A novel mRNA multi-epitope vaccine of Acinetobacter baumannii based on multi-target protein design in immunoinformatic approach.

Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.

A novel Saclayvirus Acinetobacter baumannii phage genomic analysis and effectiveness in preventing pneumonia.

Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. KEY POINTS: •A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. •The whole genome was determined, analyzed, and compared to other phages. •Assaying the effect of phage in preventing infection in neutrophil-deficient models.

Outer membrane vesicles generated by an exogenous bacteriophage lysin and protection against Acinetobacter baumannii infection.

BACKGROUND: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.

Prevalence of Acinetobacter baumannii and Candida auris in Patients Receiving Mechanical Ventilation.

Importance: To date, only 1 statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the US, and no statewide prevalence survey has been performed for Candida auris, making the current burden of these emerging pathogens unknown. Objective: To determine the prevalence of A baumannii and C auris among patients receiving mechanical ventilation in Maryland. Design, Setting, and Participants: The Maryland Multi-Drug Resistant Organism Prevention Collaborative performed a statewide cross-sectional point prevalence of patients receiving mechanical ventilation admitted to acute care hospitals (n = 33) and long-term care facilities (n = 18) between March 7, 2023, and June 8, 2023. Surveillance cultures (sputum, perianal, arm/leg, and axilla/groin) were obtained from all patients receiving mechanical ventilation. Sputum, perianal, and arm/leg cultures were tested for A baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by polymerase chain reaction for C auris. Main Outcomes and Measures: Prevalence of A baumannii, carbapenem-resistant A baumannii (CRAB), and C auris. Prevalence was stratified by type of facility. Results: All 51 eligible health care facilities (100%) participated in the survey. A total of 482 patients receiving mechanical ventilation were screened for A baumannii and 470 were screened for C auris. Among the 482 patients who had samples collected, 30.7% (148/482) grew A baumannii, 88 of the 148 (59.5%) of these A baumannii were CRAB, and C auris was identified in 31 of 470 (6.6%). Patients in long-term care facilities were more likely to be colonized with A baumannii (relative risk [RR], 7.66 [95% CI, 5.11-11.50], P < .001), CRAB (RR, 5.48 [95% CI, 3.38-8.91], P < .001), and C auris (RR, 1.97 [95% CI, 0.99-3.92], P = .05) compared with patients in acute care hospitals. Nine patients (29.0%) with cultures positive for C auris were previously unreported to the Maryland Department of Health. Conclusions: A baumannii, carbapenem-resistant A baumannii, and C auris were common among patients receiving mechanical ventilation in both acute care hospitals and long-term care facilities. Both pathogens were significantly more common in long-term care facilities than in acute care hospitals. Patients receiving mechanical ventilation in long-term care facilities are a high-risk population for emerging pathogens, and surveillance and prevention efforts should be targeted to these facilities.

Promising targets for immunotherapeutic approaches against Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic pathogen associated with the occurrence of outbreaks in hospital settings, especially in Intensive Care Units (ICUs). Pneumonia, septicemias, urinary tract infections, and recurrent infections associated with the use of hospital devices are some of the most frequent complications. Due to the increase of A. baumannii strains resistant to multiple antimicrobials, associated with their high capacity to form biofilms on biotic and abiotic surfaces, the therapeutic strategies routinely applied have become increasingly restricted and ineffective, resulting in high mortality rates. Many studies have focused on the development of new therapeutic approaches, mainly non-antibiotic-based. Polyclonal (pAb) and monoclonal (mAb) antibodies are increasingly cited in the literature as alternative strategies to the use of antimicrobial drugs and are evaluated for the prevention and treatment of these infections. In this context, this review aimed to synthesize the main strategies based on the use of antibodies that are being evaluated for the control of A. baumannii infections. Here, we describe the main A. baumannii antigenic targets used in studies to assess their potential to induce the formation of antibodies and their possible application in immunotherapy strategies.

Preoptimized phage cocktail for use in aerosols against nosocomial transmission of carbapenem-resistant Acinetobacter baumannii: A 3-year prospective intervention study.

