Therapeutic Antibiotics Research Articles

New Antibiotic Prescription Pattern in Critically Ill Patients ("Ant-critic"): Prospective Observational Study from an Indian Intensive Care Unit.

This study aimed to address the issue of antibiotic prescription processes in an Indian Intensive care unit (ICUs). In a prospective longitudinal study, all adult patients admitted in the ICU for 24 hours or above between 01 June 2020 and 31 July 2021 were screened for any new antibiotic prescription throughout their ICU stay. All new antibiotic prescriptions were assessed for baseline variables at prescription, any modifications during the course, and the outcome of antibiotic prescription. A total of 1014 patients fulfilled entry criteria; 59.2 and 7.2% of days they were on a therapeutic and prophylactic antibiotic(s). Patients, who were prescribed therapeutic antibiotic(s), had worse ICU outcomes. A total of 49.5% of patients (502 of 1,014) received a total of 552 new antibiotic prescriptions during their ICU stay. About 92.13% of these prescriptions were empirical and blood or other specimens were sent for culture in 78.81 and 60.04% of instances. A total of 31.7% of episodes were microbiologically proven and were more likely to be prescribed by an ICU consultant. A total of 169 modifications were done in 142 prescription episodes; 73 of them after sensitivity results. Thus, the overall rate of de-escalation was 13.95%. Apart from the negative culture result (36.05%), an important reason for a relatively low rate of de-escalation was the absence of sampling (12.32%). Longer ICU stay before antibiotic prescription, underlying chronic liver disease (CLD), worse organ dysfunction, and septic shock were independently associated with unfavorable treatment outcomes. No such independent association was observed between antibiotic appropriateness and patient outcome. Future antibiotic stewardship strategies should address issues of high empirical prescription and poor microbiological sampling hindering the de-escalation process. Ghosh S, Salhotra R, Singh A, Lyall A, Arora G, Kumar N, et al. New Antibiotic Prescription Pattern in Critically Ill Patients ("Ant-critic"): Prospective Observational Study from an Indian Intensive Care Unit. Indian J Crit Care Med 2022;26(12):1275-1284.

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130ml/min were included in the study. The first group received 15mg/kg of vancomycin every 12h and the second group 15mg/kg every 8h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12h and every 8h groups was 44.04 ± 16.55 and 42.86 ± 11.83years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32ml/min in the every 12h group and 171.78 ± 48.56ml/min in the every 8h group. 46.42% of patients in the every 12h group and 82.14% of patients in the every 8h group attained AUC/MIC of more than 400mg × hr/L. None of the patients in the every 12h group reached more than 15mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15mg/kg every 8h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

246 Pathogenic Escherichia Coli Populations within the gut Microbiota of Commercial Swine Herds in the U.S

Abstract Enteropathogenic E. coli (ETEC) is a common infection in neonatal and nursery pigs resulting in significant economic losses from morbidity, mortality, and production inefficiencies. Due to the plasticity of its genome, E. coli can be particularly challenging to manage in swine production systems. Populations of E. coli are continuously changing their genome content via multiple methods of genomic modification to better adapt and compete within ecological niches in the intestinal tract. This ability to acquire genetic information allows individuals within E. coli populations to exchange virulence and antibiotic resistance genes, developing into disease-causing ETEC strains that are difficult to manage with therapeutic antibiotics and other antimicrobial methods. Virulence genes associated with ETEC are harbored within healthy swine populations and usually result in disease when individual strains acquire four or more genes associated with virulence. Monitoring and enumerating the virulence gene pool of E. coli populations within U.S. commercial swine herds indicates that incorporating methods to manage the potentially pathogenic E. coli population in its entirety may be a more effective strategy than focusing on disease mitigation.

Restarting Therapeutic Antibiotics Following Postoperative Prophylaxis in Head and Neck Microvascular Free Tissue Transfer.

