Susceptibility Of Gram-negative Bacteria Research Articles

In Vitro Assessment of Antimicrobial Activity of Novel Fluoroquinolone, Levonadifloxacin (WCK 771) Against Multi-Drug-Resistant Clinical Isolates from Cancer Patients in India.

Introduction: Rapid increase in antimicrobial-resistance is leading to urgent need for newer broad-spectrum antimicrobials. Therefore, we have evaluated the antimicrobial résistance spectrum of India-discovered novel antibiotics (levonadifloxacin) against clinical isolates recovered from cancer patients. Materials and Methods: The study was conducted in the microbiology department, over a period of 1 year between May 2021 and June 2022 and 374 consecutive and nonduplicate Gram-positive (GPC) and MDR Gram Negative Bacteria (GNB) isolate were analyzed from 3,880 cancer patients in study. The identification and antimicrobial sensitivities of bacterial isolates were performed according to standard laboratory protocols by using automated identification system (VITEK-2-8.01; BioMérieux, Germany). The activity of levonadifloxacin and comparator antibiotics was evaluated using disk diffusion methods as per Clinical and Laboratory Standards Institute 2022 guidelines. Results: The mean age of the patients were 51.6 ± 14.59 years with male: female ratio of 1.2:1. The prevalence of GPC was 167 (44.65%) and MDR-GNB was 207 (55.34%). The most common GPC was Staphylococcus aureus; 97 (58.08%) followed by Enterococcus species 66 (39.52%). In GNB, Escherichia coli; 93 (44.92%) was the most common followed by Klebsiella pneumoniae; 45 (21.73%). Levonadifloxacin susceptibility was present in 98.7% methicillin-resistant S. aureus and 96% methicillin-susceptible S. aureus and 77.1% Enterococcus-species. Additionally, all the fluoroquinolones-resistant S. aureus isolates were susceptible to levonadifloxacin (WCK-771) except one isolate. Also, levonadifloxacin-(WCK-771) exhibits 100% susceptibility fluoroquinolone susceptible GNB, such as E. coli, K. pneumoniae, Pseudomonas species, and Acinetobacter species. Interestingly, all fluoroquinolones-resistant Salmonella species and Stenotrophomonas maltophilla exhibited 100% susceptibility to levonadifloxacin (WCK-771). Conclusion: Levonadifloxacin (WCK-771) possesses potent activity against all the MDR Gram-positive pathogens including the coverage of susceptible Enterobacterales and MDR S. maltophilla and Burkholderia cepacia suggesting its potential utility in the management of polymicrobial infections.

Phytochemical profile, assessment of antimicrobial and antioxidant properties of essential oils of Artemisia herba-alba Asso., and Artemisia dracunculus L.: Experimental and computational approaches

Artemisia herba alba and Artemisia dracunculus are widely used in folk medicine by many ethnic groups to relieve and treat various ailments, including diabetes, cancer, and infectious diseases. The current investigation aims to determine the phytochemical profile, antibacterial, anticandidal and antioxidant activities of Moroccan A. herba alba and A. dracunculus essential oils (EOs). Antioxidant activity was carried out using four complementary assays, namely ABTS and DPPH radical scavenging techniques, ferric-reducing power (FRAP) and lipid peroxidation tests. The antimicrobial potential of A. herba-alba and A. dracunculus EOs was examined against a variety of Gram-positive and Gram-negative bacteria, and yeasts, namely Staphylococcus aureus, Bacillus cereus Micrococcus luteus, Escherichia coli, Klebsiella aerogenes, Candida albicans and Candida tropicalis. The results demonstrated that the A. herba-alba and A. dracunculus EOs exhibited remarkable inhibitory effects against all tested microorganisms using disk-diffusion method and were competitor to the examined antibiotics, demonstrating a maximum inhibition diameter of the Gram-positive bacteria. The most susceptible was B. cereus (31.33 ± 4.04 mm), and the most susceptible Gram-negative bacteria was K. aerogenes (19.79 ± 1.53 mm), and C. tropicalis was the most susceptible Candida spp. to A. herba alba EOs (27.00 ± 0.66 mm). The MIC, MBC, and MFC values indicate that these EOs were highly effective at minimal concentrations. However, toxicological assessment, pharmacodynamics and pharmacokinetic investigations are necessary to confirm the safety and the beneficial effects of these oils in human healthcare and industrial applications as potential sources of natural antioxidants and preservative agents.

