Broad-spectrum Cephalosporins Research Articles

Efficacy of ceftobiprole in a murine model of bacteremia and disseminated infection.

Introduction. Ceftobiprole is an advanced-generation broad-spectrum parenteral cephalosporin with activity against MSSA and MRSA.Gap Statement. Ceftobiprole is not currently approved for use to treat S. aureus bacteremia and phase three clinical trials are taking place. Drug approval requires further pre-clinical evidence to support this new indication.Aim. The aim of this study was to evaluate the efficacy of ceftobiprole at the human equivalent efficacious exposure (considering a 500 mg q8h dosing regimen infused over 2 h) against MSSA and MRSA strains in a neutropenic murine model of bacteremia and disseminated infection.Methodology. Two bioluminescent-tagged strains (one MSSA and one MRSA strain) were selected based on their in vitro susceptibility and in vivo growth profiles. Bacterial c.f.u. counts in the blood, lung, kidney, and liver were determined 48 h post-infection or after death. The bioluminescent-tag allowed the visualization of the real-time effects of ceftobiprole therapy compared to the natural progression of the infection in untreated controls.Results. Treatment with ceftobiprole resulted in a significant reduction of the bacterial load with the bioluminescence reduced by 2-log units and bacterial c.f.u. counts reduced by 3- to 6-log units, depending on the organ and bacterial strain. Survival was 100 % in the ceftobiprole-treated group compared to only 0-20 % survival in the untreated control animals for both strains tested.Conclusion. These results suggest that treatment with ceftobiprole using a 500 mg q8h dosing regimen studied in several successful phase three trials, has potential as an antibiotic therapy to treat bacteremia and associated disseminated infections caused by either methicillin-susceptible or methicillin-resistant strains of S. aureus.

Emergence of KPC-113 and KPC-114 variants in ceftazidime-avibactam-resistant Klebsiella pneumoniae belonging to high-risk clones ST11 and ST16 in South America.

Two novel variants of Klebsiella pneumoniae carbapenemase (KPC) associated with resistance to ceftazidime-avibactam (CZA) and designated as KPC-113 and KPC-114 by NCBI were identified in 2020, in clinical isolates of Klebsiella pneumoniae in Brazil. While K. pneumoniae of ST16 harbored the blaKPC-113 variant on an IncFII-IncFIB plasmid, K. pneumoniae of ST11 carried the blaKPC-114 variant on an IncN plasmid. Both isolates displayed resistance to broad-spectrum cephalosporins, β-lactam inhibitors, and ertapenem and doripenem, whereas K. pneumoniae producing KPC-114 showed susceptibility to imipenem and meropenem. Whole-genome sequencing and in silico analysis revealed that KPC-113 presented a Gly insertion between Ambler positions 264 and 265 (R264_A265insG), whereas KPC-114 displayed two amino acid insertions (Ser-Ser) between Ambler positions 181 and 182 (S181_P182insSS) in KPC-2, responsible for CZA resistance profiles. Our results confirm the emergence of novel KPC variants associated with resistance to CZA in international clones of K. pneumoniae circulating in South America. IMPORTANCE KPC-2 carbapenemases are endemic in Latin America. In this regard, in 2018, ceftazidime-avibactam (CZA) was authorized for clinical use in Brazil due to its significant activity against KPC-2 producers. In recent years, reports of resistance to CZA have increased in this country, limiting its clinical application. In this study, we report the emergence of two novel KPC-2 variants, named KPC-113 and KPC-114, associated with CZA resistance in Klebsiella pneumoniae strains belonging to high-risk clones ST11 and ST16. Our finding suggests that novel mutations in KPC-2 are increasing in South America, which is a critical issue deserving active surveillance.

Culture-Independent Multiplexed Detection of Drug-Resistant Bacteria Using Surface-Enhanced Raman Scattering.

The rapid and accurate detection of bacteria resistance to β-lactam antibiotics is critical to inform optimal treatment and prevent overprescription of potent antibiotics. Here, we present a fast, culture-independent method for the detection of extended-spectrum β-lactamases (ESBLs) using surface-enhanced Raman scattering (SERS). The method uses Raman probes that release sulfur-based Raman active molecules in the presence of β-lactamases. The released thiol molecules can be captured by gold nanoparticles, leading to amplified Raman signals. A broad-spectrum cephalosporin probe R1G and an ESBL-specific probe R3G are designed to enable duplex detection of bacteria expressing broad-spectrum β-lactamases or ESBLs with a detection limit of 103 cfu/mL in 1 h incubation. Combined with a portable Raman microscope, our culturing-free SERS assay has reduced screening time to 1.5 h without compromising sensitivity and specificity.

