Negative Bacterial Infections Research Articles

Colistin: A mainstay antibiotic for treatment of fatal Gram negative bacterial infections

Colistin: A mainstay antibiotic for treatment of fatal Gram negative bacterial infections

Rapid Determination of Positive-Negative Bacterial Infection Based on Micro-Hyperspectral Technology.

To meet the demand for rapid bacterial detection in clinical practice, this study proposed a joint determination model based on spectral database matching combined with a deep learning model for the determination of positive-negative bacterial infection in directly smeared urine samples. Based on a dataset of 8124 urine samples, a standard hyperspectral database of common bacteria and impurities was established. This database, combined with an automated single-target extraction, was used to perform spectral matching for single bacterial targets in directly smeared data. To address the multi-scale features and the need for the rapid analysis of directly smeared data, a multi-scale buffered convolutional neural network, MBNet, was introduced, which included three convolutional combination units and four buffer units to extract the spectral features of directly smeared data from different dimensions. The focus was on studying the differences in spectral features between positive and negative bacterial infection, as well as the temporal correlation between positive-negative determination and short-term cultivation. The experimental results demonstrate that the joint determination model achieved an accuracy of 97.29%, a Positive Predictive Value (PPV) of 97.17%, and a Negative Predictive Value (NPV) of 97.60% in the directly smeared urine dataset. This result outperformed the single MBNet model, indicating the effectiveness of the multi-scale buffered architecture for global and large-scale features of directly smeared data, as well as the high sensitivity of spectral database matching for single bacterial targets. The rapid determination solution of the whole process, which combines directly smeared sample preparation, joint determination model, and software analysis integration, can provide a preliminary report of bacterial infection within 10 min, and it is expected to become a powerful supplement to the existing technologies of rapid bacterial detection.

The co-infection of pulmonary hydatid cyst, lophomoniasis and tuberculosis in a patient with resistant respiratory symptoms; a case report study

BackgroundLophomonas blattarum is a rare protozoan that causes opportunistic infections, and the co-infection of lophomonas with tuberculosis and human hydatidosis is a serious public problem in the co-endemic areas of developing countries.Case reportWe presented a 58-year-old female with fever, losing weight, and cough with whitish-yellow sputum that started one month ago. Increasing inflammatory markers and hypereosinophilia in laboratory tests, and a cavity with thick, regular walls and undulating air-fluid levels measuring 43 × 30, evident in the upper segment of the right lower lobe (RLL), along with consolidation and the ground glass opacity of the upper segment and posterior basal of the RLL is apparent in CT scan were reported. Then, a bronchoscopy was requested, and the BAL specimen reported a negative fungal and bacterial infection in the samples. Several live and oval flagellated lophomonas protozoa, hydatid cyst protoscoleces (the larval forms of the parasites), and M. tuberculosis were observed in microscopic evaluation. The patient was treated with metronidazole, oral albendazole, and a combination of TB regimen.ConclusionPhysicians should always consider the possibility of co-infections of lophomonas with tuberculosis and human hydatidosis and investigate patients with risk factors such as immunodeficiency conditions or treated with immunosuppressive medications.

Approach to multidrug resistant infections in pediatric transplant recipients.

There is increasing recognition of infections due to multidrug-resistant Gram negative (MDRGN) bacterial infections among children undergoing solid organ and hematopoietic cell transplantation, which may be associated with morbidity and mortality. We present two vignettes that highlight the clinical challenges of evaluation, management, and prevention of MDRGN bacterial infections in children prior to and after transplantation. The goal of this discussion is to provide a framework to help develop an approach to evaluation and management of these infections. Source control remains the utmost priority in management of MDR infections and is paired with antibiotic selection guided by in vitro susceptibilities, adverse effect profiles, and clinical response. Identification and confirmation of resistance can be challenging and often requires additional testing for recognition of complex mechanisms. Current antimicrobial approaches to MDRGN infections include use of novel agents, prolonged infusion, and/or combination therapy. We also discuss preventative efforts including infection control, antimicrobial stewardship, targeted pre-emptive or prophylactic treatment, and decolonization. The impact of MDRGN infections on patient and graft survival highlights the need to optimize treatment and prevention strategies.