Implications of reducing antibiotic treatment duration for antimicrobial resistance in hospital settings: A modelling study and meta-analysis.

Reducing antibiotic treatment duration is a key component of hospital antibiotic stewardship interventions. However, its effectiveness in reducing antimicrobial resistance is uncertain and a clear theoretical rationale for the approach is lacking. In this study, we sought to gain a mechanistic understanding of the relation between antibiotic treatment duration and the prevalence of colonisation with antibiotic-resistant bacteria in hospitalised patients. We constructed 3 stochastic mechanistic models that considered both between- and within-host dynamics of susceptible and resistant gram-negative bacteria, to identify circumstances under which shortening antibiotic duration would lead to reduced resistance carriage. In addition, we performed a meta-analysis of antibiotic treatment duration trials, which monitored resistant gram-negative bacteria carriage as an outcome. We searched MEDLINE and EMBASE for randomised controlled trials published from 1 January 2000 to 4 October 2022, which allocated participants to varying durations of systemic antibiotic treatments. Quality assessment was performed using the Cochrane risk-of-bias tool for randomised trials. The meta-analysis was performed using logistic regression. Duration of antibiotic treatment and time from administration of antibiotics to surveillance culture were included as independent variables. Both the mathematical modelling and meta-analysis suggested modest reductions in resistance carriage could be achieved by reducing antibiotic treatment duration. The models showed that shortening duration is most effective at reducing resistance carriage in high compared to low transmission settings. For treated individuals, shortening duration is most effective when resistant bacteria grow rapidly under antibiotic selection pressure and decline rapidly when stopping treatment. Importantly, under circumstances whereby administered antibiotics can suppress colonising bacteria, shortening antibiotic treatment may increase the carriage of a particular resistance phenotype. We identified 206 randomised trials, which investigated antibiotic duration. Of these, 5 reported resistant gram-negative bacteria carriage as an outcome and were included in the meta-analysis. The meta-analysis determined that a single additional antibiotic treatment day is associated with a 7% absolute increase in risk of resistance carriage (80% credible interval 3% to 11%). Interpretation of these estimates is limited by the low number of antibiotic duration trials that monitored carriage of resistant gram-negative bacteria, as an outcome, contributing to a large credible interval. In this study, we found both theoretical and empirical evidence that reducing antibiotic treatment duration can reduce resistance carriage, though the mechanistic models also highlighted circumstances under which reducing treatment duration can, perversely, increase resistance. Future antibiotic duration trials should monitor antibiotic-resistant bacteria colonisation as an outcome to better inform antibiotic stewardship policies.

Prevalence and determinants of antimicrobial resistance of pathogens isolated from cancer patients in an intensive care unit in Alexandria, Egypt

BackgroundInfections caused by multidrug-resistant organisms (MDROs) are a globally increasing threat among critically ill patients, especially those with underlying malignancies. We aimed to assess the prevalence and susceptibility patterns of MDROs among cancer patients in intensive care units (ICU), and their predictors.MethodsOver 4 years, we retrospectively reviewed medical records of 497 malignancy patients in the ICU of a tertiary hospital in Alexandria, Egypt. The data for various factors, such as demographic characteristics, comorbidities, causative pathogen, and antimicrobial resistance (AMR), were collected and analyzed using univariate analysis. Logistic multivariate regression analysis was used to estimate the probability of developing MDROs among this population.ResultsA total of 748 isolates were obtained from 1249 specimens. Gram-negative bacteria detected (459) comprised 61.4% of all isolates, while only 75 (10%) were gram-positive, and 214 (28.6%) were fungal pathogens. The most frequently encountered isolate was Klebsiella pneumoniae (n = 183), of which 107 were carbapenem-resistant (CR) and 62 were extended-spectrum beta-lactamase (ESBL)-producing. This was followed by Escherichia coli (n = 136), of which 17 were CR and 100 were ESBL-producing strains, while 3 were resistant to quinolones. Acinetobacter baumannii came in third (n = 67), with 63 being CR. The overall susceptibility of gram-negative bacteria was recorded as highest to colistin (97.3%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcal species among gram-positive bacteria were 54.6% and 33.3%, respectively, with no resistance reported to vancomycin or linezolid. Among the MDRO infection predictors were neutropenia, recent antibiotics use, and receiving chemotherapy. Neutropenia had the highest odds ratio (OR: 2.3, CI: 1.28–4.09), followed by recent antibiotics use (OR: 1.8, CI: 1.22–2.59).ConclusionGram-negative bacilli were the most frequently reported MDROs, with resistance to higher generation cephalosporins and even carbapenems limiting antibiotic treatment options to older class antibiotics, such as colistin, with potential side effects, including nephrotoxicity. Estimating AMR probability using the prediction model of risk factors, such as neutropenia and previous antibiotics use, may be functional in the rapid identification of higher-risk patients.

