Anti-infectious Drug Research Articles

Advances of Cobalt Nanomaterials as Anti-Infection Agents, Drug Carriers, and Immunomodulators for Potential Infectious Disease Treatment.

Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy.

Structure of the Active Nanocomplex of Antiviral and Anti-Infectious Iodine-Containing Drug FS-1

Chromatographic analysis shows that the ionic nanostructured complex of the FS-1 drug contains nanocomplexes of α-dextrin with a size of ~40–48 Å. Based on good agreement between the UV spectra of the model structures and the experimental spectrum of the FS-1 drug, the structure of the active FS-1 nanocomplex is proposed. The structure of the active centers of the drug in the dextrin ring was calculated using the quantum-chemical approach DFT/B3PW91. The active centers, i.e., a complex of molecular iodine with lithium halide (I), a binuclear complex of magnesium and lithium containing molecular iodine, triiodide (II), and triiodide (III), are located inside the dextrin helix. The polypeptide outside the dextrin helix forms a hydrogen bond with dextrin in Complex I and coordinates the molecular iodine in Complex II. It is revealed that the active centers of the FS-1drug can be segregated from the dextrin helix and form complexes with DNA nucleotide triplets. The active centers of the FS-1 drug are only segregated on specific sections of DNA. The formation of a complex between the DNA nucleotide and the active center of FS-1 is a key stage in the mechanisms of anti-HIV, anti-coronavirus (Complex I) and antibacterial action (Complex II).

Therapeutic Potential, Synthesis, Patent Evaluation and SAR Studies of Thieno[3,2-d]pyrimidine Derivatives: Recent Updates.

Thieno[3,2-d]pyrimidine ring framework comprises a significant class of heterocyclics that serve as a promising platform showing different pharmacological activities. The interest in thieno[3,2-d]pyrimidine cores for pharmaceutical products makes this scaffold an exceptionally helpful building block for organic chemistry. This review presents current research on thieno[3,2- d]pyrimidines and elucidates their biological importance in anti-cancer, anti-infectious, anticonvulsant, anti-diabetic, CNS, and osteoporosis drug discoveries. Patents on the thieno[3,2- d]pyrimidines are also elaborated as a piece of useful information. Here, we additionally focus on the synthesis of this vital ring and the discovery of new thieno[3,2-d]pyrimidines.

Bisphosphonates, Old Friends of Bones and New Trends in Clinics.

Bisphosphonates, used for a long time in osteoporosis management, are currently the target of intensive research, from pre-formulation studies to more advanced stages of clinical practice. This review presents an overview of the contributions of this family of compounds to human health, starting with the chemistry and clinical uses of bisphosphonates. Following this, their pharmacology is described, highlighting administration-borne handicaps and undesirable effects. The last three sections of the review describe the research efforts that seek to curb delivery-related issues and expand bisphosphonate use. Innovative routes and strategies of administration, such as nano-encapsulation for oral intake or injectable cements for local or in-bone delivery are presented, as well as the latest results of case studies or preclinical studies proposing new therapeutic indications for the clinically approved bisphosphonates. Finally, a selection of anti-infectious bisphosphonate new drug candidates is shown, with focus on the molecules reported in the last two decades.

A Combinative Assembly Strategy Inspired Reversibly Borate-Bridged Polymeric Micelles for Lesion-Specific Rapid Release of Anti-Coccidial Drugs

HighlightsA combined assembly strategy from hydrophobicity-driving and reversible borate bridges is proposed for high drug-loading efficiency and superior stability.Intestinal environment-triggered drug delivery system represents an effective treatment for local infection due to the site-specific targeting and shuttling of drugs.The reduced dosage brought by the drug-loading micelles could solve the problem of drug residue in breeding industry.Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs. Herein, chitosan conjugates (SPCS) installed with sialic acid (SA) and phenylboronic acid (PBA) were synthesized, of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA. The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges. The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract. After reaching the lesions, the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release, while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside. The drug-micelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation. The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable, safe and flexible anti-infectious drug delivery systems.