730. Emerging patterns of multidrug resistance Gram negative bacterial infections and its clinical outcome at a tertiary medical center

Abstract Background Antimicrobial resistance (AMR) is a complex threat to global health security and universal health coverage. The continued escalation of AMR among Gram-negative bacteria (GNB) is a major concern due to the endemic presence of MDR and extremely drug-resistant (XDR) pathogens.In this regard, the present study aimed to asses the magnitude of MDR, its risk factors, and mortality in MDR/XDR - GNB. Methods GNB isolates were retrieved from patients, identified and assessed for antibiotic resistance pattern using VITEK® 2 compact system. The extended spectrum β-lactamase (ESBL) production in 100 GNB isolates was determined by double disk synergy test and genes confirmed by PCR in retrospective cohort study (2011-2012). The carbapenemase production in 100 isolates was confirmed by modified carbapenem inactivation method in prospective cross-sectional study (2021-2022). The metallo β-lactamase (MBLs) were screened by combined disk test and carbapenemase genes detected by multiplex-PCR. Minimum inhibitory concentration (MIC) of colistin was determined by Broth Micro dilution method and clonal relatedness was evaluated by Multilocus sequence typing (MLST). Results In retrospective study, all cases confirmed ESBL with high incidence of antibiotic resistance in cephalosporins,chloramphenicol and ciprofloxacin. All isolates were susceptible to carbapenem. bla TEM and bla CTX-M were prevalent ESBL genes, with 7 % mortality. In prospective study, isolates were positive for carbapenemase with XDR pattern and 47% of mortality. 90% isolates were MBLs positive and 30% had at least two carbapenemase genes, the combination of bla OXA-48 and bla NDM-1 was highly prevalent. Colistin resistance was observed in 20% and 30% isolates with 8 and 4 µg/ml MICs, respectively. Further, multiplex-PCR confirmed the mcr genes and clonal relatedness was determined. Conclusion The high prevalence rate of MDR-GNB from producing ESBLs (2011-12) to carbapenemase (2021-2022) was observed. Our results emphasize on antibiotic stewardship policies and regular surveillance programmes for monitoring AMR and screening of drug resistance genes. MLST, molecular surveillance, is valuable tool for rapid epidemiological investigation with precision in determining clonal relatedness Disclosures All Authors: No reported disclosures

2122. In Vitro Activity of Cefepime-Taniborbactam Against Clinically Significant Gram-Negative Bacteria Isolated from Patients with Cancer

Abstract Background Gram negative (GN) bacterial infections are on the rise in patients with cancer (PWC). There is an urgent need for new therapies to address the rise of infections caused by multidrug resistant (MDR) GN pathogens. Taniborbactam is a β-lactamase inhibitor in combination with cefepime may offer a potential treatment option for patients with serious GN bacterial infections. This study aimed to evaluate the in vitro activity of a novel combination of cefepime-taniborbactam and comparators against recent Gram-negative clinical isolates from PWC. Methods Recent GN clinical isolates from PWC were tested against cefepime-taniborbactam and comparators. Clinical and laboratory Standards Institute (CLSI) approved broth microdilution method was used. Appropriate ATCC controls were included. MIC90, and percent of susceptibility calculations were made using FDA breakpoints when available. We tested 100 GN isolates and further testing is ongoing. Results Cefepime-taniborbactam and comparators antibiotics susceptibility percentage (S: %), and MIC90 are shown in the table below. Cefepime-taniborbactam demonstrated highly potent activity against all of tested Enterobacterales including extended spectrum Beta-lactamase (ESBL), and carbapenem-resistant Enterobacterales (CRE) as well as against P. aeruginosa and Stenotrophomonas maltophilia. At a provisional breakpoint of 16/4 mg/L, cefepime-taniborbactam showed highest activity against all tested isolates when compared to cefepime and other comparators, including activity against ESBL, CRE, MDR P. aeruginosa and S. maltophilia. Comparative study between cefepime-taniborbactam and comparators for MIC90 (mg/L.) and Susceptibility (%) results against Gram-negative bacteria isolated from patients with cancer Conclusion Our data demonstrate that cefepime-taniborbactam has promising activity against clinically significant multidrug-resistant (MDR) GN bacterial pathogens isolated from PWC and it showed high activity compared to other commonly used broad spectrum antimicrobial agents. Disclosures Joel Rosenblatt, PhD, Novel Anti-Infective Technologies, LLC: Licensed Technology Issam I. Raad, Distinguished Professor, Novel Anti-Infective Technologies, LLC: Technology License