Synthesis, chemical characterization, and antimicrobial potency of picolinate-based half-sandwich Ru(II) complexes

Eleven new and three reported half-sandwich Ru(II) arene complexes were synthesized using [Ru(η6-benzene)Cl(μ-Cl)]2 and [Ru(η6-toluene)Cl(μ-Cl)]2 and four pyridine carboxylic acid-based ligands (dicarboxylic acids and halogen derivatives). The structures and purity of synthesized compounds were confirmed using 1H and 13C NMR spectroscopy, infrared spectroscopy, mass spectrometry, and elemental analysis. The stability of synthesized compounds in dimethyl sulfoxide solution was confirmed using 1H NMR spectroscopy. The seven ligands, two complex precursors (CP1 and CP2), and 14 half-sandwich Ru(II) picolinate complexes (C1–C14) were evaluated for in vitro antibacterial and antifungal activity against pathogens, such as Staphylococcus aureus, Bacillus cereus, Proteus mirabilis, Klebsiella pneumoniae, Ecsherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Enterobacter aerogenes, and yeast Candida albicans, using the microwell-dilution method. Among the tested samples, the ligands showed better inhibitory effect against Gram-positive bacteria when compared to the metal complexes. The most susceptible Gram-negative bacteria was Ecsherichia coli, with a MIC value of 1.25 mg/mL, for C3, C6, and C10. All synthesized complexes showed similar, slightly better activity against Candida albicans.

Species Distribution of Bacteria Isolated From Blood Cultures and Antibiotic Susceptibilities of Gram Negative Bacteria in Prof. Dr. Süleyman Yalçın City Hospital Between 2018-2021

Species Distribution of Bacteria Isolated From Blood Cultures and Antibiotic Susceptibilities of Gram Negative Bacteria in Prof. Dr. Süleyman Yalçın City Hospital Between 2018-2021

Eradication of Resistant and Susceptible Aerobic Gram-Negative Bacteria From the Digestive Tract in Critically Ill Patients; an Observational Cohort Study.

BackgroundSelective Decontamination of the Digestive tract (SDD) aims to prevent nosocomial infections, by eradication of potentially pathogenic micro-organisms from the digestive tract.ObjectivesTo estimate the rate of and the time to eradication of resistant vs. susceptible facultative aerobic gram-negative bacteria (AGNB) in patients treated with SDD.MethodsThis observational and retrospective study included patients admitted to the ICU between January 2001 and August 2017. Patients were included when treated with SDD (tobramycin, polymyxin B, and amphotericin B) and colonized in the upper or lower gastro-intestinal (GI) tract with at least one AGNB present on admission. Decontamination was determined after the first negative set of cultures (rectal and throat). An additional analysis was performed of two consecutive negative cultures.ResultsOf the 281 susceptible AGNB in the throat and 1,087 in the rectum on admission, 97.9 and 93.7%, respectively, of these microorganisms were successfully eradicated. In the upper GI-tract no differences in eradication rates were found between susceptible and resistant microorganisms. However, the median duration until eradication was significantly longer for aminoglycosides resistant vs. susceptible microorganisms (5 vs. 4 days, p < 0.01). In the lower GI-tract, differences in eradication rates between susceptible and resistant microorganisms were found for cephalosporins (90.0 vs. 95.6%), aminoglycosides (84.4 vs. 95.5%) and ciprofloxacin (90.0 vs. 95.2%). Differences in median duration until eradication between susceptible and resistant microorganisms were found for aminoglycosides and ciprofloxacin (both 5 days vs. 6 days, p = 0.001). Decontamination defined as two negative cultures was achieved in a lower rate (77–98% for the upper GI tract and 64–77% for the lower GI tract) and a median of 1 day later.ConclusionThe vast majority of both susceptible and resistant microorganisms are effectively eradicated from the upper and lower GI tract. In the lower GI tract decontamination rates of susceptible microorganisms are significantly higher and achieved in a shorter time period compared to resistant strains.