Simulation program of a cytotoxic compounding robot for monoclonal antibodies and anti-infectious sterile drug preparation

The aim of this study was to develop a specific simulation program for the validation of a cytotoxic compounding robot, KIRO® Oncology, for the preparation of sterile monoclonal antibodies and anti-infectious drugs. The impact of excipient formulations was clearly measured using simulation accuracy tests with worst case excipient (i.e. viscous, foaming) and allowed to correct the robotic settings prior to real production. Corrections brought accuracies within the acceptable range of ±5%. KIRO® Oncology robot has also the capacity of self-cleaning and a simulation combining media fill test, and environmental monitoring was able to validate the aseptic process including simulation of worst case conditions and highlighting the areas not accessible to self-cleaning to be corrected by additional manual cleaning measures. The risk of chemical contamination was simulated by using fluorescent dye of the process with high-risk excipient formulation and overpressure vials. Quality control reliability was simulated by using a model drug, and final concentration was determined by high-performance liquid chromatography-ultraviolet detection. Finally, productivity was simulated using different models of production showing the impact of the type of drug, the number of vials and the poor standardization of the process.

1216P - Impact of anti-infectious and corticosteroids on immunotherapy: Nivolumab and pembrolizumab follow-up in a French study

Background: Immunotherapy is a new paradigm with EMA approval in melanoma and lung cancer. However, B Routy and al has recently published a decrease of efficacy of immunotherapy via gut microbiome antiobiotics influence and potential drug interactions between antiobiotics/corticoids and immunotherapy associated with decrease of overall survival have been underlined too. The Observatory of Drugs, Medical Device and Therapeutic Innovations (OMEDIT) Bretagne/ Pays de la Loire (B-PL), in collaboration with French Regional Health Insurance System (FRHIS), wanted to carry out a study about the impact of these treatments on the efficacy of immunotherapy. Methods: FRHIS (PL) has made an extract in its database for patients who initiated treatment with Nivolumab/OpdivoÒ and Pembrolizumab/KeytrudaÒ between January 2016 and end of June 2017. Dispensing of antibiotics, corticoids and antifungals 60 days before initiation of immunotherapy and after the beginning of treatment (within 30 or 150 days after). The patient‘s clinical data (age, sex; diagnosis, indication, grade III/IV side-effects, response rate, survival) would be crossed with the use or not of anti-infectious drug treatment in order to define the impact of taking these drugs on the treatment of immunotherapy. Results: 798 patients were identified including 377 in 2016 and 421 in the first half of 2017: 148 with malignant melanoma and 650 with lung cancer. 763 were treated with nivolumab and 35 with pembrolizumab. Before the beginning of immunotherapy, 14% of these patients received an antibiotic, 17% a corticoid and 2% an antifungal. After the beginning of immunotherapy (within 30 days after), 8% received a corticoid, 6% an antibiotic and 2% an antifungal. Response to treatment, Progression Free Survival and Overall Survival (PFS and OS) in correlation with the use or not of these drugs for Bretagne and PL areas would be presented at the meeting. Conclusions: The good use of immunotherapy was crucial to optimize the response rate and to increase OS. Use of anti-infectious and corticosteroids was usual in routine. Antibiotics were found to be prescribed in 20% of the patients receiving immunotherapy. Results about their impact in term of response, PFS and OS would be shown at the meeting. Legal entity responsible for the study: Cancer Observatoire BPL, OMEDIT B and PL. Funding: Has not received any funding. Disclosure: J-P. Metges: Trial coordination without remuneration: MSD. All other authors have declared no conflicts of interest.

Phytochemical investigation and biological activities of Echium arenarium (Guss) extracts

The present work was developed to evaluate the in vitro antioxidant, antibacterial, antileishmanial and cytotoxic activities of Echium arenarium (Guss) extracts, and to analyze their phytochemical composition. The highest content of total phenolic compounds was obtained in the ethyl acetate extract which showed the best DPPH scavenging activity and β-carotene bleaching inhibition (IC50 = 1.1 and 9.94 μg/mL respectively). It also exhibited the highest antibacterial activity against Gram-positive bacteria (L. monocytogenes; S. aureus; MRSA, E. faecalis and B. cereus) and antileishmanial activity against L. major (IC50 = 13.91 ± 0.43 μg/mL) and L. infantum (IC50 = 9.91 ± 0.15 μg/mL). Moreover, the active extract exhibited potent antiamastigote activity (IC50 = 22.48 ± 0.14 μg/mL and 18.59 ± 0.09 μg/mL against L. major and L. infantum respectively). Cytotoxicity studies revealed low toxicity against Raw 264.7 macrophage cell line (IC50 = 145.80 ± 0.84 μg/mL, SI < 10). Luteolin-7-O-glucoside was identified as the major flavonoid component by RP-HPLC analysis. In conclusion, Echium arenarium (Guss) extract was characterized by a wide range of biological activities and could be used as a potential natural anti-infectious drug.