Evaluation of Antimicrobial Potential of a Gel loaded with Silver Nanoparticles of Argemone mexicana for Topical Application

Argemone mexicana is widely known for its antibacterial potential in the traditional system of medicine. With this background, the present study was designed to formulate a gel incorporated with nanoparticles synthesized from Argemon mexixana for topical application. Green synthesis of nanoparticles was carried out from the whole plant extract and latex of A. mexicana. The biosynthesized nanoparticles were characterized by SEM-EDAX, HR-TEM, SAED, XRD before it was incorporated into the gel. The biosynthesized nanoparticles were found to be stable, uniform, spherical, and ranged from 9.21nm to 14.03nm in size. The SAED pattern reveals the presence of a varying degree of crystallinity of nanoparticles. The physicochemical parameters of the gel such as pH, homogeneity, grittiness, viscosity, spreadability, and extrudability were characterized. Both the formulation showed the nanoparticles are well dispersed in the gel with pH (6.90, 6.92), viscosity (1542 scps, 1583 scps), spreadability (5.7 cm/sec, 5.90.1 cm/sec), and extrudability of 86% and 89% respectively. The gel loaded with nanoparticles exhibited strong antimicrobial potential against Escherichia coli, Bacillus subtilis, Staphylococcus aureus as compared to the crude form of the plant extract and latex. Among the two formulations, the highest zone of inhibition (22mm, 16mm, 13mm) was observed by the gel incorporated with methanol extract nanoparticles. Our result demonstrates the nanoparticulate gel of A. mexicana can be effectively used as topical gel for gram positive and negative bacterial infection.

THE CONTINUING MENACE OF EXTENDED SPECTRUM BETA LACTAMASE (ESBLS) - A CENTRE BASED STUDY

Abstract:
 Objective: To determine the occurrence of Extended-spectrum β-lactamase (ESBL) producing gram negative bacteria (GNB) and their sensitivity patterns in a tertiary care hospital.
 Methods: In this cross-sectional study, conducted in the Microbiology section of Pathology lab, in a tertiary care hospital Lahore, various specimens such as blood, body fluids, urine, and pus were included during a period starting from October 2020 till September 2021. The samples having growth of gram negative bacteria were processed further for determination of ESBL production. After isolation, antimicrobial susceptibility pattern was determined for each isolate.
 Results: GNB were isolated from 130 samples, among those 46 (35.4%) were labelled as ESBL. The commonest ESBL producing bacteria was E. coli, followed by pseudomonas aeruginosa found in 17.39% samples. In E. Coli, Imipenem (IPM) showed highest sensitivity of 84.8%, other sensitive drugs were Amikacin (AK), gentamicin (CN), and Tazobactam-piperacillin(TZP). For Pseudomonas aeruginosa, Imipenem and Tazobactam-piperacillin showed sensitivity of 75%, AK and CN were 50% sensitive. Against Klebsiella pneumoniae , IPM was 100% sensitive, AK and TZP were 85.7% sensitive. IPM, CN, and AK were 100% sensitive against Morganella morganii. AK and CN were 100% sensitive against Citrobacter species.
 Conclusion: It was concluded that, there was significant prevalence of ESBL producing strains amongst Gram negative bacterial infections. E. Coli and Pseudomonas aeruginosa were the commonest ESBL producers. IPM, AK, and TZP were sensitive against majority of the ESBL producing GNB.

