Pan-drug Resistant Acinetobacter Baumannii Infection Research Articles

Phage therapy combats pan drug-resistant Acinetobacter baumannii infection safely and efficiently

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.

Excess mortality due to pandrug-resistant Acinetobacter baumannii infections in hospitalized patients

Pandrug-resistant Acinetobacter baumannii (PDRAB) is increasingly being reported as a nosocomial pathogen worldwide, but determining its clinical impact is challenging. To assess the spectrum of excess mortality attributable to PDRAB infection in acute care settings. This four-year cohort study was conducted in a tertiary-care referral hospital in Greece to estimate excess in-hospital mortality due to PDRAB infection by comparing patients infected to those colonized with PDRAB by means of competing risks survival analysis. The study cohort comprised 91 patients (median age: 67 years; 77% men). For most patients, PDRAB was first isolated in the intensive care unit (ICU) (N= 51; 57%) or following ICU discharge (N= 26; 29%). Overall in-hospital mortality was 68% (95% confidence interval (CI): 57.5-77.5%). PDRAB-infected patients (N= 62; 68%) and PDRAB-colonized patients (N= 29; 32%) had similar baseline characteristics, but the absolute excess risk of 30-day mortality in infected patients compared to colonized patients was 34% (95% CI: 14-54%). Multivariable competing risks regression showed that PDRAB infection significantly increased the daily hazard of 30-day in-hospital death (cause-specific hazard ratio (csHR): 3.10; 95% CI: 1.33-7.21) while simultaneously decreasing the daily rate of discharge (csHR: 0.24; 95% CI: 0.08-0.74), thereby leading to longer hospitalization. Stronger effects were observed for bloodstream infections. New effective antimicrobials would be expected to prevent mortality in one of every three patients treated for PDRAB infection and reduce their length of hospitalization. However, available therapeutic options remain extremely limited and emphasis on preventing healthcare-associated transmission of PDRAB is ever more important.

Risk Factor Analysis of Pan-drug Resistant Acinetobacter baumannii-induced Ventilator-associated Pneumonia in ICU

This study was to investigate the risk factors of ventilator-associated pneumonia caused by pan-drug resistant Acinetobacter baumannii in emergency intensive care unit so as to provide related basis for clinical prevention. A total of 105 intensive care unit patients, who were treated with ventilator over 48 h in the First Affiliated Hospital of Anhui Medical University and developed Acinetobacter baumannii-induced ventilator-associated pneumonia from January 2017 to December 2018 were enrolled in this study, including 70 cases with pan-drug resistant Acinetobacter baumannii infection served as the pan-drug resistant group and 35 cases with non-pan-drug resistant Acinetobacter baumannii infection served as the control group. The univariate analysis and Logistic regression method were used to explore the risk factors of ventilator-associated pneumonia caused by pan-drug resistant Acinetobacter baumannii. The result of univariate analysis showed that the risk factors of pan-drug resistant Acinetobacter baumannii-induced ventilator-associated pneumonia included tracheotomy, enteral nutrition, the use of carbapenems and use of more than 3 antibiotics before infection. Logistic regression analysis showed that enteral nutrition and the use of carbapenems were independent risk factors of pan-drug resistant Acinetobacter baumannii-induced ventilator-associated pneumonia. In conclusion, enteral malnutrition and the use of carbapenems were the two significant risk factors for pan-drug resistant Acinetobacter baumannii-induced ventilator-associated pneumonia, which are necessary to take active preventive measures in clinical practice.

Risk Factors For Nosocomial Pan Drug Resistant Acinetobacter Baumannii Infections

Aim: Acinetobacter baumannii is an important nosocomial pathogen. The purpose of this study was to identify risk factors and mortality of nosocomial infections caused by pan drug resistant (PDR) Acinetobacter baumannii and to characterize their effects on mortality.Patients and Methods: This study was performed at the Afyonkarahisar Helath Science University, Faculty of Medicine. Nosocomial infections were defined accor-ding to the American Center for Disease Control (CDC). Patients with nosocomial infections caused by Acinetobacter baumannii were included in the study. Patients identified as PDR Acinetobacter baumannii and non-PDR Acinetobacter baumannii infection were com-pared in terms of risk factors.Results: Two different groups were constructed, one group consisting of 145 PDR and the other of 145 non-PDR Acinetobacter baumannii cases. Stay history in an internal intensive care unit (p=0.001), their duration of hospital stay (p=0.031), renal disease (p=0.003), mechanical ventilation (p=0.001), prior usage history of carbap-enem (p=0.001), presence of nosocomial pneumonia (p=0.001), were independent risk factors associated with PDR Acinetobacter baumannii infections. The mortality rate for the PDR group was 61.8% and it was 38.2% in the non-PDR group (p=0.008).Conclusion: PDR Acinetobacter baumannii infections are important nosocomial in-fections with a high mortality rate. Patients’ carbapenem usage, stay history in an internal intensive care unit, renal comorbid diseases, and a diagnosis of nosocomial pneumonia are important risk factors for PDR Acinetobacter baumannii infections. In nosocomial infections caused by PDR Acinetobacter baumannii, many risk factors were modifiable.