Association between infection and severe drug adverse reactions: an analysis using data from the Japanese Adverse Drug Event Report database.

It has been reported recently that immune reactions are involved in the pathogenesis of certain types of adverse drug reactions (ADRs). We aimed to determine the associations between infections and drug-induced interstitial lung disease (DILD), rhabdomyolysis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), or drug-induced liver injury (DILI) using a spontaneous adverse drug event reporting database in Japan. The reported cases were classified into three categories (anti-infectious drug group, concomitant infection group, and non-infection group) based on the presence of anti-infectious drugs (either as primary suspected drug or concomitant drug) and infectious disease. We assessed the association between four severe ADRs and the presence and seriousness of infection using logistic regression analysis. We identified 177,649 cases reported in the study period (2009-2013). Logistic regression analysis showed significant positive associations between infection status and onset of SJS/TEN or DILI (SJS/TEN: anti-infectious drug group: odds ratio (OR) 2.04, 95% CI [1.85-2.24], concomitant infection group: OR 2.44, 95% CI [2.21-2.69], DILI: anti-infectious drug group: OR 1.27, 95% CI [1.09-1.49], concomitant infection group: OR 1.25, 95% CI [1.04-1.49]), compared to the non-infection group. By contrast, there were negative or no associations between infection and DILD or rhabdomyolysis. A significantly positive association between infection and SJS/TEN seriousness (OR 1.48, 95% CI [1.10-1.98]) was observed. This study suggested that infection plays an important role in the development of SJS/TEN and DILI. For the patients with infection and/ or anti-infectious drugs, careful monitoring for severe ADRs, especially SJS/TEN, might be needed.

Infectious risk of biological drugs versus conventional systemic treatments in moderate to severe psoriasis

INfeCTIouS rISk of bIologICal drugS VerSuS CoNVeNTIoNal SySTemIC TreaTmeNTS IN moderaTe To SeVere pSorIaSIS S. Couderc; R. Bourrel; C. Paul; J.L. Montastruc; M. Lapeyre-Mestre; and A. Sommet UMR 1027, Inserm, Universite Toulouse III, Toulouse, France; Caisse Nationale d’Assurance Maladie Midi-Pyrenees, Toulouse, France; Service de Dermatologie, Centre Hospitalier Universitaire, Toulouse, France; and Pharmacologie Medicale et Clinique, Centre Hospitalier Universitaire, Toulouse, France Introduction: Moderate to severe psoriasis affects about 0.5% of the population. Its management is based on conventional systemic treatments (TSC: phototherapy, acitretin, methotrexate, and cyclosporine) and biological second-line drugs (etanercept, infliximab, ustekinumab, adalimumab, golimumab). Results of studies comparing the infectious risk of TSC and biological drugs are divergent. Objective: To compare the infectious risk associated with biological drugs versus TSC for moderate to severe psoriasis. Material and Methods: We conducted a retrospective cohort in the French Health Insurance Database for the Midi-Pyrenees region from 01/01/2010 to 31/12/2013, with patients treated incidentally for moderate to severe psoriasis. After a 6-month observation period with all patients exposed to TSC, we compared patients exposed to biological drugs (“exposed”) versus TSC (“unexposed”). We performed a Cox model on the first infectious event, for up to 6 months after the last dispensation of psoriasis drug. An infectious event was defined as delivery of any anti-infectious systemic drug or a hospital diagnosis of infection. Results: The 101 “exposed: patients and 788 “unexposed” patients were comparable in terms of socio-demographic data and comorbidities. Considering the first infectious event over a period of 2 years, no significant difference was found between “exposed” and “unexposed” (HR = 0.94; 95% CI, 0.71–1.22; P = 0.62). Being a woman (HR = 1.23), benefit from the Universal Health Coverage (HR = 1.44), suffering from chronic hepatitis B or C (HR = 2.74), history of neoplasia (HR = 1.70), a previous infectious event during the observation period (HR = 1.74), and the number of drugs consumed during the observation period (HR = 1.03) significantly increased the risk of infection. Conclusions: We did not reveal any difference in infection risk between the TSC and biological drugs in the management of moderate to severe psoriasis. This risk appears constant the first 2 years of use.