Fabrication of a citrus flavonoid hesperetin-capped gold nanoparticles-reduced graphene oxide nanocomposites (Hes-Au/rGONCs) as a potential therapeutic agent for triple negative breast cancer and bacterial infections

Hesperetin (Hes) is a Citrus Flavonoid, which is confirmed to have extensive therapeutic effects, comprising antimicrobial, antioxidant, anticancer, cardiovascular protection, and so forth. To overcome the poor solubility, here we attempt to synthesize the Hes-mediated gold nanoparticles bio-functionalized in reduced Graphene oxide (Hes-Au/rGONCs) to increase the therapeutic efficacy of Hes. The characterization of synthesized Hes-Au/rGONCs were analysed using UV–vis spectrophotometry, FT-IR, Raman spectroscopy, X-ray diffraction analysis (XRD), XPS, HPLC, SEM, EDX and HR-TEM. The absence of vibrations at 1516 and 1381 cm−1 shows the involvement of hydroxyl groups of phenols and enols in anchoring Au on the surface of rGO. In XRD, the planes at (111), (200), (220) and (311) revealed the face centered cubic (fcc) crystalline structure of gold nanoparticles that were functionalized on rGO nanosheets. Hes-Au/rGONCs synthesised produced a highly negative zeta potential of -36.44 mV due to their stability. The Hes-rGO/Au-NPs were analysed for their surface morphology by SEM. The HR-TEM micrographs exhibited uniform distribution and homogenous spherical shaped AuNPs with an average size of 21.37±5.7 nm on rGO sheets. The bio reduction percentage was calculated as 98.86% by using HPLC. The inhibitory concentration (IC50) of free-Hes and nanocomposites were 157.57 and 38.41 µM, respectively. The Hes-Au/rGONCs possess effective bactericidal activity against gram positive bacterial species than against gram negative bacterial strains. The resazurin dye assay confirms the MIC values of Hes-Au/rGONCs. Hereby, the outcome of these studies suggested that the fabricated Hes-Au/rGONCs have potential biomedical applications.

Pluronic F127-chitosan modified magnesium oxide hybrid nanomaterials prepared via a one-pot method: Potential uses in antibacterial and anticancer agents

The utilization of Organic/inorganic hybrid nanomaterials (HNMs) combining chitosan (Cs)-Pluronic F127 (PF) and magnesium oxide (MgCsPF) has considerably augmented the antibacterial, anticancer, and biocompatibility properties, thus playing a pivotal role in the biomedical industry. This study aims to synthesize a MgCsPF HNMs capable of effectively eradicating negative bacterial infections and cervical cancer Hela cells while ensuring no harmful effects on normal fibroblast cells. Various techniques are employed to analyze the biological, physical, and chemical characteristics of the synthesized HNMs. The antibacterial and anticancer properties of the MgCsPF HNMs rely on the generation of active free radicals (ROS), which is influenced by various factors, including particle size, larger surface area, oxygen vacancy, ion release, and diffusion ability. These factors contribute to the enhanced production of ROS, leading to effective antibacterial and anticancer effects of the MgCsPF HNMs. The antibacterial activity of MgCsPF HNMs showed enhanced antibacterial activity compared to MgO when tested against a variety of Gram-negative bacteria. The zone of inhibition is between 11 to 16 mm. Furthermore, the anticancer activity of the synthesized Cs, PF127, MgO, and MgCsPF HNMs is evaluated against cervical cancer HeLa cells. The IC50 values for cell inhibition were 14.2 μg/mL for MgCsPF HNMs, 22.8 μg/mL for Cs, 24.8 μg/mL for PF, and 17.5 μg/mL for MgO. The results demonstrate that MgCsPF HNMs exhibit superior anticancer properties compared to Cs, PF, and MgO samples. Consequently, MgCsPF HNMs show promise for application in the biomedical industry, given their desirable antibacterial and anticancer properties, as well as biocompatibility.

A Rapid Method to Screen for Multi Drug Resistance (MDR) Trait in Clinical Isolates of Acinetobacter baumannii-Acyl Homoserine Lactone (AHL) Screening in CRAB and CSAB Isolates

