Gram-negative Bacteria Infection Research Articles

New insights into the regulation mechanism of Litopenaeus vannamei hepatopancreas after lipopolysaccharide challenge using transcriptome analyses

Litopenaeus vannamei (L. vannamei) is the most economically valuable cultured shrimp in the world, while Gram-negative bacteria infection causes huge economic losses to shrimp culture. In this study, we performed transcriptome sequencing of the hepatopancreas in L. vannamei after lipopolysaccharide (LPS, the cell wall component of Gram-negative bacteria) injection to investigate the response of shrimp under Gram-negative bacteria invasion. A total of 306 differentially expressed genes (DEGs) (70 up- and 236 down-regulated) were identified in the LPS treatment group (L group) when compared to their expression levels in the control group (C group). The oxidoreductase activity (GO:0016491) in the molecular function category was enriched in the LPS-responsive DEGs in GO annotation, and the metabolism of xenobiotics by cytochrome P450 (ko00980) was the most enriched pathway in KEGG annotation. The transcriptome profiling revealed that the toll like receptor, C-type lectin receptor, and β-1,3-glucan binding protein were involved in the recognition of LPS during its early invasion stage. Although LPS could reduce the metabolic ability of exogenous substances, induce inflammation and reduce antioxidant capacity, L. vannamei could maintain its homeostasis by improving immunity, enhancing anti-stress ability and reducing apoptosis. Our research provides the first transcriptome profiling for the L. vannamei hepatopancreas after LPS injection. These results could offer a valuable reference on the mechanism of shrimp against Gram-negative bacteria and could provide guidance for shrimp farming.

Naringenin restores colistin activation against colistin-resistant gram-negative bacteria in vitro and in vivo.

Colistin is used as the “last line of defense” against multidrug-resistant (MDR) Gram-negative bacteria (GNB). However, improper use of colistin may further lead to an increasing number of colistin-resistant (Col-R) strains worldwide, which greatly limits antibiotic treatment options. In this study, we investigated the antibacterial and antibiofilm activities of naringenin (NG) combined with colistin against Col-R GNB in vitro and in vivo. The checkerboard method and time-kill test showed that NG combined with colistin has better antibacterial activity (FICI < 0.5) compared with NG and colistin alone. Biofilm formation inhibition tests demonstrated that combining the two drugs could inhibit biofilm formation; scanning electron microscopy (SEM) confirmed that the combination of the two significantly reduces the number of cells in the biofilm compared with the drug alone. The in vivo experiment showed that the combination of NG and colistin can improve the survival rate of the Galleria mellonella (G. mellonella) and reduce the microbial load in the mouse thigh infection model. Mechanistically, the combination of NG and colistin synergistically enhances the antibacterial activity and changes the permeability of the bacterial outer membrane. More importantly, cytotoxicity tests showed no cell cytotoxicity of NG in combination with colistin. In conclusion, our data revealed that NG combined with colistin exhibited good synergistic effects in vivo and in vitro, thus providing a new therapeutic option for clinical Col-R GNB infections.

Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) have become a major global public health threat.Ceftazidime-avibactam (CAZ-AVI) is a newer combination of β-lactam/β-lactamase inhibitor, with activity againstcarbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Theaim of this review is to describe the recent real-world experience of CAZ-AVI for the infections due to MDR-GNB. We searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI forMDR-GNB infections. Reference lists were reviewed and synthesized for narrative review. MDRGNBinfections are associated with higher mortality significantly comparing to drug-susceptible bacterial infections.Fortunately, CAZ-AVI shows significant benefits for infections due to KPC or OXA-48 CRE, comparing to colistin,carbapenem, aminoglycoside and other older agents, even in those with immunocompromised status. The efficacyof CAZ-AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated withimproved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ-AVI is still superior to other GNBactive antibiotics. CAZ-AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, forinfections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate thebenefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development ofresistance in CRE and MDR-PA against CAZ-AVI is alarming, and more investigations and studies are needed toprevent, diagnose, and treat infections due to CAZ-AVI-resistant pathogens. CAZ-AVIappears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improveefficacy and decrease the emergence of resistance is important.

Epidemiology, Outcomes and Resource Utilisation in Patients with Carbapenem Non-susceptible Gram-Negative Bacteria in the UK: A Retrospective, Observational Study (CARBAR UK).