Using bacteriophages (phages) as environmental sanitizers has been recognized as a potential alternative method to remove bacterial contamination in vitro; however, very few studies are available on the application of phages for infection control in hospitals. Here, we performed a 3-year prospective intervention study using aerosolized phage cocktails as biocontrol agents against carbapenem-resistant Acinetobacter baumannii (CRAB) infection in the hospital. When a CRAB-infected patient was identified in an intensive care unit (ICU), their surrounding environment was chosen for phage aerosol decontamination. Before decontamination, 501 clinical specimens from the patients were subjected to antibiotic resistance analysis and phage typing. The optimal phage cocktails were a combination of different phage families or were constructed by next-evolutionary phage typing with the highest score for the host lysis zone to prevent the development of environmental CRAB phage resistance. The phage infection percentage of the antibiotic-resistant A. baumannii strains was 97.1%, whereas the infection percentage in the antibiotic-susceptible strains was 79.3%. During the phage decontamination periods from 2017 to 2019, the percentage of carbapenem-resistant A. baumannii in test ICUs decreased significantly from 65.3% to 55%. The rate of new acquisitions of CRAB infection over the three years was 4.4 per 1000 patient-days, which was significantly lower than that in the control wards (8.9 per 1000 patient-days) where phage decontamination had never been performed. In conclusion, our results support the potential of phage cocktails to decrease CRAB infection rates, and the aerosol generation process may make this approach more comprehensive and time-saving.

Semi-Synthetic Glycoconjugate Vaccine Lead Against Acinetobacter baumannii 17978.

Acinetobacter baumannii is a opportunistic bacterial pathogen responsible for serious nosocomial infections that is becoming increasingly resistant against antibiotics. Capsular polysaccharides (CPS) that cover A. baumannii are a major virulence factor that play an important role in pathogenesis, are used to assign serotypes and provide the basis for vaccine development. Synthetic oligosaccharides resembling the CPS of A. baumannii 17978 were printed onto microarray slides and used to screen sera from patients infected with A. baumannii as well as a monoclonal mouse antibody (mAb C8). A synthetic oligosaccharide emerged from glycan array screening as lead for the development of a vaccine against A. baumannii 17978. Tetrasaccharide 20 is a key epitope for recognition by an antibody and is a vaccine lead.

Anti-Omp34 antibodies protect against Acinetobacter baumannii in a murine sepsis model.

Acinetobacter baumannii, an opportunistic extracellular pathogen is one of the major causes of nosocomial infections. Omp34, also known as Omp33-36, is a bacterial porin protein involved in the virulence and fitness of this pathogen by adhesion to the host cell. This antigen nominated as an appropriate candidate for immunization against A. baumannii. In this study, the expression of the recombinant Omp34 (rOmp34) was carried out in E. coli BL21 (DE3). The immunogenicity of the rOmp34 in A. baumannii was studied in a murine sepsis model. Antibody response in mice injected with the recombinant protein was assessed using indirect ELISA. Bactericidal activity of rOmp34-immunized mice sera (1:10 dilution) against A. baumannii ATCC 19606 after 0, 1, 2, 4, and 8 h of incubation at 37 °C was assessed. In addition to survival rate, load of bacteria in liver and spleen of the infected mice were evaluated. A high titer of specific antibody equivalent to optical density of 1.54 ± 0.06 against rOmp34 was elicited in the immunized mice sera. Viability of the A. baumannii incubated 8 h with immunized mice sera was 64%. Homogenized liver and spleen samples of the control mice challenged with A. baumannii were loaded with 8 × 103 and 9 × 103 CFU per gram tissue respectively 48 h post-challenge as against complete clearance of A. baumannii in the immunized group. The protective immunity was achieved by challenging the mice groups with 5 × LD50 of live A. baumannii. Omp34 can be nominated as an immunogen that can bring about protection against Acinetobacter baumannii.

A hypothetical adhesin protein induces anti-biofilm antibodies against multi-drug resistant Acinetobacter baumannii.

