Effective Antibiotic Treatment Research Articles

Screening of Machine Learning Predicted Inhibitors of Mur‐E Ligase

Antibiotic resistance is an ever‐growing threat, which necessitates the development of novel antibiotics. Peptidoglycan (PTG) is an ideal target for antibiotic development as it is necessary for the structural integrity of the cell and is unique to bacterial cells. Mur‐E, a cytoplasmic ligase, is an integral component of PTG synthesis and shares many conserved structures with PTG ligases in other bacterial species. Thus, inhibitors of Mur‐E are likely to be effective broad‐spectrum antibiotics. Mur‐E's role in PTG synthesis is to add meso‐A2pm or L‐lysine to a nucleotide precursor of PTG, UMAG; this reaction is facilitated by ATP hydrolysis. Residues N449, R451, K157, E220, D392 were identified in a mutagenesis study as having significant impacts on enzyme kinetics. This project combines the knowledge of each residue’s known impact on kinetics with an analytical, dynamics‐based investigation of protein structure using Essential Sit Scanning Analysis (ESSA) and ClustENMD. These two methodologies implement elastic network models of proteins to predict allosteric pockets and alternate conformations of the protein, respectively. This will give insight into which pockets are likely to be effective drug targets based on their impact on enzyme kinetics and protein dynamics; these pockets will be evaluated using a library of predicted ligands for Mur‐E to identify potential inhibitors with AutoDock Vina. By evaluating ligand binding sites and affinities, probable antibiotics can be determined. Targeting residue pockets that facilitate key Mur‐E functions, like ATP binding and substrate addition, will produce the most effective antibiotic treatment by compromising PTG production.

Involvement of a Phage-Encoded Wzy Protein in the Polymerization of K127 Units To Form the Capsular Polysaccharide of Acinetobacter baumannii Isolate 36-1454.

ABSTRACTA comprehensive understanding of capsular polysaccharide (CPS) diversity is critical to implementation of phage therapy to treat panresistant Acinetobacter baumannii infections. Predictions from genome sequences can assist identification of the CPS type but can be complicated if genes outside the K locus (CPS biosynthesis gene cluster) are involved. Here, the CPS produced by A. baumannii clinical isolate 36-1454 carrying a novel K locus, KL127, was determined and compared to other CPSs. KL127 differs from KL128 in only two of the glycosyltransferase (gtr) genes. The K127 unit in 36-1454 CPS was the pentasaccharide β-d-Glcp-(1→6)-d-β-GalpNAc-(1→6)-α-d-Galp-(1→6)-β-d-Glсp-(1→3)-β-d-GalpNAc in which d-Glcp at position 4 replaces d-Galp in K128, and the glycosyltransferases encoded by the different gtr genes form the surrounding linkages. However, although the KL127 and KL128 gene clusters encode nearly identical Wzy polymerases, the linkages between K units that form the CPS chains are different, i.e., β-d-GalpNAc-(1→3)-d-Galp in 36-1454 (K127) and β-d-GalpNAc-(1→4)-d-Galp in KZ-1093 (K128). The linkage between K127 units in 36-1454 is the same as the K-unit linkage in five known CPS structures, and a gene encoding a Wzy protein related to the Wzy of the corresponding K loci was found encoded in a prophage genome in the 36-1454 chromosome. Closely related Wzy proteins were encoded in unrelated phage in available KL127-carrying genomes. However, a clinical isolate, KZ-1257, carrying KL127 but not the prophage was found, and K127 units in the KZ-1257 CPS were β-d-GalpNAc-(1→4)-d-Galp linked, confirming that WzyKL127 forms this linkage and thus that the phage-encoded WzyPh1 forms the β-d-GalpNAc-(1→3)-d-Galp linkage in 36-1454.IMPORTANCE Bacteriophage therapy is an attractive innovative treatment for infections caused by extensively drug resistant Acinetobacter baumannii, for which there are few effective antibiotic treatments remaining. Capsular polysaccharide (CPS) is a primary receptor for many lytic bacteriophages, and thus knowledge of the chemical structures of CPS produced by the species will underpin the identification of suitable phages for therapeutic cocktails. However, recent research has shown that some isolates carry additional genes outside of the CPS biosynthesis K locus, which can modify the CPS structure. These changes can subsequently alter phage receptor sites and may be a method utilized for natural phage resistance. Hence, it is critical to understand the genetics that drive CPS synthesis and the extent to which genes outside of the K locus can affect the CPS structure.