Aims: Our proposal aimed to evaluate Acyl Homoserine Lactones (AHL) as a functional marker for Multi drug resistant (MDR) potential in clinical isolates of Acinetobacter baumannii. We investigated the AHL production potential of clinical isolates using a biosensor assay directly on a commonly used agar media.
 Place and Duration of Study: Department of Molecular Diagnostics and Biomarkers, Gleneagles Global Hospitals, Lakdikapul, Hyderabad-500004.
 Methodology: Antimicrobial drug sensitivity testing (AST) was performed on 72 clinical isolates of A. baumannii against two front-line antibiotics, Imipenem (10µg) and Meropenem (10µg), by Kirby-Bauer disk diffusion method. Production of long chain Acyl Homoserine lactone (AHLs) in the clinical isolates of A. baumannii was tested by cross streaking with the biosensor Chromobacterium violaceum mutant strain CV026 and Agrobacterium tumefaciens (NTL4pZLR4) by agar plate diffusion assay. Screening and identification of the quorum sensing mediator gene abaI was done by PCR to confirm its presence in all the 72 clinical isolates.
 Results: Out of the 72 clinical isolates, 58 were Carbapenem resistant Acinetobacter baumannii (CRAB) and 14 were Carbapenem sensitive Acinetobacter baumannii (CSAB) for AST by agar disc diffusion method. None of our isolates produced short chain AHLs whereas all the isolates could produce varying amounts of long chain AHLs. Genotypic confirmation of AHL gene was obtained by abaI gene PCR.
 Conclusion: Carbapenems are the front-line antibiotics used to treat gram negative bacterial infections in emergencies and in the critical care units of hospitals. Clinical isolates A. baumannii has innate resistance to several antibiotics due to various mechanisms, biofilms forming the first line of defense against antibiotics for the bacterium. Our study used AST to carbapenem as the leading marker for MDR, assuming the innate resistance of A. baumannii to other beta lactam antibiotics. Our study brought out certain important observations namely: a) All clinical isolates of A. baumannii produced Quorum Sensing signal molecules, the AHLs b) the clinical isolates of A. baumannii did not produce any short chain AHLs b) All the clinical isolates of A. baumannii produced long chain AHLs c) AHL production is not specific to carbapenem drug resistance because even CSAB isolates produced AHL d) AHL production is inherent to all clinical isolates of A. baumannii and it apparently indicates an underlying biofilm potential and MDR trait in these A. baumannii isolates. e) AHLs could be a universal marker for revealing MDR trait and biofilm potential in clinical microbiology AST profiling protocols.

PATHOGENIC BACTERIAL ISOLATES FROM DIABETIC FOOT INFECTIONS PATIENTS AND THEIR SUSCEPTIBILITY TO ANTIBIOTICS IN SELECTED PUBLIC HOSPITALS, SANA’A, YEMEN

Sickle cell disease (SCD) is a group of blood genetic disorders resulting in an abnormality in the Diabetic foot infections remain a major public health problem and cause socioeconomic burdens to affected people. Clinically infected foot ulcers require treatment guided by appropriate cultures and antimicrobial susceptibility testing. This study aimed to assess the bacterial profile and antimicrobial susceptibility pattern of isolates from diabetic foot infections in selected public hospitals, Sana'a, Yemen. A cross-sectional study was conducted from June 2021 to July 2022 at Al-Gomhori teaching hospital, Kuwait teaching hospital, and AlThawrah public hospital in Sana'a, the capital city of Yemen. The study included 135 adult patients with infected diabetic foot ulcers. Convenient sampling was employed. Wound aspirates from the foot ulcers were collected aseptically and inoculated into Blood, MacConkey, Chocolate and Mannitol salt Agar. The antimicrobial susceptibility patterns were conducted by disk diffusion method. The data was analyzed with SPSS v.20 for windows. The results revealed that; One hundred ninety bacterial isolates were identified among 135 patients. Among them, 62.96% had mono-bacterial infection while 37.04% had mixed bacterial infections. Gram negative aerobic bacterial infections were more accounting cases 63.7% than, Gram positive aerobic bacteria 36.3%. The most commonly isolated bacteria were S. aureus 26.3%, followed by Klebsiella spp 22.1% and Proteus spp 11.1%. In general, 73.68% of the isolates developed multidrug resistance to at least one drug in three different classes of antibiotics. Meropinem and amikacin appeared to be the best antibiotics for therapy against Gram negative and cefoxitin and vancomycin against Gram positive organisms.

