Antimicrobials For Treatment Of Infections Research Articles

Recommendations on diagnosis and antimicrobial treatment of infections after anterior cruciate ligament reconstruction (ACL-R) endorsed by ESSKA and EBJIS

Infection after anteriorcruciate ligament reconstruction (ACL-R) is a rare but devastating complication affecting predominantly young and sportive individuals. A timely and correct diagnosis as well as optimized management is paramount to circumvent serious sequelae and compromise in life quality. These recommendations are primarily intended for use by infectious disease specialists and microbiologists, but also orthopedic surgeons and other healthcare professionals who care for patients with infections after ACL-R. They are based on evidence mainly originating from observational studies and opinions of experts in the field, and cover the management of infections after ACL-R with a special focus on etiology, diagnosis, antimicrobial treatment and prevention. Comprehensive recommendations on surgical treatment and rehabilitation are presented separately in a document primarily addressing orthopedic professionals.

Study on the Synthesis and Antibacterial Activity of Cobalt-Metal Organic Framework

Hydrogen peroxide (H2O2) has been widely used in the treatment of antimicrobial infections, but high doses of H2O2 can cause damage to normal tissues. Avoiding the use of high doses of H2O2 as well as being effective against multidrug-resistant bacteria, nanomaterials with peroxidase-like properties have been developed as a new class of antimicrobial agents. Here, we have synthesized Co-TCPP(Fe)(Co-MOF), a metal-organic framework material with a laminar folded structure and a heterogeneous surface morphology, using a solvothermal method, which exhibits good bactericidal activity against Pseudomonas aeruginosa with the help of low concentrations of H2O2.

1101. Implementing a Beta-Lactam Therapeutic Drug Monitoring Program: Experience from a Large Academic Medical Center

BackgroundBeta-lactams (BL) are the cornerstone of antimicrobial treatment for infections. Beta-lactam therapeutic drug monitoring (BL-TDM) optimizes drug concentrations to ensure maximal efficacy and minimal toxicity. The goals of this study were to describe the implementation process of a BL-TDM program and to further describe our experience using BL-TDM in clinical practice. MethodsThis was a retrospective review of adult patients with available BL-TDM between January 2016 and November 2019 at the University of Florida (UF) Health Shands Hospital. Total serum concentrations of BL were measured in the Infectious Diseases Pharmacokinetics Lab (IDPL) at UF, using a validated ultrahigh pressure liquid chromatography assay with triple quadrupole mass spectroscopy (LC-MS-MS). At our institution, TDM is available for 11 BLs and in-house assays are performed from Mon-Fri for most BLs.ResultsA total of 3,030 BL concentrations were obtained. An analysis was performed on the first BL-TDM encounter in 1,438 patients. The median age was 57 years (IQR, 41-69) and the median BMI was 27.5 kg/m2 (IQR, 22.5-34.5). On the day of BL-TDM, the median serum creatinine was 0.83 (IQR, 0.59-1.30). Fifty-one percent of patients (n=735) were in an ICU at the time of BL-TDM with a median SOFA score of 6 (IQR, 3-9). BL-TDM was most frequently performed on cefepime (61%, n=882), piperacillin (15%, n=218), and meropenem (11%, n=151). The BL was administered as a continuous infusion in 211 (15%) patients. An interim analysis of 548 patients showed that BL-TDM was performed a median of 2 days (IQR, 1-4) from the start of BL therapy and resulted in a dosage adjustment in 26% (n=145). ConclusionBL-TDM was performed in older, non-obese patients with normal renal function. Over half of the evaluated patients were in an ICU at the time of TDM. This finding emphasizes the value of BL-TDM in the ICU setting because altered pharmacokinetics during critical illness has been linked to enhanced BL clearance. Interestingly, BL-TDM resulted in dosage adjustment in 1 in 4 patients who were receiving licensed BL dosing regimens, thus highlighting the role of TDM in dose individualization. BL-TDM was performed most commonly within the 72-hours of therapy initiation. Early BL-TDM has been shown to improve patient outcomes and should be promoted.Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry) Charles A. Peloquin, Pharm.D., Nothing to disclose

Antibiotics in the Pipeline for Treatment of Infections due to Gram-Negative Organisms

We systematically review the literature on antibiotics approved by the Food and Drug Administration since 2015 or that are in development through phase III trials for the treatment of infections due to gram-negative organisms. The crisis of antimicrobial resistance creates a dire need for the development of novel antimicrobials with enhanced activity against resistant bacteria. Of the agents that are currently in the pipeline or recently approved, few are from new classes and most represent modifications of preexisting agents. There continues to be a lack of treatment options especially for infections caused by organisms that produce metallo-β-lactamases. Furthermore, there is a paucity of data investigating the efficacy of these new antimicrobials for treatment of infections due to multidrug-resistant organisms. This review outlines the antimicrobials in development for the treatment of infections due to gram-negative bacteria. There are various agents in development that seem promising, but more studies are needed to evaluate the efficacy of these agents in treating infections, especially those due to multidrug-resistant organisms. The development of new antimicrobials is critical to combat the crisis of antimicrobial resistance.