The increase in multidrug-resistant (MDR) Acinetobacter baumannii strains in hospital environments has generated great concern around the world. Biofilm is one of the forms of bacterial adaptation that is increasingly leading to antimicrobial resistance and therapeutic failure. The search for alternative therapeutic strategies, especially non-antibiotic-based, is urgently needed. In this study, we produce polyclonal antibodies (pAbs) in murine models against recombinant CAM87009.1 antigen, an A. baumannii fimbriae protein. The pAbs produced were isotyped and anti-biofilm activity evaluated in the A. baumannii ATCC® 19606 standard strain and nine MDR clinical isolates. All clinical isolates were analyzed for the presence of the cam87009.1 gene using the PCR technique, and one of the isolates did not have the gene in its genome. After four intraperitoneal immunizations (days 0, 14, 21, and 28) of mice with rCAM87009.1 and Freund's adjuvant, a significant antibody titer was detected by indirect enzyme-linked immunosorbent assay (ELISA) since the first immunization (1:6400), and the level increased until the 4th immunization (1:819,200). IgM, IgA, IgG1, IgG2a, IgG2b, and IgG3 isotypes were identified in the serum of immunized mice (P < 0.001). The anti-rCAM87009.1 pAb was able to inhibit biofilm formation in 80 % of the strains evaluated in this study, including the ATCC® 19606 strain. The rCAM87009.1 proves to be a promising target in the development of alternative strategies to control biofilm-forming in A. baumannii MDR strains.

The combination of CipA and PBP-7/8 proteins contribute to the survival of C57BL/6 mice from sepsis of Acinetobacter baumannii.

Due to the emergence of multi-drug resistant Acinetobacter baumannii strains, there is an urgent need to develop several new strategies to control this bacterium. In this context, vaccination may be the best approach to reduce the morbidity and mortality associated with MDR isolates in vulnerable groups. Serum resistance factors have a key role in the pathogenesis of A. baumannii and can be considered as potential vaccine candidates. This project aimed to evaluate the immunological reactivity of CipA and PBP-7/8 as two serum resistance factors in a combination form against sepsis infections of A. baumannii. Recombinant proteins were obtained and immunological evaluations were performed against sepsis infection in the C57BL/6 mouse model. The data showed a statistically significant increase in total IgG levels in all three immunization regimens (CipA, PBP-7/8, and CipA + PBP-7/8) compared to the control group. The ratios of IgG2c/IgG1 in the CipA, PBP-7/8, and CipA + PBP-7/8 schedules were 8.7, 46.50, and 33.29, respectively. It appears that the immunization schedules developed a strong polarized Th1 response. The cytokine profiles of the three plans showed that IFN-γ was highly concentrated in the combination plan. However, the highest concentration of IL-17 belonged to the PBP-7/8 plan. In conclusion, the data of total IgG, survival rates and splenic bacterial loads showed that the CipA + PBP-7/8 plan was more effective than each protein individually.

A conserved region of Acinetobacter trimeric autotransporter adhesion, Ata, provokes suppression of Acinetobacter baumannii virulence.

The Acinetobacter trimeric autotransporter adhesin (Ata) is an important virulence factor. The conserved region from the genomic sequence of a 6777bp/2258 amino acid of Acinetobacter baumannii ATCC®19606™ ata was explored. A 263aa of the C-terminal of Ata (rcAta263) was expressed. The effect of rcAta263 on A. baumannii virulence was studied in a murine model. IgG and IgA were elicited and the mice groups challenged with A. baumannii showed significant survival rates from 66 to 100%. The bacterial loads were determined in the spleens, livers, and lungs of both control and test groups. The adhesion rate of A. baumannii to A549 cells in the presence of serum, cytotoxicity, mutagenicity, and biofilm disruption potential of rcAta263 were determined. Intraperitoneally challenged groups showed a significantly reduced bacterial load in the organs of the immunized mice. Intranasal challenge reduced 4 logs of bacterial CFU/g in the test group. The immunized mice sera reduced adherence of A. baumannii to A549 cells to 80%. No cytotoxic or mutagenic effect was detected. Biofilm disruption was significantly increased in the presence of immunized mice sera. Immunization with the conserved region of Ata significantly combats the virulence of A. baumannii which could be considered as a therapeutic strategy to control A. baumannii infections.

