Risk factors for transmission of carbapenem-resistant Acinetobacter baumannii in outbreak situations: results of a case-control study.

BACKGROUND: An increase in patients with multidrug-resistant organisms and associated outbreaks during the COVID-19 pandemic have been reported in various settings, including low-endemic settings. Here, we report three distinct carbapenem-resistant Acinetobacter baumannii (CRAB) outbreaks in five intensive care units of a university hospital in Berlin, Germany during the COVID-19 pandemic. METHODS: A case-control study was conducted with the objective of identifying risk factors for CRAB acquisition in outbreak situations. Data utilized for the case-control study came from the investigation of three separate CRAB outbreaks during the COVID-19 pandemic (August 2020- March 2021). Cases were defined as outbreak patients with hospital-acquired CRAB. Controls did not have any CRAB positive microbiological findings and were hospitalized at the same ward and for a similar duration as the respective case. Control patients were matched retrospectively in a 2:1 ratio. Parameters routinely collected in the context of outbreak management and data obtained retrospectively specifically for the case-control study were included in the analysis. To analyze risk factors for CRAB acquisition, univariable and multivariable analyses to calculate odds ratios (OR) and 95% confidence intervals (CI) were performed using a conditional logistic regression model. RESULTS: The outbreaks contained 26 cases with hospital-acquired CRAB in five different intensive care units. Two exposures were identified to be independent risk factors for nosocomial CRAB acquisition by the multivariable regression analysis: Sharing a patient room with a CRAB patient before availability of the microbiological result was associated with a more than tenfold increase in the risk of nosocomial CRAB acquisition (OR: 10.7, CI: 2.3-50.9), while undergoing bronchoscopy increased the risk more than six times (OR: 6.9, CI: 1.3-38.1). CONCLUSIONS: The risk factors identified, sharing a patient room with a CRAB patient and undergoing bronchoscopy, could point to an underperformance of basic infection control measure, particularly hand hygiene compliance and handling of medical devices. Both findings reinforce the need for continued promotion of infection control measures. Given that the outbreaks occurred in the first year of the COVID-19 pandemic, our study serves as a reminder that a heightened focus on airborne precautions should not lead to a neglect of other transmission-based precautions.

Colistin resistance in carbapenem non-susceptible Acinetobacter baumanii in a tertiary care hospital in India: clinical characteristics, antibiotic susceptibility and molecular characterization.

INTRODUCTION: Acinetobacter baumanii (AB) is a bacterium of concern in the hospital setup due to its ability to thrive in unfavorable conditions and the rapid emergence of antibiotic resistance. Carbapenem resistance in this organism is disheartening, further clouded by the emergence of colistin resistance. AIM: The present prospective study aims to note the epidemiology, molecular profile, and clinical outcome of patients with colistin resistance AB infections in a multispecialty tertiary care setup in Odisha, Eastern India. METHODS: All AB strains received from March 2021 to February 2022, identified by Vitek2 (Biomerieux) and confirmed by oxa-51 genes, were included. Carbapenem and colistin resistance were identified as per CLSI guidelines. Known mutations for blaOXA-23-like, blaIMP, blaVIM, blaKP, lpxA, lpxC, pmrA, pmrB, and plasmid mediated mcr (mcr1-5) were screened by conventional PCR techniques. The clinical outcome was noted retrospectively from case sheets. Data was entered in MS Excel and tabulated using SPSS software. RESULTS: In the study period, 350 AB were obtained, of which 317(90.5%) were carbapenem resistant (CRAB). Among the CRAB isolates, 19 (5.9%) were colistin resistant (ABCoR). The most valuable antibiotics in the study were tigecycline (65.4% in ABCoI; 31.6% in ABCoR) and minocycline (44.3% in CI; 36.8% in CR). There was a significant difference in mortality among ABCoI and ABCoR infections. bla OXA was the predominant carbapenem resistance genotype, while pmrA was the predominant colistin resistant genotype. There were no plasmid mediated mcr genes detected in the present study.

Extensively Drug-Resistant Acinetobacter baumannii Nosocomial Pneumonia Successfully Treated with a Novel Antibiotic Combination.