Recent Advances in the Biocontrol of Nosemosis in Honey Bees (Apis mellifera L.).

Nosemosis is a disease triggered by the single-celled spore-forming fungi Nosema apis and Nosema ceranae, which can cause extensive colony losses in honey bees (Apis mellifera L.). Fumagillin is an effective antibiotic treatment to control nosemosis, but due to its toxicity, it is currently banned in many countries. Accordingly, in the beekeeping sector, there is a strong demand for alternative ecological methods that can be used for the prevention and therapeutic control of nosemosis in honey bee colonies. Numerous studies have shown that plant extracts, RNA interference (RNAi) and beneficial microbes could provide viable non-antibiotic alternatives. In this article, recent scientific advances in the biocontrol of nosemosis are summarized.

Review on Antimicrobial Resistant Genes, Mechanisms and Next-Generation Antibiotics for effective treatment of MDR Pathogens

Antimicrobial resistance is a global threat to human health, food and economic development. It has extended beyond sex, age and geographical location. Though antimicrobial resistance occurs naturally, it has also been caused due to misuse and overuse of antibiotics. The threat involves the rapid extension of the infections and the limited number of drugs available for the treatment. Bacteria also exhibit adaptation, genomic alterations, competency and individual mutational variations conferring the sensitivity towards antibiotics leading to increased morbidity and mortality, prolonged hospitalization and excessive hospital charges and the economic burden on the nation's productivity. This global hit problem had caused the lack of development of novel drugs, time-consuming process, limitations for novel drug discovery and challenging regulatory requirements. This study focuses on understanding and exploiting the significant information on genes involved in prioritized antibioticresistant bacteria, a novel class of next-generation antibiotics. It also elaborates on the other treatment measures available and drug repurposing.

What Is the Most Effective Empirical Antibiotic Treatment for Early, Delayed, and Late Fracture-Related Infections?

Antibiotic treatment strategies for fracture-related infections (FRI) are often extrapolated from periprosthetic joint infections (PJI), although, in contrast to PJI, detailed analysis of pathogens and their antibiotic resistance is missing. Therefore, this study aimed to investigate antibiotic susceptibility profiles to identify effective empiric antibiotic treatment for early-, delayed-, and late-onset FRI. Patients treated for FRI from 2013 to 2020 were grouped into early (<2 weeks), delayed (3–10 weeks), and late (>10 weeks) onset of infection. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. In total, 117 patients (early n = 19, delayed n = 60, late n = 38) were enrolled. In early-onset FRI, 100.0% efficacy would be achieved by meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide, ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide. For patients with delayed FRI, the highest susceptibility was revealed for meropenem + vancomycin, gentamicin + vancomycin and ciprofloxacin + glycopeptide (96.7%). Meropenem + vancomycin was the most effective empiric antimicrobial in patients with late-onset of infection with 92.1% coverage. No subgroup differences in antibiotic sensitivity profiles were observed except for the combination ciprofloxacin + glycopeptide, which was significantly superior in early FRI (F = 3.304, p = 0.04). Across all subgroups meropenem + vancomycin was the most effective empiric treatment in 95.7% of patients with confirmed susceptibility. Meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide are the best therapeutic options for FRI, regardless of the onset of infection. To avoid multidrug resistance, established antibiotic combinations such as co-amoxiclav with a glycopeptide seem to be reasonable as a systemic antibiotic therapy, while vancomycin + gentamicin could be implemented in local antibiotic therapy to reduce adverse events during treatment.