Accessible Agent-Fatty Acid Coatings of Titanium Prostheses for Local Prevention and Treatment of Anti-Microbial Infections

Prosthetic joint infection represents a major issue in arthroplasty. Local anti-infective treatment is not established in cementless prosthetic surgery. The aim of this study was to perform simulate a perioperative application of agent-fatty acid complexes on surfaces of primary and revision prosthetic material. Further, it was aimed to investigate the efficacy of these coatings by in vitro microbiological tests. Coating of cemetless titanium prostheses with gentamicin-palmitate and octenidine-laurate was performed by using a spray gun system. Coating with vancomycin eluted in trilaurin was performed by dipping of the prostheses in the solution. The prostheses were incubated in phosphate buffered saline for 7 days. Microbiological testing was performed with inhibition areolae testing for S. aureus, S. epidermidis, MRSA and C. albicans. Coating of prosthetic material was reliable and reproducible with two different techniques, dipping and spraying. The surface-concentrations of agents have reached 195μg/cm2 for gentamicin, 460μg/cm2 for octenidine and 323μg/cm2 for vancomycin. Agents inhibited S. epidermidis and S. aureus growth for seven days, C. albicans for three days and MRSA for two days. Agent-fatty acid coatings used in this study represent a biodegradable layer with good biocompatibility and comparable anti-infective efficacy as in cemented surgery due to the use of established agents, even if low concentrations are used. Modular and individual anti-infective coating was reproducibly and reliably performed by dipping coating, which may represent a potential perioperative coating approach.

Antibacterial Activity and Time-kill Kinetics of Positive Enantiomer of α-pinene Against Strains of Staphylococcus aureus and Escherichia coli.

Research on new antimicrobial agents is needed, as more and more microorganisms that cause antibiotic-resistant diseases are emerging commercially. In this group, we can find strains of Staphylococcus aureus and Escherichia coli, which are highly opportunistic species. Faced with this perspective, research using essential oils present in plants is emerging as a therapeutic alternative for the treatment of antimicrobial infections. Many of these oils have, in their composition, monoterpene α-pinene, that shows to have antibacterial activity. The purpose of this research is to evaluate the antimicrobial activity of the positive enantiomer of α-pinene against strains of Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. The methodologies used were: Disc-diffusion test, broth microdilution and bacterial death kinetics, all of which were standardized by CLSI. As a result, inhibition halos of 11 mm was obtained for the gram-positive strain and 12 mm for the gram-negative strain, both at the same concentration, 160 µl / ml. In addition, it was possible to observe with the death curve that the concentrations (1.25 µl/mL and 2.5 µl/mL of the (+)-α-pinene were able to eliminate the formation of bacterial colonies at one time of exposure of 2 hours for the E. coli strain. However, the death curve of the S. aureus strain was characterized by non-elimination of bacterial colonies at a 24 hours exposure time used for the experiment. Only amikacin evidenced its bacterial killing rate of all colonies within two hours of exposure. At the end, it was possible to verify the activity of the phytoconstituent against Escherichia coli strains ATCC 25922 and Staphylococcus aureus ATCC 25923, recommending the continuity of the studies with the use of different methodologies so that (+) - α-pinene in the future can be a compound used in antimicrobial therapy.

Detection of Carbapenem Resistant Gram-Negative Bacteria in Clinical Isolates from a Tertiary Care Hospital

Carbapenem resistance is one of the major threats faced in antimicrobial treatment of infections caused by Gram negative organisms. In India and throughout the world the use of carbapenems has increased resulting in an increased resistance of pathogens to this class of antibiotics. Bacteria are capable enough to become resistant to antibiotics by a number of mechanisms both intrinsic and acquired, most common of which include enzymatic degradation of antibiotics. Carbapenem resistant Gram-negative bacteria usually spreads in the hospital settings to other patients and caregivers or relatives by unwashed hands or from contact with soiled equipment and surfaces such as bedrails, tables, chairs, countertops and door handles. These carriers are the ultimate sources of dissemination in the community. Detection of carbapenems is a crucial infection control issue because they are often associated with extensive antibiotic resistance, treatment failures and infection-associated mortality. The present study was undertaken to determine Carbapenem resistant Gram-negative bacteria in clinical isolates from a tertiary care hospital.

