∆9-THC, CBD is the sole cannabinoid that has been thoroughly .. lack of difference between study arms . Oromucosal CBD/∆9-THC. Stereoisomers. N/A. Methods and Ease of Illicit Manufacturing compositions comprise: principal cannabinoids (∆9-THC (>90% of the cannabinoid fraction in pharmacokinetics of THC/CBD oromucosal spray. ∆9-THC, CBD is the sole cannabinoid that has been thoroughly tested in humans Oromucosal CBD/∆9-THC. Five trials administered CBD/∆9-THC via.
Oromucosal CBD/∆9-THC 5.2.3.
Paradoxically, some animal studies have found that the dose-response of CBD follows an inverted U shape, leading to an anxiogenic effect through its agonism of TRPV 1—2 receptors which are believed to be responsible for detection and regulation of body temperature, and thermal nociception [ 82 ]. Consequently, it is yet unclear whether there is a role for inhibition of endocannabinoid catabolic enzymes in the anxiolytic effects of CBD. However, both studies administered low doses of CBD 2.
The same group later demonstrated that the synthetic CBD derivative—HU—exerted more potent effects in the same direction [ 91 ]. More recently, there is evidence that cannabidiol derivative, O, reduced movement-evoked firing of nociceptive C fibres in a rat model of acute inflammatory joint pain [ 92 ].
As a whole, these data indicate that CBD and its analogues may be beneficial for pain resulting from inflammation, however, human studies on this topic are lacking. The strength of the antiepileptic effects of CBD may be difficult to judge clinically because of its potent antagonism of multiple CYP isoenzymes, potentially reducing plasma levels of concomitant anticonvulsants.
Preclinical data has indicated that CBD displays antiepileptiform and antiseizure properties in vitro and in vivo CBD may possess antiepileptic properties via different mechanisms. For instance, there is evidence that CBD can block low-voltage-activated T-type Ca 2 channels, and increase the activity of inhibitory glycine receptors [ 33 , 34 ].
More recently, Jones et al. The antiepileptic effects associated with CBD were suggested to be due a potentially CB 1 independent mechanism because CBD acted with only low affinity at CB 1 receptor and displayed no agonist activity in [ 35 S]guanosine 5'- O - 3-thio -triphosphate assays in cortical membranes. Despite its putative benefits for social anxiety disorder, insomnia and epilepsy studies suggest that high-dose CBD — mg may increase mental sedation in normal individuals and aggravate cognitive deficits in schizophrenia—without altering physical sedation [ 42 , 62 , 67 ].
However, the treatments were not significantly different from placebo on digit symbol substitution, choice reaction, sustained attention, six-letter memory recall, digit memory recall. Moreover, Karniol et al. On the other hand, Dalton et al. Current evidence is equivocal regarding a potential antipsychotic effect of CBD. For example, Zuardi et al. Likewise, the CB 1 antagonist, SR, was ineffective for the treatment of positive or negative symptoms in schizophrenia [ 94 ].
In another study, oral CBD mg enhanced the psychomotor activating effects of intravenous ketamine, without significantly altering ketamine-induced psychiatric symptoms [ 47 ]. On the other hand, preliminary data from a four-week, randomized-controlled trial of CBD mg versus amisulpride mg for schizophrenia did not reveal any significant differences between the groups—suggesting that the former exerted an antipsychotic effect [ 64 ]. For example, Karniol et al. A dose-dependent interaction was also evidenced in the study by Ilan et al.
By contrast, Dalton et al. Another group found significantly greater MMN amplitude values at central electrodes following treatment with combined CBD 5. Finally, a study using nabilone 1 mg showed that the molecule significantly impaired binocular depth inversion an illusion of visual perception that provides a model of impaired perception during psychotic states and this effect was partially reversed by CBD mg [ 48 ].
By contrast, Nadulski et al. Nevertheless, the pharmacokinetic impact of CBD was small compared to other factors such as gender and body mass index.
Indeed, Karniol et al. Some of the variability in results may be attributed to the fact that studies contained small sample sizes and measured multiple variables, leading to the possibility of a Type-I error s.
Such an effect may be one reason why some studies found contradictory results using similar dose-ratios between the cannabinoids [ 51 , 55 ]. A balance between pharmacokinetic and pharmacodynamic factors may be responsible for the disparate findings, depending on the measure, route of administration and dose-ratio between the cannabinoids.