To determine factors associated with restarting therapeutic antibiotics within 30 days of head and neck microvascular free tissue transfer (HN-MFTT). Retrospective study of consecutive HN-MFTTs performed from January 2015 to July 2020. Tertiary academic medical center. Thirty-day postoperative antibiotic use and post-HN-MFTT surgical and medical complications were assessed. Univariable analyses and multivariable logistic regression were used to evaluate risk factors associated with restarting antibiotics. overall 482 patients with 501 HN-MFTTs were stratified by duration of prophylaxis: ≤24 hours (n = 136, 27.1%), 25-72 hours (n = 54, 10.8%), and >72 hours (n = 311, 62.1%). Antibiotics were restarted in 199 patients (209 procedures, 42%). The most common indications for antibiotic reinitiation were flap recipient site infection (n = 59, 28%); hospital-acquired pneumonia (n = 44, 21%); and wound dehiscence, fluctuance, or change in quality of drain output (n = 44, 21%). Shorter antibiotic prophylaxis (≤24 hours) (odds ratio [OR], 1.95; 95% CI, 1.2-3.0; P = .003), osteocutaneous flaps (OR, 2.15; 95% CI, 1.3-3.4; P = .001), and prior immunotherapy/chemotherapy (OR, 2.29; 95% CI, 1.2-4.3; P = .01) were associated with reinitiation of antibiotics for surgical infections. Restarting antimicrobials for nosocomial infections was associated with aerodigestive defects (OR, 2.45; 95% CI, 1.1-5.2; P = .019), cardiovascular disease (OR, 3.00; 95% CI, 1.5-5.9; P = .001), and medical comorbidities approximated by American Society of Anesthesiologists class 3 or 4 (OR, 2.83; 95% CI, 1.5-5.4; P = .002). Aerodigestive reconstruction, 24-hour postoperative antimicrobial prophylaxis, American Society of Anesthesiologists class 3 and 4, prior chemotherapy/immunotherapy, cardiovascular disease, and osteocutaneous flaps are associated with reinitiation of antibiotics within 30 days of HN-MFTT.

Evaluation of a Dietary Grape Extract on Oxidative Status, Intestinal Morphology, Plasma Acute-Phase Proteins and Inflammation Parameters of Weaning Piglets at Various Points of Time.

Reports of the underlying mechanisms of dietary grape extract (GE) in overcoming weaning challenges in piglets have been partly inconsistent. Furthermore, evaluations of the effects of GE at weaning in comparison to those of widely used therapeutic antibiotics have been scarce. To explore the mode of action of GE in selected tissues and plasma, we evaluated gut morphology, antioxidant and inflammation indices. Accordingly, 180 weaning piglets were allocated to three treatment groups: negative control (NC), NC and antibiotic treatment for the first 5 days of the trial (positive control, PC), and NC and GE (entire trial). The villus surface was positively affected by GE and PC on day 27/28 of the trial in the jejunum and on day 55/56 of the trial in the ileum. In the colon, NC tended (p < 0.10) to increase crypt parameters compared to PC on day 55/56. The PC group tended (p < 0.10) to increase catalase activity in the ileum and decrease Cu/Zn-SOD activity in the jejunum, both compared to NC. There were no additional effects on antioxidant measurements of tissue and plasma, tissue gene expression, or plasma acute-phase proteins. In conclusion, GE supplementation beneficially affected the villus surface of the small intestine. However, these changes were not linked to the antioxidant and anti-inflammatory properties of GE.

Comparison of Therapeutic Antibiotics, Probiotics, and Synthetic CpG-ODNs for Protective Efficacy Against Escherichia coli Lethal Infection and Impact on the Immune System in Neonatal Broiler Chickens.