Investigation of O25b-ST131 Clone Frequency and Presence of Carbapenem and Fosfomycin Resistance Genes in Escherichia coli Isolates: First Detection of fosA3 from Escherichia coli O25bSTf131 Clone from Türkiye

Escherichia coli ST131 clone was first reported in 2008 and defined as a 'high-risk pandemic clone'. This clone plays a critical role in the spread of antimicrobial resistance worldwide. It was reported in many studies that the E.coli ST131 clone is widespread worldwide and can carry virulence and antibiotic resistance genes. E.coli ST131 clone is associated with a fluoroquinolone and broad-spectrum cephalosporin resistance. The agents used in the treatment of infections caused by the E.coli ST131 clone are limited. For this reason, monitoring the resistance status of these limited agents is crucial. In this study, we aimed to investigate the prevalence of the O25b-ST131 clone, and the presence of carbapenem and fosfomycin resistance genes in fluoroquinolone-resistant E.coli isolates isolated from mid-stream urine samples. For the detection of the O25b-ST131 clone in fluoroquinolone-resistant E.coli isolates, amplification was performed with primers O25pabBspe-F and O25pabBspe-R. For the determination of resistance genes, carbapenem resistance genes blaNDM, blaVIM, blaKPC, blaIMP, and blaOXA-48 in carbapenem resistant isolates and plasmid-mediated fosfomycin resistance genes fosA3 and fosC2 in fosfomycin resistant isolates were investigated by multiplex PCR method. According to PCR results, the prevalence of E.coli O25b-ST131 isolates was 51.2%. Carbapenem resistance rate was 3.41%, and fosfomycin resistance rate was 3.41% in fluoroquinolone-resistant E.coli isolates. Carbapenem and fosfomycin resistance rates in E.coli O25bST131 isolates were determined as 0.83% and 2.5%, respectively. At least one of the carbapenem-resistance genes (blaNDM and/or blaOXA-48) was detected in six of the eight carbapenem-resistant isolates. Fosfomycin resistance gene fosA3 was seen in four of eight fosfomycin-resistant isolates. fosC2 gene was not detected in any of the isolates. In addition, the plasmid-mediated fosfomycin resistance gene fosA3 was detected in an E.coli O25b-ST131 isolate, and this result was confirmed by sequence analysis. To the best of our knowledge, this is the second report about fosA3 positivity in E.coli ST131 isolates from the world and the first reported from Europe and Türkiye. As a result, approximately half of the fluoroquinolone-resistant E.coli isolates were identified as E.coli ST131 clones. Despite the high rate of this clone, the carbapenem and fosfomycin resistance rates are still relatively low, which is pleasing for the future of treatment. However, it should not be forgotten that resistance rates and the prevalence of resistance genes should be constantly monitored.

Bacterial conversion of Cephalosporin C: Optimization in Achromobacter xylosooxidans

Achromobacter xylosooxidans was isolated from the soil and studied for conversion of the cephalosporin C antibiotic. In order to synthesize broad-spectrum semi-synthetic cephalosporins 7-aminocephalosporanic acid (7-ACA) is a crucial intermediary product. This study identifies crucial variables and the best values for each for the synthesis of the cephalosporin C acylase (CCA) enzyme by Achromobacter xylosooxidans. An enzyme activity measured to be 31.1 and 32.2 U/ml using the substrates cephalosporin C (CPC) and glutaryl p-nitroanilide (GpNA), respectively, under optimal parameters. The CCA activity in Achromobacter xylosooxidans species was detected maximum at 72 h after incubation. HPLC revealed the species of Achromobacter xylosooxidans with the highest CCA activity (36.6 U/ml).

Use of Clinical Practice Guideline to Improve Management of Osteoarticular Infections in Children.