Extensively drug-resistant Acinetobacter baumannii carrying blaOXA-23-like and armA in a hospital after an intervention in the intensive care unit which ended a long-standing endemicity.

The aim of the study was to evaluate for a long time the effectiveness of an intervention designed to reduce carbapenem-resistant Acinetobacter baumannii (CRAB) and its impact on colistin usage in the ICU of a tertiary hospital in Spain. The rate of carbapenem resistance declined drastically during the period of study (2015 to 2018), from 93.57 to 74.65%, especially in the ICU. A significant decrease in colistin usage, from 1.16 to 0.39 DOTs, was observed. Forty-nine CRAB isolates recovered nearly 1 year after starting the intervention were characterized. Most of them were recovered from patients admitted in wards other than ICU and were extensively drug-resistant, carried blaOXA-23-like and armA, and belonged to ST218. Implementation of control measures is crucial to CRAB control in ICUs but must be extended to all wards in order to eradicate CRAB from hospitals.

Wall painting following terminal cleaning with a chlorine solution as part of an intervention to control an outbreak of carbapenem-resistant Acinetobacter baumannii in a neurosurgical intensive care unit in Israel.

BACKGROUND: To describe the use of wall painting as part of an intervention to control an outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: An interrupted time-series analysis was performed analyzing an intervention in a neurosurgical intensive care unit (NSICU) and an inpatient hematology department in a tertiary level medical center in Israel. The intervention involved wall painting using a water based acrylic paint following patient discharge and terminal cleaning with sodium troclosene as part of an infection control bundle for an outbreak of CRAB in a NSICU and concurrent outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) colonization/infection in the same NSICU and the hematology department. RESULTS: Between January 2013 and December 2018, 122 patients hospitalized in the NSICU were identified with new CRAB colonization/infection. The median incidence in the periods prior to/post intervention were 2.24/1000 HD (interquartile range [IQR] 0.84-2.90/1000) vs. 0/1000 HD (IQR 0-0.49/1000), respectively. Poisson regression indicated a decrease of 92% in the CRAB incidence following the intervention onset (relative risk [RR] 0.080, 95% confidence interval [CI] 0.037-0.174, p < 0.001). Forty-seven patients in the NSICU and 110 in the hematology department were colonized/infected with CRE in the same time period; a significant change was not observed following the start of the intervention in either department (for NSICU RR 1.236, 95% CI 0.370-4.125, p = 0.731; for hematology RR 0.658, 95% CI 0.314-1.378, p = 0.267). CONCLUSIONS: A. baumannii is able to survive on environmental surfaces despite decontamination efforts; wall-painting as part of a bundle may be a successful infection control measure.

Microorganisms and clinical outcomes of early- and late-onset ventilator-associated pneumonia at Srinagarind Hospital, a tertiary center in Northeastern Thailand.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common nocosomial infection in intensive care unit (ICU). Local microbiological surveillance of pathogens and resistance patterns for early-onset VAP (EOVAP) and late-onset VAP (LOVAP) will help to choose appropriate empiric antibiotics. OBJECTIVE: To compare the multi-drug resistant (MDR) pathogens, treatment outcomes, and factors associated with hospital mortality of VAP. METHOD: A cross-sectional study between 1 January 2015 and 31 December 2017 at Srinagarind hospital, Khon Kaen University was conducted. The demographic data, causative pathogens, hospital length of stay (LOS), ICU LOS, mechanical ventilator (MV) days, and hospital mortality were retrospectively reviewed. RESULTS: One hundred and ninety patients were enrolled; 42 patients (22%) were EOVAP and 148 patients (78%) were LOVAP. Acinetobacter baumannii was the most common pathogen in both groups (50% EOVAP vs 52.7% LOVAP). MDR pathogens were significant greater in LOVAP (81.8%) than EOVAP (61.9%) (p = 0.007). The EOVAP had a significantly better ICU LOS [median (interquartile range, IQR) 20.0 (11.0, 30.0) vs. 26.5 (17.0, 43.0) days], hospital LOS [median (IQR) 26.5 (15.0, 44.0) vs. 35.5 (24.0, 56.0) days] shorter MV days [median (IQR) 14.0 (10.0, 29.0) vs. 23.0 (14.0, 35.5) days] and lower hospital mortality (16.7% vs 35.1%) than LOVAP (p < 0.05). The factor associated with hospital mortality was having simplified acute physiology (SAP) II score ≥ 40 with an adjusted odds ratio (aOR) of 2.22 [95% confidence interval (CI), 1.08-4.54, p = 0.02]. CONCLUSION: LOVAP had significantly higher MDR pathogens, MV days, ICU LOS, hospital LOS and hospital mortality than EOVAP. A broad-spectrum antibiotic to cover MDR pathogens should be considered in LOVAP. The factor associated with hospital mortality of VAP was a SAPII score ≥ 40.

Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains.

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.

Recombinant N-terminal outer membrane porin (OprF) of Pseudomonas aeruginosa is a promising vaccine candidate against both P. aeruginosa and some strains of Acinetobacter baumannii.

Pseudomonas aeruginosa is an evolving pathogen which can cause serious infections especially to immunocompromised patients. Its high resistance profile to antibiotics results in difficulty, and sometimes impossibility, in treating afflicted patients. Developing an effective vaccine against P. aeruginosa is an important approach to tackle this problem. A similar problematic situation exists for Acinetobacter baumannii. Several vaccine candidates have been investigated up till now but still there is no approved vaccine in the market. One important antigen of P. aeruginosa is the outer membrane protein F (OprF) which functions as a porin with relevant important roles in virulence. Previous studies focused mainly on the C-terminal peptidoglycan binding domain of OprF as a vaccine candidate. In the current study, we have investigated the N-terminal porin domain of OprF as a potential vaccine candidate against P. aeruginosa. Histidine-tagged recombinant N-terminal OprF (amino acid range 25-200; OprF25-200) was overexpressed in Escherichia coli and purified using metal affinity chromatography. Swiss albino mice were immunized with OprF25-200 adjuvanted with Bacillus Calmette-Guérin (BCG) and alum and the immune response was evaluated. Immunized mice developed antigen-specific IgG1 and IgG2a and were protected against challenge by both P. aeruginosa and a clinical isolate of A. baumannii expressing OprF. Serum from OprF25-200-immunized mice showed cross-reactivity with both pathogens using western blotting and whole cell enzyme-linked immunosorbent assay (ELISA). To our knowledge, this is the first report to demonstrate that the N-terminal domain of OprF is sufficiently immunogenic to protect against the two pathogens.

New putative vaccine candidates against Acinetobacter baumannii using the reverse vaccinology method.

Infections caused by multi-drug resistance Acinetobacter baumannii are increasing worldwide. Discovery of the vaccine against this bacterium as a cost-effective and preventive strategy seems necessary. This study has introduced 11 new putative vaccine candidates against A. baumannii using the reverse vaccinology method. We considered 33 genomes of A. baumannii strains and selected the outer membrane and secreted proteins as putative vaccine candidates using Vaxign web tool. Finally, 11 proteins were confirmed as promising vaccine candidates. These targets belonged to proteins involved in cell division (NlpD), fimbria or pili assembly (FimA, PapC, and PapC associated with usher system), iron acquisition (FhuA, BfnH, FatA-like protein, and IutA), DcaP-like protein and two novel hypothetical proteins (HP-1 and HP-2). The analysis of linear and conformational B-cell epitopes showed that the outer membrane proteins including DcaP-like protein and HP-2 had high conserved surface-exposed epitopes that they can consider as excellent putative vaccine targets in the upcoming immunological assays.

Device associated -health care associated infections monitoring, prevention and cost assessment at intensive care unit of University Hospital in Poland (2015-2017).