Likewise, studies did not consistently observe benefits of CBD monotherapy in bipolar mania or schizophrenia patients. Future studies should investigate clinical applications of high-dose oral CBD for disorders such as anxiety, neuropathic pain, inflammatory pain, multiple sclerosis, insomnia and epilepsy. If CBD is not found to be beneficial in these trials, new more selective and more bioavailable molecules need to be developed in order to harness the full therapeutic potential of cannabinoid molecules.
Currently, the most promising candidates are inhibitors of endocannabinoid catabolic enzymes e. National Center for Biotechnology Information , U. Journal List Pharmaceuticals Basel v. Published online May Author information Article notes Copyright and License information Disclaimer. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license http: This article has been cited by other articles in PMC.
Abstract Cannabidiol CBD , a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. Pharmacokinetics CBD undergoes a significant first-pass effect leading to the formation of a number of metabolites, most notably, 7-hydroxy-CBD and CBDoic acid [ 13 , 14 ].
Results A total of 34 studies were identified. Table 1 Experimental studies. Open in a separate window. Table 2 Clinical trials. Experimental Studies in Healthy Controls 5. Clinical Trials in Patient Populations 5.
Discussion Experimental studies suggest that high-dose CBD may decrease anxiety and increase mental sedation in healthy individuals. History of cannabis as a medicine: Chemical constituents of marijuana: The complex mixture of natural cannabinoids. The effects of cannabinoids on the brain. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo.
Potential antipsychotic properties of central cannabinoid CB1 receptor antagonists. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Interaction between non-psychotropic cannabinoids in marihuana: The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain.
From an inactive cannabinoid to a drug with wide spectrum of action. A promising drug for neurodegenerative disorders? Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man.
Metabolites of cannabidiol identified in human urine. Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration. The Medicinal Uses of Cannabis and Cannabinoids. Randomized, double-blind, placebo-controlled study about the effects of cannabidiol CBD on the pharmacokinetics of deltatetrahydrocannabinol THC after oral application of THC verses standardized cannabis extract.
Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Potent inhibition of human cytochrome P 3A isoforms by cannabidiol: Role of phenolic hydroxyl groups in the resorcinol moiety.
Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P 2C9 activity. Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man. Anticonvulsant properties of cannabidiol. Cannabidiol-antiepileptic drug comparisons and interactions in experimentally induced seizures in rats.
The orphan receptor GPR55 is a novel cannabinoid receptor. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Agonistic properties of cannabidiol at 5-HT1a receptors. Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide.
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes.
Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alphabeta glycine receptor function. Distribution and characterization of anandamide amidohydrolase in mouse brain and liver. Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: Focus on G-protein-coupled receptors and transient receptor potential channels.
Cannabidiol and cannabinol in man. Interaction of cannabidiol and alcohol in humans. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers. Effects of ipsapirone and cannabidiol on human experimental anxiety.
Effects of cannabidiol CBD on regional cerebral blood flow. Neural basis of deltatetrahydrocannabinol and cannabidiol: Effects during response inhibition.
Modulation of auditory and visual processing by deltatetrahydrocannabinol and cannabidiol: Modulation of effective connectivity during emotional processing by deltatetrahydrocannabinol and cannabidiol.
The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects.
Different effects of nabilone and cannabidiol on binocular depth inversion in man. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man. Interactions in man of deltatetrahydrocannabinol. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects.
Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity. Effects of acute oral deltatetrahydrocannabinol and standardized cannabis extract on the auditory P event-related potential in healthy volunteers.
Psychomotor performance in relation to acute oral administration of deltatetrahydrocannabinol and standardized cannabis extract in healthy human subjects. Effect of deltatetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Influence of cannabidiol on deltatetrahydrocannabinol effects. Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids.
Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for Staphylococcus aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis.
In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentration levels of photo-activated TAPP could be used to boost the activity of waning antibiotics.
This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy. Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.
Enterococci are common causes of infective endocarditis IE in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. Is there an improvement of antibiotic use in China?
Evidence from the usage analysis of combination antibiotic therapy for type I incisions in hospitals. The improvement of antibiotic rational use in China was studied by usage analysis of combination antibiotic therapy for type I incisions in hospitals.
Five kinds of hospitals, including general hospital, maternity hospital, children's hospital, stomatological hospital and cancer hospital, from 30 provinces were surveyed.
A systematic random sampling strategy was employed to select outpatient prescriptions and inpatient cases in and A total of 29 outpatient prescriptions and 73 inpatient cases from hospitals in each year were analyzed. Data were collected with regards to the implementation of the national antibiotic stewardship program NASP , the overall usage and the prophylactic use of antibiotic for type I incisions.