The poultry industry needs alternatives to antibiotics, as there are growing public concerns about the emergence of antimicrobial resistance owing to antimicrobial use in animal production. We have reported that the administration of neonatal chicks with synthetic DNA oligodeoxynucleotides containing unmethylated cytosine guanine dinucleotide (CpG) motifs (CpG-ODN) can protect against bacterial pathogens in chickens. The objective of this study was to compare the immunoprotective effects of CpG-ODN and probiotics against Escherichia coli infection vs. commonly used therapeutic antibiotics. Day-old broiler chicks were divided into five groups (n = 35/group; 30 for the challenge experiment and 5 for the flow cytometry analysis). The chicks in Group 1 received a single dose of CpG-ODN by the intramuscular route on day 4 (D4) posthatch (PH), and Group 2 received drinking water (DW) with a probiotic product (D1-D15 PH, DW). The Group 3 chicks received tetracycline antibiotics during D9-D13 in DW; the Group 4 chicks got sodium sulfamethazine on D9, D10, and D15 PH in DW; and the Group 5 chicks were administered intramuscular (IM) saline D4 PH, DW. We challenged all the groups (n = 30/group) with E. coli (1 × 105 or 1 × 106 colony-forming units/bird) on D8 PH through the subcutaneous route. Our data demonstrated that the CpG-ODNs, but not the probiotics, could protect neonatal broiler chickens against lethal E. coli septicemia, as would the tetracycline or sodium sulfamethazine. The flow cytometry analysis (n = 5/group) revealed enrichment of immune cells in the CpG-ODN group and a marked decrease in macrophages and T-cell numbers in antibiotics-treated groups, indicating immunosuppressive effects. Our data showed that, like therapeutic antibiotics, CpG-ODNs reduced clinical signs, decreased bacterial loads, and induced protection in chicks against E. coli septicemia. Unlike therapeutic antibiotics-induced immunosuppressive effects, CpG-ODN caused immune enrichment by increasing chicken immune cells recruitment. Furthermore, this study highlights that, although therapeutic antibiotics can treat bacterial infections, the ensuing immunosuppressive effects may negatively impact the overall chicken health.

Effects of Low-dose Antibiotic Exposure on Fetal Growth and Development

Objective To analyze maternal blood exposure to non-therapeutic antibiotics in late pregnancy and explore the effects of low-dose antibiotics on fetal growth and development.Methods A total of 104 pregnant women in late pregnancy (28-32 weeks) without serious pregnancy complications were enrolled,who had regular antenatal examination and delivery in Peking Union Medical College Hospital and did not use therapeutic antibiotics 2 months before pregnancy and in the whole pregnant process.The levels of antibiotics in the maternal blood were detected by liquid chromatography-tandem mass spectrometry,and the pregnant women were assigned into an antibiotic exposure group (antibiotic positive) and a non-exposure group (antibiotic negative).The length,weight,placental weight,and placental volume of the newborns in the two groups were measured,and the data were statistically analyzed by t test or χ2 test.Results The maternal blood antibiotic test showed 7 positive cases (6.73%,antibiotic exposure group) and 97 negative cases (93.27%,non-exposure group). The average length of newborns in the antibiotic exposure group and the non-exposure group was (49.57±1.40) cm and (48.85±1.77) cm,respectively,with no significant difference (t=1.060,P=0.363).The average weight of newborns in the antibiotic exposure group and the non-exposure group was (3558.57±382.95) g and (3275.36±356.41) g,respectively,with significant difference (t=2.021,P=0.046).The mean placental weight in the antibiotic exposure group and the non-exposure group was (676.43±124.59) g and (631.96±129.25) g,respectively,with no significant difference (t=0.881,P=0.380).The mean placental volume in the antibiotic exposure group and the non-exposure group was (724.67±174.91) cm3 and (676.82±220.86) cm3,respectively,with no significant difference (t=0.560,P=0.388).Compared with those in the non-exposure group,the neonatal length,neonatal weight,placental weight,and placental volume in the antibiotic exposure group increased by 1.47%,8.65%,7.04%,and 7.07%,respectively.Conclusion There are antibiotics in the environment,and maternal blood exposure to non-therapeutic antibiotics can promote the growth and development of the fetus and placenta,especially increasing the fetal weight.

Zinc Oxide and Tea Theaflavin Suppress Enterotoxigenic Salmonella Isolated From Swine Livestock