Osteoarticular infections (OAIs) in children pose significant risks if incorrectly managed. We introduced a clinical practice guideline (CPG) to decrease use of broad-spectrum and intravenous (IV) antibiotics for OAI treatment. The primary aims of our project were to decrease the percent of patients with empirical broad cephalosporin use to 10% and decrease IV antibiotic therapy on discharge to 20% while increasing narrow-spectrum oral antibiotic use to 80% within 24 months. We used quality improvement methodology to study patients diagnosed with OAIs. Interventions included multidisciplinary workgroup planning, CPG implementation, education, information technology, and stakeholder feedback. Outcome measures were the percentage of patients prescribed empirical broad-spectrum cephalosporins, percent discharged on IV antibiotics, and percent discharged on narrow-spectrum oral antibiotics. Process measures included percent of patients hospitalized on medicine service and infectious diseases consultation. Balancing measures included rates of adverse drug reactions, disease complications, length of stay, and readmission within 90 days. The impact of the interventions was assessed with run and control charts. A total of 330 patients were included over 96 months. The percentage of patients with empirical broad cephalosporin coverage decreased from 47% to 10%, percent discharged on IV antibiotics decreased from 75% to 11%, and percent discharged on narrow-spectrum oral antibiotics increased from 24% to 84%. Adverse drug reactions decreased from 31% to 10%. Rates of complications, readmissions, and length of stay were unchanged. Through development and implementation of a CPG for OAI management, we demonstrated decreased use of empirical broad-spectrum antibiotics and improved definitive antibiotic management.

Phenotypic and Molecular Characterization of an Enterobacter ludwigii Clinical Isolate Carrying a Plasmid-Mediated blaIMI-6 Gene.

We report a plasmid-encoded IMI-6 carbapenemase in a clinical isolate of Enterobacter ludwigii from Spain. The isolate belongs to ST641 and was susceptible to expanded-spectrum cephalosporins and resistant to carbapenems. The modified carbapenem inactivation method (mCIM) test was positive, but β-Carba was negative. Whole-genome sequencing identified the blaIMI-6 gene located in a conjugative IncFIIY plasmid and associated with the LysR-like regulator imiR. Both genes were bracketed by an ISEclI-like insertion sequence and a putatively defective ISEc36 insertion sequence. IMPORTANCE IMI carbapenemases confer an unusual resistance pattern of susceptibility to broad-spectrum cephalosporins and piperacillin-tazobactam but decreased susceptibility to carbapenems, which may make them difficult to detect in routine practice. Commercially available molecular methods for the detection of carbapenemases in clinical laboratories do not usually include blaIMI genes, which could contribute to the hidden dissemination of bacteria producing these enzymes. Techniques should be implemented to detect minor carbapenemases that are not very frequent in our environment and control their dissemination.

Physico-chemical study of the effects of electrolytes and hydrotropes on the clouding development of TX-100 and ceftriaxone sodium drug mixture

The potential interactions between third-generation broad-spectrum cephalosporin antibiotic ceftriaxone sodium (CTS) and nonionic surfactant triton X-100 (TX-100) in the absence and existence of various sodium based electrolytes (sodium chloride (NaCl), sodium acetate (NaAc), sodium sulphate (Na2SO4)) /hydrotropic salts (sodium benzoate (NaBenz) and sodium salicylate (NaSal)) were investigated. The CTS drug is widely used to treat bacterial infections and it showed remarkable reactivity towards Gram-positive and Gram-negative bacteria. The assessments of CP in the TX-100 + CTS system with NaSal demonstrated the hydrophilic interaction which was not found significant when NaBenz solutions were used. The CP values observed for TX-100 + CTS system in aq. electrolytes and hydrotropic salts media demonstrated the order: CPaq.NaSal>CPaq.NaBenz>CPaq.NaCl>CPaq.NaAc>CPaq.Na2SO4. Different thermodynamic variables such as Gibbs free energy (ΔGco), enthalpy (ΔHco), and entropy (ΔSco) changes of clouding were computed to evaluate the nature of interactions between CTS and TX-100 in various electrolytes and hydrotropes medium. The ΔGco was found to be positive in every case indicating the non-spontaneity of the phase separation process. The enthalpy–entropy compensation was analyzed in the respective mixtures and the plot of ΔHc0 vs ΔSc0 showed a linear relationship between them. The findings of this study may be highly useful in different pharmaceutical formulations. These interesting results can also be utilized as significant tools to understand the behaviors of drugs-surfactants interactions in various systems used in different pharmaceutical industries as well as in medical science.