ReDuNing, a patented Chinese medicine, reduces the susceptibility to H1N1 influenza of mice loaded with restraint stress

IntroductionReDuNing (RDN), a patented traditional antipyretic-detoxicate Chinese medicine, has been widely applied as an anti-inflammatory and anti-infectious drug in Chinese clinics. However, relative experimental data on anti-influenza virus and its subsequent viral pneumonia by RDN are limited. In this study, restraint stress mice model, which could mimic the physiological conditions of the population susceptible to influenza infection, was applied to investigate the protective effect of RDN against influenza. MethodsMice were infected with H1N1 influenza virus 3 days after restraint, and RDN was administered to mice the day after stress by intraperitoneal injection for 7 days. Body weight and mortality were recorded every day. Histopathologic changes, lung index, nucleoprotein (NP) gene expressions and inflammatory markers in the lungs were also measured. ResultsRDN administration significantly decreased lung index, ameliorated lung histopathologic damage and decreased lung NP gene expression in influenza-infected mice loaded with restraint stress. It also decreased phosphorylated inhibitor of nuclear factor kappa B (p-IκB), nuclear factor-kappa B (NF-κB) protein level and interleukin-1β (IL-1β) mRNA expression, increased interferon inducible transmembrane 3 (IFITM3) and mitochondrial antiviral signaling (MAVS) gene expression. ConclusionsThis study provided preliminary support to suggest that RDN can reduce the susceptibility to, and the severity of influenza in restraint-stressed mice. The study also supported the potential of implementing RDN as an antiviral and its impact as potential anti-influenza treatments which rebalances homeostasis in the body caused by stress.

Multivalent glycoconjugates as vaccines and potential drug candidates

Pathogens adhere to the host cells during the first steps of infection through multivalent interactions which involve protein–glycan recognition. Multivalent interactions are also involved at different stages of immune response. Insights into these multivalent interactions generate a way to use suitable carbohydrate ligands that are attached to a basic scaffold consisting of e.g., dendrimer, polymer, nanoparticle, etc., with a suitable linker. Thus a multivalent architecture can be obtained with controllable spatial and topology parameters which can interfere with pathogen adhesion. Multivalent glycoconjugates bearing natural or unnatural carbohydrate antigen epitopes have also been used as carbohydrate based vaccines to stimulate an innate and adaptive immune response. Designing and synthesizing an efficient multivalent architecture with optimal ligand density and a suitable linker is a challenging task. This review presents a concise report on the endeavors to potentially use multi- and polyvalent glycoconjugates as vaccines as well as anti-infectious and anti-inflammatory drug candidates.

Ganglioside for hand, foot and mouth disease complicated with central nervous system damage

Objective To explore the efficacy of Ganglioside for hand, foot and mouth disease ( HFMD )complicated with central nervous system damage in pediatric patients.Methods 140 pediatric patients with HFMD complicated with central nervous system damage who were hospitalized into our hospital from Feb.2009 to Feb.2011 were randomly divided into treatment group and control group,70 for each group.All patients in both groups were treated with anti-virus drug and anti-infectious drug and received symptomatic treatment.Besides these,patents in treatment group were intravenously cured with 20 mg ganglioside for 10 days,while patients in control group were intravenously treated with citicoline,0.125-0.25 g/d.The electroencephalogram ( EEG ) and neuron-specific enolase ( NSE ),the duration of main symptoms and signs,time to recover,and hospital stay of the two groups were compared and analyzed.Results 65( 92.8％ ) patients in treatment group recovered in electroencephalogram( EEG )and neuron-specific enolase( NSE ).the duration of the main symptoms and signs,time to recover,and hospital stay were significantly shorter in treatment group than in control group ( P ＜ 0.05 ).Conclusions Ganglioside for hand,foot and mouth disease ( HFMD ) complicated with central nervous system damage is efficacious safe,and reliable and can reduce sequelae incindence. Key words: Hand, foot and mouth disease; Central nervous system; Ganglioside; Citicoline

