narrative review. Contrary to previous belief, the incidence of VAP and VAT might actually be lower in immunocompromised than non-immunocompromised patients. Further, the relationship between immunosuppression and the incidence of VAP and VAT related to multidrug-resistant (MDR) bacteria has also been challenged recently. Etiological diagnosis is essential to select the most appropriate treatment, and the role of invasive sampling, specifically bronchoscopy with bronchoalveolar lavage, as well as new molecular syndromic diagnostic tools will be discussed. While bacteria—especially gram negative bacteria—are the most commonly isolated pathogens in VAP and VAT, several opportunistic pathogens are a special concern among immunocompromised patients, and must be included in the diagnostic workup. Finally, the impact of immunosuppression on VAP and VAT outcomes will be examined in view of recent papers using improved statistical methodologies and treatment options—more specifically empirical antibiotic regimens—will be discussed in light of recent findings on the epidemiology of MDR bacteria in this population. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
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Other

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19 pages, 596 KiB  
Systematic Review
The Impact of Care Bundles on Ventilator-Associated Pneumonia (VAP) Prevention in Adult ICUs: A Systematic Review
by Maria Mastrogianni, Theodoros Katsoulas, Petros Galanis, Anna Korompeli and Pavlos Myrianthefs
Antibiotics 2023, 12(2), 227; https://doi.org/10.3390/antibiotics12020227 - 20 Jan 2023
Cited by 23 | Viewed by 14310
Abstract
Ventilator-associated pneumonia (VAP) remains a common risk in mechanically ventilated patients. Different care bundles have been proposed to succeed VAP reduction. We aimed to identify the combined interventions that have been used to by ICUs worldwide from the implementation of “Institute for Healthcare [...] Read more.
Ventilator-associated pneumonia (VAP) remains a common risk in mechanically ventilated patients. Different care bundles have been proposed to succeed VAP reduction. We aimed to identify the combined interventions that have been used to by ICUs worldwide from the implementation of “Institute for Healthcare Improvement Ventilator Bundle”, i.e., from December 2004. A search was performed on the PubMed, Scopus and Science Direct databases. Finally, 38 studies met our inclusion criteria. The most common interventions monitored in the care bundles were sedation and weaning protocols, semi-recumbent positioning, oral and hand hygiene, peptic ulcer disease and deep venus thrombosis prophylaxis, subglottic suctioning, and cuff pressure control. Head-of-bed elevation was implemented by almost all studies, followed by oral hygiene, which was the second extensively used intervention. Four studies indicated a low VAP reduction, while 22 studies found an over 36% VAP decline, and in ten of them, the decrease was over 65%. Four of these studies indicated zero or nearly zero after intervention VAP rates. The studies with the highest VAP reduction adopted the “IHI Ventilator Bundle” combined with adequate endotracheal tube cuff pressure and subglottic suctioning. Multifaced techniques can lead to VAP reduction at a great extent. Multidisciplinary measures combined with long-lasting education programs and measurement of bundle’s compliance should be the gold standard combination. Full article
(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)
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