IntroductionAntimicrobial resistance is an urgent medical challenge. In this two-part study, we investigated the epidemiology and management of carbapenem non-susceptible (Carb-NS) Gram-negative bacteria (GNB) in the UK.MethodsWe conducted a retrospective review of data from UK hospitals (ten in part 1, nine in part 2). In part 1, epidemiological data were collected from patients hospitalised between April 2017 and March 2018 with any laboratory detection of Carb-NS GNB, encompassing both colonisation and infection. In part 2, diagnosis and management pathways in a randomly selected population of adults from part 1 with confirmed Carb-NS GNB infection were assessed. Data were obtained from a detailed medical chart review for ≥ 3 months from index (collection date of first positive Carb-NS GNB sample).ResultsOf 42,340 GNB isolates from 36,098 patients colonised/infected with GNB in part 1, 7% were Carb-NS. In 157 patients included in part 2, 234 GNB index samples were collected, of which 197 (82%) were Carb-NS (median number of Carb-NS pathogens per patient, 1; range 1–3). The most frequent Carb-NS isolates were Pseudomonas aeruginosa (36%), Stenotrophomonas maltophilia (29%) and Klebsiella pneumoniae (10%). Median length of hospitalisation was 34 days. Median time from index to appropriate therapy was 3 days, with empirical therapy initiated a median of 1 day before index. Carb-NS infection was believed to contribute to 21 (28%) of 76 deaths during the study.ConclusionsThis study highlights the high incidence of Carb-NS GNB colonisation and infection in the UK and the need for improved management of patients with Carb-NS GNB infection.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02177-3.

A retrospective observational study of the treatment with polymyxin B for liver transplantation recipients infected by multidrug-resistant gram-negative bacteria.

Only a few studies about polymyxin B (PMB) against multidrug-resistant gram-negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR-GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30-day all-cause mortality. Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30-day all-cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30-day all-cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016-1.423, p= 0.032) was an independent risk factor for 30-day all-cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019-0.860, p= 0.034) was an independent risk factor for clinical cure with PMB. This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety.

Drosophila Relish Activating lncRNA-CR33942 Transcription Facilitates Antimicrobial Peptide Expression in Imd Innate Immune Response.

Long noncoding RNAs (lncRNAs) are an emerging class of regulators that play crucial roles in regulating the strength and duration of innate immunity. However, little is known about the regulation of Drosophila innate immunity-related lncRNAs. In this study, we first revealed that overexpression of lncRNA-CR33942 could strengthen the expression of the Imd pathway antimicrobial peptide (AMP) genes Diptericin (Dpt) and Attacin-A (AttA) after infection, and vice versa. Secondly, RNA-seq analysis of lncRNA-CR33942-overexpressing flies post Gram-negative bacteria infection confirmed that lncRNA-CR33942 positively regulated the Drosophila immune deficiency (Imd) pathway. Mechanistically, we found that lncRNA-CR33942 interacts and enhances the binding of NF-κB transcription factor Relish to Dpt and AttA promoters, thereby facilitating Dpt and AttA expression. Relish could also directly promote lncRNA-CR33942 transcription by binding to its promoter. Finally, rescue experiments and dynamic expression profiling post-infection demonstrated the vital role of the Relish/lncRNA-CR33942/AMP regulatory axis in enhancing Imd pathway and maintaining immune homeostasis. Our study elucidates novel mechanistic insights into the role of lncRNA-CR33942 in activating Drosophila Imd pathway and the complex regulatory interaction during the innate immune response of animals.

The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study

BackgroundThe importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.MethodsThis was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67).ResultsThe loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan–Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups.ConclusionsThe administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

A bundle of infection control measures reduces postoperative sternal wound infection due to Staphylococcus aureus but not Gram-negative bacteria: a retrospective analysis of 6903 patient episodes

Prevention of cardiac surgical site infection has largely focused on reducing infection due to Staphylococcus aureus, although other bacteria also play an important role in this complication. To assess the impact of an evolving infection control programme on the incidence of sternal wound infection (SWI), and the changing incidence of non-staphylococcal infections. A retrospective cohort study of all patients who underwent primary sternotomy at a single UK centre between September 2010 and May 2018 was undertaken. Data were collated from the 2 years preceding the stepwise introduction of a broad-ranging infection control programme, including S. aureus decolonization. In total, 6903 primary sternotomies were performed, of which 2.6% (N=178) were complicated by SWI. Gram-negative bacteria (GNB) and S. aureus were most commonly identified as causative pathogens (45.5% and 30.3%, respectively). Following programme introduction, there was a reduction in the rate of SWI from 3.9 to 1.8 cases/100 patients/month. This was mainly due to a sustained reduction in cases of S. aureus infection, with no discernible impact on GNB. Multi-variable logistic regression analysis identified coronary artery bypass grafting, procedural urgency, and procedures performed in the third quarter of the calendar year (July to September) as independent risk factors for postoperative infection. A multi-faceted infection control programme was successful at reducing the rate of SWI, primarily due to a reduction in S. aureus infections. GNB also play an important role in SWI, and traditional preventative measures fail to address these. Future intervention and impact assessments should consider GNB infections when measuring effectiveness.