Distribution pattern of antibiotic resistance genes in Escherichia coli isolated from colibacillosis cases in broiler farms of Egypt.

Multidrug resistance (MDR) of Escherichia coli has become an increasing concern in poultry farming worldwide. However, E. coli can accumulate resistance genes through gene transfer. The most problematic resistance mechanism in E. coli is the acquisition of genes encoding broad-spectrum β-lactamases, known as extended-spectrum β-lactamases, that confer resistance to broad-spectrum cephalosporins. Plasmid-mediated quinolone resistance genes (conferring resistance to quinolones) and mcr-1 genes (conferring resistance to colistin) also contribute to antimicrobial resistance. This study aimed to investigate the prevalence of antimicrobial susceptibility and to detect β-lactamase and colistin resistance genes of E. coli isolated from broiler farms in Egypt. Samples from 938 broiler farms were bacteriologically examined for E. coli isolation. The antimicrobial resistance profile was evaluated using disk diffusion, and several resistance genes were investigated through polymerase chain reaction amplification. Escherichia coli was isolated and identified from 675/938 farms (72%) from the pooled internal organs (liver, heart, lung, spleen, and yolk) of broilers. Escherichia coli isolates from the most recent 3 years (2018-2020) were serotyped into 13 serotypes; the most prevalent serotype was O125 (n = 8). The highest phenotypic antibiotic resistance profiles during this period were against ampicillin, penicillin, tetracycline, and nalidixic acid. Escherichia coli was sensitive to clinically relevant antibiotics. Twenty-eight selected isolates from the most recent 3 years (2018-2020) were found to have MDR, where the prevalence of the antibiotic resistance genes ctx, tem, and shv was 46% and that of mcr-1 was 64%. Integrons were found in 93% of the isolates. The study showed a high prevalence of E. coli infection in broiler farms associated with MDR, which has a high public health significance because of its zoonotic relevance. These results strengthen the application of continuous surveillance programs.

In vitro Activity of Ceftaroline Against an International Collection of Kingella kingae Isolates Recovered From Carriers and Invasive Infections.

Improvements in blood culture techniques and molecular-based diagnostics have led to increased recognition of Kingella kingae as an invasive human pathogen causing bacteremia, septic arthritis, osteomyelitis and endocarditis in young children. Serious disease and potentially life-threatening complications of infection due to K. kingae necessitate timely identification and appropriate antimicrobial therapy. Ceftaroline is a fifth-generation broad spectrum cephalosporin that possesses activity against Gram-negative and Gram-positive pathogens similar to third-generation cephalosporins, but also includes methicillin-resistant Staphylococcus aureus . This study reports the in vitro activity of ceftaroline and comparator agents against an international collection of K. kingae isolates. A collection of 308 K. kingae isolates was obtained primarily from children with bacteremia, endocarditis, osteoarticular infections or from asymptomatic pediatric carriers. Isolates were tested for antibiotic susceptibility using Clinical and Laboratory Standard Institute broth microdilution methodology and screened for β-lactamase production using a nitrocefin chromogenic test. Ceftaroline inhibited all K. kingae isolates at ≤0.06 mg/L (MIC 50/90 , 0.015/0.03 mg/L). Ceftaroline MICs were similar to results with ceftriaxone (MIC 50/90 , 0.015/0.015 mg/L), meropenem (MIC 50/90 , 0.015/0.015 mg/L) and ampicillin-sulbactam (MIC 50/90 , 0.06/0.06 mg/L). Ceftaroline MICs were slightly lower than MICs for cefuroxime and amoxicillin/clavulanate (MIC 50/90 , 0.06/0.12 mg/L). MICs were high for clindamycin (MIC 50/90 , 2/4 mg/L) and oxacillin (MIC 50/90 , 4/8 mg/L). Sixteen isolates (5.2%) yielded a positive nitrocefin test indicating production of β-lactamase; ceftaroline demonstrated equivalent MICs against β-lactamase - positive and β-lactamase - negative strains (MIC 50/90 , 0.015/0.3 mg/L). The potent activity of ceftaroline against this large international collection of K. kingae isolates supports further clinical evaluation in children.

Cefiderocol against Multi-Drug and Extensively Drug-Resistant Escherichia coli: An In Vitro Study in Poland.