Univariate analysis was used for microbiological diagnosis rate before antimicrobial therapy , prophylactic use of antibiotics for type I incision operation, and so on. For multivariate analysis, the use of antibiotics was dichotomized according to the guidelines, and entered as binary values into logistic regression analysis. The results were compared with the corresponding criteria given by the guidelines of this campaign.
Hospital type appeared to be a factor statistically associated with stewardship outcome. The prophylactic use of antibiotics on type I incision operations decreased by Region and bed size were the main determinants on surgical prophylaxis for type I incision. This national analysis of hospitals on antibiotic use and stewardship allows relevant comparisons for bench marking.
More efforts addressing the root cause of antibiotics abuse would continue to improve the rational use of antibiotics in China. Combination therapy including serratiopeptidase improves outcomes of mechanical- antibiotic treatment of periimplantitis. This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase SPEP or non-steroidal anti-inflammatory drugs NSAIDs.
Clinical charts of partially edentulous patients treated for periimplantitis between June and December were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs.
The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered.
The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.
Comparative study of the efficacy of topical steroid and antibiotic combination therapy versus oral antibiotic alone when treating acute rhinosinusitis.
Acute rhinosinusitis arises as a consequence of viral rhinitis, and bacterial infection can subsequently occur. Intranasal antibiotics as an adjunct to corticosteroids usually demonstrate the greatest symptom relief. We wanted to clinically evaluate the effects of a topical antibiotic and steroid combination administered intranasally, versus an oral antibiotic alone when treating acute rhinosinusitis. Forty patients with acute bacterial rhinosinusitis were divided into two groups.
Group A received an antibiotic and steroid combination ofloxacin 0. Eight hours after commencing treatment, facial pain was more severe in group B and nasal obstruction was reduced in both groups. Ten days after commencing treatment, anterior nasal discharge was 0. The application of a topical antibiotic and steroid combination into the nasal cavity is an effective way of treating uncomplicated, acute bacterial rhinosinusitis with the theoretical advantages of easy administration, high local drug concentration and minimal systemic adverse effects.
Anthrax prevention and treatment: The intentional release of anthrax spores in confirmed this pathogen's ability to cause widespread panic, morbidity and mortality.
While individuals exposed to anthrax can be successfully treated with antibiotics , pre-exposure vaccination can reduce susceptibility to infection-induced illness. Second-generation anthrax vaccines based on purified recombinant protective antigen rPA have entered clinical trials. These rPA vaccines induce neutralizing antibodies that prevent illness, but the magnitude and duration of the resultant protective response is modest. Efforts are underway to bolster the immunogenicity of rPA by combining it with adjuvants and other immunostimulatory agents.
Third generation vaccines are under development that utilize a wide variety of immunization platforms, antigens, adjuvants, delivery methods and routes of delivery to optimize the induction of a protective immunity. For the foreseeable future, vaccination will rely on first and second generation vaccines co-administered with immune adjuvants.
Optimal post-exposure treatment of immunologically naive individuals should include a combination of vaccine plus antibiotic therapy. Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy. There is some evidence to suggest that host inflammatory response has some effect on the clinical manifestations of cellulitis. The objective of this pilot study was to investigate whether the addition of oral nonsteroidal anti-inflammatory NSAI therapy to antibiotic treatment hastens resolution of cellulitis-related inflammation.
Patients were discharged as soon as possible to complete their therapy on an outpatient basis. The addition of an oral anti-inflammatory agent significantly P antibiotic alone required 6 to 7 days, and 6. Antibiotic prescription patterns in the empiric therapy of severe sepsis: Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined.
Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy , including antimicrobials with different mechanisms of action, on mortality.
This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic -prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy DCCT , with that of monotherapy and any other combination therapy possibilities non-DCCT.
We included 1, patients, 1, DCCT was administered to patients Towards a compatible probiotic- antibiotic combination therapy: To determine the antimicrobial resistance of the Japanese probiotics available in the market without a pharmacist's supervision. A total of 43 isolates were obtained from 40 samples of probiotics 30 dairy products and 10 products in tablet form. Isolates were identified using 16S rRNA gene sequencing and tested for their susceptibility to 14 antimicrobials.
They were screened using PCR for some antibiotic resistance genes. Inactivation of cefepime, clarithromycin and vancomycin by different inocula of 11 strains was evaluated using the antibiotic inactivation bioassay. None of the dairy probiotics showed a level of constitutive resistance or carried inducible resistance genes, making them suitable to be administrated with macrolides.