Efficacy and safety of Colistin-Imipenem/Cilastatin combination Therapy for Multidrug-Resistant Gram-Negative Bacteria Infections in Critically Ill Pediatric Patients

Purpose: The aim of this study was to ensure the safety and efficacy of intravenous administration of colistin-imipenem/cilastatin combination to critically ill pediatrics suffering from multidrug-resistant gram-negative sepsis. Patients and methods: The study was designed to give sixty patients in Al-Demerdash hospital pediatric intensive care units (PICU), Ain Shams University, Cairo, Egypt, either imipenem/cilastatin as a monotherapy (thirty patients) or colistin-imipenem/cilastatin intravenously as a combination (thirty patients). The interventional prospective randomized study was performed with focusing on patients' hemodynamic parameters, vital signs, sepsis markers and microbiological response. Results: Thirty patients received intravenous colistin-imipenem/cilastatin combination; with median age of 8.5 months (range: 1-36 months). The isolated bacteria were Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli. Klebsiella pneumoniae was the most common isolate (51.7%) of the overall examined sixty patients. Patient who received the combination therapy, was associated with improving in vital signs and hemodynamic parameters with significant p = 0.001, and microbiological responses were represented by the recorded cultures. No patients were defined by renal impairment or neurological toxicity as a side effect to colistin therapy. However, non-significant differences in fatality was found among the two groups with p = 0.108. Conclusion: Colistin combination therapy resulted in better clinical outcomes of PICU patients, which were represented by eradication of the multidrug-resistant gram-negative bacteria without noticeable nephrotoxicity.

Analysis of the clinical application of ceftazidime-avibactam in China

BackgroundThe efficacy and safety of ceftazidime-avibactam were mainly reported in phase II and phase III clinical trials, rarely in the real-world study. The limited real-world study which evaluated the clinical response of this drug shown inconsistent results. This study aimed to investigate the rationality of the clinical use of ceftazidime-avibactam and to evaluate its clinical response in the treatment of multidrug-resistant gram-negative bacteria (MDR-GNB) infections in China. MethodsThis retrospective study evaluated the outcomes of adult patients with MDR-GNB infections treated with ceftazidime-avibactam during September 2018 to August 2020. Patients’ characteristics, comorbidities, microbes, laboratory indicators and medication information were collected. The rationality of ceftazidime-avibactam clinical use, and its clinical response in the treatment of MDR-GNB infections were analyzed. ResultsA total of 30 patients were included in this study, of which, 66.6% received target treatment, 26.7% received empirical treatment, and 6.7% received treatment with no indication. Only 50.0% (11/22) of patients were administrated the recommended dose according to the drug instruction or guidelines, at a median treatment duration of 10 days (range: 2–74 days). The most common source of infection was pneumonia (53.6%, 15/28). Carbapenem-resistant Klebsiella pneumoniae was the predominant pathogen (65%, 13/20). A total of 16 patients (61.5%) achieved clinical response. Patients received target treatment had higher clinical response rate than that of patients received empirical treatment (77.8% vs 25.0%, P = 0.026). A total of 11 patients (61.1%) achieved microbiological response. One patient occurred gastrointestinal adverse reactions. ConclusionsIt is necessary to strengthen the monitor of the clinical application of ceftazidime-avibactam, such as the appropriate indication, reasonable dosage and duration, to improve its clinical outcome. Our results showed that ceftazidime-avibactam might be a potencial choice for the MDR-GNB infections. However, further research are still needed to identify its efficacy and safety in the real world.