Cefiderocol (CFDC) is a novel, broad-spectrum siderophore cephalosporin with potential activity against multi-drug (MDR) and extensively drug-resistant (XDR) Enterobacterales, including carbapenem-resistant strains. We assessed the in vitro susceptibility to CFDC of MDR, and XDR E. coli isolates derived from clinical samples of hospitalized patients. Disk diffusion (DD) and MIC (minimum inhibitory concentration) test strip (MTS) methods were used. The results were interpreted based on EUCAST (version 12.0 2022) recommendations. Among all E. coli isolates, 98 (94.2%) and 99 (95.2%) were susceptible to CFDC when the DD and MTS methods were used, respectively (MIC range: <0.016-4 µg/mL, MIC50: 0.19 µg/mL, MIC90: 0.75 µg/mL). With the DD and MTS methods, all (MIC range: 0.016-2 µg/mL, MIC50: 0.19 µg/mL, MIC90: 0.75 µg/mL) but three (96.6%) ESBL-positive isolates were susceptible to CFDC. Out of all the metallo-beta-lactamase-positive E. coli isolates (MIC range: 0.016-4 µg/mL, MIC50: 0.5 µg/mL, MIC90: 1.5 µg/mL), 16.7% were resistant to CFDC with the DD method, while 11.1% were resistant to CFDC when the MTS method was used. CFDC is a novel therapeutic option against MDR and XDR E. coli isolates and is promising in the treatment of carbapenem-resistant E. coli strains, also for those carrying Verona integron-encoded metallo-beta-lactamases, when new beta-lactam-beta-lactamase inhibitors cannot be used.

Prevalence of Extended-spectrum Beta-lactamase Mediated Urinary Tract Infections in a Tertiary Hospital in Enugu, South East, Nigeria

Extended-Spectrum Beta-Lactamase (ESBL) are a class of plasmid-mediated diverse, complex and rapidly evolving enzymes which hydrolyzes penicillins, monobactams and broad-spectrum cephalosporins. There is increasing prevalence of ESBL-producing bacteria globally with higher prevalence reported in developing countries. The present study was designed to determine the prevalence and antimicrobial sensitivity pattern of ESBL producing bacteria isolates in patients with Urinary Tract Infection (UTI) in Enugu. Urine samples were collected from a total of 284 subjects with self-reported UTI In the Enugu State University of Science and Technology Teaching Hospital, Enugu State, Nigeria between the periods of April to May,2019.Samples were analyzed for the presence of UTI and antimicrobial resistance pattern of ESBL-producing bacteria using standard methods. Data was analyzed by descriptive statistics using SPSS version 23 (IBM Corp Armok, NY). A total of 145 strains of Staphylococcus aureus (n= 19). Escherichia coli (n=52), Klebsiella pneumonia (n=45), Pseudomonas aeruginosa (n =12), Enterococcus faecalis (n=9) and Proteus mirabilis (n=8), were isolated from 132 subjects giving a UTI prevalence rate of 34.6%. Forty-nine (49) ESBL-producing strains comprising Staphylococcus aureus (n=5), Escherichia coli (n=15), Klebsiella pneumonia (n=16), Pseudomonas aeruginosa (n=13), Enterococcus faecalis (n=8) and Proteus mirabilis (n=7) were implicated in UTI accounting for 46.8%ESBL-producing bacteria mediated UTI. There is a high prevalence of ESBL-producing bacteria induced UTI. This portends a great danger to the management of bacterial infections.

Physical characterization of clove oil based self Nano-emulsifying formulations of cefpodoxime proxetil: Assessment of dissolution rate, antioxidant & antibacterial activity

