Pathogen detection in patients with perihilar cholangiocarcinoma:Implications for targeted perioperative antibiotic therapy

Background:Cholestasis should be relieved by biliary drainage prior to major liver resection.This condition is often associated with bacterial colonization of the otherwise sterile biliary system.Cholangitis reduces the regenerative capacity of the remaining liver.Therefore,targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma(pCCC).Methods:Between December 1999 and December 2017,251 pCCC patients were treated in our center.In total,115 patients underwent a microbiological analysis.In addition to the characterization of the specific microorganisms and antibiotic resistance,we analyzed subgroups according to preoperative intervention.Results:Enterococci(87/254,34%)and Enterobacteria(65/254,26%)were the most frequently detected genera.In 43%(50/115)of patients,Enterococcus faecalis was found in the bile duct sample.Enterococcus faecium(29/115)and Escherichia coli(29/115)were detected in 25%of patients.In patients with percutaneous transhepatic biliary drainage(3/8,38%)or stents(24/79,30%),Enterococcus faecium was diagnosed most frequently(P<0.05).Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012(P<0.05).With regard to fungal colonization,the focus was on various Candida strains,but these strains generally lacked resistance.Conclusions:pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention.Specifically,targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection.In our cohort,the combination of meropenem and vancomycin represents an effective perioperative medical approach.

Antibiotic-based small molecular micelles combined with photodynamic therapy for bacterial infections

The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics.Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs,but the mass proportion of carriers generally exceeds 90%of the nano-drug,resulting in low drug loading and limited therapeutic output.Herein,we fabricated a nanocarrier using antibiotics as the building blocks,minimizing the use of carriermaterials,significantly increasing the drug loading content and treatment effect.Firstly,we conjugated betaine carboxylate with ciprofloxacin(CIP)through an ester bond to form the amphiphilic conjugate(CIP-CB),which self-assembled into micelles(CIP-CBMs)in aqueous solutions,with a CIP loading content as high as 65.4%and pH-induced surface charge reversal properties.Secondly,a model photosensitizer(5,10,15,20-tetraphenylporphyrin(TPP))was encapsulated in CIP-CBMs,generating infection-targeted photodynamic/antibiotic combined nanomedicines(denoted as TPP@CIP-CBMs).Upon accumulation at infection sites or in deep bacterial biofilms,the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP,leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo.

Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

The practice of phage therapy, which uses bacterial viruses(phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage-or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infection. Although much about phages and human health is still being discovered, the time to take phage therapy serious again seems to be rapidly approaching.

Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

Six-year analysis of key monitoring for bacterial strain distribution and antibiotic sensitivity in a hospital

BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice.AIM To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by clinicians.METHODS Specimens from across the institution were collected by the microbiology laboratory.The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical analysis.RESULTS A total of 12062 bacterial strains of key monitoring significance were detected.Staphylococcus aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or linezolid.Moreover,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected.Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was low.Enterococcus faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus faecalis.The resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem.The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years.The resistance to amikacin remained at 0.2%over the past 3 years.CONCLUSION Our hospital’s overall antibiotic resistance rate was relatively stable from 2017 to 2022.The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital,which can guide clinical antibiotic selection.

The Utility of Procalcitonin as a Biomarker to Limit the Duration of Antibiotic Therapy in Adult Sepsis Patients

Introduction: With rising global antibiotic resistance, stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens have begun to gain acceptance. These programs stress appropriate antibiotic selection, dosage and duration. A growing literature suggests serum procalcitonin (PCT) levels may be useful in guiding antibiotic duration and de-escalation. This report sought to evaluate the evidence-based data available from prospective randomized controlled trials (RCT) on the role of PCT in guiding reductions in antibiotic duration in adult sepsis patients. Methods: A comprehensive search of all published prospective RCT(s) on the use of PCT as a tool for guiding antibiotic therapy in adult sepsis patients was conducted using PubMed, Medline Plus and Google Scholar (2007-2013). Keywords searched included, “procalcitonin”, “sepsis-therapy”, “sepsis biomarker”, “antibiotic duration”, “drug de-escalation”, and “antimicrobial stewardship”. Results:?Four RCT(s) involving 826 adult sepsis patients have evaluated the role of serum PCT levels to guide criteria for cessation of antibiotic therapy based either on specific PCT levels or PCT kinetics. Bouadma?et al.?(N = 621) stopped antibiotics when the PCT concentration was <80% of the peak PCT value, or the absolute PCT concentration was <0.5 μg/L. The PCT arm showed a 2.7-day reduction in antibiotics. Schroeder?et al.?(N = 27) discontinued antibiotics if clinical signs of infection improved and the PCT value decreased to <1 ng/mL or to <35% of the initial value within three days. The PCT arm had a 1.7-day reduction in antibiotics. Hochreiter?et al.?(N = 110) ceased antibiotics when the PCT decreased to <1 ng/mL, or to 25% - 35% of the initial value over three days if the value was >1 ng/mL. The PCT arm showed a 2-day reduction in antibiotics. Finally, Nobre?et al.?(N = 68) stopped antibiotics when PCT levels decreased by 90% or more from the initial value, but not prior to Day 3 (if baseline PCT measured <1 μg/L) or Day 5 (if baseline PCT measured ≥1 μg/L). The PCT arm showed a 4-day reduction in antibiotics. Overall, reduction of PCT levels to 10% - 35% of the initial concentration, to <80% of the peak PCT value, or to an absolute PCT value of <1 μg/L warranted antibiotic discontinuation 1.7 to 4 days earlier. No study reported a significant difference in mortality between the PCT arm and the control arm (p< 0.05). Conclusions: PCT-guided early cessation of antibiotic therapy in adult sepsis patients is associated with a significant decrease in antibiotic days, with no effect on overall mortality. Measurement of serum PCT levels may have a role in antimicrobial stewardship programs aimed at limiting antibiotic therapy duration, decreasing the selective pressure on drug-resistant bacterial strains and reducing hospital costs.