There is a limited choice of the Japanese probiotics that can be administered with clinically used antibiotics. Japanese probiotics are widely distributed all over the world. Through the findings of our study, we have attempted to provide guidance for clinicians interested in using the Japanese probiotics in combination with antibiotics.
New options of antibiotic combination therapy for multidrug-resistant Pseudomonas aeruginosa. Several antibiotic combinations have demonstrated increased activity against multidrug-resistant Pseudomonas aeruginosa MDRP in vitro compared with a single antibiotic. The aim of this study was to investigate the activity against MDRP of some aminoglycosides in combination with monobactam, piperacillin PIPC , and carbapenem.
Our new method was designed to evaluate three concentrations around the breakpoint of each drug using the Checkerboard method. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory.
One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy PDT , which requires the administration of photosensitizer, followed by light activation. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm.
In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy. Ongoing debate exists concerning the optimal choice and duration of antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic therapy for hospital-acquired infections in critically ill cardiac surgery patients.
A nationwide questionnaire was distributed to all German heart surgery centers concerning antibiotic prophylaxis and the calculated empiric antibiotic therapy. The response to the questionnaire was If sepsis is suspected, the following diagnostics are performed routinely: The calculated empiric antibiotic therapy depending on the suspected focus consists of a multidrug combination with broad-spectrum agents. This survey shows that existing national guidelines and recommendations concerning perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy are well applied in almost all German heart centers.
Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection.
Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells MSCs derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs MenSCs emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions.
Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides AMPs by quantitative reverse transcription-polymerase chain reaction.
The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.
Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.
We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance.
The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.
Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis - A systematic review with meta-analysis and trial sequential analysis. To assess benefits and harms of empirical mono- vs. We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias assessment and trial sequential analysis TSA. We included randomised clinical trials RCT assessing empirical mono- antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis.
We exclusively assessed patient-important outcomes, including mortality. Two reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Carbapenems were the most frequently used mono- antibiotic 8 of 13 trials. There was no difference in mortality RR 1.
For the other outcomes, TSA indicated lack of data and high risk of random errors. Published by Elsevier Ltd. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. There is also growing clinical data to support such combinations , including a recent pilot randomised controlled trial RCT that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone.
Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. We will perform an open-label, parallel-group, randomised 1: Adults aged 18 years or older with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion.
The primary endpoint will be a composite outcome at 90 days of 1 all-cause mortality, 2 persistent bacteraemia at day 5 or beyond, 3 microbiological relapse, or 4 microbiological treatment failure.
Inflammation occurs along with infection during sepsis. In this study, we examined the effects of epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. Mice were injected with E. The effects of epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days.
In addition, we examined the effects of epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. Treatment with epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum.
Combined treatment of epi-lipoxin A4 with antibiotics significantly improved survival in E. Taken together, these data suggested that epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without.
The efficacy of combined therapy with metronidazole and broad-spectrum antibiotics on postoperative outcomes for pediatric patients with perforated appendicitis. The aim of this study was to evaluate the efficacy of combined therapy with metronidazole and broad-spectrum antibiotics for patients with perforated appendicitis who underwent surgical intervention. Broad-spectrum antibiotic therapy is warranted in the treatment of perforated appendicitis.
Metronidazole has been used as anaerobic antimicrobial therapy. However, few studies about the use of metronidazole in perforated appendicitis have been reported. The medical records of patients treated with metronidazole combined with broad-spectrum antibiotics following perforated appendicitis surgery were reviewed retrospectively and compared with the medical records of patients treated only with broad-spectrum antibiotics.
Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including postoperative complications and length of hospital stay, were compared between the 2 groups. No differences were found between the use of combined therapy with metronidazole and the use of solely broad-spectrum antibiotic agents with regard to postoperative duration of intravenous antibiotic treatment 6.
There were also no differences in the incidence of postoperative complications, including the intra-abdominal or pelvic abscess rate 7[7. Regarding overall postoperative outcomes and complications, our study demonstrated no beneficial clinical effects of.
Abstract The aim of this study was to evaluate the efficacy of combined therapy with metronidazole and broad-spectrum antibiotics for patients with perforated appendicitis who underwent surgical intervention.
Regarding overall postoperative outcomes and complications, our study demonstrated no beneficial. Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study.
The femoral medullary cavity of 66 male Wistar rats was contaminated with S. Six treatment groups were studied: The treatment was applied for 14 days.
After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments moxifloxacin plus rifampin and flucloxacillin plus rifampin achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono- antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm.
