Acinetobacter Baumannii Pneumonia Research Articles

Combination eravacycline therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: A case series.

Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB. The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital. A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution. A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified. With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

Retracted: Polymyxin B, Cefoperazone Sodium-Sulbactam Sodium, and Tigecycline against Multidrug-Resistant Acinetobacter baumannii Pneumonia.

[This retracts the article DOI: 10.1155/2022/1968020.].

Effects of disinfectant type and dosage on biofilm's activity, viability, microbiome and antibiotic resistome in bench-scale drinking water distribution systems

Drinking water distribution systems (DWDSs) are important for supplying high-quality water to consumers and disinfectant is widely used to control microbial regrowth in DWDSs. However, the disinfectant's influences on microbial community and antibiotic resistome in DWDS biofilms and the underlying mechanisms driving their dynamics remain elusive. The study investigated the effects of chlorine and chloramine disinfection on the microbiome and antibiotic resistome of biofilms in bench-scale DWDSs using metagenomics assembly. Additionally, the biofilm activity and viability were monitored based on adenosine triphosphate (ATP) and flow cytometer (FCM) staining. The results showed that both chlorine and chloramine disinfectants decreased biofilm ATP, although chloramine at a lower dosage (1 mg/L) could increase it. Chloramine caused a greater decrease in living cells than chlorine. Furthermore, the disinfectants significantly lowered the microbial community diversity and altered microbial community structure. Certain bacterial taxa were enriched, such as Mycobacterium, Sphingomonas, Sphingopyxis, Azospira, and Dechloromonas. Pseudomonas aeruginosa exhibited high resistance towards disinfectants. The disinfectants also decreased the complexity of microbial community networks. Some functional taxa (e.g., Nitrospira, Nitrobacter, Nitrosomonas) were identified as keystones in chloramine-treated DWDS microbial ecological networks. Stochasticity drove biofilm microbial community assembly, and disinfectants increased the contributions of stochastic processes. Chlorine had greater promotion effects on antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and ARG hosts than chloramine. The disinfectants also selected pathogens, such as Acinetobacter baumannii and Klebsiella pneumonia, and these pathogens also harbored ARGs and MGEs. Overall, this study provides new insights into the effects of disinfectants on biofilm microbiome and antibiotic resistome, highlighting the importance of monitoring and managing disinfection practices in DWDSs.

Risk factors for progression to bacteremia among patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia in the Intensive Care Unit

Antibiotic-resistant Acinetobacter baumannii (A. baumannii) is a common cause of hospital-acquired infections. This study aimed to identify independent factors associated with progression from nosocomial pneumonia to bacteremia in patients infected with carbapenem-resistant A. baumannii (CR-AB). From 2019 to 2021, we conducted a retrospective anaylsis of the medical records of 159 nosocomial CR-AB pneumonia patients in our Intensive Care Unit (ICU). We employed both univariate and multivariable logistic regression models to identify factors associated with the progression of nosocomial CR-AB pneumonia to bacteremia. Among the 159 patients with nosocomial CR-AB pneumonia, 40 experienced progression to bacteremia and 38 died within 28 days following diagnosis. Patients who developed bacteremia had a significantly higher 28-day mortality rate compared to those without bloodstream infection (47.50% vs. 15.97%). Multivariable logistic regression revealed that higher levels of C-Reactive protein (CRP) (OR = 1.01) and the use of continuous veno-venous hemofiltration (CVVH) treatment (OR = 2.93) were independently associated with an elevated risk of developing bacteremia. Among patients who developed bloodstream infection, those who died within 28 days exhibited significantly higher level of interleukin-6 (IL-6), a greater frequency of antifungal drugs usage, and a longer duration of machanical ventilation compared to survivors. Furthermore, the use of antifungal drugs was the only factor that associated with 28-day mortality (OR = 4.70). In ICU patients with central venous catheters who have CR-AB pneumonia and are on mechanical ventilation, higher CRP levels and CVVH treatment are risk factors for developing bacteremia. Among patients with bacteremia, the use of antifungal drugs is associated with 28-day mortality.