1728. Real world experience with cefiderocol for multi drug resistant gram negative bacterial infection in a tertiary hospital

Abstract Background Increasing rates of antibiotic resistance has emerged as one of the top concerns in health care. New resistance mechanisms such as carbapenemase production present a challenge in treating common infections. Novel antibiotics are being developed to tackle these pathogens, and one of the newest drugs in this arsenal is cefiderocol, a siderophore cephalosporin. Real-world data regarding the clinical use and outcomes of cefiderocol is limited. Methods A single-center, retrospective chart review was completed from July 2020 to March 2022 and included adult patients who received at least one dose of cefiderocol. Patient baseline characteristics were obtained along with other variables related to the primary infection. The primary outcome was clinical failure defined as 30 day mortality following cefiderocol administration. Secondary outcomes were development of resistance to cefiderocol, clearance of bacteremia, adverse drug reactions, and hospital length of stay. Results Cefiderocol was dispensed in 22 unique patient encounters. It was most often used to treat respiratory tract (45.4%, 10/22) and cardiac device infections (40.9%, 9/22). Most infections were polymicrobial, however, the most common organisms isolated were Pseudomonas aeruginosa and Klebsiella pneumoniae. The clinical failure rate was 22.7% (5/22). One patient developed resistance to cefiderocol throughout the hospitalization. Eight patients were treated for bacteremia, and 87.5% (7/8) demonstrated microbiological cure. Minimal side effects were observed in this cohort; two patients developed diarrhea, and one of whom had confirmed C. difficile colitis. The median length of stay was 24 days. Conclusion This cohort of patients demonstrated that cefiderocol can be used in a variety of multidrug resistant infections including bacteremia. Although limited by a small sample size, this study demonstrated a low prevalence of resistance. These results are promising in the ongoing and emerging issue of antibiotic resistance, and larger studies are needed to determine true efficacy and place in therapy for cefiderocol. Disclosures All Authors: No reported disclosures.

Molecular Docking Study, Drug-Likeness and Pharmacokinetic Properties (ADMET) Prediction of Some Novel Thiophene Derivatives as Salmonella typhi Inhibitors

Typhoid fever is a gram- negative bacterial infection caused by the bacterium called Salmonella Typhi, a rod-like shaped pathogen. Salmonella typhi is both food-born and water-born pathogen. This disease is affecting people in both developed and underdeveloped countries. In this research, geometry optimization was carried out using density functional theory (DFT) at B3LYP/6-31G* level of theory in finding the most stable structures of all the studied molecules. Molecular docking studies was carried out on novel thiophene derivatives (anti-typhoid agents) against S. Typhi target (DNA gyrase B) with the pdb ID: 1TM2 to virtually screened the studied molecules. The drug-likeness and pharmacokinetic properties of the investigated molecules were also evaluated using SWISSADME and pkCSM online web tools, respectively. The molecular docking virtual screening carried out on the anti-typhoid agents has explored their theoretical binding affinities (which ranges between -7.1 to 7.8 kcal/mol) and poses with the active sites of the S. Typhi target (DNA gyrase B). Compound A11 with the highest binding affinity of -7.8 Kcal/mol interacted with the following amino acid residues LYS35, THR247, ASP166, VAL164, TRP170, ALA222, PHE41, TR266, ASP116 and PHE41 in the active site of the receptor via conventional hydrogen bond, carbon hydrogen bond, hydrophobic and electrostatic interactions, respectively. The drug-likeness of the studied compounds showed good response to the Lipinski’s rule of five filtering criterion by not violating more than one of the filtering criterion thereby confirming their drug-likeness properties and oral bioavailability, respectively. Their ADMET properties showed that they were all absorbed in the intestinal at a rate above 80% and well distributed in the brain and the central nervous system. They were all found to be both substrate and inhibitors of 3A4 which indicated their metabolic properties. And based on their predicted total clearance values, they can be excreted out. All the reported compounds had a negative AMES toxicity which mean they were all non-toxic. With reference been made to an approved already existing anti-typhoid agent ciprofloxacin with a binding affinity of -7.3 Kcal/mol to the investigated molecules (most especially compound A11), All the reported molecules have higher binding affinities than the ciprofloxacin, having good pharmacokinetic properties therefore proves the tendency of their effectiveness when been administered as drug.