Cefpodoxime proxetil (CPD) is a broad-spectrum cephalosporin widely indicated in respiratory tract infections like pneumonia. CPD is a BCS class IV drug with the constraint of low bioavailability attributable to its poor aqueous solubility (10µg/ml) and impaired permeability. Clove oil (CO) acts as a lipophilic additive for lipid-based delivery systems designed to facilitate dissolution characteristics of poorly soluble drugs, modulating drug permeability as well as stability against oxidation. The present work aims to improve CPD solubilization by developing CO-based fully dilutable self nano emulsifying formulation (SNF), and assessment of its antibacterial and antioxidant potential. The existence of nanoemulsion domains was tracked from ternary phase diagrams plotted between CO, Tween 20/PEG400 to act as oil phase, surfactant/co-surfactant (Smix) respectively at weight ratios 1:1, 1:2, and 2:1 whereas aqueous phase acted its tertiary component. Two subsets of SNF formulations coded as (DAO1-DAO5) and (DAM1-DAM3) were prepared and assessed for antioxidant and antibacterial activities respectively, along with their naive CO-counterparts (AO1-AO5) and (AM1- AM5) respectively. Physical characterization revealed SNFs were droplet size range 35-170nm, conductivities in the range 200-500uS/cm, and RI values in 1.361-1.429. The dilution-induced microstructure transition effect was observed in SNF with the addition of an aqueous phase as its oil-continuous domain transformed into water-continuous via bi-continuous structure formation as interpreted from conductivity and refractive index data. In-vitro dissolution characterization of SNF formulation exhibits a quick CPD release pattern in comparison to control in phosphate buffer at pH 6.8 and HCl buffer at pH3.0. SNF produced significant differences in the CPD release characteristics measured at different pH conditions in comparison to controls. These observations are plausible in terms of drug solubilization effect since SNFs possess a high proportion of surfactant and produce interfacial action on CO and CPD. Antioxidant activities in DAO and AO at CO 20, 40 & 100µg/ml levels were significantly different from controls as measured using the DPPH method. Comparison of antibacterial activity of DAMs against E. coli, B. subtilis, Enterobacter species, and S. aureus (scheme-II) vs CPD suspension or its coarse emulsion or even naive CO counterpart were statistically different and minimum inhibitory concentration of CPD was reduced in SNF formulations. These differences were well corroborated in the data exhibited in zones of inhibition studies. CO-based SNFs produced significantly improved dissolution characteristics of poorly soluble drugs like CPD and potentiated the antibacterial and antioxidant activities. Developed SNFs could be employed as Self nano emulsifying drug delivery systems (SNEDDS) for BCS class IV drugs.

Effect of Reduced Fluoroquinolone Use on Cephalosporin Use, Susceptibilities and Clostridioides difficile Infections.

Background: Overuse of fluoroquinolones has led to concerning rates of resistance, particularly among Gram-negative organisms. They are also highly implicated as a risk factor for Clostridioides difficile infection, and reports of other serious adverse events led to recommendations to restrict their use. Our health system began targeting the reduction in unnecessary fluoroquinolone prescribing in 2018, aiming to promote their safe and effective use. Broad-spectrum cephalosporins are often used as an alternative to fluoroquinolones. We sought to evaluate whether decreased fluoroquinolone use was associated with increased third- and fourth-generation cephalosporin use and whether these changes in utilization impacted other outcomes, including C. difficile infection (CDI) rates and susceptibilities among Gram-negative organisms. Methods: This retrospective descriptive analysis included adult patients who received a fluoroquinolone or broad-spectrum cephalosporin in a three-year time period across a large healthcare system. The primary objective was to evaluate the change in days of therapy (DOT) of fluoroquinolones and third- and fourth-generation cephalosporins. Secondary objectives included rates of resistance among common Gram-negative organisms, CDI, and analyses stratified by antibiotic indication. Results: Cephalosporin use increased by an average of 1.70 DOT/1000 PD per month (p < 0.001). Additionally, fluoroquinolone use decreased by an average of 1.18 DOT/1000 PD per month (p < 0.001). C. difficile infections decreased by 0.37 infections/10,000 patient-days per month (p < 0.001). Resistance to fluoroquinolones remained stable from 2018 to 2020, and a declining trend was observed in 2021. Conclusion: This study demonstrated that reduced fluoroquinolone use in a large healthcare system was associated with increased usage of broad-spectrum cephalosporins, decreased CDI and improvements in resistance patterns.