Passive immunization with anti-FimA egg yolk antibodies (IgYs) mitigate Acinetobacter baumannii pneumonia in mice

Acinetobacter baumannii is a formidable pathogen, characterized by high mortality rates and pan-drug-resistant strains. Current commercial antibiotics lack efficacy against drug-resistant variants, necessitating the search for alternative treatments. This study investigates the potential of egg yolk immunoglobulin (IgY) as a cost-effective biomolecule for passive protection against A. baumannii pneumonia. FimA (ABAYE2132), a key virulence factor involved in biofilm development and lung cell adherence, emerges as a promising antigen for triggering protective IgY production. Recombinant FimA was expressed, purified, and used for intramuscular immunization of laying White Leghorn hens. IgY antibodies were subsequently extracted from egg yolks, with their reactivity assessed through indirect ELISA. Neutropenic mice received intranasal administration of IgYs one hour prior to the challenge with a clinical A. baumannii isolate (10 ×LD50). The specific anti-FimA IgYs detected recombinant FimA and provided 100% protection against bacterial infection, while non-specific IgYs prolonged survival for up to 72 h. In contrast, control mice succumbed to infection within 24 h. Analysis of bacterial loads in lungs and spleens after 16 h reveals the following order: control > non-specific IgY > anti-FimA IgY. These findings highlight FimA as a suitable antigen for the development of protective IgYs against A. baumannii.

Microbial food safety of lettuce produced under irrigated wastewater from Onyasia River in Ghana

Fresh produce continues to be the main source of foodborne illness outbreaks, particularly in developing countries where water stress results in the use of surface wastewater all year round for irrigation of vegetables. The objective of the current study was to evaluate the microbial quality of lettuce irrigated with wastewater from Onyasia river. Lettuce and soil were sampled from selected vegetable farms on the Eastern gate of the Ghana Atomic Energy Commission land alongside surface wastewater from the Onyasia river, which is used as the main source for irrigation. Samples were analyzed for aerobic mesophilic plate counts, total coliforms count, fecal coliforms count, Salmonella counts and intestinal parasites using standard methods. Surface wastewater was found to be contaminated with mean fecal coliform counts of log 3.50 cfu/100 mL. Enterobacter cloacae, Acinetobacter baumannii, and Klebsiella pneumonia were also isolated from the wastewater samples. No intestinal parasite egg was detected in wastewater samples. While fecal coliforms and Salmonella spp were not detected, mean aerobic mesophilic plate counts (log 4.82 cfu/g) and total coliforms count (log 3.50 cfu/g) were recorded in the lettuce samples. Enterobacter asburiae, Acinetobacter baumannii, Klebsiella variicola and Citrobacter freundii were isolated from lettuce. Infective larvae of helminths were observed on lettuce samples at a density of 36/g-648/g with a mean of 342/g. Soil samples recorded a mean aerobic mesophilic plate counts of log 6.14 cfu/g, total coliforms count of log 4.90 cfu/g while fecal coliforms and Salmonella spp were not detected (<1 cfu/g) Soil samples yielded a mean infective larval count of 1941.5 larvae/g and a Strongyle count of 12 eggs/g. Even though less than 1 cfu/g of Salmonella spp were found, the study found lettuce to be contaminated with other foodborne bacteria pathogens, opportunistic bacteria pathogens, eggs and infective larvae of intestinal parasites of health importance. As a consequence, the microbial food safety risk associated with wastewater irrigated vegetables was observed to be high with possible public health implications. It is recommended that wastewater from the Onyasia River should be treated before use for irrigation of lettuce.

Community-Acquired, Bacteraemic Acinetobacter Baumannii Pneumonia: A Retrospective Review of Cases in Tropical Queensland, Australia.

Community-acquired Acinetobacter pneumonia (CAAP) typically presents with rapid progression to fulminant disease and is complicated by high mortality. Australian epidemiological studies are few. We conducted a retrospective study on bacteraemic cases of CAAP over twenty years (2000-2019) in North Queensland. Cases were selected on microbiologic, clinical, and radiographic parameters. Data on patient demographics were obtained, along with microbial, antibiotic, mortality and climatic data. 28 cases of CAAP were included. Nineteen (67.9%) were male, twenty-three (82.1%) were Indigenous Australians, and the mean age was 45.9 years. Most presentations were of moderate to severe pneumonia (25/28 (89.3%)). Furthermore, 90% of cases had two or more risk factors. The strongest risk factors for CAAP were alcohol excess and tobacco use. No statistically significant difference in presenting severity, ICU admission or mortality was seen between dry- and wet-season disease. Dry-season disease accounted for 35.7% of cases. Overall mortality was 28.6%. Early use of meropenem or gentamicin reduced mortality irrespective of presenting severity (mortality 17.6%) Non-targeted antibiotic therapy was associated with a non-significant difference in mortality of 44.4%. Early administration of targeted antibiotics can mitigate a high mortality rate. The choice of antibiotic therapy for community-acquired pneumonia should be based on severity, risk factors and clinical suspicion of CAAP rather than seasonality.