Advances in antibiotic therapy for infection after the surgical installation of implants to treat internal fractures

To summarize the advances in antibiotic therapy for infection after the surgical installation of implants to treat internal fractures. Recent studies on antibiotic therapy for infection after the surgical installation of implants to internal fractures were reviewed and analyzed.In general, systematic antibiotics are selected based on the results of bacterial culture. The duration of antibiotic treatment lasts for no more than 4 to 6 weeks. Orally administered and intravenously injected antibiotics have similar efficacies. Orally administered antibiotics exhibit a lower incidence of complications and are less costly than intravenously injected antibiotics. In addition, the efficacy of daptomycin in the treatment of bone infection is problematic. Rifampicin or fluoroquinolone antibiotics should be jointly administered when infection with bacterial biofilms is likely to occur. Calcium sulfate is a typical topically applied antibiotic delivery vehicle that can be completely degraded, with good biocompatibility, bone conduction, and drug release. The rational, systematic, and combined topical application of antibiotics can effectively decrease the recurrence rates of infection after the surgical installation of implants to treat internal fractures and can improve the quality of life of patients.

Successful endovascular treatment with long-term antibiotic therapy for infectious pseudoaneurysm due to Klebsiella pneumoniae:A case report

BACKGROUND Infectious common femoral artery pseudoaneurysm caused by Klebsiellapulmonary infection is a relatively infrequent entity but is potentially life andlimb threatening. The management of infectious pseudoaneurysm remainscontroversial.CASE SUMMARY We reported a 79-year-old man with previous Klebsiella pneumoniae pulmonaryinfection and multiple comorbidities who presented with a progressive pulsatemass at the right groin and with right lower limb pain. Computed tomographyangiography showed a 6 cm × 6 cm × 9 cm pseudoaneurysm of the right commonfemoral artery accompanied by occlusion of the right superficial femoral arteryand deep femoral artery. He underwent endovascular treatment (EVT) withstent–graft, and etiology of infectious pseudoaneurysm was confirmed. Then, 3-mo antibiotic therapy was given. One-year follow-up showed the stent–graft waspatent and complete removal of surrounding hematoma.CONCLUSION The femoral artery pseudoaneurysm can be caused by Klebsiella pneumoniaederiving from the pulmonary infection. Moreover, this unusual case highlights theuse of EVT and prolonged antibiotic therapy for infectious pseudoaneurysm.

Discontinuation of therapy in inflammatory bowel disease: Current views

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.

Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.

Two-day enema antibiotic therapy for parasite eradication and resolution of symptoms

BACKGROUND Blastocystis hominis(B.hominis)and Dientamoeba fragilis(D.fragilis)are two protozoan parasites of human bowel that are found throughout the world.There is still debate about the pathogenicity of these protozoans,despite them being commonly associated with gastrointestinal symptoms and can cause health issue in both children and adults.These parasites are usually transmitted through faecal-oral contact particularly under poor hygiene conditions or food/water contamination.Once a person is infected,the parasites live in the large intestine and are passed in the faeces.AIM To investigate the effect of triple antibiotic therapy using enema infusion in the treatment of B.hominis and D.fragilis infections.METHODS This retrospective longitudinal study was conducted in a single medical centre,which included fifty-four patients(≥18 years)who were positive for D.fragilis,B.hominis or both between 2017 and 2018.The treatment consisted of triple antibiotics that were infused over two consecutive days through rectal enema.Faecal samples were collected from participants pre-and post-treatment and were tested for parasites using microscopy and polymerase chain reaction.Patients’symptoms were recorded prior and after the treatment as well as patient demographic data.RESULTS Patients(n=54),were either positive for B.hominis(37%),D.fragilis(35%)or both(28%).All patients completed the two-day treatment and no serious adverse effect was reported.The most common side effect experienced by the patients during the treatment was urine discolouration which was cleared by six weeks of followup.Common symptoms reported prior to treatment were diarrhoea,abdominal pain,constipation and fatigue.Other symptoms included abdominal discomfort,dizziness and blood in the stool.Eighty-nine percent of patients completed a final stool test post-treatment.At six weeks post-treatment,79%of patients cleared the parasites from their faeces.Symptoms such as abdominal discomfort,dizziness and blood in the stool decreased significantly at both seven days and six weeks post-treatment(P<0.040).The enema retention time,bowel preparation,previous antibiotic treatment or previous gastrointestinal problems had no significant effect on parasite eradication.CONCLUSION Overall,eradication of parasites and improvement of clinical outcomes were observed in treated patients,showing the efficacy of this combination to eradicate the parasites and provide positive clinical outcome.