Objectives Salmonella infection can lead to diarrhea and diminished weight gains in livestock, as well as gastroenteritis in humans. Although antibiotics have been used historically on the farm to promote animal growth, this practice may also foster development of resistant bacterial strains and thereby deplete our arsenal of effective antibiotic therapies. Here, Salmonella typhimurium (isolated from cecal contents of swine) is shown to be vulnerable to zinc oxide (ZnO) and theaflavin 3,3'-digallate (TF3), each at gastrointestinal concentrations achievable via the diet.MethodsPropagation of Salmonella in Mueller-Hinton broth suspension was assessed in dose-response experiments involving ZnO or TF3 exposures, and subsequently in experiments using a combination of these compounds.ResultsThe minimum effective concentrations against 6-hour growth of Salmonella at 37°C were 1 mM ZnO (62% inhibition) or 25 μM TF3 (30% inhibition). Salmonella growth was inhibited up to 99.6% when exposed to 7 mM ZnO, and up to 89% when exposed to 100 μM TF3. In concurrent experiments assessing individual effects of either ZnO or TF3, as well as a combination of these treatments, the minimum effective concentration of ZnO was found to be more potent given alone than when given in combination with TF3.ConclusionsThese findings suggest that physiological concentrations of ZnO within the human gut lumen (upon consuming dietary supplements containing less than the Tolerable Upper Intake Level) may limit or prevent the ability of Salmonella to propagate. Similarly, TF3 (at human gut concentrations upon consuming less than a single cup of black tea) appears to suppress Salmonella, yet TF3 could compete or otherwise constrain the efficacy of ZnO. Applications of these findings may include customized ZnO or TF3 delivery platforms for use in humans at high risk of diarrheal disease or other gastrointestinal disorders (e.g., military personnel on deployment under austere environmental conditions), as well as in agricultural practices to support animal welfare and normal growth without need for therapeutic antibiotics.Funding SourcesSupported by USDA and Texas A&M AgriLife Research.

Does restricting therapeutic antibiotics use influence efficiency of pig farms? Evidence from Denmark’s Yellow Card Initiative

Abstract In the light of increasing awareness of public health risks from livestock-sourced antimicrobial resistance, antimicrobial use in animal agriculture is facing increased regulations around the world. The most recent and sophisticated addition is the Danish Yellow Card Initiative, which imposes quantity restriction on therapeutic antibiotic use. Using a panel $m$-order conditional efficiency analysis, this article provides one of the first empirical estimates of the association between the Danish Yellow Card Initiative and the economic efficiency of pig farms. The research design enables us to establish associations rather than causal relationships but the results suggest a small reduction (0.15 percentage points for the average farm) in revenue efficiency and a small reduction (0.03 percentage points) in cost efficiency in the short run after imposing restrictions to antibiotic use.

Rational use of antibiotics for major elective gynaecological and obstetrical surgical procedures: quality improvement journey from a tertiary care public facility

BackgroundAntibiotic resistance is a global problem. Irrational use of antibiotics is rampant. Guidelines recommend administration of single dose of antibiotic for surgical antimicrobial prophylaxis (SSAP) for elective obstetrical and gynaecological...

PCR- based detection and identification of mastitis-causing bacteria: A review

Mastitis is the most common and commercially significant infectious disease affecting dairy cattle. Mastitis is a global issue since it harms animal health, milk quality, and milk production economics, affecting every country and resulting in significant financial losses. Mastitis pathogens can be categorized into two types based on their epidemiology: infectious and environmental. The identifying procedures used in most clinical laboratories are microbiological culturing of milk and biochemical assays. However, microbiological culture has several drawbacks, including the possibility of bacteria not being isolated from subclinically infected glands due to a low number of pathogens and the presence of residual therapeutic antibiotics in the collected milk, which may limit bacterial development. As a result, non-culture-based diagnostic approaches are required. The use of PCR as a technique to detect bacterial species often linked with mastitis is evaluated in this article. To identify the bacterial species, traditional procedures based on biochemical and physiological features of bacteria will be used. Then, using species-specific primers, the PCR panel will be tuned for simultaneous detection of bacterial species. It is necessary to assess the test agreement between culture and PCR-based identification methods.

Cardamonin Antioxidant Effects Through the Modulation of Proteins and Genes Expressions in LPS‐Activated BV‐2 Microglial Cells