Extremely drug-resistant (XDR) Acinetobacter baumannii causes challenging nosocomial infections. We report the case of a patient with XDR A. baumannii pneumonia and septic shock successfully treated with cefiderocol and a novel antibiotic obtained via expanded access protocol. With focused research and drug development efforts, the poor outcomes associated with these infections may be mitigated.

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.

Outcome following postneurosurgical Acinetobacter meningitis: an institutional experience of 72 cases.

OBJECTIVE: The authors aimed to evaluate the antimicrobial susceptibility pattern of Acinetobacter isolates responsible for nosocomial meningitis/ventriculitis in the neurosurgical ICU. The authors also sought to identify the risk factors for mortality following Acinetobacter meningitis/ventriculitis. METHODS: This was a retrospective study of 72 patients admitted to the neurosurgical ICU between January 2014 and December 2018 with clinical and microbiological diagnosis of nosocomial postneurosurgical Acinetobacter baumanii meningitis/ventriculitis. Electronic medical data on clinical characteristics, underlying pathology, CSF cytology, antibiotic susceptibilities, and mortality were recorded. To evaluate the outcome following nosocomial postneurosurgical Acinetobacter meningitis/ventriculitis, patients were followed up until discharge or death in the hospital. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to compute factors affecting survival. RESULTS: The study population was divided into two groups depending on the final outcome of whether the patient died or survived. Forty-three patients (59.7%) were included in the survivor group and 29 patients (40.3%) were included in the nonsurvivor group. Total in-hospital mortality due to Acinetobacter meningitis/ventriculitis was 40.3% (29 cases), with a 14-day mortality of 15.3% and a 30-day mortality of 25%. The 43 (59.7%) patients who survived had a mean length of hospital stay of 44 ± 4 days with a median Glasgow Outcome Scale-Extended score at discharge of 6. On univariate analysis, age > 40 years (p = 0.078), admission Glasgow Coma Scale (GCS) score ≤ 8 (p = 0.003), presence of septic shock (p = 0.011), presence of external ventricular drain (EVD) (p = 0.03), CSF white blood cell (WBC) count > 200 cells/mm3 (p = 0.084), and comorbidities (diabetes, p = 0.036; hypertension, p = 0.01) were associated with poor outcome. Carbapenem resistance was not a risk factor for mortality. According to a multivariable Cox proportional hazards model, age cutoff of 40 years (p = 0.016, HR 3.21), GCS score cutoff of 8 (p = 0.006, HR 0.29), CSF WBC count > 200 cells/mm3 (p = 0.01, HR 2.76), presence of EVD (p = 0.001, HR 5.42), and comorbidities (p = 0.017, HR 2.8) were found to be significant risk factors for mortality. CONCLUSIONS: This study is the largest case series reported to date of postneurosurgical Acinetobacter meningitis/ventriculitis. In-hospital mortality due to Acinetobacter meningitis/ventriculitis was high. Age older than 40 years, GCS score less than 8, presence of EVD, raised CSF WBC count, and presence of comorbidities were risk factors for mortality.

Diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria.

The aim of the study is to explore the experiences in diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria (G-). Nineteen patients with pyogenic ventriculitis were reviewed for their treatment. The bacterial testing results of cerebrospinal fluid (CSF), the clinical intervention, and the patients' prognosis were evaluated. The bacterial smears of ventricular drainage from all the cases were G- bacteria. Head CT and MRI scans confirmed that they were intraventricular empyema. Eighteen cases of CSF bacterial test were positive, including 12 cases of Acinetobacter baumannii positive, 2 of Klebsiella pneumonia positive, 2 of Serratia marcescens positive, 1 of Pseudomonas maltophila positive, and 1 case of Escherichia coli positive. One case of the bacterial culture was negative. All patients were treated by using intraventricular lavage in combination with intravenous and intraventricular antibiotics in accordance with the clinical conditions. After treatment for 2 to 8 weeks, 14 patients were cured (74%) and 5 were died (26%). Eight patients who were cured had received ventriculoperitoneal shunt due to hydrocephalus at 2 to 6 weeks after infection controlled, and none of them had any reinfection. Twelve of the 14 cured cases came to consciousness, but 2 were persistent in vegetative state starting before the infection; they did not show any improving consciousness after infection had been cured. Suppurative ventriculitis in severe neurosurgical patients is mainly infected by G- with a higher mortality. Early diagnosis, especially in identifying pathogen types, timely ventricular irrigation, and ventricular drainage together with intravenous and intraventricular antibiotic treatment, should improve prognosis.