Femoral artery aneurysm with large hematoma from Pasteurella: case report and literature review

BackgroundPasteurella multocida is a well-known gram-negative facultative anaerobe well known for its ability to cause soft tissue infections following animal bite or scratch. Here we present a case with mycotic aneurysm of the superficial femoral artery due to P. multocida infection.Case presentationA 62 year old male patient presented with worsening right leg pain and swelling. On examination, he was found to have profound swelling and erythema of the right medial thigh and tenderness to palpation. Computerized tomography showed findings suggestive of right femoral pseudoaneurysm with a large right medial thigh hematoma. Blood cultures grew P. multocida. Patient underwent emergent open resection of the mycotic aneurysm and vascular bypass surgery. Intraoperatively, the site was noted to be grossly infected with multiple pockets of pus which were drained and pus cultures grew P. multocida. The diagnosis of P. multocida bacteremia with right femoral mycotic aneurysm and thigh abscess was made. Patient received 6 weeks of intravenous ceftriaxone and recovered.ConclusionOur case is the first report on infection of peripheral vessel with Pasteurella and highlights the importance of prompt surgical intervention and effective antibiotic treatment

Binding reaction investigation of designed miniproteins using metadynamics and massively parallel ab-initio simulation

Biofilms are an aggregation of bacteria in response to external stresses. The genesis of bacterial colonization is surface adhesion of one bacteria. From there, the colony can grow as more bacteria stick to each other, secreting their own extracellular matrix made up of polysaccharides, proteins, lipids, and nucleic acids. Biofilm formation occurs in natural, industrial, and clinical environments, where they can be an impediment to effective antibiotic treatments. In Pseudomonas fluorescens, this process is initiated by the Lap system, particularly the LapA adhesin.

Review of the Clinical Applications of Metagenomic Next-Generation Sequencing in Bloodstream Infection

Bloodstream infection (BSI) is an important cause of morbidity and mortality worldwide. If we can make early diagnosis and start effective antibiotic treatment in time, the hospitalization time of patients with bloodstream infection can be significantly shortened. However, the current diagnosis of bloodstream infection cannot achieve the ideal therapeutic effect to a large extent because of the matrix effect of blood and the long turnaround time of blood culture. Therefore, a new detection method with a short turnaround time and high sensitivity is needed for the early diagnosis and timely treatment to improve the prognosis of patients. Metagenomic next-generation sequencing (mNGS) is a recently developed method for the comprehensive analysis of all microorganisms and genetic materials in clinical samples and is expected to be the main method for the early diagnosis of bloodstream infections. This review discusses the clinical application of mNGS in bloodstream infections. We also discuss technical challenges that need to be addressed to improve the diagnostic applicability of mNGS.

A Risk-Based Clinical Decision Support System for Patient-Specific Antimicrobial Therapy (iBiogram): Design and Retrospective Analysis.

BackgroundThere is a pressing need for digital tools that can leverage big data to help clinicians select effective antibiotic treatments in the absence of timely susceptibility data. Clinical presentation and local epidemiology can inform therapy selection to balance the risk of antimicrobial resistance and patient risk. However, data and clinical expertise must be appropriately integrated into clinical workflows.ObjectiveThe aim of this study is to leverage available data in electronic health records, to develop a data-driven, user-centered, clinical decision support system to navigate patient safety and population health.MethodsWe analyzed 5 years of susceptibility testing (1,078,510 isolates) and patient data (30,761 patients) across a large academic medical center. After curating the data according to the Clinical and Laboratory Standards Institute guidelines, we analyzed and visualized the impact of risk factors on clinical outcomes. On the basis of this data-driven understanding, we developed a probabilistic algorithm that maps these data to individual cases and implemented iBiogram, a prototype digital empiric antimicrobial clinical decision support system, which we evaluated against actual prescribing outcomes.ResultsWe determined patient-specific factors across syndromes and contexts and identified relevant local patterns of antimicrobial resistance by clinical syndrome. Mortality and length of stay differed significantly depending on these factors and could be used to generate heuristic targets for an acceptable risk of underprescription. Combined with the developed remaining risk algorithm, these factors can be used to inform clinicians’ reasoning. A retrospective comparison of the iBiogram-suggested therapies versus the actual prescription by physicians showed similar performance for low-risk diseases such as urinary tract infections, whereas iBiogram recognized risk and recommended more appropriate coverage in high mortality conditions such as sepsis.ConclusionsThe application of such data-driven, patient-centered tools may guide empirical prescription for clinicians to balance morbidity and mortality with antimicrobial stewardship.