The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections. Probiotics administered intravaginally as a complementary therapy combined with antibiotics for the treatment of bacterial vaginosis: Bacterial vaginosis BV is a highly prevalent vaginal polymicrobial disorder commonly encountered in women of childbearing age.
Therapy with only recommended antibiotics results in low cure rates and unacceptably high recurrence rates. The use of probiotics as a complementary approach for use with antibiotics for the treatment of BV remains unclear. This review aims to assess the efficacy of lactobacilli administered intravaginally in conjunction with antibiotics for the treatment of BV.
Randomised controlled clinical trials using lactobacilli administered intravaginally in conjunction with antibiotics to treat BV will be included. Primary outcome will be the BV cure rate. The recurrence rate will be examined as secondary outcome. Two reviewers will independently select trials and extract data from the original publications.
The risk of bias will be assessed according to the Cochrane Risk of Bias tool. To assess heterogeneity, we will compute the I 2 statistic. This study will be a review of published data and it is not necessary to obtain ethical approval. Findings of this systematic review will be published in a peer-reviewed journal.
International Prospective Register of Systematic Reviews No commercial use is permitted unless otherwise expressly granted. Antibiotic-non-antibiotic combinations for combating extremely drug-resistant Gram-negative 'superbugs'. The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis.
The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post- antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant XDR Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non- antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens.
This review surveys the available literature on the potential benefits of employing antibiotic-non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by 'superbugs'. Acne vulgaris, a chronic condition associated with overgrowth of Propionibacterium acnes and Staphylococcus epidermidis, is commonly treated with antibiotics.
However, the emergence of antibiotic resistance has resulted in a need for alternative therapies. The aim of this study is to develop a topical preparation incorporating essential oils EOs for use against acne-associated bacteria and assess its efficacy against prescription therapies Dalacin T and Stiemycin. Antimicrobial screening of rosewood, clove bud and litsea EOs was conducted before interactions between binary and ternary combinations were determined against P.
The EOs were characterised by both gas chromatography-mass spectrometry and nuclear magnetic resonance. A combination of 0. The distillate with EO had synergistic activity against P. This formulation may serve as a valuable alternative for the control of acne vulgaris-associated bacteria. Antibiotic therapy for Shigella dysentery. All the antibiotics studied were safe.
There was inadequate evidence regarding the role of antibiotics in preventing relapses. Antibiotics reduce the duration of Shigella dysentery. Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.
In the field of antibiotic therapy , particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications. Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions. After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation.
An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria.
The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations. If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician.
Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials. This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection SSI after colorectal surgery. Fourteen trials involving participants were included.
Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy.
Current evidence suggested that probiotics in combination with antibiotics could be recommended. Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult.
The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used.
This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Published by Elsevier Inc.
Bacterial responses to antibiotics and their combinations. Antibiotics affect bacterial cell physiology at many levels. Rather than just compensating for the direct cellular defects caused by the drug, bacteria respond to antibiotics by changing their morphology, macromolecular composition, metabolism, gene expression and possibly even their mutation rate. Inevitably, these processes affect each other, resulting in a complex response with changes in the expression of numerous genes.
Genome-wide approaches can thus help in gaining a comprehensive understanding of bacterial responses to antibiotics. In addition, a combination of experimental and theoretical approaches is needed for identifying general principles that underlie these responses. Here, we review recent progress in our understanding of bacterial responses to antibiotics and their combinations , focusing on effects at the levels of growth rate and gene expression.
We concentrate on studies performed in controlled laboratory conditions, which combine promising experimental techniques with quantitative data analysis and mathematical modeling. While these basic research approaches are not immediately applicable in the clinic, uncovering the principles and mechanisms underlying bacterial responses to antibiotics may, in the long term, contribute to the development of new treatment strategies to cope with and prevent the rise of resistant pathogenic bacteria.
Antibiotic Therapy of Staphylococcal Infections. The antibiotic treatment of staphylococcal infections remains a problem. Isolation of the organism and sensitivity testing are necessary in the choice of antibiotic. Penicillin G is the most effective penicillin against non-penicillinase-producing staphy-lococci; for the penicillinase producers there is very little to choose between the semisynthetic penicillins, methicillin, cloxacillin, nafcillin and oxacillin.
For patients who are hypersensitive to penicillin, the bacteriostatic drugs erythromycin, novobiocin, tetracycline, chloramphenicol, oleandomycin are useful for mild infections, while for more severe illness the bactericidal drugs vancomycin, ristocetin, kanamycin, bacitracin, neomycin have been used successfully. Acute staphylococcal enterocolitis is probably best treated by a semisynthetic penicillin. Other antibiotics which have been found useful, with clinical trials, for staphylococcal infections are cephalosporin, fucidin, cephaloridine and lincomycin.