Intra Ventricular Colistin in Neonatal Brain Abscess Management: A Case of Multiple Brain Abscesses

Neonatal Brain abscess is a rare sever neonatal infection requiring careful medical and neurosurgical intervention strategies to reduce morbidity and mortality rates. Gram-negative bacterial agents are the most common pathogens involved in brain abscesses of neonates. The use of wide spectrum antibiotics in combination with neurosurgical drainage of abscesses larger than 2.5 cm is the mainstay of treatment. Colistin is a polymyxin antibiotic used to treat bacterial infections caused by susceptible gram-negative bacteria but with a limited penetration in blood brain barrier. However, there is limited data on using intraventricular Colistin in neonatal intracranial infections. A 12-day-old male neonate with multiple brain abscesses in frontal and parietal lobes is presented. The abscesses were successfully managed with a combination of intravenous antimicrobial agents, intraventricular Colistin and concurrent administration of Interferon-ɣ. Subsequently, he developed ventriculomegaly which was successfully managed by endoscopic third ventriculostomy. He had an acceptable neurologic outcome. Due to reduced penetration of colistin in blood brain barrier, use of intraventricular Colistin in combination with its intravenous form can be beneficial in management of neonatal brain abscesses. Concurrent administration of Interferon-ɣ may improve the treatment process and outcome given that reduced secretion of this agent by neonatal T lymphocytes may contribute to a partial immunodeficiency state at this period of life.

Proton motive force underpins respiration-mediated potentiation of aminoglycoside lethality in pathogenic Escherichia coli

It is well known that loss of aerobic respiration in Gram-negative bacteria can diminish the efficacy of a variety of bactericidal antibiotics, which has lead to subsequent demonstrations that the formation of reactive oxygen species (ROS) and the proton motive force (PMF) can both play a role in antibiotic toxicity. The susceptibility of Gram-negative bacteria to aminoglycoside antibiotics, particularly gentamicin, has previously been linked to both the production of ROS and the rate of antibiotic uptake that is mediated by the PMF, although the relative contributions of ROS and PMF to aminoglycoside toxicity has remained poorly understood. Herein, gentamicin was shown to elicit a very modest increase in ROS levels in an aerobically grown Escherichia coli clinical isolate. The well-characterised uncoupler 2,4-dinitrophenol (DNP) was used to disrupt the PMF, which resulted in a significant decrease in gentamicin lethality towards E. coli. DNP did not significantly alter respiratory oxygen consumption, supporting the hypothesis that this uncoupler does not increase ROS production via elevated respiratory oxidase activity. These observations support the hypothesis that maintenance of PMF rather than induction of ROS production underpins the mechanism for how the respiratory chain potentiates the toxicity of aminoglycosides. This was further supported by the demonstration that the uncoupler DNP elicits a dramatic decrease in gentamicin lethality under anaerobic conditions. Together, these data strongly suggest that maintenance of the PMF is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycosides.

Design SMAP29-LysPA26 as a Highly Efficient Artilysin against Pseudomonas aeruginosa with Bactericidal and Antibiofilm Activity.

ABSTRACTAntimicrobial resistance (AMR) is a major issue to global health. The multidrug-resistant (MDR) Gram-negative infections, particularly infected by carbapenem-resistant pathogens, urgently need efficient antibiotics and novel therapy. However, the scientific challenges of aiming for innovative approaches against Gram-negative bacteria have hindered the research and development of antibiotic drugs. Phage-derived endolysins are bacteriolytic and specific for a bacterial species or genus, providing a promising antibiotic strategy. However, the outer membrane of Gram-negative bacteria could prevent the peptidoglycan layer from the hydrolysis of endolysins. Antimicrobial peptides usually destabilize the outer membrane and could enhance the antibiotic activity of endolysins. In this study, we designed new artilysins with antimicrobial-peptide SMAP29 fusion at the N-terminal of LysPA26 (named as AL-3AA, AL-9AA, and AL-15AA), and evaluated them. The results showed artilysin AL-3AA to be highly bactericidal; even 0.05 mg/mL AL-3AA could reduce 5.81 log units P. aeruginosa without EDTA in 60 min. It killed P. aeruginosa rapidly and dose-dependently through cell lysis. AL-3AA inhibited P. aeruginosa PAO1 biofilm formation and significantly decreased mature P. aeruginosa biofilms. It also had potential broad-spectrum activity against susceptible Gram-negative bacteria in the hospital, including K. pneumoniae and E. coli. The antibacterial mechanism investigation has provided valuable information about the antibacterial action of AL-3AA, which can lyse and disintegrate the bacterial quickly. These results suggested AL-3AA could be a new and promising antimicrobial agent for the combat of P. aeruginosa.IMPORTANCE Antimicrobial resistance (AMR) is a major issue to global health, particularly the multidrug-resistant (MDR) Gram-negative infections, which pose great challenges. Even new antibiotics research is ongoing, antibiotics used to treat Gram-negative bacteria in the clinical are limited in a small set of molecular scaffolds, and biomolecular categories of antibiotics are urgently needed. In this study, we designed new proteins by combining antimicrobial peptides and endolysins for synergistic bactericidal effects. One of designed proteins, named AL-3AA, showed highly bactericidal, and killed P. aeruginosa rapidly and dose-dependently through cell lysis. It also killed Klebsiella pneumoniae and Escherichia coli, showing potential broad-spectrum activity against susceptible Gram-negative bacteria in the hospital. All results suggest AL-3AA could be a new and promising antimicrobial agent for the combat of P. aeruginosa.