Multicentre study of ceftazidime/avibactam for Gram-negative bacteria infections in critically ill patients

This study aimed to assess the efficacy of ceftazidime/avibactam (C/A) in the treatment of infections due to Gram-negative bacteria (GNB) in critically ill patients. A multicentre, retrospective, observational study was conducted in critically ill patients receiving C/A for GNB infections. We evaluated demographic data, localisation and severity of infection, clinical and microbiological outcomes, and mortality. A total of 68 patients received C/A for serious GNB infections. The main infections were respiratory (33.8%), intra-abdominal (22.1%) and urinary tract infections (10.3%); bacteraemia was found in 22 cases (32.4%). Most infections were complicated by septic shock (58.8%) or sepsis (36.8%) and most of them required life-supporting therapies. Enterobacterales (79.4%) and Pseudomonas aeruginosa (19.1%) were the most frequently isolated bacteria; 84.2% of isolates were carbapenem-resistant. Thirty-four patients (50.0%) received C/A in combination with other antimicrobials. Fifty patients (73.5%) presented a favourable clinical response. Microbiological eradication was documented in 25 cases (36.8%). No significant differences were found in clinical response between patients treated with monotherapy or combined therapy (79.4% vs. 67.6%; P=0.27). Overall intensive care unit (ICU) mortality was 41.2%. Univariate analysis showed that 30-day all-cause mortality was significantly (P < 0.05) associated with bacteraemia, previous corticosteroid use and the need of life-supporting therapies. C/A appears to be an effective therapy for severe infections due to GNB, including carbapenem-resistant isolates, in critically ill patients. C/A combination therapy was not associated with a higher clinical response. Mortality correlated significantly with the presence of bacteraemia, previous corticosteroid use and the need for life-supporting therapies.

Comparative genomic analysis of dwarf Vibrio myoviruses defines a conserved gene cluster for successful phage infection.

Tailed bacteriophages have been at the center of attention, not only for their ability to infect and kill pathogenic bacteria but also due to their peculiar and intriguing complex contractile tail structure. Tailed bacteriophages with contractile tails are known to have a Myoviridae morphotype and are members of the order Caudovirales. Large bacteriophages with a genome larger than 150 kbp have been studied for their ability to use multiple infection and lysis strategies to replicate more efficiently. On the other hand, smaller bacteriophages with fewer genes are represented in the GenBank database in greater numbers, and have several genes with unknown function. Isolation and molecular characterization of a newly reported bacteriophage named Athena1 revealed that it is a strongly lytic bacteriophage with a genome size of 39,826 bp. This prompted us to perform a comparative genomic analysis of Vibrio myoviruses with a genome size of no more than 50 kbp. The results revealed a pattern of genomic organization that includes sets of genes responsible for virion morphogenesis, replication/recombination of DNA, and lysis/lysogeny switching. By studying phylogenetic gene markers, we were able to draw conclusions about evolutionary events that shaped the genomic mosaicism of these phages, pinpointing the importance of a conserved organization of the genomic region encoding the baseplate protein for successful infection of Gram-negative bacteria. In addition, we propose the creation of new genera for dwarf Vibrio myoviruses. Comparative genomics of phages infecting aquatic bacteria could provide information that is useful for combating fish pathogens in aquaculture, using novel strategies.

Clinical Usefulness of BACT Count and BACT-Info Flag of UF-5000 for Screening for Urinary Tract Infection and Prediction of Gram-Negative Bacteria.

A rapid and reliable screening test for urinary tract infection (UTI) is needed to reduce the turn-around time and to rule out negative results of urine culture. The aim of this study was to evaluate the performance of BACT count and BACT-Info flag of the UF-5000 for screening for UTI. A total of 1,063 urine specimens from April to September 2019 were included in this study. We evaluated the diagnostic performance of white blood cell (WBC) count, BACT count, BACT-Info flag, and UTI flag in UF-5000 by comparing with the urine culture results. Of the urine specimens, 16.7% were culture-positive (≥ 105 CFU/mL) with 15 being yeast positive. A BACT count of > 685.3/µL showed the best diagnostic performance with 93.8% sensitivity and 90.2% specificity. We confirmed that the combination of BACT count (685.3/µL) and BACT-Info flag would be appropriate to use in a clinical laboratory (sensitivity 91.5%, specificity 90.5%). Based on this combination, the sensitivity and specificity of the Gram-negative flag were 95.5% and 94.8%. We recommend the use of a combination of BACT count (685.3/µL) and BACT-Info for UTI diagnosis. This combination is more appropriate for Gram-negative bacteria, and it would be useful for selecting empirical treatment.