Neurodegeneration is characterized by slow and progressive loss of neuronal cells and synapses in different brain regions. These pathologic effects are the major feature of Alzheimer's disease (AD), leading to a decline in learning and memory function. The main hallmarks of AD are the aggregation and deposition of amyloid‐β peptides on the extracellular surface of neuronal cells. Hyperphosphorylation of tau protein and the formation of neurofibrillary tangles is another feature of AD. Neuroinflammation and oxidative stress follow the accumulation of amyloid‐β and neurofibrillary tangles. Continuous activation of microglia cells, known as the resident, innate immune cells in the brain, participates in producing numerous neurotoxic factors, including nitric oxide and reactive oxygen species (ROS), which induce neurodegeneration. Numerous natural compounds, such as cardamonin, a bioactive compound found in many plants, have been reported to exert multiple therapeutic properties, including anti‐cancer, anti‐inflammatory, antioxidant, antiviral antibiotic, antifungal, and antiallergic activities. This study examined the effects of cardamonin on LPS‐activated BV‐2 microglial cells. Results of this study showed that cardamonin concentrations of 6.25 to 50 µM reduced over 95% the release of NO in LPS‐activated BV‐2 cells, compared to the cells treated with LPS only (P&lt;0.001). Moreover, cardamonin significantly decreased the cellular production of SOD 3‐fold (P &lt; 0.05) and increased the levels of expression of CAT 2.5‐fold (P &lt; 0.05) and glutathione 2‐fold (p &lt; 0.05) in the LPS‐activated BV‐2 cells. In RT‐PCR assays, cardamonin increased the mRNA expression of CAT and decreased the levels of NOS2, the enzyme responsible for the production of NO and associated with inflammatory processes. Furthermore, cardamonin downregulated the mRNA expression of CCL5/RANTES (5‐fold), which promotes the recruitment and activation of inflammatory cells. Also, cardamonin downregulated SLC38A1 (3‐fold), whose expression is upregulated during oxidative stress, and TXNIP (2‐fold) that regulates thioredoxin, an important redox protein that controls levels of ROS in cells. The data show cardamonin efficacy in modulating proteins and genes involved in inflammation and the control of elevated intracellular levels of ROS. In conclusion, these findings suggest that cardamonin may have potential in the therapy of microglia‐derived neurodegeneration, helping to prevent or slow the progression of the disease in the CNS.

In Vitro Activity of Ceftazidime-avibactam and Colistin Against Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates

Infections caused by multi drug-resistant gram-negative bacilli are increasingly reported worldwide. Colistin, tigecycline and aminoglycosides are almost the only and last choice antibiotics in the treatment of infections caused by carbapenem-resistant Enterobacterales members. Ceftazidime-avibactam is a novel antibiotic combination consisting of a broad-spectrum cephalosporin and avibactam with good antimicrobial activity against carbapenem-resistant Enterobacterales members. The aim of this study was to assess the in vitro activity of ceftazidime-avibactam and colistin against carbapenem-resistant Klebsiella pneumoniae isolates and to obtain local antimicrobial surveillance data. A total of 150 carbapenem-resistant K.pneumoniae isolates obtained from various clinical samples of the patients hospitalized in our hospital between 2018-2021 were included in the study. Duplicate isolates were excluded from the study. The isolates were recovered from blood (n= 72), tracheal aspirate (n= 40), wound (n= 20), biopsy and abscess (n= 10), steril body fluid (n= 5), and peripheral venous catheter (n= 3) samples. Isolates were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS, Bruker Daltonics, Germany). The minimum inhibitory concentration (MIC) values of the isolates for meropenem, colistin, ceftazidime, and ceftazidime-avibactam were determined by broth microdilution method. Susceptibility of the isolates to the tested antibiotics was evaluated by the European Committee of Antimicrobial Susceptibility Testing (EUCAST) criteria. The presence of carbapenemases (VIM, IMP, NDM, KPC, and OXA-48) was investigated by polymerase chain reaction (PCR) using specific primers. The mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes were evaluated by PCR for plasmid-mediated colistin resistance. All K.pneumoniae isolates were found to be positive for at least one of the carbapenemase genes evaluated in the study. The blaOXA-48 gene was detected in 107 (71.3%), blaKPC gene in 25 (16.7%); blaNDM gene in 7 (4.7%), co-production of blaOXA-48 and blaKPC genes in 10 (6.7%), co-production of blaOXA-48 and blaNDM genes in 1 (0.6%) isolate. None of the isolates harbored the blaVIM and blaIMP genes. None of the mcr genes screened in the study were detected among the isolates. The susceptibility of the isolates to ceftazidime-avibactam and colistin was 92.7% (139/150) and 48% (72/150), respectively. The MIC50 and MIC90 values for meropenem, ceftazidime, ceftazidime-avibactam, and colistin of the isolates were determined as 32/256, > 128/> 128, 1/8, and 4/16 µg/ml, respectively. Of the ceftazidimeavibactam resistant isolates, seven were positive for blaNDM, three for blaKPC, and one for both blaOXA-48 and blaNDM genes. High ceftazidime-avibactam MIC levels (> 128 µg/ml) were detected in metallo-betalactamase producing isolates. Consequently, our data suggested that ceftazidime-avibactam exhibited as a good alternative therapeutic choice for carbapenem-resistant K.pneumoniae isolates. It is noteworthy that high rate of colistin resistance was detected in K.pneumoniae isolates. Another notable finding of this study is the increase in K.pneumoniae isolates producing blaKPC for our country. To prevent the development of resistance which is observed even in last-choice therapeutic antibiotics, the principles of rational antibiotic use should be followed. The appropriate antimicrobial susceptibility testing should be routinely performed for surveillance of ceftazidime-avibactam and colistin.