Rapid Identification and Antimicrobial Susceptibility of Gram Negative Bacteria Detected in Positive Blood Culture Bottles

Abstract Background Blood stream infection (BSI) is one of the most serious situations in infectious disease .Accurate and timely identification of the causative agent and determination of its antimicrobial susceptibility profile are essential for guiding targeted and effective antimicrobial treatment. Current methods involve culturing of blood in a liquid medium and subsequently subculturing of signal positive bottles on solid media in order to obtain isolated colonies that can be further used in identification and susceptibility testing of the isolates. The standard method requires additional 48-72hours following the appearance of a positive signal in order to provide a reliable patient report. On the other hand, rapid identification of the causative agent and determination of its susceptibility profile by direct inoculation of the biochemical test media with the blood-broth mixtures from signal positive bottles and performing primary susceptibility testing might help reducing the time needed for provision of results compared to the standard isolated-colony based method and hence would help the rapid initiation of effective and targeted antimicrobial therapy and reduce the bacteremia-related morbidity and mortality. Objective The aim of the present study was to determine the accuracy and precision of the non-standard methods (direct identification and susceptibility testing using the blood/broth mixture) by comparing its results to those of the standard isolate-based identification and susceptibility testing methods. Material and method The study included 52 signal blood culture bottles yielding gram negative isolates. Bottles were selected amongst blood culture bottles submitted to the Main Microbiology laboratory, Ain Shams University hospital, for culture and antimicrobial susceptibility testing during the period between May 2018 and October 2018. a portion of the blood-broth mixture was aspirated from positive blood culture bottles, after being well mixed, and was subcultured onto agar media for the isolation of the causative agent and subsequently determination of its antimicrobial susceptibility profile was performed. Another part of the aspirated blood-broth mixture was diluted with sterile saline, its turbidity was adjusted against a 0.5McFarland standard and was used to inoculate directly the biochemical test media panel used for the identification of gram negative organisms as well as to perform direct (primary) antimicrobial susceptibility. Results The present study revealed there was 100% categorical agreement between the results of the direct biochemical inoculation method and those of the standard isolate-based inoculation method regarding the identification of the causative agent. The results of the direct biochemical identification method were also consistent giving rise to a 100% withinrun precision categorical agreement and a 100% between-run precision categorical agreement. The overall categorical agreement between the results of the standard isolate-based AST method and the results of the direct (primary susceptibility) AST method was 96.3% for the signal blood culture media. The major error rate was 0.5% whereas the minor error rate was 3.3% . Consistent results were also obtained for the AST done directly from the signal blood culture bottles since the between-run and within-run precision categorical agreement were 96.3% and 98.6%, respectively. Conclusion the overall performance of the AST done directly from positive blood culture bottles fulfilled the acceptable performance criteria specified in the Cumitech 31A so the direct method can be used for the earlier determination of AST and identification of Gram negative bacteria and thus to reduce the time for early initiation of appropriate antibiotic

Imipenem/cilastatin/relebactam: A new carbapenem β-lactamase inhibitor combination.