Probabilistic Antibiotic Therapy in the Infectious Diseases Department of the Yalgado Ouédraogo University Hospital (CHU-YO) in Ouagadougou, Burkina Faso

Introduction: In Burkina Faso, as in most developing countries, limited access to biological tests forces practitioners to resort very often to probabilistic antibiotic therapy. The objective of this study is to determine the extent of this prescription. Patients and Methods: This was a cross-sectional study with retrospective data collection of patients hospitalized in the infectious diseases department in the period from January 1, 2005 to December 31, 2020. The records of patients who received probabilistic antibiotic therapy were included. Results: During the study period, 330 patients had received probabilistic antibiotic therapy. The majority of patients were male (53%), with a sex ratio of 1.12. The mean age of the patients was 33 years ± 14. The age range of 20 to 40 years was the most represented (42%). Fifteen percent (15%) of patients were living with HIV. The majority of patients were from urban areas (56.4%). Forty-nine percent (49%) of the patients worked in the informal sector. Clinically, the reasons for consultation were dominated by fever, alteration of general condition, neurological disorders, digestive disorders, respiratory signs, urinary signs and diffuse pain. The physical examination showed that 48.1% of the patients had meningeal irritation syndrome, 10% had convulsions and 10% had focal signs, trismus was present in 4% of the patients and facial paralysis in 3%. In the digestive system, hepatomegaly was present in 29% of patients and digestive candidiasis in 31%. Respiratory examination showed crepitus and fluid effusion syndrome in 26.83% and 20.62% of patients respectively. The presumptive diagnosis was dominated by bacterial meningitis, salmonellosis and bronchopneumonia with banal germs. In terms of treatment, the beta-lactam family of drugs was the most prescribed. They were followed by aminoglycosides and fluoroquinolones. The evolution was marked by the death of 50 patients (15%). Conclusion: The most prescribed molecules belong to the family of Beta-lactam. And this prescription improved the outcome of patients. Bacterial susceptibility studies will allow better orientation of probabilistic antibiotic therapy in order to limit the emergence of multi-resistant bacteria.

High antibiotic resistance rate: A difficult issue for Helicobacter pylori eradication treatment

Helicobacter pylori(H. pylori) infection is associated with a variety of upper gastrointestinal diseases, including gastric cancer. With the wide application of antibiotics in H. pylori eradication treatment, drugresistant strains of H. pylori are increasing. H. pylori eradication treatment failure affects the outcome of a variety of diseases of the upper gastrointestinal tract. Therefore, antibiotic resistance that affects H. pylori eradication treatment is a challenging situation for clinicians. The ideal H. pylori eradication therapy should be safe, effective, simple, and economical. The eradication rate of triple antibiotic therapy is currently less than 80% in most parts of the world. Antibiotic resistance is the main reason for treatment failure, therefore the standard triple regimen is no longer suitable as a first-line treatment in most regions. H. pylori eradication treatment may fail for a number of reasons, including H. pylori strain factors, host factors, environmental factors, and inappropriate treatment.

De-escalating therapy in gastric aggressive lymphoma

The treatment of primary gastric diffuse large B-cell lymphoma(DLBCL) has changed radically over the last 10–15 years, with the abandonment of routine gastrectomy in favor of more conservative therapies. Low-level evidence suggests that consolidation radiotherapy could be avoided in patients with limited-stage DLBCL of the stomach who achieve complete remission after rituximab-CHOP combination. Small, recent prospective trials suggest that selected patients with limited-stage Helicobacter pylori(H. pylori)-positive DLBCL of the stomach and favorable prognostic factors can be managed with antibiotics alone, with excellent disease control and cure rates, keeping chemo-radiotherapy for unresponsive patients. This recommendation should equally regard patients with mucosa-associated lymphoid tissue-related or de novo DLBCL. Future studies should be focused on the establishment of reliable variables able to distinguish the best candidates for exclusive treatment with H. pylori eradication from those who need for conventional chemo-immunotherapy.