Adult Native Joint Septic Arthritis: A Nine-Year Retrospective Analysis in a Portuguese University Hospital

Septic arthritis of a native joint represents a medical emergency. Drainage and effective antibiotic treatment are critical toavoid joint destruction and long-term impairment. The aim of this study was to evaluate epidemiological and clinical characteristics of patients with the diagnosis of septic arthritis to help establish local guidelines for empirical antibiotic treatment. Retrospective analysis of adult patients admitted at Centro Hospitalar Universitário do Porto from 2009 to 2017 with suspected native joint septic arthritis. Relevant demographics, microbiology findings and respective antibiotic susceptibilities were analysed. Ninety-seven patients, predominantly males (59.8%) with a median age of 61 years old were included. The most commonly reported comorbidity associated with septic arthritis was diabetes mellitus (20.6%). The knee was the most commonly affected joint (71.1%). Arthrocentesis was performed in all patients, but only 50.5% had positive microbial growth in the synovial fluid. Staphylococcus aureus was the most frequently identified microorganism, 86% of which were methicillin susceptible. Gram-negative bacteria were the causative agent in 15% of cases. A wide range of empirical antibiotic regimens were prescribed with a combination of vancomycin/carbapenem being the most common (30.9%). Analysis of antibiotic susceptibility profiles revealed that amoxicillin/clavulanate would have been appropriate as the initial regimen in 89% of cases. The main causative pathogen was Staphylococcus aureus, with methicillin resistant Staphylococcus aureus remaining rare. The proportion of Gram-negative bacteria implies that these agents should be covered by empirical treatment, although no case of Pseudomonas infection has been identified. Therefore, antipseudomonal coverage is not necessary in empirical regimens. Routine coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is not warranted but must be considered when specific risk factors are found. Amoxicillin/clavulanate can provide adequate antibiotic coverage as an empirical treatment for adult native joint septic arthritis. Its use may allow a reduction in use of broader spectrum antibiotics.

Community-acquired pneumonia: Trends in and research on drug resistance and advances in new antibiotics.

Community-acquired pneumonia (CAP) refers to infectious inflammation of the lung parenchyma developing outside of a hospital. CAP has quite a high mortality and morbidity rate worldwide, and especially among elderly patients. The increasing burden of CAP is due to antibiotic resistance, the growth of the elderly population, and underlying comorbidities. Streptococcus pneumoniae remains the most common bacterial pathogen causing CAP, but multi-drug resistance bacteria and potential pathogens have increased the difficulty and challenges of managing CAP. Although preventive measures, diagnostic techniques, and treatment strategies are constantly advancing and improving, the susceptibility of multi-drug resistant pathogens, such as including Methicillin-Resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa, has not improved significantly in recent decades, thus highlighting the importance and necessity of developing new antibiotics for the treatment of CAP. New antimicrobials have been approved over the past few years that will expand treatment options for CAP, and especially for patients with potential comorbidities. This situation also offers the chance to reduce the abuse of antibiotics, their toxicities, and their adverse reactions and to provide effective personalized antibiotic treatment.

Natural extracts as potential control agents for Nosema ceranae infection in honeybees, Apis mellifera

Nosema disease is one factor that can cause colony decline in honeybees (Apis mellifera L.) worldwide. Nosema ceranae has outcompeted Nosema apis in the Western honeybee (A. mellifera) which is its original host. Fumagilin is an effective antibiotic treatment to control Nosema infection but currently it is forbidden in many countries. In this study, 12 plant extracts were evaluated for their toxicity to adult bees and antimicrosporidian activity under laboratory and field conditions. N. ceranae-infected adult bees were fed ad libitum with 50% sucrose solution containing 1% and 5% (w/v) of each plant extract. Bee mortality in N. ceranae-infected groups fed with plant extracts was higher than that in the control group treated with fumagilin. The results demonstrated that 9 of 12 extracts had high antimicrosporidian activity against N. ceranae and their efficacies were comparable to fumagilin. Spore reduction in infected bees was 4–6 fold less after extract treatment. Following laboratory screening, Annona squamosa, Ocimum basilicum, Psidium guajava and Syzygium jambos were tested in honeybee colonies. Plant extracts of 2% concentration (w/v) inhibited the development of Nosema spores after 30 days of treatment. At the end of experiment (90 days), spores in the plant extract treated groups were lower than in group treated with fumagilin but there was no significant difference. Although, extracts tested in this study showed high toxicity to bee in laboratory cages, they did not show negative affects on bees under whole colony conditions. Therefore, the effectiveness of plant extracts tested in this study was notable and warrants further study as potential Nosema control agents in honey bees. Plant extracts would offer a non-antibiotic alternative for Nosema control and help reduce the overuse of antibiotics in livestock.