Polydopamine-based nano adjuvant as a promising vaccine carrier induces significant immune responses against Acinetobacter baumannii-associated pneumonia.

The objective of this study was to assess the effectiveness of polydopamine nanoparticles (PDANPs) as a delivery system for intranasal antigen administration to prevent Acinetobacter baumannii (A. baumannii)-associated pneumonia. In the in vitro phase, the conserved outer membrane protein 22 (Omp22)-encoding gene of A. baumannii was cloned, expressed, and purified, resulting in the production of recombinant Omp22 (rOmp22), which was verified using western blot. PDANPs were synthesized using dopamine monomers and loaded with rOmp22 through physical adsorption. The rOmp22-loaded PDANPs were characterized in terms of size, size distribution, zeta potential, field emission scanning electron microscopy (FESEM), loading capacity, Fourier transform infrared spectroscopy (FTIR), release profile, and cytotoxicity. In the in vivo phase, the adjuvant effect of rOmp22-loaded PDANPs was evaluated in terms of eliciting immune responses, including humoral and cytokine levels (IL-4, IL-17, and IFN-γ), as well as protection challenge. The rOmp22-loaded PDANPs were spherical with a size of 205 nm, a zeta potential of -14 mV, and a loading capacity of approximately 35.7 %. The released rOmp22 from nontoxic rOmp22-loaded PDANPs over 20 days was approximately 41.5 %, with preserved rOmp22 integrity. The IgG2a/IgG1 ratio and IFN-γ levels were significantly higher in immunized mice with rOmp22-loaded-PDANPs than in rOmp22-alum, naive Omp22, and control groups. Furthermore, rOmp22-loaded PDANPs induced effective protection against infection in the experimental challenge and showed more normal structures in the lung histopathology assay. The results of this study suggest the potential of PDANPs as a nano-adjuvant for inducing strong immune responses to combat A. baumannii.

Case report: Successful treatment of OXA-23 Acinetobacter baumannii neurosurgical infection and meningitis with sulbactam-durlobactam combination therapy.

Meningitis caused by Acinetobacter species is a rare complication of neurosurgical procedures, although it is associated with high morbidity and mortality. Carbapenem-resistant Acinetobacter is particularly difficult to treat, considering the limited selection and tolerability of effective antimicrobials. Sulbactam-durlobactam was approved by the FDA in 2023 for treatment of hospital-acquired and ventilator-associated pneumonia due to susceptible strains of Acinetobacter, including carbapenem-resistant Acinetobacter baumannii. Here, we present a case of carbapenem-resistant Acinetobacter baumannii neurosurgical infection and meningitis successfully treated with sulbactam-durlobactam combination therapy.

Prevalence of Healthcare-Associated Infections in a Tertiary Hospital in Casablanca, Morocco, 2021.

BACKGROUND: During the COVID-19 pandemic, healthcare professionals experienced an increased workload, which may have affected infection prevention and control (IPC) programs and consequently healthcare-associated infection (HAI) rates. The objective of this study was to estimate the prevalence of HAI in Ibn Rochd University Hospital Center (IRUHC) and identify associated factors. METHODS: A survey was conducted on November 30, 2021 at IRUHC, including all patients hospitalized for at least 48 hours. Data was collected using a questionnaire, and analyzed using SPSS IBM software version 16. The significance level was set at 0.05. RESULTS: Among 887 patients, the prevalence of HAI was 9.7% (7.7%; 11.6%). The highest prevalence was observed in intensive care units (ICUs) (44.2%). Nosocomial pneumonia was the most common site (26.8%). The main isolated microorganisms were Acinetobacter baumannii (18.0%) and Escherichia coli (16.0%). All Acinetobacter baumannii isolated strains were imipenem-resistant. The presence of HAI was significantly associated with the presence of an invasive medical device (p<0.001), a higher physical status score of American Society of Anesthesiologists (ASA) (p<0.001), and a longer hospital stay (p<0.001). Conclusion : The emergence of imipenem-resistant Acinetobacter baumannii (IRAB) represents a serious therapeutic and epidemiological problem requiring the establishment of a system for monitoring the microbial environment and the application of strict hygiene measures.