BACKGROUND: Device-associated health care-associated infections (DA-HAIs) in intensive care unit (ICU) patients constitute a major therapeutic issue complicating the regular hospitalisation process and having influence on patients' condition, length of hospitalisation, mortality and therapy cost. METHODS: The study involved all patients treated > 48 h at ICU of the Medical University Teaching Hospital (Poland) from 1.01.2015 to 31.12.2017. The study showed the surveillance and prevention of DA-HAIs on International Nosocomial Infection Control Consortium (INICC) Surveillance Online System (ISOS) 3 online platform according to methodology of the INICC multidimensional approach (IMA). RESULTS: During study period 252 HAIs were found in 1353 (549F/804M) patients and 14,700 patient-days of hospitalisation. The crude infections rate and incidence density of DA-HAIs was 18.69% and 17.49 ± 2.56 /1000 patient-days. Incidence density of ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLA-BSI) and catheter-associated urinary tract infection (CA-UTI) per 1000 device-days were 12.63 ± 1.49, 1.83 ± 0.65 and 6.5 ± 1.2, respectively. VAP(137) constituted 54.4% of HAIs, whereas CA-UTI(91) 36%, CLA-BSI(24) 9.6%.The most common pathogens in VAP and CA-UTI was multidrug-resistant (MDR) Acinetobacter baumannii (57 and 31%), and methicillin-resistant Staphylococcus epidermidis (MRSE) in CLA-BSI (45%). MDR Gram negative bacteria (GNB) 159 were responsible for 63.09% of HAIs. The length of hospitalisation of patients with a single DA-HAI at ICU was 21(14-33) days, while without infections it was 6.0 (3-11) days; p = 0.0001. The mortality rates in the hospital-acquired infection group and no infection group were 26.1% vs 26.9%; p = 0.838; OR 0.9633;95% CI (0.6733-1.3782). Extra cost of therapy caused by one ICU acquired HAI was US$ 11,475/Euro 10,035. Hand hygiene standards compliance rate was 64.7%, while VAP, CLA-BSI bundles compliance ranges were 96.2-76.8 and 29-100, respectively. CONCLUSIONS: DA-HAIs was diagnosed at nearly 1/5 of patients. They were more frequent than in European Centre Disease Control report (except for CLA-BSI), more frequent than the USA CDC report, yet less frequent than in limited-resource countries (except for CA-UTI). They prolonged the hospitalisation period at ICU and generated substantial additional costs of treatment with no influence on mortality. The Acinetobacter baumannii MDR infections were the most problematic therapeutic issue. DA-HAIs preventive methods compliance rate needs improvement.

A Systematic and Critical Review of Bacteriophage Therapy Against Multidrug-resistant ESKAPE Organisms in Humans.

Bacteriophages (phages) may constitute a natural, safe, and effective strategy to prevent and control multidrug-resistant organisms (MDROs), and ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens in particular. Few clinical studies have assessed the safety and efficacy of phages in patients infected with MDROs. This systematic review summarizes and critically evaluates published studies of phages in clinical practice and presents the appropriate phage selection criteria, as well as recommendations for clinicians and scientists for a successful therapy. Articles were identified through a search of the PubMed, Ovid, EMBASE, and Cochrane Library databases. Among 1102 articles and abstracts, 30 studies were selected and evaluated using selective inclusion criteria, phage criteria, and study characteristics. Most studies showed efficacy (87%) and safety (67%) of the tested phages, but few studies examined phage resistance (35%). Clinical studies and regulatory changes are needed to determine the safety and efficacy of phages and to advance their use in patients with MDRO infections.

Control and Elimination of Extensively Drug-Resistant Acinetobacter baumanii in an Intensive Care Unit.

We decreased antimicrobial drug consumption in an intensive care unit in Lebanon by changing to colistin monotherapy for extensively drug-resistant Acinetobacter baumanii infections. We saw a 78% decrease of A. baumanii in sputum and near-elimination of blaoxa-23-carrying sequence type 2 clone over the 1-year study. Non-A. baumanii multidrug-resistant infections remained stable.