Bacteriological Profile and Resistance of Escherichia coli to Beta-lactam for Patients Consulted at Douala Laquintinie Hospital

Enterobacteriaceae are the most common causes of community-acquired and nosocomial infections. They are usually treated with beta-lactam antibiotics, i.e., penicillins, broad-spectrum cephalosporins, and carbapenems (Imipenem, meropenem, ertapenem). In order to evaluate the resistance profile of Escherichia coli (E. coli) to beta-lactam antibiotics, a 3-year retrospective study was carried out in the medical biology laboratory of the Laquintinie Hospital in Douala. The aim was to compare the behavior of Escherichia coli bacteria to penicillins, carbapenems, and cephalosporins. In order to achieve this objective, we used the results obtained from E. coli strains isolated from urine, cervico-vaginal fluid, puncture fluid, pleural fluid and pus samples. Identification was confirmed using the API 20 E Enterobacteriaceae system of biochemical testing and the VITEK 2 system. The VITEK 2 system was used to perform the antibiogram. Statistical analyses obtained from GraphPad Prim V 5.0 software allowed us to perform tests such as ANOVA, Kruskal-Wallis test, and Spearman correlations. Preliminary results show that E. coli bacteria are highly resistant to penicillins and significantly susceptible to cephalosporins of all generations if they are not ESBL (extended-spectrum beta-lactamases). Data on carbapenem behavior show less resistance and moderate susceptibility.

Trend in healthcare-associated infections due to vancomycin-resistant Enterococcus at a hospital in the era of COVID-19: More than hand hygiene is needed.

BackgroundVariable control measures for vancomycin-resistant Enterococcus (VRE) infections were adopted among different hospitals and areas. We investigated the burden and patient characteristics of healthcare-associated VRE infections in 2018–2019 and 2020, when multiple preventive measures for COVID-19 were taken.MethodsDuring the COVID-19 pandemic, mask waring and hand hygiene were enforced in the study hospital. The incidence densities of healthcare-associated infections (HAIs), including overall HAIs, methicillin-resistant Staphylococcus aureus (MRSA) HAIs, VRE HAIs, and VRE healthcare-associated bloodstream infections (HABSIs), consumption of broad-spectrum antibiotics and hygiene products, demographic characteristics and medical conditions of affected patients, were compared before and after the pandemic.ResultsThe incidence density of both VRE HAIs and VRE HABSIs did not change statistically significantly, however, the highest in 2020 than that in 2018 and 2019. This was in spite of universal mask waring and increased consumption of 75% alcohol in 2020 and consistent implementation of an antibiotic stewardship program in three observed years. The increased prescriptions of broad-spectrum cephalosporins might partially explain the increase of VRE infection.ConclusionIncreased mask wearing and hand hygiene may not result in the decline in the development of VRE HAIs in the hospital during the COVID-19 pandemic, and continued monitoring of the dynamics of HAIs remains indispensable.

A Retrospective Study of Risk Factors, Mortality, and Treatment Outcomes for Infections with Carbapenemase-Producing Enterobacterales in a Tertiary Hospital in Havana, Cuba.

(1) Background: The spread of carbapenem-resistant Enterobacterales in hospitals constitutes an important epidemiological and therapeutic problem that especially affects vulnerable patients such as perioperative patients. (2) Methods: We conducted a descriptive, observational, retrospective case-control study of patients infected with carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) and carbapenem-susceptible Enterobacterales during the perioperative period in a tertiary hospital. (3) Results: Metallo-β-lactamase was detected in all 124 CRE isolates, with NDM-type carbapenemase being dominant, while 3 isolates coproduced KPC-type enzyme and showed high resistance rates against all antibiotics except colistin (25.2%). By analyzing the risk factors for infection, steroid use (OR: 3.22, p < 0.01), prior use of two or more antibiotics (OR: 4.04, p = 0.01), prior use of broad-spectrum cephalosporins (OR: 2.40, p = 0.04), and prior use of carbapenem (OR: 4.77, p = 0.03) were found to be independent risk factors for CP-CRE infection. In addition, in this study, we observed that the clinical outcomes of bloodstream infections and pneumonia associated with CP-CRE posed higher mortality risks. However, by analyzing the associations between treatment options and mortality, it was found that, in bloodstream infections caused by CP-CRE, colistin-based regimens showed a significant advantage (PR = 0.40, p = 0.03). (4) Conclusions: High mortality is associated with nosocomial infections in the perioperative period caused by carbapenemase-producing Enterobacterales, the dissemination of which in health care settings in Cuba remains a public health challenge.