Infection Prevention and Control Strategies According to the Type of Multidrug-Resistant Bacteria and Candida auris in Intensive Care Units: A Pragmatic Resume including Pathogens R0 and a Cost-Effectiveness Analysis.

Multidrug-resistant organism (MDRO) outbreaks have been steadily increasing in intensive care units (ICUs). Still, healthcare institutions and workers (HCWs) have not reached unanimity on how and when to implement infection prevention and control (IPC) strategies. We aimed to provide a pragmatic physician practice-oriented resume of strategies towards different MDRO outbreaks in ICUs. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios; education, isolation, decolonization, screening, and hygiene practices; outbreak reporting; cost-effectiveness; reproduction numbers (R0); and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician lose sight of the big picture. IPC strategies have proven their cost-effectiveness regardless of typology, country, and pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, the elaboration of a rapid outbreak recognition tool (i.e., an easy-to-use mathematical model) would improve early diagnosis and prevent spreading. Further studies are needed to express views in favor or against MDRO decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategy application has made and still makes ICUs major MDRO reservoirs in the community. In a not-too-distant future, genetic engineering and phage therapies could represent a plot twist in MDRO IPC strategies.

Prediction of Antigenic Vaccine Peptide Candidates From BfmRS Associated With Biofilm Formation in Acinetobacter baumannii.

INTRODUCTION:  A. baumannii is categorized as a priority pathogen due to its propensity for multi-drug resistance, exhibiting resistance against the last resort of antibiotics. It is also considered a potent nosocomial pathogen, so targeting the microbe using novel strategies would be the need of the hour. In this context, the in-silico computational approach would serve the best to design the possible epitope peptides, which may be further considered for the experimental trials for their immunological response.  Objective: To predict the immune-dominant epitope peptide candidates against the bfmR and bfmS proteins mediating the two-component system adaptation in the formation of biofilm in A. baumannii. MATERIALS AND METHODS: 11 different FASTA sequences of bfmR and bfmS from A. baumannii strains retrieved based on the blast-p similarity search tool were subjected to linear epitope B-cell epitope predictions under the IEDB B-cell epitope prediction server. Further analysis on antigenicity, allergenicity, and toxigenicity was achieved using the AntigenPro, Vaxijen, and AlgPred tools, with the physical and chemical properties evaluated using the Expasy Protparam server. Selection of the immunodominant peptides for T-cells was done through the databases under IEDB. The final assessment of protein-TLR2 interactions was done by MHC cluster servers. RESULTS: Four peptide sequences (E1-E4) were predicted for B-cell dominance, with E1, E2, and E4 as probable antigens. All were soluble and non-toxigenic. E1 and E3 were considered non-allergens. GRAVY values were negative for all the peptides, indicating the protein to be hydrophilic in nature. Analysis of the T-cell epitopes was promising, with 100% conservancy for class-I HLA alleles, high interaction scores for similarity with TLR2, and more hydrogen bonds for E2, followed by other epitope peptides. CONCLUSION: The promising four epitopes, as predicted for bfmR and bfmS in the present study, suggest their potent role as possible candidates for the design of vaccines targeting the TCS of A. baumannii, recommending further in vitro and in vivo experimental validation.

Risk factors and outcome associated with coinfection with carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumanii: a descriptive analysis.