A bovine myeloid antimicrobial peptide (BMAP-28) and its analogs kill pan-drug-resistant Acinetobacter baumannii by interacting with outer membrane protein A (OmpA).

Antimicrobial peptides (AMPs) exhibit multiple activities against bacteria and fungi. A bovine myeloid antimicrobial peptide (BMAP-28) belongs to the cathelicidin-derived AMPs and has antimicrobial activity. Due to the rapidly increasing number of infections and outbreaks caused by pan-drug-resistant Acinetobacter baumannii (PDRAB), we sought to determine whether BMAP-28 and its 4 analog peptides (A837, A838, A839, and A840) have antimicrobial activity against PDRAB. Furthermore, we clarified the possible mechanism of inhibition by which of BMAP-28 acts against PDRAB. In the current study, we examined the inhibitory effect of BMAP-28 and its 4 analog peptides on the growth of PDRAB through minimal inhibitory concentration (MIC) analysis and short time killing assays. We also evaluated the effects of BMAP-28 and its analogs on the bacterial cell surface through the use of field emission scanning electron microscopy (FE-SEM). In order to determine the inhibitory mechanism of BMAP-28, we examined the interaction between BMAP-28 and outer membrane proteins (OMPs), especially the interaction between BMAP-28 and A. baumannii OmpA (AbOmpA), which is the main component of OMPs, by using a quartz crystal microbalance (QCM). BMAP-28 and its 4 analogs were effective in inhibiting the growth of PDRAB and had rapid killing ability. BMAP-28 showed exceptionally strong and rapid inhibitory effects on PDRAB when compared to the other peptides and was also shown to cause damage to the cell surface of PDRAB. Moreover, QCM analysis provided evidence of potential interaction between BMAP-28 and AbOmpA. These data indicate that BMAP-28 is a promising candidate for the treatment of PDRAB infections and that its inhibitory effects were related with its binding to AbOmpA.

Effects of specific egg yolk immunoglobulin on pan-drug-resistant Acinetobacter baumannii

With the growing emergence of pan-drug-resistant Acinetobacter baumannii (PDR-Ab) strains in clinical, new strategies for the treatment of PDR-Ab infections are urgently needed. Egg yolk immunoglobulin (IgY) as a convenient and inexpensive antibody has been widely applied to the therapy of infectious diseases. The aim of this study was to produce IgY specific to PDR-Ab and investigate its antibacterial effects in vitro and in vivo. IgYs specific to two PDR-Ab strains were produced by immunizing hens with formaldehyde inactivated PDR-Ab cells and isolated from yolks with a purity of 90% by water dilution, salt precipitations and ultrafiltration. IgYs showed high titers when subjected to an ELISA and inhibited the growth of PDR-Ab in a dose-dependent manner in liquid medium. Scanning electron microscopy assay showed structural modification and aggregation of PDR-Ab treated with specific IgYs. Freshly cultured PDR-Ab cells were nasally inhaled in BALB/c mice to induce acute pneumonia. The infected mice were intraperitoneally injected with specific IgYs using cefoperazone/sulbactam and dexamethasone as positive controls. The IgYs specific to PDR-Ab lowered the mortality of mice with PDR-Ab-induced acute pneumonia, decreased the level of TNF-α and IL-1β in serum and reduced inflammation in lung tissue. Specific IgY has the potential to be used as a new therapeutic approach for the treatment of A. baumannii-induced infections.

Investigation and control of a suspected nosocomial outbreak of pan-drug resistant Acinetobacter baumannii in an intensive care unit.

Acinetobacter baumannii, a non-fermenting Gram-negative bacterium, is a common pathogen in intensive care units (ICU) that is easily spread through contact and can cause nosocomial outbreaks. This study investigated the risk factors associated with outbreaks of pan-drug resistant Acinetobacter baumannii (PDR-Ab) infection by studying a suspected nosocomial outbreak in a comprehensive ICU in a teaching hospital in China, and discusses the effectiveness of current prevention and control measures.Pathogen detection methods involving pulsed field gel electrophoresis (PFGE) were employed to survey patients infected or colonized with PDR-Ab. An epidemiological investigation was conducted to determine the risk factors for infection or colonization with PDR-Ab between 1 October 2014 and 16 January 2015.The rate of PDR-Ab infection in the ICU was higher during the period from 1 October 2014 to 16 January 2015 than it was between 1 October 2013 and 16 January 2014. Only two cases were confirmed to have the same genotype. Risk factors were explored and the rate of infection was found to be controlled by interventions targeting these risk factors.A decrease in the number of infections was observed after multiple prevention and control measures were implemented, preventing the outbreak of a nosocomial infection.