Diagnosis and Treatment-Spectrum Beta-Lactamase and Multidrug Resistance Bacterial

Multidrug-resistant (MDR) is a condition resistant to at least one type of antibiotic from 3 classes of antibiotics. Extended-Spectrum Beta Lactamases are globular proteins that consist of alpha-helices and beta-pleated sheets. β-lactamase hydrolyze broad-spectrum cephalosporin with oxyimino side chain. ESBL hydrolyze antibiotics group penicillin, cephalosporin first, second, third, fourth generation, and monobactam aztreonam. Multidrug resistance occurs through two mechanisms, bacteria accumulate multiple genes encoding resistance to one antibiotic, and due to increased expression of genes encoding multidrug effluent pump, enzymatic inactivation and target structure change. Multidrug-resistant (MDR) caused by extended-spectrum resistance beta-lactamase (ESBL) can be detected by phenotyping and genotyping methods. Treatment for MDR ESBLs other than carbapenems can be β-lactam/β-lactamase inhibitor combinations (BLBLIs), namely piperacillin/tazobactam (PZT).

Clinical Pharmacokinetics and Pharmacodynamics of Cefepime.

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion over 30-60 min or as a prolonged infusion with infusion times from 3 h to continuous administration. Cefepime is widely distributed in biological fluids and tissues with an average volume of distribution of ~0.2 L/kg in healthy adults with normal renal function. Protein binding is relatively low (20%), and elimination is mainly renal. About 85% of the dose is excreted unchanged in the urine, with an elimination half-life of 2-2.3 h. The pharmacokinetics of cefepime is altered under certain pathophysiological conditions, resulting in high inter-individual variability in cefepime volume of distribution and clearance, which poses challenges for population dosing approaches. Consequently, therapeutic drug monitoring of cefepime may be beneficial in certain patients including those who are critically ill, have life-threatening infections, or are infected with more resistant pathogens. Cefepime is generally safe and efficacious, with a goal exposure target of 70% time of the free drug concentration over the minimum inhibitory concentration for clinical efficacy. In recent years, reports of neurotoxicity have increased, specifically in patients with impaired renal function. This review summarizes the pharmacokinetics, pharmacodynamics, and toxicodynamics of cefepime contemporarily in the setting of increasing cefepime exposures. We explore the potential benefits of extended or continuous infusions and therapeutic drug monitoring in special populations.

Histological Changes in Ovary Treated with Dexamethasone and Cefotaxime Sodium.

Dexamethasone (DEX), which is a corticosteroid hormone (glucocorticoid), has been used to treat different conditions, such as immune system disorders, certainskinandeyedisorders, as well as breathing problems. Cefotaxime sodium, also called Claforan, is synthesized from a naturally occurring material (semisynthetic). It is a broad-spectrum cephalosporin antibiotic that could be utilized forparenteraladministration. The present study aimed to investigate histological changes occurring in the tissues and cells of the rats' ovary (primordial, primary, secondary, antral, and mature follicle) treated with Cefotaxime sodium, as well as DEX, and evaluate the impacts of these medications on animals' fertility. In total, 40 female adult Wistar rats were divided into four groups (n=10). The control group received 0.5 ml/kg of distilled water daily for five days as a placebo. The second group was injected with 0.5 mg/kg of DEX daily for five days. The same amount of Claforan (0.5 mg/kg) was injected into the third group daily for five days, and the fourth group received 0.5 mg/kg of both Claforan and DEX daily for five days. Afterward, the ovaries were prepared for histological examination. The ImageJ image analysis system was used to detect morphometric parameters and calculate the area of these organs. The findings of the present study showed that the DEX and Claforan brought changes to the ovarian area and the number of follicles. The ovarian area significantly increased (P<0.007) in the DEX-treated group (mean±SEM=7.3±0.5 mm2), compared to the control group (mean±SEM=4.6±0.20 mm2). However, DEX was found to decrease body weight. Furthermore, the ovarian area significantly increased in the Claforan-treated group (mean±SEM=8.6±0.6 mm2); however, their body weight significantly decreased (P<0.008), in comparison with the control and DEX-treated groups. The combination treatment (i.e., DEX + Cefotaxime sodium) significantly increased (P<0.009) the area of ovaries even more, compared to single treatments (mean±SEM=9.6±0.4 mm2). Overall, both DEX and Claforan brought histological changes to ovaries. However, the effect of DEX on ovaries was less than that of Claforan. The concurrent administration of both medications was found to have more significant effects on rats' ovaries.