The latter drug has been reported of value in the treatment of osteomyelitis. There is little justification for the prophylactic use of antibiotics to prevent staphylococcal infection.
Surgical drainage is still an important adjunct in the treatment of many staphylococcal infections. Adjunctive use of antibiotics in periodontal therapy. Periodontal diseases are infectious diseases with a mixed microbial aetiology and marked inflammatory response leading to destruction of underlying tissue.
Periodontal therapy aims to eliminate pathogens associated with the disease and attain periodontal health. Periodontitis is generally treated by nonsurgical mechanical debridement and regular periodontal maintenance care.
Periodontal surgery may be indicated for some patients to improve access to the root surface; however, mechanical debridement alone may not be helpful in all cases. In such cases, adjunctive systemic antibiotic therapy remains the treatment of choice. It can reach microorganisms at the base of the deep periodontal pockets and furcation areas via serum, and also affects organisms residing within gingival epithelium and connective tissue.
This review aims to provide an update on clinical issues regarding when and how to prescribe systemic antibiotics in periodontal therapy. The points discussed are the mode of antibiotic action, susceptible periodontal pathogens, antibiotic dosage, antibiotic use in treatment of periodontal disease, and mechanism of bacterial resistance to each antibiotic. Bactericidal antibiotic -phytochemical combinations against methicillin resistant Staphylococcus aureus.
Due to its multi-drug resistant nature, treatment with conventional antibiotics does not assure desired clinical outcomes. Combination therapies using conventional antibiotics and phytochemicals fulfill both requirements. In this study, the efficacy of different phytochemicals in combination with selected antibiotics was tested against 12 strains of S. Out of the six phytochemicals used, tannic acid was synergistic with fusidic acid, minocycline, cefotaxime and rifampicin against most of strains tested and additive with ofloxacin and vancomycin.
Quercetin showed synergism with minocycline, fusidic acid and rifampicin against most of the strains. Gallic acid ethyl ester showed additivity against all strains in combination with all antibiotics under investigation except with vancomycin where it showed indifference effect. Eugenol, menthone and caffeic acid showed indifference results against all strains in combination with all antibiotics. Interestingly, no antagonism was observed within these interactions.
Based on the fractional inhibitory concentration indices, synergistic pairs were further examined by time-kill assays to confirm the accuracy and killing rate of the combinations over time. The study suggests a possible incorporation of effective phytochemicals in combination therapies for MRSA infections. Broad-spectrum antibiotics are commonly used by physicians to treat various infections.
The source of infection and causative organisms are not always apparent during the initial evaluation of the patient, and antibiotics are often given empirically to patients with suspected sepsis. Fear of attempting cephalosporins and carbapenems in penicillin-allergic septic patients may result in significant decrease in the spectrum of antimicrobial coverage. Empiric antibiotic therapy should sufficiently cover all the suspected pathogens, guided by the bacteriologic susceptibilities of the medical center.
It is important to understand the major pharmacokinetic properties of antibacterial agents for proper use and to minimize the development of resistance. In several septic patients, negative cultures do not exclude active infection and positive cultures may not represent the actual infection. This article will review the important differences in the spectrum of commonly used antibiotics for nosocomial bacterial infections with a particular emphasis on culture-negative sepsis and colonization.
From penicillin to pharmacogenomic]. Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible.
Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. In hospitals, infections caused by antibiotic -resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic -susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use.
Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies.
Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost.
These evidence-based guidelines are not a substitute for clinical. Antibiotic combination efficacy ACE networks for a Pseudomonas aeruginosa model.
The spread of antibiotic resistance is always a consequence of evolutionary processes. The consideration of evolution is thus key to the development of sustainable therapy.
Two main factors were recently proposed to enhance long-term effectiveness of drug combinations: We systematically assessed these factors by performing over 1, evolution experiments with the opportunistic nosocomial pathogen Pseudomonas aeruginosa in single- and multidrug environments.
Based on the growth dynamics during these experiments, we reconstructed antibiotic combination efficacy ACE networks as a new tool for characterizing the ability of the tested drug combinations to constrain bacterial survival as well as drug resistance evolution across time. Subsequent statistical analysis of the influence of the factors on ACE network characteristics revealed that i synergistic drug interactions increased the likelihood of bacterial population extinction—irrespective of whether combinations were compared at the same level of inhibition or not—while ii the potential for evolved collateral sensitivities between 2 drugs accounted for a reduction in bacterial adaptation rates.