LEMIERRE'S SYNDROME: THE FORGOTTEN DISEASE

TYPE: Case Report TOPIC: Chest Infections INTRODUCTION: Septic thrombophlebitis of the internal jugular vein (IJV) is a rare complication of anaerobic oropharyngeal infection. We present a case of Lemierre’s syndrome which was managed without systemic anticoagulation therapy. CASE PRESENTATION: A 63 year old female presented to the hospital with left jaw pain for one week. The admission labs were pertinent for leukocytosis, lactic acidosis, acute kidney injury and thrombocytopenia. Oral physical exam was significant for submandibular tenderness, ulcerative pharyngitis and tonsillitis. She was initiated on broad spectrum antibiotics. A venous ultrasound of the left upper extremity revealed an acute deep vein thrombosis in her left IJV and an acute superficial venous thrombosis in the right cephalic vein. The blood culture later grew an anaerobic gram negative bacteremia, identified to be part of the Fusobacterium species. The patient was managed on IV Unasyn for two weeks; she improved and her abnormal labs resolved. She was discharged with Amoxicillin for two weeks. DISCUSSION: The typical clinical picture of Lemierre’s syndrome is an acute oropharyngeal infection, anaerobic gram negative bacterial infection and an acute thrombosis of the internal jugular vein. Antibiotics are currently the primary treatment of this condition. Despite thrombosis of IJV, treatment with anticoagulation therapy remains unclear. CONCLUSIONS: We wish to highlight the importance of recognising Lemierre’s syndrome due to its increasing resurgence and high mortality rate (25%) if not treated adequately with antibiotics. This case also emphasises septic thrombophlebitis in the hospital setting and the need for further controlled studies to establish the role of anticoagulation therapy. DISCLOSURE: Nothing to declare. KEYWORD: lemierre's syndrome

Colistin A Last Resort Antibiotic

Colistin is an antibiotic of last resort, works as a last line of defense against illness caused by the multiple drug resistant (MDR) gram negative bacteria. Polimixins consist of aqua phobic acyl tail, linear tripeptide part, and heptapeptide ring. Chemical formula of colistin is C52H98N16O13. Colistin is given in two forms, colistin methane sulfonate (CMS) and colistin sulfate.
 Findings: Colistin disturbs or destroys the outer membrane of bacteria, or stops the respiratory enzymes of the inner membrane of bacteria. Colistin also works as an antiendotoxin. Colistin has great bactericidal activity against gram negative rods. Colistin resistance is a serious concern of present time. High rate of the spread of MDR gram negative bacterial infections is leading to high use of colistin for treatment, due to which prevalence of colistin resistance is increasing worldwide. As bacterial outer membrane is the main target of colistin, resistance against it develop by modification of outer membrane LPS. There are several mechanisms of colistin resistance. Intrinsic mechanism involves expression of arnBCADTEF operon and eptB gene. Acquired non-transferable resistance involves pmrAB, PhoPQ, and CrrAB two component systems (TCSs), mgrB gene and ramA. Transferable resistance is more serious concern as it can be spread in population by horizontal gene transfer. Mcr genes are responsible for transferable or plasmid-mediated colistin resistance.
 Conclusion: This review focuses on the chemistry of colistin, mechanism of action, spectrum of action, colistin resistance and different mechanisms behind it.

Febrile neutropenia management and outcomes in hematopoietic cell transplantation for chronic granulomatous disease.

We analyzed events and therapies related to febrile neutropenia in patients receiving hematopoietic cell transplantation (HCT) for chronic granulomatous disease (CGD). Three protocols for HCT were used to extract the relation between conditioning and infectious complications during transplantation for CGD, especially the relation of fever and neutropenia to microbiological events and antibiotic therapy. Sixty-nine recipients received either reduced intensity conditioning with matched related or unrelated donors or conditioning specific to haploidentical-related donors utilizing posttransplant cyclophosphamide. Fever prior to neutropenia was common (52) and in eight recipients, Gram negative bacterial infection occurred prior to neutropenia, and in nine during neutropenia. Alemtuzumab as conditioning was associated with preneutropenic infection. Empiric therapy (noncarbapenem) by institutional guideline was given in 40. Carbapenems were given before neutropenia (8) or as empiric therapy in neutropenia (18), or a switch to a carbapenem (n=22) occurred in 48 cases. No deaths related to infection associated with neutropenia occurred. The management of febrile neutropenia in HCT for CGD led to no deaths related to infection associated with neutropenia. Bacteremias occurred both prior to neutropenia and during neutropenia. Bacteria isolated may have represented the recrudescence of prior infection, representing the population transplanted and the platform for HCT. The treatment of prior infections may have had an influence on the necessity of carbapenem use as either empiric or directed therapy for bacterial infections.