In vitro activity of cefiderocol against Gram-negative bacterial pathogens in Germany

Widespread antimicrobial resistance in Gram-negative bacteria (GNB), particularly carbapenem resistance, represents a major clinical challenge. Cefiderocol is a novel siderophore cephalosporin active against all carbapenemase classes. We evaluated the in vitro activity of cefiderocol and other antibacterial agents (ceftazidime/avibactam, ceftolozane/tazobactam, colistin and meropenem) against GNB isolates collected in Germany (2013-2018) as part of two multinational studies. Antimicrobial susceptibility testing was performed by broth microdilution. Minimum inhibitory concentrations were interpreted according to EUCAST breakpoints. Cefiderocol had high activity against GNB isolates (N=2298), encompassing both Enterobacterales (n=1562) and non-fermenter species (n=736), and maintained high activity against carbapenem-resistant strains (n=211). The activity of cefiderocol against Enterobacterales was equivalent to that of ceftazidime/avibactam and colistin, while ceftolozane/tazobactam was somewhat less active. Against non-fermenter species, cefiderocol displayed equivalent activity to colistin; both of these agents were more active than ceftazidime/avibactam and ceftolozane/tazobactam. Colistin had similar activity to cefiderocol against the majority of species. These patterns of activity were echoed in carbapenem-resistant isolates. The high activity of cefiderocol was independent of infection site, whereas other antibacterial agents demonstrated slightly lower activity against isolates causing pneumonia compared with those from other key infection sites. Cefiderocol exhibited consistently high in vitro activity against a variety of GNB isolates collected in Germany, including resistant phenotypes, across multiple infection sites. These data suggest that cefiderocol is an effective choice of antibacterial agent in patients with GNB infection, regardless of species and resistance phenotype to other agents.

Cefiderocol: An Overview of Its in-vitro and in-vivo Activity and Underlying Resistant Mechanisms.

Treatment of multidrug-resistant (MDR) Gram-negative bacteria (GNB) infections has led to a global public health challenging due to the bacterial resistance and limited choices of antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin possessed unique drug delivery systems and stability to β-lactamases, has the potential to become first-line therapy for most aggressive MDR Gram-negative pathogens infection. However, there have been reports of drug resistance in the course of using CFDC. This study provides an overview of the in-vitro and in-vivo activity of CFDC and potential resistance mechanism was also summarized. In general, CFDC shows excellent activity against a broad range of MDR GNB pathogens including Enterobacteriaceae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The expressions of metallo-β-lactamases such as inosine 5'-monophosphate (IMP), Verona integron-mediated metallo-β-lactamase (VIM), and New Delhi metallo-β-lactamase (NDM) are associated with a higher resistance rate of CFDC. Carbapenem-resistant phenotype has little effect on the resistance rate, although the acquisition of a particular carbapenemase may affect the susceptibility of the pathogens to CFDC. For potential resistance mechanism, mutations in β-lactamases and TonB-dependent receptors, which assist CFDC entering bacteria, would increase a minimum inhibitory concentration (MIC)90 value of CFDC against MDR pathogens. Since the development of CFDC, resistance during its utilization has been reported thus, prudent clinical applications are still necessary to preserve the activity of CFDC.

1242. Efficacy and Safety of Intravenous Fosfomycin for the Treatment of Multi-resistant Gram Negative Infections

BackgroundTo describe the clinical use, efficacy and safety of intravenous (IV) fosfomycin in the treatment of infections caused by Gram-negative bacteria (GNB). MethodsHospitalized patients who received ≥48 hours of IV fosfomycin therapy during September 27, 2017 thru January 31, 2020 were included. The primary outcome was the proportion of subjects with clinical improvement at the end of IV fosfomycin therapy; defined as resolution of baseline signs and symptoms of infection. ResultsThirty patients were included, of which 19 (63.3%) were males, and the median age was 63.5 years (interquartile range 46─73). Frequent risk factors for GNB infection included hospitalization (23, 76%), receipt of broad-spectrum antibiotics (15, 50%), and surgery (10, 33.3%), all within the preceding 90 days. Urinary tract infection (17, 56.7%) was the most common indication for use of IV fosfomycin, followed by bacteremia (4, 13.3), and skin and soft tissue infections (4, 13.3%). Kelbsiella pneumoniae (17, 56.7%), Escherichia coli (7, 23.3%) and Pseudomonas species (4, 13.3%) were the most common target pathogens. Almost all target pathogens (29, 96.7%) were resistant in vitro to ≥1 agent from ≥3 different antimicrobial classes. The primary outcome was achieved in 22 (73.3%) patients. The most frequently observed adverse events were hypokalemia (13, 43.3%) and hypernatremia (7, 23.3%). However, the majority of adverse events were classified as Grade 1 or Grade 2 severity. Microbiological characteristics The table describes microbiological characteristics of the isolated organism species, resistance pattern, development of fosfomycin resistanceManagement outcomes and safety profile The table describes percentage of primary outcome (clinical success ) along with safety profile and mortality rateConclusionIV fosfomycin is a potentially effective and safe option for the treatment of patient with GNB infections.Disclosures All Authors: No reported disclosures

Effective Strategies to Deal With Infection in Burn Patient.