Diagnostic value of ultrasound in cases of pneumonia admitted at intensive care unit: A comparative study with chest x-ray

Abstract Background Pneumonia is consistently among the leading causes of morbidity and mortality worldwide. Defined as acute infection of the lung parenchyma, it is caused by a wide variety of microorganisms, including bacteria, viruses, and fungi. However, pneumonia is often misdiagnosed even now. Early and effective antibiotic treatment is important. An adequate treatment is thus reliant on an early diagnosis of pneumonia, yet the diagnosis is not always clear at presentation to the emergency department (ED). In a retrospective chart review of patients admitted with pneumonia, 22% of patients presented some reason for diagnostic uncertainty that could result in delayed antibiotics delivery. Objective The aim of the study was to evaluate the efficacy of LUS in the diagnosis of pneumonia. Methods This is a prospective observational study which was conducted on 36 consecutive patients with suspected pneumonia. All patients were admitted to the Hospital, in the period from May 2019 to January 2020. Results Chest x-ray diagnosed pneumonia in 66.7% of patients, while lung U/S diagnosed pneumonia in 75% of patients. Lung ultrasound was more sensitive and highly specific for diagnosis of pneumonia as sensitivity and specificity of lung ultrasound was 96.3% and 88.9% respectively while for chest xray was 81.5% and 77.8% respectively. Accuracy of lung ultrasound was 94.4% and that of chest x-ray was 80.6% in relation to CT chest the gold standard with accuracy 100%. Superiority of lung US findings over CXR findings could be explained by high sensitivity &amp; specificity of lung US in diagnosing pneumonia in comparison with chest x ray as high resolution CT is a gold standred for the study. Conclusion LUS is a sensitive and highly specific diagnostic tool in pneumonia. Therefore, we hypothesize that Lung US may be considered as the first imaging test inpatients with suspicion of pneumonia. It should be noted, however, that the ability of LUS to detect lung consolidations located in peri-hilar regions is limited. A diagnostic algorithm of pneumonia which includes Lung US should be validated in prospective studies. Monitoring there solution of pneumonia can be another application of Lung US inpatients with pneumonia.

The Case against Antibiotics and for Anti-Virulence Therapeutics.

Although antibiotics have been indispensable in the advancement of modern medicine, there are downsides to their use. Growing resistance to broad-spectrum antibiotics is leading to an epidemic of infections untreatable by first-line therapies. Resistance is exacerbated by antibiotics used as growth factors in livestock, over-prescribing by doctors, and poor treatment adherence by patients. This generates populations of resistant bacteria that can then spread resistance genes horizontally to other bacterial species, including commensals. Furthermore, even when antibiotics are used appropriately, they harm commensal bacteria leading to increased secondary infection risk. Effective antibiotic treatment can induce bacterial survival tactics, such as toxin release and increasing resistance gene transfer. These problems highlight the need for new approaches to treating bacterial infection. Current solutions include combination therapies, narrow-spectrum therapeutics, and antibiotic stewardship programs. These mediate the issues but do not address their root cause. One emerging solution to these problems is anti-virulence treatment: preventing bacterial pathogenesis instead of using bactericidal agents. In this review, we discuss select examples of potential anti-virulence targets and strategies that could be developed into bacterial infection treatments: the bacterial type III secretion system, quorum sensing, and liposomes.