The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of imipenem/cilastatin/relebactam are reviewed. Imipenem/cilastatin/relebactam is a newly approved anti-infective combination of a well-established β-lactam and a new β-lactamase inhibitor for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by susceptible gram-negative bacteria in patients 18 years of age or older with limited or no alternative treatment options. The antibiotic is also indicated for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The antibiotic is active in vitro against a wide range of pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales (CRE) such as Klebsiella pneumoniae carbapenemase. The addition of relebactam does not restore the activity of imipenem against metallo-β-lactamase (MBL)-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. Two phase 3 clinical trials of imipenem/cilastatin/relebactam were conducted. In the RESTORE-IMI 1 trial, the efficacy and safety of imipenem/cilastatin/relebactam was found to be comparable to that of imipenem/cilastatin plus colistin for the treatment of infections caused by imipenem-nonsusceptible gram-negative bacteria in patients with HABP/VABP, cUTIs, and cIAIs, with a significantly lower incidence of nephrotoxicity reported with the new antibiotic. The RESTORE-IMI 2 trial demonstrated the noninferiority of imipenem/cilastatin/relebactam to piperacillin/tazobactam for the treatment of HABP/VABP. Commonly reported adverse events in clinical trials included anemia, elevated liver enzymes, electrolyte imbalances, nausea, vomiting, diarrhea, headache, fever, phlebitis and/or infusion-site reactions, and hypertension. Imipenem/cilastatin/relebactam is a new β-lactam/β-lactamase inhibitor combination with activity against MDR gram-negative bacteria, including many CRE but excluding MBL-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. It is approved for the treatment of cUTIs, cIAIs, and HABP/VABP.

Prevalence and Antimicrobial Susceptibility Pattern of Bacterial Agents Involved in Lower Respiratory Tract Infection at a Tertiary Care Hospital, Jaipur, Rajasthan, India

Introduction: Lower Respiratory Tract Infection (LRTI) is one of the commonest health problems which is not a single disease but a group of specific infections with varying aetiology and symptomatology. These infections are the leading cause of illness and mortality in children and adults across the world because of different epidemiology, pathogenesis, clinical presentation, and outcomes. Aim: To find out the prevalence, bacteriological profile and antimicrobial susceptibility pattern of clinical isolates causing LRTI. Materials and Methods: This was a laboratory based observational study which was carried out between June 2019 to May 2020. All the lower respiratory tract samples (sputum, Endotracheal (ET) aspirate, Bronchoalveolar Lavage (BAL) etc.,) were collected and sample processing was done for isolation and identification by standard methods and antimicrobial susceptibility testing was done using Kirby Bauer disc diffusion method. The data was analysed in Microsoft Office excel worksheet. Results: A total number of 1364 samples were processed in which 615 were culture positive. ET aspirates 65.04% (n=400) showed higher positivity rate than sputum 32.03% (n=197). In this study, gram positive and gram negative bacteria (GNB) were 4.23% (n=26) and 92.19% (n=567) respectively with yeast recovered in only 3.58% (n=22) of the specimens. Among the isolates, Klebsiella pneumoniae 171 (30.15%) was the most common organism. The overall susceptibility of GNB was highest towards tigecycline (51.85%) followed by gentamicin (38.62%). Conclusion: Specific antibiotic utilisation strategies like antibiotic restriction, combination therapy may help to decrease or prevent the emergence of resistance. There is a need for further community based studies to identify the best treatment protocol for individual patients.

5-minute synthesis of gelatinous silver nanoparticles using microwave radiation: Plasmonic optical spectroscopy and antimicrobial activity

It is well known that silver nanoparticles (AgNPs) show impressive antimicrobial effects toward various bacterial types and yeast. Microwave and thermal mediated synthesis of AgNPs in gelatin permit stable Ag NPs without stabilizing or capping agents using an eco-friendly strategy. In biomedical applications, the developed AgNPs were more successful than those synthesized via chemical methods. The morphological structure and particle size were obtained by TEM. The particle size distribution for the studied samples under microwave and thermal heating processes was analyzed and described. The optical properties were studied via UV–vis spectroscopy. The surface resonance plasmon (SPR) band is located approximately at 400 nm. Antimicrobial study of AgNPs embedded in gelatin media by the thermal method is more effective than that embedded by microwave method against Bacillus subtilis, E-coli, Pseudomonas aeruginosa, Candida albicans, and Staphylococcus aureus. Moreover, the susceptibility of Gram-negative bacteria is greater than that of Gram-positive bacteria. Alongside this, the increase in gelatin concentration led to a decrease in bioactivity. Silver nanoparticles are essential nanoparticles in medicine, food, industrials, and material engineering for future medical technology.

US Food and Drug Administration (FDA): Benefit-Risk Considerations for Cefiderocol (Fetroja®).