Green Tea (Camellia sinensis) Products as Alternatives to Antibiotics in Poultry Nutrition: A Review.

The overuse and misuse of antibiotics in poultry feeds increase the total cost of production and compromise the quality of poultry products, which poses a serious threat to human health. Globally, health-conscious poultry consumers have long called for the alternate use of natural additives to mitigate the development and spread of multidrug resistant pathogens. Phytogenic plants, such as green tea (Camellia sinensis) products, contain putative nutraceuticals with antibiotic properties that can be used as alternatives to therapeutic, metaphylactic, prophylactic, and growth-promoting antibiotics. However, there are limited studies in the literature that have evaluated the potential of green tea (GT) products when used as replacements to in-feed antibiotics, with most studies focusing on their potential as sources of dietary nutrients in poultry feeds. Thus, this review paper discusses the potential of GT products to replace various antibiotics in poultry diets while presenting GT bioactive substances that can improve the growth performance, carcass and meat quality traits, and health status of the birds. We postulate that the utilisation of GT products in place of antibiotics could deliver sustainable, organic poultry production systems that would contribute significantly to global food and nutrition security.

Appropriateness of antibiotic prescriptions during hospitalization and ambulatory care: a multicentre prevalence survey in Korea

Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea. The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated. The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699). This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

The Impact of Multiplex PCR in Diagnosing and Managing Bacterial Infections in COVID-19 Patients Self-Medicated with Antibiotics.

The multiplex PCR is a powerful and efficient tool that was widely used during the COVID-19 pandemic to diagnose SARS-CoV-2 infections and that has applications for bacterial identification, as well as determining bacterial resistance to antibiotics. Therefore, this study aimed to determine the usability of multiplex PCR, especially in patients self-medicated with antibiotics, where bacterial cultures often give false-negative results. A cross-sectional study was developed in two COVID-19 units, where 489 eligible patients were included as antibiotic takers and non-antibiotic takers. Antibiotic takers used mostly over-the-counter medication; they suffered significantly more chronic respiratory conditions and were self-medicated most often with cephalosporins (41.4%), macrolide (23.2%), and penicillin (19.7%). The disease severity in these patients was significantly higher than in non-antibiotic takers, and bacterial superinfections were the most common finding in the same group (63.6%). Antibiotic takers had longer hospital and ICU admissions, although the mortality rate was not significantly higher than in non-antibiotic takers. The most common bacteria involved in secondary infections were Staphylococcus aureus (22.2%), Pseudomonas aeruginosa (27.8%), and Klebsiella spp (25.0%). Patients self-medicating with antibiotics had significantly higher rates of multidrug resistance. The multiplex PCR test was more accurate in identifying multidrug resistance and resulted in a quicker initiation of therapeutic antibiotics compared with instances where a bacterial culture was initially performed, with an average of 26.8 h vs. 40.4 h, respectively. The hospital stay was also significantly shorter by an average of 2.5 days when PCR was used as an initial assessment tool for secondary bacterial infections. When adjusted for age, COVID-19 severity, and pulmonary disease, over-the-counter use of antibiotics represented a significant independent risk factor for a prolonged hospitalization (AOR = 1.21). Similar findings were observed for smoking status (AOR = 1.44), bacterial superinfection (AOR = 1.52), performing only a conventional bacterial culture (AOR = 1.17), and a duration of more than 48 h for bacterial sampling from the time of hospital admission (AOR = 1.36). Multiplex PCR may be a very effective method for diagnosing secondary bacterial infections in COVID-19 individuals self-medicating with antibiotics. Utilizing this strategy as an initial screen in COVID-19 patients who exhibit signs of sepsis and clinical deterioration will result in a faster recovery time and a shorter period of hospitalization.