Background: Nearly 30% of patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) were previously shown to be coinfected with carbapenem-resistant Pseudomonas aeruginosa (CRPA) or Acinetobacter baumannii (CRAB). Infections caused by multiple carbapenem-resistant pathogens present significant challenge to infection control and therapeutic management. The study objective was to identify risk factors for acquisition of multiple carbapenem-resistant pathogens and associated outcomes. Methods: A descriptive analysis of adults infected with either CRKP alone or coinfected with CRPA or CRAB was performed. Patient groups were compared on demographics, clinical characteristics, treatment, and outcome. Results: 86 patients with CRKP monoinfection and 60 patients with coinfections were evaluated. Respiratory tract was the predominant infection site for coinfected patients involving mostly CRPA whereas urinary tract was the primary site for CRKP-only group. More coinfected patients were severely debilitated, had prior carbapenem exposure (37% vs 13%, p<0.001) and history of pneumonia in the past year (67% vs 41%, p<0.01). More coinfected patients required direct ICU admission (45% vs 27%, p=0.02) and had prolonged length of stay (median 15 vs 10 days, p<0.01) than the CRKP-only group but mortality rates (18% vs 16%) were similar. Conclusions: CRKP coinfection with another carbapenem-resistant pathogen adds significant morbidity and healthcare burden overall. Empiric therapy with reliable activity against both CRKP and carbapenem-resistant Pseudomonas aeruginosa may be prudent for at risk patients with pneumonia.

Acinetobacter baumannii Early-Onset Sepsis After Home Delivery Into Toilet Water.

Early-onset sepsis (EOS) is an important cause of morbidity and mortality in newborns, usually caused by pathogens acquired intrapartum. We present the case of a term neonate born by home delivery in the toilet, after an unsupervised pregnancy. He developed a culture-proven early-onset sepsis caused by Acinetobacter baumannii. This was the first case of neonatal sepsis by this pathogen in our unit. The microorganism was susceptible to all antibiotics tested. The neonate was treated empirically with ampicillin and cefotaxime and completed 21 days of directed therapy with meropenem, as meningitis could not be excluded. During the clinical course, the newborn developed severe and persistent thrombocytopenia and neutropenia. In this report, we discuss the etiology behind this clinical presentation. We intend to raise awareness for the consideration of Acinetobacter baumannii as a potential pathogen in EOS, particularly in the presence of adverse birth circumstances.

Assesment of polyphenolic compounds against biofilms produced by clinical Acinetobacter baumannii strains using in silico and in vitro models.

Several types of microbial infections are caused by Acinetobacter baumanii that has developed resistance to antimicrobial agents. We therefore investigated the role of plant polyphenols against A. baumannii using in silico and in vitro models. The clinical strains of A. baumannii were investigated for determination of resistance pattern and resistance mechanisms including efflux pump, extended spectrum beta lactamase, phenotype detection of AmpC production, and Metallo-ß-lactamase. The polyphenolic compounds were docked against transcription regulator BfmR (PDB ID 6BR7) and antimicrobial, antibiofilm, and anti-quorum sensing activities were performed. The antibiogram studies showed that all isolated strains were resistant. Strain A77 was positive in Metallo-ß-lactamase production. Similarly, none of strains were producers of AmpC, however, A77, A76, A75 had active efflux pumps. Molecular docking studies confirmed a strong binding affinity of Rutin and Catechin towards transcription regulator 6BR7. A significant antimicrobial activity was recorded in case of quercetin and syringic acid (MIC 3.1 µg/mL) followed by vanillic acid and caffeic acid (MIC 12.5 µg/mL). All tested compounds presented a strong antibiofilm activity against A. baumanii strain A77 (65 to 90%). It was concluded that all tested polyphenols samples posess antimicrobial and antibiofilm activities, and hence they may be utilized to treat multidrug resistance A. baumannii infections.

Antimicrobial activity of photosensitizers: arrangement in bacterial membrane matters.

Porphyrins are well-known photosensitizers (PSs) for antibacterial photodynamic therapy (aPDT), which is still an underestimated antibiotic-free method to kill bacteria, viruses, and fungi. In the present work, we developed a comprehensive tool for predicting the structure and assessment of the photodynamic efficacy of PS molecules for their application in aPDT. We checked it on a series of water-soluble phosphorus(V) porphyrin molecules with OH or ethoxy axial ligands and phenyl/pyridyl peripheral substituents. First, we used biophysical approaches to show the effect of PSs on membrane structure and their photodynamic activity in the lipid environment. Second, we developed a force field for studying phosphorus(V) porphyrins and performed all-atom molecular dynamics simulations of their interactions with bacterial lipid membranes. Finally, we obtained the structure-activity relationship for the antimicrobial activity of PSs and tested our predictions on two models of Gram-negative bacteria, Escherichia coli and Acinetobacter baumannii. Our approach allowed us to propose a new PS molecule, whose MIC50 values after an extremely low light dose of 5 J/cm2 (5.0 ± 0.4 µg/mL for E. coli and 4.9 ± 0.8 µg/mL for A. baumannii) exceeded those for common antibiotics, making it a prospective antimicrobial agent.