Dihydrofolate Reductase As A Therapeutic Target for Infectious Diseases: Opportunities And Challenges

Infectious diseases caused by parasites continue to take a massive toll on human health in the poor regions of the world. Filling the anti-infective drug-discovery pipeline has never been as challenging as it is now. The organisms responsible for these diseases have interesting biology with many potential biochemical targets. Inhibition of metabolic enzymes has been established as an attractive strategy for anti-infectious drug development. In this field, dihydrofolate reductase (DHFR) is an important enzyme in nucleic and amino acid synthesis and an extensively studied drug target over the past 50 years. The challenges for novel DHFR inhibition-based chemotherapeutics for the treatment of infectious diseases are now focused on overcoming the resistance problem as well as cost-effectiveness. Each year, the large number of literature citations attest the continued popularity of DHFR. It becomes truly the 'enzyme of choice for all seasons and almost all reasons'. Herein, we summarize the opportunities and challenges in developing novel lead based on this target.

Sarcandra glabraExtract Reduces the Susceptibility and Severity of Influenza in Restraint-Stressed Mice

Sarcandra glabra, as a type of “antipyretic-detoxicate drugs”, has always been widely used in traditional Chinese medicine (TCM). The Sarcandra glabra extract (SGE) is applied frequently as anti-inflammatory and anti-infectious drug in folk medicine. However, relative experiment data supporting this effective clinical consequence was limited. In order to mimic the physiological conditions of the susceptible population, we employed restraint stress mouse model to investigate the effect of SGE against influenza. Mice were infected with influenza virus three days after restraint, while SGE was orally administrated for 10 consecutive days. Body weight, morbidity, and mortality were recorded daily. Histopathologic changes, susceptibility genes expressions and inflammatory markers in lungs were determined. Our results showed that restraint stress significantly increased susceptibility and severity of influenza virus. However, oral administration of SGE could reduce morbidity, mortality and significantly prolonged survival time. The results further showed that SGE had a crucial effect on improving susceptibility markers levels to recover the balance of host defense system and inhibiting inflammatory cytokines levels through down-regulation of NF-κB protein expression to ameliorate the lung injury. These data showed that SGE reduced the susceptibility and severity of influenza.

Systematics-guided bioprospecting for bioactive microbial natural products

Advances in the taxonomic characterization of microorganisms have accelerated the rate at which new producers of natural products can be understood in relation to known organisms. Yet for many reasons, chemical efforts to characterize new compounds from new microbes have not kept pace with taxonomic advances. That there exists an ever-widening gap between the biological versus chemical characterization of new microorganisms creates tremendous opportunity for the discovery of novel natural products through the calculated selection and study of organisms from unique, untapped, ecological niches. A systematics-guided bioprospecting, including the construction of high quality libraries of marine microbes and their crude extracts, investigation of bioactive compounds, and increasing the active compounds by precision engineering, has become an efficient approach to drive drug leads discovery. This review outlines the recent advances in these issues and shares our experiences on anti-infectious drug discovery and improvement of avermectins production as well.

Total Synthesis and Determination of the Absolute Configuration of Guadinomines B and C2

This article describes the determination of the absolute configurations of the guadinomines, which are novel cyclic guanidyl natural products that are inhibitors of the type III secretion system (TTSS) of bacteria. Any compound that interrupts the TTSS of bacteria is potentially an ideal anti-infectious drug. The reliable asymmetric synthesis of guadinomines has revealed their absolute configurations, which could not have been defined without this synthetic approach. Our report not only describes the asymmetric total synthesis of the title compounds, but also demonstrates the novel concise synthesis of tri-substituted piperazinone cores as optically pure forms. The novel feature of our method is an intramolecular S(N)2 cyclization that uses PPh(3) and I(2) to construct the unique 5-membered cyclic guanidine substructure.