In November 2019, the Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible gram-negative bacteria in adults with limited to no alternative treatment options based on a randomized, double-blind, noninferiority cUTI trial (APEKS-cUTI). In a randomized, open-label trial (CREDIBLE-CR) in patients with cUTI, nosocomial pneumonia, bloodstream infections, or sepsis due to carbapenem-resistant gram-negative bacteria, an increase in all-cause mortality was observed in patients treated with cefiderocol as compared to best available therapy. The cause of the increased mortality was not established, but some deaths were attributed to treatment failure. Preliminary data from a randomized, double-blind trial (APEKS-NP) in patients with nosocomial pneumonia due to carbapenem-susceptible gram-negative bacteria showed a similar rate of mortality as compared to meropenem. We describe the uncertainties and challenges in the interpretation of the CREDIBLE-CR trial and some benefit-risk considerations for the use of cefiderocol in clinical practice. Clinical Trials Registration: NCT02321800.

Intravenous vs intravenous plus aerosolized colistin for treatment of ventilator-associated pneumonia – a matched case–control study in neonates

ABSTRACT Background Recently intravenous (IV) and aerosolized (ASZ) colistin have been used for treating ventilator-associated pneumonia (VAP) due to colistin susceptible multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin has limited lung penetration. We compared the efficacy and safety of IV-alone versus IV+ASZ-colistin for treating VAP in neonates. Methods This retrospective matched case–control study was performed at NICU of the Aga Khan University Hospital, Pakistan between January 2015 and December 2018. Sixteen neonates with MDR-GNB associated VAP received IV-ASZ-colistin and were matched for date of birth, gestational age, birth weight, Apgar score, antenatal steroid history, disease severity, and duration of mechanical ventilation with 16 control neonates who received IV-colistin alone. Results Both groups had similar MDR-GNB isolates and Acinetobacter baumannii (78%) was the most common pathogen. No colistin-resistant strain was isolated. Duration of IV-colistin and concomitant antibiotics use was significantly (p < 0.05) shorter in the IV-ASZ-colistin group. Significantly (p < 0.05) higher clinical cure and microbial eradication, along with lower ventilatory requirements, mortality rate, and colistin induced nephrotoxicity and electrolyte imbalance was observed in the IV-ASZ-colistin group. Conclusions With better lung penetration, ASZ-colistin offers effective and safe microbiological and clinical benefits as adjunctive or alternate treatment of VAP due to colistin susceptible MDR-GNB in neonates.

Bacteriological spectrum of urinary, wound and respiratory infection with antibiogram of gram negative bacteria in a Bangladeshi tertiary care hospital

Infection remains the main cause of morbidity and mortality in man, particularly in developing areas where it is associated with poverty and overcrowding. Infectious disease cause nearly 25% of all human deaths. This rate of mortality is increasing day by day due to antibiotic resistance, which is a major concern nowadays. Wound, respiratory tract and urinary tract are commonly associated with bacterial infection in both hospital and community settings. Area-specific monitoring studies aimed to gain knowledge about the type of bacterial pathogens responsible for these kinds of infections and resistance pattern of the causative agents may help clinicians to choose correct treatment regimen. So, the present study was aimed to investigate the pattern of bacteria which are responsible for Urinary tract, respiratory tract and wound infection. In addition, we also determined the antibiotic susceptibility profile of gram negative bacteria isolated from the patients who were attending both in and out patient departments at Sir Salimullah Medical College &amp; Mitford Hospital (SSMC &amp; MH) during January, 2009 to December, 2009. In this cross-sectional study, out of 308 clinical samples, a total of 159 (51.62%) samples were found to be positive for bacterial culture. Among the isolates 139 (87.42%) were Gram negative bacteria (Esch. coli, Klebsiella spp., Proteus spp., Pseudomonas spp., Acinetobacter spp.) and 20 (12.57%) were Gram positive bacteria (Staphylococcus aureus, Coagulase negative Staphylococcus). Antibiotic susceptibility of gram negative bacteria showed members of the Enterobacteriaceae were 100% sensitive to imipenem while they were found variably resistance to other commonly used antibiotics. We conclude that infections in the wound, respiratory and urinary tract are caused by both gram negative and gram positive bacteria. However, the frequency of gram negative bacteria is higher than the gram positive bacteria for these infections. Gram negative bacteria showed sensitive to imipenem and most of them were resistant to commonly used antibiotics. Therefore, clinicians should choose imipenem for patients who would be unresponsive to commonly used antibiotics.&#x0D; Mediscope Vol. 7, No. 1: Jan 2020, Page 17-24

In vitro antibacterial activity of curcumin-meropenem combination against extensively drug-resistant (XDR)bacteria isolated from burn wound infections.