Analysis of Pathogens of Urinary Tract Infections Associated with Indwelling Double-J Stents and Their Susceptibility to Globularia alypum.

Ureteral double-J stents are frequently used to prevent urinary obstruction. They can develop bacterial colonization and encrustation, which leads to persistent infections that seldom respond to antibiotic treatment. Thus, the goal of this study was to evaluate the local spectrum of bacterial pathogens and their susceptibility to natural compounds. A total of 59 double-J ureteral stents from 59 consecutive patients were examined. The samples were inoculated on agar culture mediums. Extracts of Globularia alypum L. were evaluated for their antibacterial activity with the diffusion and broth dilution methods; for antibiofilm activity, the crystal violet assay was used. The identification and the quantification of the different constituents of extracts were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Bacterial growth was found in three patients (5.1%). Enterococcus faecalis (1.7%), Acinetobacter baumanii (1.7%), and Pseudomonas putida (1.7%) strains were more commonly detected. They were resistant to several common antibiotics. All extracts presented several components, mainly nepetin-7-glucoside and trans-ferulic-acid, and they had antibacterial activity (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties, especially against Acinetobacter baumanii. The results achieved confirm the important role of this plant as a source of therapeutic activities.

Catheter-Associated Vancomycin-Resistant Enterococcus faecium Ventriculitis and Multidrug-Resistant Acinetobacter baumannii Pneumonia With Subsequent Acinetobacter Ventriculitis: A Case Report.

Ventriculitis is associated with cerebrospinal fluid (CSF) shunts, and rare microorganisms associated with infection include vancomycin-resistant Enterococcus (VRE) faecium and Acinetobacter baumannii. Both organisms are known to cause nosocomial infections, and the emergence of multidrug-resistant (MDR) strains presents a treatment challenge. There is a lack of consensus on antimicrobial agent selection for ventriculitis involving VRE faecium or MDR A. baumannii, which are life-threatening conditions. We present a case of a 59-year-old male presenting with CSF catheter-associated VRE faecium ventriculitis and MDR A. baumannii pneumonia who subsequently developed a nosocomial MDR A. baumannii ventriculitis. Both instances of ventriculitis were successfully treated with combination antibiotic therapy. VRE faecium ventriculitis was successfully treated with linezolid and intrathecal daptomycin. While daptomycin is not approved for Enterococcal infections, the synergistic effect of daptomycin in combination with linezolid proved effective. Although the MDR A. baumannii pneumonia was not cured with cefiderocol monotherapy, the MDR A. baumannii ventriculitis was successfully treated with combination therapy including cefiderocol, ampicillin/sulbactam, and intrathecal colistin. This highlights life-saving combination antibiotic therapies for ventriculitis caused by multiple rare and drug-resistant microorganisms.

Apolipoprotein E mimetic peptide COG1410 combats pandrug-resistant Acinetobacter baumannii.

The emergence of pandrug-resistant bacteria breaks through the last line of defense and raises fear among people of incurable infections. In the post-antibiotic era, the pharmaceutical field turns to seek non-conventional anti-infective agents. Antimicrobial peptides are considered a prospective solution to the crisis of antimicrobial resistance. In this study, we evaluated the antimicrobial efficiency of an ApoE mimetic peptide, COG1410, which has been confirmed to exhibit strong neural protective activity and immunomodulatory function. COG1410 showed potent antimicrobial activity against pandrug-resistant Acinetobacter baumannii, even eliminating large inocula (108 CFU/ml) within 30 min. LC99.9 in PBS and 50% pooled human plasma was 2 µg/ml (1.4 µM) and 8 µg/ml (5.6 µM), respectively. Moreover, COG1410 exhibited biofilm inhibition and eradication activity, excellent stability in human plasma, and a low propensity to induce resistance. Although COG1410 easily entered bacterial cytoplasm and bound to DNA nonspecifically, the major mechanism of COG1410 killing was to disrupt the integrity of cell membrane and lead to leakage of cytoplasmic contents, without causing obvious pores on the cell surface or cell lysis. Additionally, transcriptome analysis showed that treatment with COG1410-enriched genes involved a series of oxidation-reduction processes. DCFH-DA probe detected an increased ROS level in the presence of COG1410, indicating ROS was another hit of this AMP. Furthermore, the action of COG1410 did not depend on the electronic interaction with the LPS layer, in contrast to polymyxin B. The strong synergistic interaction between COG1410 and polymyxin B dramatically reduced the working concentration of COG1410, expanding the safety window of the application. C. elegans infection model showed that combined therapy of COG1410 and polymyxin B was capable of significantly rescuing the infected nematodes. Taken together, our study demonstrates that COG1410 is a promising drug candidate in the battle against pandrug-resistant A. baumannii.