Population pharmacokinetics of polymyxin B: a systematic review.

BackgroundPolymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by Bacillus polymyxa, and is one of the last options for treating multi-drug-resistant negative bacterial infections in clinical practice. In recent years, many population pharmacokinetic studies of PMB have been conducted. This paper sought to comprehensively summarize the characteristics of population pharmacokinetic models of PMB and provide a theoretical basis for the individualized use of PMB.MethodsIn this review, we systematically searched the PubMed and Embase databases to find articles on population pharmacokinetic models published from database establishment to August 2021.ResultsA total of 10 studies were included in this review, including studies on various types of severe infections caused by multi-drug-resistant bacteria, hospital-acquired infections with fibrosis and other male and female populations, and a study of 2 continuous renal replacement therapy (CRRT) patients, aged 16–94 years, who received PMB doses of 10–360 mg/day (0.13–3.45 mg/kg/day), at an administration time of 0.5–6 hours. First-order linear elimination was used in all the studies; a 1-compartment model was used in 5 studies, and a 2-compartment model was used in 5 studies. The most common covariates were creatinine clearance (CrCL) and body weight.DiscussionAlthough these studies included several covariates and total clearance (CL) was close, but the external validation of some models was poorly correlated between the actual and predicted value. Novel or potential covariates represent important directions for further study.

Evaluation of ceftazidime-avibactam efficacy in gram negative bacteria

In recent years, the emergence of multidrug-resistant Enterobacterales and Pseudomonas aeruginosa strains has become a serious problem due to high morbidity/mortality rates and difficulty in treatment.Treatment options are very limited in infections caused by carbapenem-resistant microorganisms.Ceftazidime/avibactam (CZA) is a newly developed cephalosporin/beta-lactamase inhibitor combination for the treatment of infections caused by resistant Gram negative microorganisms.In this study, the in vitro activity of CZAagainst various carbapenem resistant Gram negative microorganisms was evaluated.122 carbapenem-resistant Gram negative bacteria species were included in the study. Identification of the strains and their antimicrobial susceptibility were performed using conventional methods as well as a BD Phoenix (BectonDickinson, MD, USA) fully automated system. Ceftazidime-avibactam susceptibility was determined using the disk diffusion method (Bioanalyse, Ankara, Turkey) and the gradient diffusion test (Liofilchem MIC strip test, Italy).In carbapenem-resistant K. pneumoniae strains, gentamicin/amikacin susceptibility was found in 14 strains (14.3%) and ceftolozane-tazobactam susceptibility was found in only one strain. In P. aeruginosa strains, gentamicin/amikacin susceptibility was seen in 8 strains (33.3%) and piperacillin tazobactam susceptibility was found in 7 strains (29.2%), and other than these all strains were found to be resistant to all the other antibiotics studied. CZA susceptibility rates in carbapenem resistant K. pneumoniae and P. aeruginosa strains were found to be 85.7% and 83.3%, respectively.ESBL production and carbapenemase activity were positive in the strains included in the study.The results obtained from this study show that CZA can be a treatment alternative in carbapenem-resistant Gram negative bacterial infections. More studies are needed in order to monitor the resistance status of these new treatment options against the increasing resistance threat in hospitals and to determine the appropriate treatment option.

POSA238 Hospital Length of Stay and Antibiotic Prescription Practices for Patients Diagnosed with Gram Negative Infections - Evidence from Hospitals in Romania

ECDC indicates that Romania is among the member states with the highest levels of antimicrobial resistance (AMR) in Europe. However, there is no National Antimicrobial Stewardship Program (ASP) implemented to facilitate national guidelines on antibiotic prescription. Furthermore, studies using local hospital data monitoring cases with bacterial infections are scarce. The aim of this study is to estimate the inpatient average length of stay (ALoS) and observe the prescription practices when treating gram negative bacterial infections in public hospitals in Romania.