Clinical Importance of Carbapenemase Production in Gram-Negative Bacteria

Carbapenem resistance is one of the major threats faced in antimicrobial treatment of infections caused by Gram negative organisms. In India and throughout the world the use of carbapenems has increased resulting in an increased resistance of pathogens to this class of antibiotics. Bacteria are capable enough to become resistant to antibiotics by a number of mechanisms both intrinsic and acquired, most common of which include enzymatic degradation of antibiotics. Carbapenem resistant Gram-negative bacteria usually spreads in the hospital settings to other patients and caregivers or relatives by unwashed hands or from contact with soiled equipment and surfaces such as bedrails, tables, chairs, countertops and door handles. These carriers are the ultimate sources of dissemination in the community. Detection of carbapenemase is a crucial infection control issue because they are often associated with extensive antibiotic resistance, treatment failures and infection-associated mortality. For the identification of carbapenemase producers different nonmolecular methods are used such as E- test (Epsilometer Test), Modified hodge test, MIC by Agar Dilution Method, Carba NP Test, EDTA disk synergy test, Boronic Acid Test, 2-mercaptopropionic acid inhibition (2-MPA) test. Molecular techniques remain the gold standard for the precise identification of carbapenemase genes. Most of these techniques are based on PCR and may be followed by a sequencing step if a precise identification of the carbapenemase gene is needed. This review article describes clinical importance and methods used for the identification of carbapenemase producers.

Identification and Differentiation of Carbapenemases in Klebsiella Pneumoniae: A Phenotypic Test Evaluation Study from Jaipur, India

Carbapenem resistance is one of the major threats faced in antimicrobial treatment of infections caused by gram negative organisms. In recent years, carbapenem resistance has emerged in Klebsiella pneumoniae isolates due to acquisition of carbapenemases which belong to Ambler class A KPC type enzymes or to Ambler class B metallo-β-lactamases (MBL). Routine lab detection of carbapenemase producing K. pneumoniae isolates is crucial, both for a therapeutic management and an efficient infection control. A study was conducted on 60 carbapenem resistant Klebsiella pneumoniae strains which were isolated from various clinical samples over a period of one year (September 2010-August 2011), at a tertiary care hospital in Jaipur. Phenotypic confirmatory test was done by using discs of Meropenem alone and those with phenyl boronic acid (PBA) or Ethylenediaminetetraacetic acid (EDTA) or both, for detection of carbapenemase production and differentiation of KPC and MBL enzymes. Of the 60 carbapenem resistant Klebsiella pneumoniae isolates, 53 (88.33%) were found to be MBL producers, 4(6.66%) were found to be MBL and KPC co-producers and the rest of the 3(5%) isolates were negative for both MBL and KPC production, as was seen by combined disc testing. The combined disc test is a simple test which can be used for differentiation of carbapenemases and it can be easily incorporated in routine microbiology lab testing.

Comparison of antigen and two molecular methods for the detection of Clostridium difficile toxins

Clostridium difficile (CD) is considered an important cause of diarrhoea associated with the antimicrobial treatment of infections. The pathogenicity of CD is due to toxins A and B, produced by toxigenic CD strains. We evaluated 3 methods for detecting CD toxins: the RIDASCREEN® enzyme immunoassay (EIA) (R-Biopharm)--one detecting toxins directly in the stool specimens and another detecting toxins from isolated CD strains--and 2 molecular methods, the illumigene™ loop-mediated isothermal amplification (LAMP) assay (Meridian) and RIDA®GENE polymerase chain reaction (PCR) assay (R-Biopharm), as direct identification methods from stool specimens. Toxigenic culture (TC) was used as the reference method. Altogether 884 stool samples were analyzed, of which 253 (29%) were positive by TC. Six hundred and seventy-two specimens were tested by RIDASCREEN EIA, 430 were tested with the illumigene LAMP assay, and 212 were tested with the RIDA GENE PCR assay. CD toxin A and B antigen tests by EIA were very insensitive, both directly from stool specimens (2 series; 57-61%) and in isolated CD strains (53%); consequently the negative predictive value remained low (84-93% and 91%, respectively). Specificity, however, was very good at 98-100%. The 2 molecular methods detected CD toxin genes excellently and equally, resulting in sensitivities, specificities, and positive and negative predictive values of 98%, 100%, 100%, and 98%, respectively. Both molecular assays were easy to use, rapid, sensitive, and specific for the detection of toxigenic CD strains.