Clinical Evaluation of Metagenomic Next-Generation Sequencing and Identification of Risk Factors in Patients with Severe Community-Acquired Pneumonia.

Severe community-acquired pneumonia (SCAP) is the leading cause of death among patients with infectious diseases worldwide. This study aimed to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) through detecting pathogens in bronchoalveolar lavage fluid (BALF) and identifying risk factors for recovery in SCAP patients. This prospective study recruited 158 SCAP patients admitted to respiratory intensive care unit that were randomly divided into control and study groups, with receiving conventional tests and the same conventional tests plus mNGS, respectively. The diagnostic efficiency of mNGS was evaluated by comparing with conventional tests. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for recovery in SCAP patients, and a nomogram prediction model was established based on these factors. Within the study group, the pathogen detection rate was significantly higher with mNGS than that with conventional tests (84.81% vs 45.57%, P < 0.001), with a positive coincidence rate of 94.44%. Acinetobacter baumannii (21.52%, 17/79), Candida albicans (17.72%, 14/79), and Klebsiella pneumonia (15.19%, 12/79) were the top three common pathogens detected by mNGS. Of note, the improvement rate of patients in the study group was significantly higher than that in the control group. The further analysis revealed that the increased levels of interleukin-6, blood urea nitrogen, procalcitonin, the longer length of hospital stay, and bacterial infection were independent risk factors for recovery of SCAP patients, while mNGS detection status was a protective factor. The predictive model showed a good performance for the modeling and validation sets. Early mNGS exhibited a superior diagnostic efficiency to conventional tests in SCAP patients, which can reduce the risk of death in SCAP patients. Moreover, the clinical factors could also be used for the management and prognosis prediction of SCAP patients.

Egg-yolk antibodies raised to VacJ passively immunize mice against Acinetobacter baumannii pneumonia in a neutropenic murine model

There is no effective antibiotic against emerging highly resistant Acinetobacter baumannii strains, and there is a need for alternative treatment options. Egg-yolk antibodies (IgYs) are the avian equivalent of mammalian IgG that could confer passive protection against various infections. VacJ is a virulence factor of the pathogen in the lungs. In addition, previous studies have shown that immunization of mice with this antigen resulted in decreased bacterial burden in the lung. Hence, it could be a suitable antigen to achieve protective IgYs. In the current study, the recombinant VacJ was expressed, purified, and administered to laying White Leghorn hens followed by IgY extraction from egg yolks. Indirect ELISA showed maximum IgY titers against VacJ raised two weeks following the last immunization. The immunoprotective effects of IgYs were investigated in neutropenic mice. The mice received intranasal IgYs one hour before the nasal instillation of the 10 ×LD50 with a clinical isolate of A. baumannii. A significant reduction in bacterial population loaded in the lungs and spleen was noted. A 100% survival was recorded in the group receiving anti-VacJ antibodies. The results indicate that VacJ is a good immunogen for the production of anti-A. baumannii IgY.

Acinetobacter Baumannii Pneumonia Associated with Mechanical Ventilation in COVID-19 Pandemic