Treatment of bacterial infection is difficult. Treatment protocol of burned patient is hard. Furthermore, treatment in burned patients is accompanied with problems such as complexity in diagnosis of infection's agent, multiple infections, being painful, and involving with different organelles. There are different infections of Gram-positive and Gram-negative bacteria in burned patients. From important bacteria can be noted to Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus that have high range of morbidity and mortality. Treatment of those bacterial infections is extremely important. Hence, many studies about methods of treatment of bacterial infections have published. Herein, we have suggested practical methods for example ant virulence therapies, nanotechnology, vaccine, and photodynamic therapy in treatment of bacterial infections. Those methods have been done in many researches and had good effect.

Several key points that need to be concerned in the clinical application of ceftazidime/avibactam

Ceftazidime/avibactam is a new enzyme inhibitor combination medication composed of ceftazidime and avibactam. It forms an enzyme-inhibitor complex by covalently binding β-lactamase, which can effectively restore the antibacterial activity of ceftazidime against a variety of carbapenemase-producing enterobacteriaceae strains, covering Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Klebsiella pneumonia (CRKP) and other common drug-resistant gram-negative bacteria infections. The related issues of anti-infective effects of ceftazidime/avibactam on lung infections, abdominal infections, bloodstream infections, urinary tract infections and other different infections were discussed in this article. The clinical safety and indications of ceftazidine/avibatan were referred in the article.

INFECTIOUS ENDOPHTHALMITIS AFTER SCLERAL FIXATION OF AN INTRAOCULAR LENS.

To determine the mechanism of infection, clinical features, and risk factors of endophthalmitis after scleral fixation of an intraocular lens. We included 15 patients with infectious endophthalmitis after scleral fixation of an intraocular lens between April 2004 and December 2017, as well as four patients found through a literature search. Thus, a total of 19 patients were analyzed. Among 19 eyes, infectious endophthalmitis developed at a mean of 23 months (range: 1 day-10 years) after scleral fixation surgery. Nine eyes (47.4%) had early-onset endophthalmitis (≤6 weeks), and 10 eyes (52.6%) had delayed-onset endophthalmitis (>6 weeks). Eleven eyes (57.9%) had presumed microbial influx due to suture exposure. Those with delayed-onset endophthalmitis showed a higher rate of suture-related infection (80.0% vs. 33.3%) and culture of gram-negative bacteria (70.0% vs. 12.5%) than did those with early-onset endophthalmitis. Infectious endophthalmitis can develop late after scleral fixation of an intraocular lens, usually related to the exposed sutures, and the visual prognosis is poor. Eyes that have sutured scleral fixation should be monitored regularly, and preventive measures should be performed if an exposed suture is found.

Efficacy and safety of intravenous fosfomycin for the treatment of difficult-to-treat Gram-negative bacterial infections

We reviewed the efficacy and safety of intravenous (IV) fosfomycin for the treatment of infections caused by Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR). Data were retrospectively retrieved for all hospitalized patients who received IV fosfomycin for ≥48 h for the treatment of a DTR GNB between September 27, 2017 and January 31, 2020. A total of 30 patients were included, of which 63.3% were males, and the median age was 63.5 years (IQR 46–73). The median Charlson Comorbidity Score was 6 (IQR 3.8–9). The urinary tract (56.7%) was the most frequent site of infection, and the most frequent target organisms were Klebsiella pneumoniae (56.7%), and Escherichia coli (23.3%). The majority (76.%) received IV fosfomycin in combination with other antibacterial agents. Clinical improvement was observed in 22 (73.3%), eradication of baseline pathogens in 20 (66.7%), 30-day all-cause mortality in 7 (23.3%), and documented emergent resistance to fosfomycin in 5 (16.7%) patients. Treatment-related adverse events were infrequent and generally mild or moderate in severity. In conclusion, IV fosfomycin is a potentially efficacious and safe treatment option for the treatment of DTR GNB infections. Randomized trials are urgently required to confirm the utility of IV fosfomycin as monotherapy and in combination with other agents.