In vitro study of a HPγ-cyclodextrin grafted PET vascular prosthesis for application as anti-infectious drug delivery system

Hydroxypropyl-γ-cyclodextrin (HPγ-CD) was grafted onto woven polyester (PET) vascular prosthesis by using citric acid (CTR) as crosslinking agent. A polyCTR-HPγ CD polymer was physically fixed onto the PET fibers. An optimal compromise between fixation temperature and fixation time was found and a grafting rate of 6.7% was obtained. The study of the inclusion of ciprofloxacin (CFX) and HPγ-CD was evidenced by using spectrophotometry. Sorption tests also showed that modified prosthesis could adsorb 5 times more CFX than the control. Biological tests revealed proliferation rates of human pulmonary micro-vascular endothelial cells (HPMEC) of 73 and 48% on virgin and modified prostheses respectively. We demonstrated that this was rather due to the increase of surface roughness of the fibers after their modification than to a toxic effect the polyCTR-HPγCD polymer coating. Prostheses samples modified with HPγCD and impregnated with CFX stayed up to 24 h in blood plasma. At various moments some aliquots were withdrawn from the medium and a positive antibacterial activity against Staphylococcus epidermidis was observed within the 24 h period for the grafted sample, whilst that of the virgin one had disappeared within 4 h. So, cyclodextrin coating of vascular prostheses may be suitable for the controlled release of CFX, and thus should help to the prevention of post surgery complications.

Biliary Tract Candidiasis: Diagnostic and Therapeutic Approaches in a Case Series

Biliary obstruction with its wide range of potential causes is a common disorder in gastroenterology. Infections of the biliary tract with Candida and other fungal species leading to obstructive jaundice have increasingly been recognized in the last few years. Besides a few case reports, there are few data in the literature giving us an idea how to diagnose and treat these patients. We report on a series of seven patients suffering from biliary tract candidiasis who were diagnosed and treated at our institution. Predisposition factors, reliability of various diagnostic modalities, and treatment options based on our own experience are presented and discussed. Besides the general diagnostic modalities such as laboratory findings or ultrasonography, we often observed mycelia in the bile duct system endoscopically. Typical morphological changes in peripheral bile ducts could be detected during endoscopic retrograde cholangiopancreatography (ERCP). Aspiration of bile and subsequent microbiological analysis in combination with ERCP findings revealed diagnosis of bile duct candidiasis in all cases. Treatment included both antiinfectious drugs and endoscopic therapy such as bile duct drainage, lavage, or débridement. With respect to fungal eradication, therapy was successful in 71% of cases as proven by microbiological analysis of bile aspirates. Since many of these patients suffer not only from biliary mycosis but also from disease necessitating immunosuppression, the prognosis was poor in some cases. Biliary tract candidiasis because of immunosuppression is an increasingly recognized disease and remains a major clinical challenge. Besides laboratory analysis and ultrasonography, diagnostic modalities should include aspiration of bile during ERCP and microbiological analysis. Antiinfectious drug treatment as the main therapeutic column for biliary candidiasis should be complemented by endoscopic intervention.

Antibiotic Dosage Regimens in Respiratory Tract Infections in the Pharmacokinetic/Pharmacodynamic Era

The increasing occurrence of antibiotic-resistant pathogens influences the treatment approach to respiratory tract infections and complicates the selection of the anti-infectious drug and dosing regimen. Pharmacokinetic (PK) and pharmacodynamic (PD) characteristics both influence dosing regimens of antimicrobials. PK (the overall disposition of the drug in the body) is reflected by the serum concentration profile over time. PD can be characterized by the susceptibility of the pathogen to the drug, determined by measuring the minimum inhibitory concentration (MIC), which is a potency of the drug. There is an increasing need to identify new therapeutic approaches which improve the chance to reduce the morbidity and obtain successful outcomes. So far, antibiotic dosing has been focused on PK concepts, mainly the penetration of drug into sites of infection and its elimination half-life. Recently, a new appealing approach integrating PK and PD features has been suggested to implement optimal antibiotic dosing regimens, since several studies in animals and humans found a striking correlation between bacteriological outcome and specific PK/PD indices. It appears it would lead to better results not only in terms of clinical and bacteriological cure but also in the whole patient care.