Infekcije uzrokovane bakterijom Acinetobacter baumannii predstavljaju veliki javnozdravstveni problem. Acinetobacter baumannii kontaminira bolničko okruženje, kožu i sluznice pacijenata te se prenosi rukama osoblja uzrokujući oportunističke infekcije kao što su upale pluća povezane s mehaničkom ventilacijom, bakterijemije, infekcije rana te urinarne infekcije. Ventilatorom uzrokovana upala pluća druga je po učestalosti nozokomijalna infekcija u jedinicama intenzivnog liječenja. Vodeći čimbenik rizika za razvoj ventilatorom uzrokovane upale pluća jest invazivna mehanička ventilacija. U pacijenata s bolešću COVID-19, liječenje u jedinicama intenzivnog liječenja često je zahtijevalo intubaciju i uporabu mehaničke ventilacije izlažući ih riziku od razvoja ventilatorom uzrokovane upale pluća. S obzirom na brojna preklapanja u kliničkoj slici COVID upale pluća i upale pluća povezane s ventilatorom, teško je sa sigurnošću odrediti njezinu prevalenciju. Oštećenja pluća uzrokovana bolešću COVID-19, imunosupresivna terapija, često profilaktičko korištenje antibiotika i organizacijske teškoće – prenapučenost u jedinicama intenzivnog liječenja, manjak osoblja, potreba za zaštitom osoblja od virusa SARS-CoV-2 (engl. Severe acute respiratory syndrome coronavirus 2) infekcije i dr., pridonijeli su povećanoj pojavnosti ventilatorom izazvane upale pluća uzrokovane Acinetobacter baumannii u pacijenata oboljelih od COVID-a. Brojni mehanizmi otpornosti na antibiotike, uz posljedično sve veću prevalenciju višestruko otpornih sojeva Acinetobacter baumannii predstavljaju izazov u liječenju. U osjetljivih sojeva, monoterapija karbapenemima dovodi do pozitivnog ishoda. Liječenje karbapenem-otpornih Acinetobacter baumannii sojeva u kompliciranim infekcijama provodi se uglavnom kolistinom. Kolistin se može primjenjivati intravenski i inhalacijski te ga se preporučuje koristiti u kombinaciji s drugim djelotvornim antibioticima.

The Protective Role of Interleukin 17A in Acinetobacter baumannii Pneumonia Is Associated with Candida albicans in the Airway.

Recent studies have found that the coexistence of fungi and bacteria in the airway may increase the risk of infection, contribute to the development of pneumonia, and increase the severity of disease. Interleukin 17A (IL-17A) plays important roles in host resistance to bacterial and fungal infections. The objective of this study was to determine the effects of IL-17A on Acinetobacter baumannii-infected rats with a previous Candida albicans airway inoculation. The incidence of A. baumannii pneumonia was higher in rats with C. albicans in the airway than in noninoculated rats, and it decreased when amphotericin B was used to clear C. albicans, which influenced IL-17A levels. IL-17A had a protective effect in A. baumannii pneumonia associated with C. albicans in the airway. Compared with A. baumannii-infected rats with C. albicans in the airway that did not receive IL-17A, recombinant IL-17A (rIL-17A) supplementation decreased the incidence of A. baumannii pneumonia (10/15 versus 5/17; P = 0.013) and the proportion of neutrophils in the lung (84 ± 3.5 versus 74 ± 4.3%; P = 0.033), reduced tissue destruction and inflammation, and decreased levels of myeloperoxidase (MPO) (1.267 ± 0.15 versus 0.233 ± 0.06 U/g; P = 0.0004), reactive oxygen species (ROS) (132,333 ± 7,505 versus 64,667 ± 10,115 AU; P = 0.0007) and lactate dehydrogenase (LDH) (2.736 ± 0.05 versus 2.1816 ± 0.29 U/g; P = 0.0313). In vitro experiments revealed that IL-17A had no significant effect on the direct migration ability and bactericidal capability of neutrophils. However, IL-17A restrained lysis cell death and increased apoptosis of neutrophils (2.9 ± 1.14 versus 7 ± 0.5%; P = 0.0048). Taken together, our results suggest that C. albicans can depress IL-17A levels, which when supplemented may have a regulatory function that limits the accumulation of neutrophils in inflammatory areas, providing inflammatory response homeostasis.

The clinical differentiation of blood culture-positive and -negative sepsis in burn patients: a retrospective cohort study.