Epidemiological investigation after hospitalising a case with pandrug-resistant Acinetobacter baumannii infection

Pandrug-resistant Acinetobacter baumannii (PDRAB) emerged in Taiwan in the early 2000s but was not identified in the Children's Hospital (Hospital A) until March 2005 when a patient was transferred from a respiratory care hospital (Hospital B). PDRAB was recovered from an eye swab taken on admission; once aware of the culture result, in addition to implementing infection control precautions, an epidemiological investigation was conducted in both hospitals. A total of 212 specimens were taken from 30 hospital inpatients (seven in Hospital A, 23 in Hospital B), clinical equipment and ward environment. Thirteen (15.5%) of 84 specimens obtained from Hospital A and 23 (18%) of 128 specimens obtained from Hospital B were positive for A. baumannii; of these, six isolates from two patients and clinical equipment in Hospital A and five from three patients in Hospital B were PDRAB. One patient stayed in both hospitals, and had one PDRAB isolate detected at each. Of the 36 A. baumannii isolates, there were nine IRS-PCR (infrequent restriction site-polymerase chain reaction) patterns, 12 PFGE (pulsed-field gel electrophoresis) patterns and six antibiogram patterns identified. Twenty-five isolates belonged to a major IRS-PCR type (four PFGE patterns) and presented with either pandrug resistance (all 11 PDRAB isolates clustered in this type) or multidrug resistance (only susceptible to imipenem). A. baumannii is an ubiquitous organism that can be isolated from patients and their equipment. A clone of A. baumannii with multi- or pandrug resistance was circulating in both hospitals.

A Multifaceted Intervention to Reduce Pandrug‐ResistantAcinetobacter baumanniiColonization and Infection in 3 Intensive Care Units in a Thai Tertiary Care Center: A 3‐Year Study

We sought to determine the long-term effect of a multifaceted infection-control intervention to reduce the incidence of pandrug-resistant Acinetobacter baumannii infection in a Thai tertiary care center. A 3-year, prospective, controlled, quasi-experimental study was conducted in medical intensive care, surgical intensive care, and coronary care units for a 1-year period before intervention (period 1), a 1-year period after intervention (period 2), and a 1-year follow-up period (period 3). The interventions in period 2 included strictly implementing contact isolation precautions and appropriate hand hygiene, active surveillance, cohorting patients who were colonized or infected with pandrug-resistant A. baumannii, and environmental cleaning with 1:100 sodium hypochlorite solution. All interventions were continued in period 3, but environmental cleaning solutions were changed to detergent and phenolic agents. Before the intervention, the rate of pandrug-resistant A. baumannii colonization and/or infection was 3.6 cases per 1000 patient-days. After the intervention, the rate of pandrug-resistant A. baumannii colonization and/or infection decreased by 66% in period 2 (to 1.2 cases per 1000 patient-days; P < .001) and by 76% in period 3 (to 0.85 cases per 1000 patient-days; P < .001). The monthly hospital antibiotic cost of treating pandrug-resistant A. baumannii colonization and/or infection and the hospitalization cost for each patient in the intervention units were also reduced by 36%-42% (P < .001) and 25%-36% (P < .001), respectively, during periods 2 and 3. A multifaceted intervention featuring active surveillance and environmental cleaning resulted in sustained reductions in the rate of pandrug-resistant A. baumannii colonization and infection, the cost of antibiotic therapy, and the cost of hospitalization among intensive care unit patients in a developing country.

Treatment of pan-drug resistant Acinetobacter baumannii

The objective of this study was to investigate the role of sulbactam in the treatment of pan-drug resistant Acinetobacter baumannii (PDRAB). We studied 89 patients with PDRAB infection treated with different antibiotic regimens. Group A (n = 39) were treated with carbapenem with sulbactam and group B (n = 30) with second and third generation cephalosporins, antipseudomonas penicillins, or fluoroquinolones with aminoglycosides. We also studied the MICs for 48 PDRAB strains by using antimicrobial agents with and without sulbactam. The clinical outcomes of the 2 groups did not differ significantly, either in terms of resolution of infection (25/59, 42% in group A vs 12/30, 40% in group B) or survival (35/59, 59% vs 17/30, 57%). However, the MICs indicated that 16 of the 48 strains were sensitive to imipenem/sulbactam, compared with only 2 of the 48 to imipenem alone. The addition of sulbactam thus reversed the response in 30% (14/46) of strains initially resistant or only intermediate sensitive to imipenem. The MICs for meropenem/sulbactam were in the sensitive range for 8 of 48 strains compared to only 3 of the meropenem alone, indicating an 11% (5/45) reversal rate when sulbactam was added to meropenem. For the 38 isolates initially resistant to both carbapenems alone, imipenem/sulbactam reversed the resistance in 16% (6/38), while meropenem/sulbactam did so in only 3% (1/38). Thus, the carbapenem-sulbactam combinations did not clearly improve clinical outcome, but they did demonstrate lower MICs for the PDRAB strains tested. It may be that aggressive, early treatment of A. baumannii infections with these agents might prevent the emergence of PDRAB strains.