In sum, our systematic experimental analysis allowed us to pinpoint 2 complementary determinants of combination efficacy and to identify specific drug pairs with high ACE scores. Our findings can guide attempts to further improve the sustainability of antibiotic therapy by simultaneously reducing pathogen load and resistance evolution.
May stereotactic intracavity administration of antibiotics shorten the course of systemic antibiotic therapy for brain abscesses? Despite advances in surgical techniques in the management of the brain abscess, continuous systemic long-term antibiotics are necessary and crucial. This study was designed to evaluate the effect of intracavity administration of high-dose antibiotics on the course of antibiotic therapy. Between and , 55 patients with bacterial brain abscesses 83 abscesses were treated with stereotactic aspiration and intracavity injection of high-dose antibiotics combined with a short course systemic antibiotic therapy.
Antibiotics of one-eighth daily systemic dosage were injected into the abscess cavity after stereotactic aspiration and intravenous antibiotics were given in all patients for 3 to 4 weeks. The results of the group treated with stereotactic aspiration and intracavity injection of antibiotic solution were compared to the results of our previous patients treated by stereotactic aspiration only.
Thirty-nine males and 16 females age ranging from 1. During the follow-up mean No adverse effects related to topical use of antibiotics occurred.
At the end of follow-up, 38 patients had good outcomes, 11 had mild neurological deficits, 3 had moderate deficits, 1 was in vegetative state, and 2 died of accidents not related to brain abscesses.
Compared with conventional stereotactic aspiration and drainage, intracavity injection of antibiotics shorted the course of consecutive systemic intravenous antibiotics by average Our results indicate that topical application of antibiotics into the brain abscess cavity helps to reduce the length of systemic antibiotic therapy , decreases the abscess recurrence rate, avoids the side effects of long-term high dose antibiotics , shortens the hospitalization and reduces treatment costs.
Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections.
Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia.
A cross-sectional study was conducted during January December at the medical wards of the Chaim Sheba Medical Center, Israel.
The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed. A total of eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria.
Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination.
Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.
The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria NTM.
These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM.
However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.
Conditions such as cystic fibrosis CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa , Methicillin-resistant Staphylococcus aureus , Burkholderia species and non-tuberculous Mycobacteria NTM. Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.
The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics , or as an adjunctive therapy to other pharmaceutical treatments.
Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract.
The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD. Repaglinide in combination therapy.
Type 2 diabetes mellitus T2DM is a progressive disorder requiring increasingly aggressive treatment to achieve and maintain target blood glucose concentrations in the presence of deteriorating insulin secretion and increasing insulin resistance.
Diet and lifestyle modification are often sufficient initially; however, most patients eventually require pharmacological intervention. With disease progression, monotherapy becomes less effective, so combination therapy is required, using drugs with complementary modes of action to maximise glycaemic control. The prandial glucose regulator repaglinide has been studied in combination with metformin an inhibitor of hepatic glucose production , neutral protamine Hagedorn NPH -insulin which has a long duration of effect, but at the risk of early hypoglycaemia and late hyperglycaemia in the dosing interval and three thiazolidinediones TZDs--troglitazone, rosiglitazone and pioglitazone, which stimulate nuclear receptors to increase insulin sensitivity and reduce insulin resistance in patients whose diabetes was inadequately controlled by previous monotherapy or combination therapy.
The combination of repaglinide and metformin resulted in reduced fasting plasma glucose concentrations by 2. Combination therapy with repaglinide and bedtime NPH-insulin resulted in reductions in fasting plasma glucose by 5. The combination of repaglinide and each TZD also resulted in consistent decreases in fasting plasma glucose concentrations and HbA1c. No severe hypoglycaemic episodes were reported in the three studies.
In conclusion, repaglinide has additive, and often synergistic, effects on glycaemic control when given in combination regimens and should be a valuable option in the management of patients with T2DM. Patients were required to be aged years with moderate to severe acne grades acne on the Investigator's Global Assessment [IGA] and deemed potential candidates for treatment with isotretinoin. A total of 97 patients were enrolled in the study. Triplecombination therapy was not associated with any serious AEs or AEs leading to discontinuation.
Antibiotic resistance and biofilm tolerance: Since the introduction of antibiotics into human medicine in the 's, antibiotic resistance has emerged at an alarming rate and is now a major threat to public health.