Sepsis is a potentially life-threatening condition that occurs when the body's response to infection leads to widespread inflammation and tissue damage. Negative cultures can make it difficult for clinicians to make a diagnosis and may raise questions about the validity of the definition of sepsis. In addition, the clinical distinctions between burn patients with blood culture-positive and -negative sepsis are also poorly understood. Therefore, this study aimed to examine the clinical differences between blood culture-positive and -negative sepsis in burn patients in order to improve the understanding of the pathophysiology and epidemiology of sepsis in this population. This study had a retrospective design, and the participants were adults aged ≥18 years. Patients diagnosed with sepsis were divided into two groups based on their blood culture results within 1 week of sepsis diagnosis. We enrolled 1643 patients admitted to our institution's burn intensive care unit between January 2010 and December 2021. pH, platelet count, bicarbonate and haematocrit were significant in both the positive and negative groups. However, lymphocyte, red cell distribution widthand blood urea nitrogen were significant only in the positive group, whereas lactate dehydrogenase was significant only in the negative group. Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumonia are common gram-negative bacterial species, and Staphylococcus aureus and Staphylococcus epidermidis are common gram-positive bacterial species seen in burn patients with positive blood cultures. Carbapenem resistance was found to be associated with an unfavourable prognosis in gram-negative bacteria, with the exception of P. aeruginosa. pH, platelet count, bicarbonate and haematocrit were routine biomarkers that demonstrated statistical significance in both groups. Lactate dehydrogenase was significant in the blood-negative group, while red cell distribution width, blood urea nitrogenand lymphocyte count were significant in the positive group. Furthermore, the most common causes of sepsis are gram-negative bacteria, including A. baumannii, K. pneumoniae and P. aeruginosa. Additionally, resistance to carbapenems is associated with unfavourable outcomes.

1705. Filamentous Hemagglutinin Polyclonal Antibodies Protect against Multidrug resistant Gram-negative bacteria

Abstract Background Multidrug-resistant (MDR) Gram-negative bacteria (GNB) are among the major healthcare-associated infections and have high mortality especially in immunocompromised patients. Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PA) are classified as “critical organism” by CDC. Therefore, new anti-infective therapies are critically needed. Our studies showed that passive immunization using antibodies against Candida Hyr1 peptide#5 are protective in AB pneumonia mouse model and this was attributed to the structure homology between Candida Hyr1 and AB Filamentous hemagglutinin protein B (FhaB). In this study, we identified FhaB epitopes that shared sequence homology with Candida Hyr1 peptide#5. We aim to evaluate antibody-based therapy targeting these epitopes against AB and PA infection. Designing and evaluating FhaB peptides that share sequence similarity to Hyr1#5 In vivo protection of FhaB antibodies in mouse model on different MDR GNB A) AB B)PA Methods Sequence homology was done using BLAST online tool. FhaB peptides and their polyclonal antibodies (pAbs) were commercially produced. Indirect ELISA was done to test recognition FhaB peptides to Hyr1#5 Abs. Binding ability of FhaB pAbs was tested against AB and PA using flow cytometry. The efficacy of pAbs in protecting against AB- or PA-induced pneumonia was studied in immunosuppressed CD1 mice by administering 30 µg of pAbs (i.p.) on Day +1 relative to infection. Survival of mice served as an endpoint. Results We identified seven FhaB peptides that shared ∼50% sequence homology with Hyr1#5. These peptides are conserved among many GNB including AB and PA. Two peptides (FhaB#4 &amp; FhaB#5) showed strong binding to Hyr1 Abs in ELISA. The pAbs generated against these two peptides showed ∼90% and 50% binding to AB and PA, respectively. Finally, pAbs targeting FhaB#4 protected mice from lethal dose of both AB and PA with 70% and 40% survival efficacies, respectively (p&amp;lt; 0.05). Conclusion We used FhaB to generate protective pAb against MDR AB and PA. Our results warrant the further development of these Ab as novel immunotherapeutics against MDR GNB. Disclosures All Authors: No reported disclosures.

Acinetobacter baumannii pneumonia increases surfactant proteins SP-A, SP-B, and SP-D levels, while decreasing SP-C level in bronchoalveolar lavage in rats

Acinetobacter baumannii is an opportunistic pathogen which causes nosocomial infections and high mortality. It is one of the most isolated microorganisms from patients with nosocomial pneumonia. Lung surfactant proteins (SP) are crucial for lung functions, and levels of SP-A, SP-B, SP-C, and SP-D change in the presence of infection. How they are affected in A. baumannii pneumonia, however, has not been conclusively researched. Therefore, the aim of the present study is to investigate the effect of A. baumannii pneumonia on surfactant proteins. 54 six-to-seven-month-old Sprague–Dawley rats were divided into two groups: sham and A. baumannii. The rats were administered 100 μl 0.5 McFarland A. baumannii or sterile saline intratracheally according to their group. Following the inoculation, lung and bronchoalveolar lavage fluids (BALF) were collected on the 3rd, 24th, and 48th hours of instillation. The lungs were examined histopathologically and the SP-A, SP-B, SP-C, and SP-D levels in BALF were measured with ELISA. The rats challenged with A. baumannii had significantly higher SP-A, SP-B, and SP-D levels while having a significantly lower SP-C level compared to their sham equivalents. Furthermore, a strong positive correlation between SP-A and SP-D, and a moderate negative correlation between SP-B and SP-C were observed.