Mode Action Prediction of Butein as Antibacterial Oral Pathogen against Enterococcus faecalis ATCC 29212 and an Inhibitor of MurA Enzyme: In Vitro and In Silico Study

Background: The MurA enzyme, enolpyruvyl UDP-N-acetylglucosamine transferase, is one of the targeted proteins by antibiotics for effective treatment of diseases provided by pathogenic bacteria. It plays a key role in the cell wall biosynthesis of Gram-positive bacteria such as Enterococcus faecalis. Butein is a flavonoid that showed antioxidant and anticancer activities, but recently it is a promising antibacterial agent and reported can inhibit E. faecelis, Eschericia coli, and Mycobacterium tuberculosis. It was isolated from medicinal plants, including Sarang Semut (Myrmecodia pendans). However, the molecular mechanism of butein inhibits bacteria that is no clear. Objective: This study aims to predict the molecular action of the butein against MurA, catalyzing the first step of peptidoglycan biosynthesis. Material and Methods: Butein isolation used a combinational separation technique and characterization using spectroscopic methods. Then, in silico method used was virtual screening using programs including Autodock Vina in PyRx, protein. plus, and ligplots. Butein and UDP-N-acetylglucosamine (UNAG as a positive control) act as ligand were subject binding to 3KQJ MurA as protein. To evaluate in vitro antibacterial activity, we used the Kirby-Bauer method. Results: Butein from M. pendans is a potential compound to inhibit the MurA with binding affinity - 7.6 kcal.mol-1. It is lower than UNAG but higher than Fosfomycin as a MurA inhibitor. Butein attaches to MurA in the same position as UNAG so that it concludes that both is a competitive inhibitor. Meanwhile, in vitro study showed that butein inhibits the E. faecalis growth with inhibit zone of 8.37 mm at 1 mg/ml. Conclusions: Butein as a potent antibacterial agent through blocking MurA enzyme in cell wall formation.

Challenges to Early Discharge of Patients with Upper Urinary Tract Infections by ESBL Producers: TMP/SMX as a Step-Down Therapy for Shorter Hospitalization and Lower Costs.

BackgroundUrinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing pathogens have increased and are treated with carbapenem in general. Carbapenem use is associated with prolonged hospitalization or daily outpatient visit. The aim of this study was to investigate patients with UTIs by ESBL-producing pathogens for early discharge using an old oral antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), which is susceptible to ESBL-producing pathogens.MethodsData on UTIs caused by ESBL-producing pathogens from a single tertiary hospital were collected retrospectively. Patients who had been treated with intravenous carbapenems or oral TMP/SMX were included. Patients’ clinical and microbiological outcomes were compared between oral TMP/SMX and ertapenem treatment groups.ResultsA total of 103 patients were included, 21 of whom had been treated with TMP/SMX, whereas 82 with ertapenem. Clinical outcomes between the two groups were not significantly different (TMP/SMX: 90.5%; ertapenem: 84.1%, p = 0.73). The microbiological cure rate was higher in the TMP/SMX group than in the ertapenem group (90.5% vs 58.5%, respectively, p = 0.01). The mean duration of hospitalization was significantly shorter in the TMP/SMX group than in the ertapenem group (8.00 ± 10.50 days vs 14.00 ± 37.00 days, p = 0.07). The mean duration of antibiotic treatment was longer in the ertapenem group than in the TMP/SMX group (16.45 ± 4.77 vs 12.76 ± 5.37 days, p = 0.006).ConclusionFor susceptible pathogens, TMP/SMX may enable early discharge as an effective oral antibiotic treatment option for UTIs caused by ESBL-positive pathogens. Additionally, use of oral antibiotics can shorten hospital stays and reduce medical costs.

A Rapid Single-Cell Antimicrobial Susceptibility Testing Workflow for Bloodstream Infections.

Bloodstream infections are a significant cause of morbidity and mortality worldwide. The rapid initiation of effective antibiotic treatment is critical for patients with bloodstream infections. However, the diagnosis of bloodborne pathogens is largely complicated by the matrix effect of blood and the lengthy blood tube culture procedure. Here we report a culture-free workflow for the rapid isolation and enrichment of bacterial pathogens from whole blood for single-cell antimicrobial susceptibility testing (AST). A dextran sedimentation step reduces the concentration of blood cells by 4 orders of magnitude in 20–30 min while maintaining the effective concentration of bacteria in the sample. Red blood cell depletion facilitates the downstream centrifugation-based enrichment step at a sepsis-relevant bacteria concentration. The workflow is compatible with common antibiotic-resistant bacteria and does not influence the minimum inhibitory concentrations. By applying a microfluidic single-cell trapping device, we demonstrate the workflow for the rapid determination of bacterial infection and antimicrobial susceptibility testing at the single-cell level. The entire workflow from blood to categorical AST result can be completed in less than two hours.