Burn wound infection is a severe complication of thermal injury. Patients with severe burn injuries need urgent care to diminish complications after severe burns. Wound infections are commonly considered one of the most serious burn complications, particularly those that are caused by extensively drug-resistant (XDR) bacteria with few therapeutic choices. The objective of this study was to determine in vitro activity of meropenem and curcumin, alone and in combination, against antibiotic-susceptible Gram-positive, and antibiotic-resistant and antibiotic susceptible gram-negative bacteria isolated from burn wound infections. The antimicrobial activity of meropenem and curcumin was investigated alone and in combination, against antibiotic-susceptible and antibiotic-resistant bacterial (XDR) strains isolated from burn patients. In addition, the cytotoxic effect of curcumin on human's epithelial cell lines, was determined. In this study, minimum inhibitory concentrations of meropenem decreased considerably in the presence of curcumin (2- to 16-fold reductions), with synergy observed. Curcumin exerted no cytotoxic effect at concentrations 256-512 µg/ml on human epithelial cell lines. We suggest that curcumin-antibiotic combinations may provide an alternative approach for treating infections with multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria.

Synthesis and antibacterial evaluation against resistant Gram-negative bacteria of monobactams bearing various substituents on oxime residue.

Based on the structural characteristics of aztreonam (AZN) and its target PBP3, a series of new monobactam derivatives bearing various substituents on oxime residue were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative bacteria. Among them, compounds 8p and 8r displayed moderate potency with MIC values of 0.125-32μg/mL against most tested Gram-negative strains, comparable to AZN. Meanwhile, the combination of 8p and 8r with avibactam as a β-lactamases inhibitor, in a ratio of 1:16, showed a promising synergistic effect against both ESBLs- and NDM-1-producing K. pneumoniae, with significantly reduced MIC values up to 8-fold and >256-fold respectively. Furthermore, both of them demonstrated excellent safety profiles both in vitro and in vivo. The results provided powerful information for further structural optimization of monobactam antibiotics to fight β-lactamase-producing resistant Gram-negative bacteria.

2288. Role of Β Lactam-Β Lactamase Inhibitors in Indian Tertiary Care Hospitals: Results from a Nationwide Survey

BackgroundBroad-spectrum antibiotics, particularly third-generation cephalosporins, are routinely used in the treatment of nosocomial infections. The emergence of Extended Spectrum Β-Lactamase (ESBL)-producing pathogens in Indian tertiary care hospitals warrants the need to reassess β-lactam–β-lactamase inhibitors (BL-BLIs) as better alternative treatments.MethodsAn online survey was conducted by Pfizer India to understand the usage of BL-BLIs across Indian hospitals. The survey was administered to 334 clinicians across multiple specialties out of which 195 were from tertiary care hospitals. Results were analyzed using MS-Excel statistical tools.ResultsOne-hundred ninety-five (195) clinicians from tertiary care hospitals completed the survey. About 78% of HCPs revealed the resistance to third-generation cephalosporins (e.g., ceftriaxone, ceftazidime) to be between 10–60% in their clinical settings. BL-BLIs were mostly preferred for treatment based on hospital antibiograms (64%) and used as first-line options for hospitalized adults with mild-moderate severe infections caused by ESBL-producing organisms (71%) and in mild-moderate infections caused by susceptible Gram-negative bacteria such as Enterobacteriaceae (54%). The average duration of IV BL-BLI treatment was 5–7 days (66%). The HCPs considerations while choosing BL-BLIs were mainly based on anti-microbial spectrum (81%), and rationality of BL/BLI combination (63%) and clinical experience with the BL-BLI molecule (63%). Cefoperazone-Sulbactam (CS) and Piperacillin–tazobactam (PT) were most commonly prescribed BL-BLIs and HCPs preferred the latter for pneumonia (67%), skin and soft-tissue infections (57%), bloodstream infections (67%) and cancer-associated febrile neutropenia (64%); while they preferred former for urinary tract infections (64%). CS and PT were preferred for intra-abdominal infections (57% and 64% respectively) and post-surgical infections (56% and 53% respectively).ConclusionCS and PT were the most commonly prescribed BL-BLIs probably due to their wide antimicrobial spectrum, rationality of the BL/BLI combination and the clinical experience with the molecules. BL-BLIs are still a mainstay of treatment for infections due to ESBL producing organisms. Disclosures All authors: No reported disclosures.