Sulbactam combined with tigecycline improves outcomes in patients with severe multidrug-resistant Acinetobacter baumannii pneumonia

BackgroundThe purpose of this study was to review the treatment plan of patients with multidrug-resistant Acinetobacter baumannii (MDR-AB) pneumonia and analyze the factors associated with patient deaths and the medication regimen.MethodsWe collected 1,823 qualified respiratory specimens that were culture-positive for MDR-AB. 166 patients confirmed to have hospital-acquired MDR-AB pneumonia were selected as the research subjects. The differing clinical characteristics and treatment interventions between the surviving group and death group within 28 days were analyzed.ResultsThe mortality rate was high for those aged > 75 years (p = 0.001). Patients who underwent invasive catheter placement (p < 0.001) and mechanical ventilation (p = 0.046) had a higher mortality rate. Combination therapy with tigecycline can reduce the mortality rate (p < 0.001) of MDR-AB pneumonia in patients with carbapenem-resistant AB(CRAB). Combination therapy with sulbactam was shown to reduce the mortality rate (p < 0.001), and high-dose sulbactam (> 3 g/day) might be better than low-dose sulbactam (≤ 3 g/day).ConclusionReducing the time of invasive catheter placement and mechanical ventilation in patients in the intensive care unit (ICU), antimicrobial treatment, combined with tigecycline and sulbactam, might help reduce the mortality rate in patients with severe MDR-AB hospital-acquired pneumonia.

A Randomized Controlled Trial of Colistin Combined with Sulbactam: 9 g per Day versus 12 g per Day in the Treatment of Extensively Drug-Resistant Acinetobacter baumannii Pneumonia: An Interim Analysis.

Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB pneumonia were randomly assigned (1:1) to receive colistin in combination with sulbactam at either 9 g/day or 12 g/day. The primary outcome was the 28-day mortality rate in the intention-to-treat population. A total of 88 patients received colistin in combination with sulbactam at a dosage of either 12 g/day (n = 45) or 9 g/day (n = 43). Trends toward a lower mortality rate were observed in the 12 g/day group at 7 days (11.1% vs. 23.3%), 14 days (33.3% vs. 41.9%), and 28 days (46.7% vs. 58.1%). The microbiological cure rate at day 7 was significantly higher in the 12 g/day group (90.5% vs. 58.1%; p = 0.02). Factors associated with mortality at 28 days were asthma, cirrhosis, APACHEII score ≥ 28, and a dosage of sulbactam of 9 g/day for mortality at any timepoint. Treatment with colistin combined with sulbactam at 12 g/day was not superior to the combination treatment with sulbactam at 9 g/day. However, due to being an interim analysis, this trial was underpowered to detect mortality differences.

Gram-negative multidrug-resistant organisms were dominant in neurorehabilitation ward patients in a general hospital in southwest China

This study aimed to investigate the prevalence of and risk factors for multidrug-resistant organism (MDRO) infection in the rehabilitation ward of a general hospital in Southwest China. We analyzed rehabilitation patients with nosocomial infections caused by MDROs from June 2016 to June 2020. MDRO infection pathogens and associated antibiotic resistance were calculated. Possible risk factors for MDRO-related infection in the neurorehabilitation ward were analyzed using chi-square, and logistic regression. A total of 112 strains of MDRO were found positive from 96 patients. The MDRO test-positive rate was 16.70% (96/575). Ninety-five MDRO strains were detected in sputum, of which 84.82% (95/112) were gram-negative bacteria. Acinetobacter baumannii (A. Baumannii), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumonia (K. pneumonia) were the most frequently isolated MDRO strains. The logistic regression model and multifactorial analysis showed that long-term (≥ 7 days) antibiotic use (OR 6.901), history of tracheotomy (OR 4.458), and a low albumin level (< 40 g/L) (OR 2.749) were independent risk factors for the development of MDRO infection in patients in the rehabilitation ward (all P < 0.05). Gram-negative MRDOs were dominant in rehabilitation ward patients. Low albumin, history of a tracheostomy, and long-term use of antibiotics were independent risk factors for MRDO infection and are worthy of attention.