This problem is amplified by pathogenic bacteria existing most commonly in biofilm form, creating additional bacterial tolerance to antimicrobial agents. Biofilm is now considered to be a primary cause of chronic infection, and antibiotic -resistant bacteria are prevalent in biofilm form. In particular, chronic non-healing wounds commonly harbour complex polymicrobial, pathogenic biofilm that is tolerant to systemic and topical antimicrobial therapy.
Antibiotic stewardship programmes have emerged globally to improve antibiotic prescribing practices, and to curb the emergence and spread of bacterial resistance. This strategy is being considered in several clinical conditions, one of which is chronic non-healing wounds, where antibiotics are used excessively and often indiscriminately.
This approach must be considered as part of antibiotic stewardship programmes to reduce the usage and implications of antibiotic therapy , and improve outcomes associated with chronic infections. Coping with antibiotic resistance: The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths.
New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties.
Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium- antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance.
In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics , as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic -resistant bacteria.
Duration of antibiotic therapy in the intensive care unit. There are certain well defined clinical situations where prolonged therapy is beneficial, but prolonged duration of antibiotic therapy is associated with increased resistance, medicalising effects, high costs and adverse drug reactions.
The best way to decrease antibiotic duration is both to stop antibiotics when not needed sterile invasive cultures with clinical improvement , not to start antibiotics when not indicated treating colonization and keep the antibiotic course as short as possible. The optimal duration of antimicrobial treatment for ventilator-associated pneumonia VAP is unknown, however, there is a growing evidence that reduction in the length of antibiotic courses to days can minimize the consequences of antibiotic overuse in critical care, including antibiotic resistance, adverse effects, collateral damage and costs.
Biomarkers like C-reactive protein CRP and procalcitonin PCT do have a valuable role in helping guide antibiotic duration but should be interpreted cautiously in the context of the clinical situation. On the other hand, microbiological criteria alone are not reliable and should not be used to justify a prolonged antibiotic course, as clinical cure does not equate to microbiological eradication. We do not recommend a 'one size fits all' approach and in some clinical situations, including infection with non-fermenting Gram-negative bacilli NF-GNB clinical evaluation is needed but shortening the antibiotic course is an effective and safe way to decrease inappropriate antibiotic exposure.
Toyota production system quality improvement initiative improves perioperative antibiotic therapy. To assess the role of a Toyota production system TPS quality improvement QI intervention on appropriateness of perioperative antibiotic therapy and in length of hospital stay LOS among surgical patients.
Pre-post quasi-experimental study using local and national retrospective cohorts. We used TPS methods to implement a multifaceted intervention to reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a Veterans Affairs surgical unit, which led to a QI intervention targeting appropriate perioperative antibiotic prophylaxis. Appropriate perioperative antibiotic therapy was defined as selection of the recommended antibiotic agents for a duration not exceeding 24 hours from the time of the operation.
The local computerized medical record system was used to identify patients undergoing the 25 most common surgical procedures and to examine changes in appropriate antibiotic therapy and LOS over time. Overall, surgical admissions were identified from the local computerized medical records. The proportion of surgical admissions receiving appropriate perioperative antibiotics was significantly higher P antibiotic therapy duration rather than appropriate antibiotic selection.
There was no statistically significant decrease in LOS over time. The use of TPS methods resulted in a QI intervention that was associated with an increase in appropriate perioperative antibiotic therapy among surgical patients, without affecting LOS. This paper is published as second part of a survey on antibiotic utilisation of 8 Hungarian hospitals in January, Examining diagnoses perioperative profilaxis It was found that the rate of the achieved microbiological examinations and targeted therapy was low even if microbiological samples were easy to obtain.
Cannabidiol in Humans—The Quest for Therapeutic Targets
CBGs are inactive at cannabinoid receptors as compared to ∆9-THC,2 . Sativex is a mixture of THC and CBD in the form of oromucosal spray. Pharmacological Evaluation of Analogs Lacking Geminal Dimethyl group at C1′ . Effect of CBD on COX-2, iNOS, phospho-Akt and caspase-3 protein expression in colonic tissues. 87 Conclusions. THC BDS. Cannabis extract with high content in ∆. 9. -tetrahydrocannabinol. TNF-α oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid. 'The detection of THC and CBD in the oral fluid of Sativex® patients using two ' Recovery of deltatetrahydrocannaЛinol in oral fluid from Instrumentation. Sativex®ǰ an oromucosal spray containing THC and cannaЛidiol (CBD)ǰ precursor, ∆9-tetrahydrocannabinolic acid A (THCA-A).