Application and research status of pharmacokinetics/pharmacodynamics in the optimization of antibiotic treatmentregimens for critically ill patients

<p indent=0mm>Effective antibiotic treatment of critically ill patients remains a significant challenge to intensivists world-wide with persisting high mortality and morbidity rates. Pathophysiological changes in critically ill patients lead to changes in the pharmacokinetics (PK)/pharmacodynamics (PD) of antibiotics. Optimizing the current antibiotic delivery regimen is an important strategy to cope with this problem. In this paper, we review the PD characteristics and the potential changes of PK of antibiotics in critically ill patients, and the application and research progress of PK/PD in the optimization of antibiotic treatment regimens for them.

Articles of Significant Interest in This Issue.

Streptococcus uberis is one of the most prevalent pathogens responsible for bovine mastitis, one of the most costly animal diseases. Its ability to form biofilms can prevent effective antibiotic treatment. A potential alternative to the use of antibiotics is the bacteriocin nisin. However, it has been shown that many strains of S. uberis possess a nisin resistance protein (NSR). Pérez-Ibarreche et al. (e00391-21) demonstrate that a novel nisin derivative (nisin PV) can not only bypass the NSR system but also eradicate S. uberis biofilms. These findings will add new therapeutic possibilities for the control of S. uberis-associated mastitis.

Acinetobacter baumannii Infections in Hospitalized Patients, Treatment Outcomes.

Background Acinetobacter baumannii (AB), an opportunistic pathogen, could develop into serious infections with high mortality and financial burden. The debate surrounding the selection of effective antibiotic treatment necessitates studies to define the optimal approach. This study aims to compare the clinical outcomes of commonly used treatment regimens in hospitalized patients with AB infections to guide stewardship efforts. Material and methods: Ethical approval was obtained, 320 adult patients with confirmed AB infections admitted to our tertiary care facility within two years were enrolled. The treatment outcomes were statistically analyzed to study the relation between antibiotic regimens and 14, 28, and 90-day mortality as the primary outcomes using binary logistic regression—using R software—in addition to the length of hospitalization, adverse events due to antibiotic treatment, and 90-day recurrence as secondary outcomes. Results: Among 320 patients, 142 (44%) had respiratory tract, 105 (33%) soft tissue, 42 (13%) urinary tract, 22 (7%) bacte iemia, and other infections 9 (3%). Nosocomial infections were 190 (59%) versus community-acquired. Monotherapy was significantly associated with lower 28-day (p < 0.05, OR:0.6] and 90-day (p < 0.05, OR:0.4) mortality rates, shorter length of stay LOS (p < 0.05, Median: −12 days] and limited development of adverse events (p < 0.05, OR:0.4). Subgroup analysis revealed similar results ranging from lower odds of mortality, adverse events, and shorter LOS to statistically significant correlation to monotherapy. Meropenem (MEM) and piperacillin/tazobactam (PIP/TAZ) monotherapies showed non-significant high odd ratios of mortalities, adverse events, and disparate LOS. There was a statistical correlation between most combined therapies and adverse events, and longer LOS. Colistin based and colistin/meropenem (CST/MEM) combinations were superior in terms of 14-day mortality (p = 0.05, OR:0.4) and (p < 0.05, OR:0.4) respectively. Pip/Taz and MEM-based combined therapies were associated with statistically non-significant high odd ratios of mortalities. Tigecycline (TGC)-based combinations showed a significant correlation to mortalities (p < 0.05, OR:2.5). Conclusion: Monotherapy was associated with lower mortality rates, shorter LOS, and limited development of adverse events compared to combined therapies. Colistin monotherapy, colistin/meropenem, and other colistin combinations showed almost equivalent mortality outcomes. Patients on combined therapy were more susceptible to adverse events and comparable LOS. The possible adverse outcomes of PIP/TAZ and MEM-based therapies in the treatment of MDRAB infections and the association of TGC with a higher mortality rate raise doubts about their treatment role.