Alert Germ Infections: Chest X-ray and CT Findings in Hospitalized Patients Affected by Multidrug-Resistant Acinetobacter baumannii Pneumonia.

Acinetobacter baumannii (Ab) is an opportunistic Gram-negative pathogen intrinsically resistant to many antimicrobials. The aim of this retrospective study was to describe the imaging features on chest X-ray (CXR) and computed tomography (CT) scans in hospitalized patients with multidrug-resistant (MDR) Ab pneumonia. CXR and CT findings were graded on a three-point scale: 1 represents normal attenuation, 2 represents ground-glass attenuation, and 3 represents consolidation. For each lung zone, with a total of six lung zones in each patient, the extent of disease was graded using a five-point scale: 0, no involvement; 1, involving 25% of the zone; 2, 25–50%; 3, 50–75%; and 4, involving >75% of the zone. Points from all zones were added for a final total cumulative score ranging from 0 to 72. Among 94 patients who tested positive for MDR Ab and underwent CXR (males 52.9%, females 47.1%; mean age 64.2 years; range 1–90 years), 68 patients underwent both CXR and chest CT examinations. The percentage of patients with a positive CT score was significantly higher than that obtained on CXR (67.65% > 35.94%, p-value = 0.00258). CT score (21.88 ± 15.77) was significantly (p-value = 0.0014) higher than CXR score (15.06 ± 18.29). CXR and CT revealed prevalent bilateral abnormal findings mainly located in the inferior and middle zones of the lungs. They primarily consisted of peripheral ground-glass opacities and consolidations which predominated on CXR and CT, respectively.

Immunosuppression broadens evolutionary pathways to drug resistance and treatment failure during Acinetobacter baumannii pneumonia in mice

Acinetobacter baumannii is increasingly refractory to antibiotic treatment in healthcare settings. As is true of most human pathogens, the genetic path to antimicrobial resistance (AMR) and the role that the immune system plays in modulating AMR during disease are poorly understood. Here we reproduced several routes to fluoroquinolone resistance, performing evolution experiments using sequential lung infections in mice that are replete with or depleted of neutrophils, providing two key insights into the evolution of drug resistance. First, neutropenic hosts acted as reservoirs for the accumulation of drug resistance during drug treatment. Selection for variants with altered drug sensitivity profiles arose readily in the absence of neutrophils, while immunocompetent animals restricted the appearance of these variants. Secondly, antibiotic treatment failure in the immunocompromised host was shown to occur without clinically defined resistance, an unexpected result that provides a model for how antibiotic failure occurs clinically in the absence of AMR. The genetic mechanism underlying both these results is initiated by mutations activating the drug egress pump regulator AdeL, which drives persistence in the presence of antibiotic. Therefore, antibiotic persistence mutations present a two-pronged risk during disease, causing drug treatment failure in the immunocompromised host while simultaneously increasing the emergence of high-level AMR.

Hematogenous dissemination of pulmonary mucormycosis manifested as multiple subcutaneous nodules: a case report and review of the literature

BackgroundDisseminated mucormycosis presenting with multiple subcutaneous nodules is a rare condition with a poor prognosis, and delayed diagnosis and treatment is common.Case presentationWe report a case of 64-year-old Thai woman with colorectal cancer who initially presented with Acinetobacter baumannii pneumonia and respiratory failure. Following 10 days after her admission to the intensive care unit, she developed hospital-acquired pneumonia. Five days later, multiple subcutaneous nodules appeared on both arms and both legs. Bronchoalveolar lavage and skin biopsy cultures both grew Mucor spp. She was diagnosed with disseminated mucormycosis and was treated with liposomal amphotericin B at a dose of 5 mg/kg/day. Despite treatment, our patient succumbed to septic shock and multiorgan failure on the third day after definitive diagnosis.ConclusionsThis case demonstrates that the subcutaneous nodules caused by hematogenously disseminated mucormycosis are unusual in a patient with a solid tumor. Clinicians should be aware of this atypical presentation of mucormycosis in patients with solid tumors.