Chemical and Antimicrobial Evaluation of Supercritical and Conventional Sideritis scardica Griseb., Lamiaceae Extracts

Sideritis scardica Griseb., Lamiaceae (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of antimicrobial infections, gastrointestinal complaints, inflammation and rheumatic disorders. This study reports a comparison between conventional (hydrodistillation HD and solvent extraction SE) and alternative (supercritical carbon dioxide SC CO2) extraction methods regarding the qualitative and quantitative composition of the obtained extracts as analyzed by GC and GC-MS techniques and their anitimicrobial activity. Different types of extracts were tested, the essential oil EO obtained by HD, EO-CO2 and AO-CO2 obtained by SC CO2 at different preasures 10 and 30 MPa, at 40 °C, respectively, and the fractions A, B, C and D obtained by successive solvent extraction (SE) A: ethanol, B: diethyl ether, C: ethyl acetate and D: n-butanol). While EO was characterized by the presence of the high percentage of oxygenated monoterpenes and sesquiterpenes (30.01 and 25.54%, respectively), the rest of the investigated samples were the most abundant in fatty acids and their esters and diterpenes (from 16.72 to 71.07% for fatty acids and their esters, and from 23.30 to 72.76%, for diterpenes). Microbial susceptibility tests revealed the strong to moderate activity of all investigated extracts against the tested microorganisms (MIC from 40 to 2,560 μg/mL). Although differences in the chemical compositions determined by GC and GC-MS analysis were established, the displayed antimicrobial activity was similar for the all investigated extracts.

Modelling treatment effects in a clinical Bayesian network using Boolean threshold functions

Appropriate antimicrobial treatment of infections in critically ill patients should be started as soon as possible, as delay in treatment may reduce a patient's prognostic outlook considerably. Ventilator-associated pneumonia (VAP) occurs in patients in intensive care units who are mechanically ventilated and is almost always preceded by colonisation of the respiratory tract by the causative microorganisms. It is very difficult to clinically diagnose VAP and, therefore, some form of computer-based decision support might be helpful for the clinician. As diagnosing and treating VAP involves reasoning with uncertainty, we have used a Bayesian network as the primary tool for building a decision-support system. The effects of usage of antibiotics on the colonisation of the respiratory tract by various pathogens and the subsequent antibiotic choices in case of VAP were modelled using the notion of causal independence. In particular, the conditional probability distribution of the random variable that represents the overall coverage of pathogens by antibiotics was modelled in terms of the conjunctive effect of the seven different pathogens, usually referred to as the noisy-AND model. In this paper, we investigate different coverage models, as well as generalisations of the noisy-AND, called noisy-threshold models, and test them on clinical data of intensive care unit (ICU) patients who are mechanically ventilated. Some of the constructed noisy-threshold models offered further improvement of the performance of the Bayesian network in covering present causative pathogens by advising appropriate antimicrobial treatment. By reconsidering the modelling of interactions between the random variables in a Bayesian network using the theory of causal independence, it is possible to refine its performance. This was clearly shown for our Bayesian network concerning VAP, indicating that only specific noisy-threshold models might be appropriate for the modelling of the interaction between pathogens and antimicrobial treatment with respect to susceptibility. The results obtained also provide evidence that the noisy-OR and noisy-AND might not always be the best functions to model interactions among random variables.

Therapeutic Considerations in the Treatment of Respiratory Infections Caused by Ceftazidime-Resistant Klebsiella Pneumoniae

Klebsiella pneumoniae are important human pathogens, particularly as causes of nosocomial respiratory tract infections. Intrinsically resistant to ampicillin, in recent years K. pneumoniae strains have acquired resistance to a broad variety of extended-spectrum cephalosporins. This resistance is most commonly mediated by the extended-spectrum beta-lactamases (ESBLs), plasmid-mediated enzymes that have evolved through point mutations in the genes encoding the more susceptible penicillinases TEM-1 and SHV-1. In a small minority of cases, K. pneumoniae have also been found to express extended-spectrum cephalosporin resistance by the elaboration of plasmid-mediated AmpC-type enzymes. These mutant enzymes confer resistance to extended-spectrum cephalosporins, penicillins, and in some cases cefamycins or beta-lactam-beta-lactamase inhibitor combinations. The most reliable and effective antimicrobial treatment of infections caused by these strains are the carbapenems imipenem and meropenem.

Ochrobactrum anthropi bacteremia: case report and review of the literature.

Ochrobactrum anthropi bacteremia: case report and review of the literature.

The incidence and antimicrobial treatment of infections of the foot.

The incidence and antimicrobial treatment of infections of the foot.