Bloodstream infection with Acinetobacter baumanii in a Plasmodium falciparum positive infant: a case report.

BACKGROUND: The increasing incidence of multi-antibiotic-resistant bacterial infections, coupled with the risk of co-infections in malaria-endemic regions, complicates accurate diagnosis and prolongs hospitalization, thereby increasing the total cost of illness. Further, there are challenges in making the correct choice of antibiotic treatment and duration, precipitated by a lack of access to microbial culture facilities in many hospitals in Ghana. The aim of this case report is to highlight the need for blood cultures or alternative rapid tests to be performed routinely in malaria patients, to diagnose co-infections with bacteria, especially when symptoms persist after antimalarial treatment. CASE PRESENTATION: A 6-month old black female child presented to the Agogo Presbyterian Hospital with fever, diarrhea, and a 3-day history of cough. A rapid diagnostic test for malaria and Malaria microscopy was positive for P. falciparum with a parasitemia of 224 parasites/µl. The patient was treated with Intravenous Artesunate, parental antibiotics (cefuroxime and gentamicin) and oral dispersible zinc tablets in addition to intravenous fluids. Blood culture yielded Acinetobacter baumanii, which was resistant to all of the third-generation antibiotics included in the susceptibility test conducted, but sensitive to ciprofloxacin and gentamicin. After augmenting treatment with intravenous ciprofloxacin, all symptoms resolved. CONCLUSION: Even though this study cannot confirm whether the bacterial infection was nosocomial or otherwise, the case highlights the necessity to test malaria patients for possible co-infections, especially when fever persists after parasites have been cleared from the bloodstream. Bacterial blood cultures and antimicrobial susceptibility testing should be routinely performed to guide treatment options for febril illnesses in Ghana in order to reduce inappropriate use of broad-spectrum antibiotics and limit the development of antimicrobial resistance.

The novel outer membrane protein from OprD/Occ family is associated with hypervirulence of carbapenem resistant Acinetobacter baumannii ST2/KL22.

Acinetobacter baumannii has become a major healthcare threat that causes nosocomial infections, especially in critically ill patients. The spread of carbapenem-resistant A. baumannii (CRAB) strains has long been a clinical concern. It is important to study the epidemiology and virulence characteristics of different CRAB isolates in order to tailor infection prevention and antibiotic prescribing. In this study, a total of 71 CRAB isolates were collected in the hospital, and clinical characteristics of infections were analyzed. The genomic characteristics and phylogenetic relationships were elucidated based on genome sequencing and analysis. The isolates were assigned to three sequence types (STs, Pasteur) and nine capsular polysaccharide (KL) types, among which ST2/KL22 was the most prevalent CRAB in the hospital. Even though all the ST2/KL22 isolates contained the same reported virulence genes, one specific clade of ST2/KL22 showed more pathogenic in mouse infection model. Complete genomic analysis revealed differences at the oprD locus between the low- and high-virulent isolates. More specifically, a premature stop codon in the low-virulence strains resulted in truncated OprD expression. By evaluating pathogenicity in C57BL/6 J mice, knock-out of oprD in high-virulent isolate resulted in virulence attenuation, and complementing the avirulent strain with full-length oprD from high-virulent isolate enhanced virulence of the former. The oprD gene may be associated with the enhanced virulence of the specific ST2/KL22 clone, which provides a potential molecular marker for screening the hypervirulent A. baumannii strains.