The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine.

The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized “mold” for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.

Comparison between Ceftriaxone with Ceftriaxone and Metronidazole Combination in Maxillofacial Fracture (at KSM Reconstruction and Aesthetic Plastic Surgery, RSUD Dr. Soetomo)

The purpose of the research is to evaluate infection rate on maxillofacial fracture in Plastic Surgery and Aesthetic at Dr.Soetomo General Hospital Surabaya, Indonesia, from January 2015 to December 2019. The research is an analytic descriptive study with retrospective cohort design. The affordable population were maxillofacial fracture patients with reconstructive treatment who were given therapeutic antibiotics, namely ceftriaxone at a dose of 2 x 1 g and metronidazole 3 x 500 mg intravenously. The collected data is then transferred to IBM Statistical Package for Social Sciences (SPSS) 20 software for statistical analysis with non-parametric statistics. Descriptive and analytical data will be presented in a series of texts and tables. A total of 621 patients medical record were obtained with a characteristic distribution based on gender, age, and history of trauma from 2015 to 2019 where total cases of postoperative infection after facial bone fracture reconstruction were 10 patients (1.61%), the incidence of infection with a single antibiotic ceftriaxone were 6 patients (0.97%) and cases in the administration of combination of antibiotics ceftriaxone, metronidazole were 4 patients (0.64%). The incidence of post-operative infection for facial fracture reconstruction given single ceftriaxone antibiotics was higher than that given the combination of ceftriaxone, metronidazole at KSM Reconstructive and Aesthetic Plastic Surgery, Dr. Soetomo General Hospital, Surabaya, Indonesia from 2015 until 2019. Keywords: ceftriaxone-metronidazole, infection, maxillofacial fracture DOI: 10.7176/JHMN/97-03 Publication date: January 31 st 2022

Laccase-mediated synthesis of bioactive natural products and their analogues.

Laccases are a class of multicopper oxidases that catalyse the one-electron oxidation of four equivalents of a reducing substrate, with the concomitant four-electron reduction of dioxygen to water. Typically, they catalyse many anabolic reactions, in which mostly phenolic metabolites were subjected to oxidative coupling. Alternatively, laccases catalyse the degradation or modification of biopolymers like lignin in catabolic processes. In recent years, laccases have proved valuable and green biocatalysts for synthesising compounds with therapeutic value, including antitumor, antibiotic, antimicrobial, and antioxidant agents. Further up to date applications include oxidative depolymerisation of lignin to gain new biomaterials and bioremediation processes of industrial waste. This review summarizes selected examples from the last decade's literature about the laccase-mediated synthesis of biologically active natural products and their analogues; these will include lignans and neolignans, dimeric stilbenoids, biflavonoids, biaryls and other compounds of potential interest for the pharmaceutical industry. In addition, a short section about applications of laccases in natural polymer modification has been included.

High anion gap metabolic acidosis as a result of 5-oxoproline

High anion gap metabolic acidosis is a common acid–base disorder encountered in hospitalized patients and more so in the intensive care unit. The most common causes are accumulation of lactate, ketones, and urea and ingestion of certain toxins. In the absence of these, lesser-known etiologies such as accumulation of D-lactate or pyroglutamic acid (PGA) should be suspected. PGA (5-oxoproline) is an endogenous organic acid that can accumulate in serum to cause anionic gap metabolic acidosis. This can occur with inherited defects in enzymes that participate in the y-glutamyl cycle or can be acquired in association with therapeutic paracetamol use, malnutrition, sepsis, antibiotics, and renal impairment. Our case illustrates that prompt recognition of this entity and discontinuation of offending agents such as paracetamol result in rapid recovery, thus reducing the hospital stay.