Methodology in improving antibiotic implementation policies

The basic requirements of antibiotic prescribing are components of methodology; knowledge, logical reasoning, and analysis. Antimicrobial drugs are valuable but limited resources, different from other drugs and they are among the most commonly prescribed drugs all over the world. They are the only drugs which do not intentionally affect the patient. They affect the pathogens which invade the host. The emergence and spread of antibiotic-resistant pathogens are accelerated by heavy antibiotic usage. The effective antimicrobial stewardship and infection control program have been shown to limit the emergence of antimicrobial-resistant bacteria. In this respect, education for antibiotic prescribing could be designed by going through the steps of scientific methodology. A defined leadership and a coordinated multidisciplinary approach are necessary for optimizing the indication, selection, dosing, route of administration, and duration of antimicrobial therapy. In scenarios, knowledge is also as important as experience for critical decision making as is designated. In this setting, the prevalence and resistance mechanisms of antimicrobials, and their interactions with other drugs need to be observed. In this respect, infectious disease service should play an important role in improving antimicrobial use by giving advice on the appropriate use of antimicrobial agents, and implementing evidencebased guidelines.

Antibiotic Resistance Phenotypes of <i>Enterobacteriaceae</i>Isolated from Household Wastewater in Brazzaville, Republic of Congo

Household wastewater is a source of pollution and can present health risks when discharged into the environment. Thus, samples of household wastewater from a few neighborhoods in Brazzaville were analyzed for microbiological quality. The various samples were cultured for isolation on solid media using conventional microbiological methods. The bacteria isolated were identified by the Enterobacter System gallery. Sensitivity tests were performed using the standard antibiotic susceptibility test by diffusion on Mueller Hinton medium. At the end of the analysis, 51 Enterobacteriaceae were isolated and identified. They included: 8 (15.68%) Escherichia coli, 8 (15.68%) Salmonella spp., 8 (15.68%) Shigella spp., 8 (15.68%) Klebsiella spp., 5 (9.80%) Enterobacter aerogenes, 8 (15.68%) Enterobacter cloacae, 3 (5.90%) Arizona spp., 3 (5.90%) Proteus spp. The results obtained show that the bacteria tested showed total resistance to the following antibiotics: amoxicillin, amoxicillin + clavulanic acid, cloxacillin and nalidixic acid. On the other hand, imipenem, cefuroxime, cefotaxime, cefftriazone and kanamycin were the most active antibiotics with low levels of resistance. The low resistance rates observed for imipenem, cefotaxime, cefuroxime and cefftriazone show that these antibiotics can be used for the treatment of infections caused by household wastewater bacteria.

Effect of Photoactivated Hypericin on Growth and Antibiotic Susceptibility of Hospital-Related Staphylococcus aureus and Enterococcus sp. Clinical Strains

Resistance against commonly used antibiotics is a serious clinical problem in recent medical practice. There exist several bacterial strains in which the possibilities of their inhibition are very limited due to multidrug resistance. Antimicrobial photodynamic therapy (aPDT) represents an option how to effectively suppress the growth of resistant pathogens. In this work we have studied interactions of potent photosensitizer hypericin (Hyp) with hospital-related gram positive (Gram+) and gram negative (Gram-) bacterial strains and the effects of photodynamic activated Hyp on bacterial susceptibility and/or resistance of these strains to antibiotics. We demonstrated a significant influence of photoactivated Hyp on growth of Staphylococcus aureus and Enterococcus sp. We have also shown that it is extremely important to use the effective concentrations of Hyp for aPDT, which completely inhibit the growth of microorganisms. Otherwise, there appears an increase in resistance, probably due to the activation of efflux mechanisms, which are involved in the efflux of Hyp and antibiotics as well.

Antibiotic Treatment for Chronic Rhinosinusitis after Endoscopic Surgery: How Long Should Macrolide Antibiotics Be Given?

Background: The purpose of this study was to determine an appropriate period for macrolide antibiotic therapy, and to investigate whether this period could be shorter, for patients with chronicrhino sinusitis (CRS) after functional endoscopic sinus surgery (FESS). Methods: A retrospective analysis of 41 patients undergoing FESS for CRS was performed. All patients underwent pre-operative computed tomography (CT). Patients with fungal sinusitis, allergic fungal sinusitis, and eosinophilic sinusitis were excluded. After FESS, normalized sinus mucosa was confirmed by CT and endoscopy in all patients. Postoperative antibiotic therapy consisted of first-line and second-line regimens. Garenoxacin (GRNX), or clarithromycin (CAM, 400 mg/day) was used as the first-line regimens and low-dose macrolide therapy (CAM, 200 mg/day) was used as the second-line regimen and was prescribed at outpatient visits based on our clinical criteria. Results: Second-line antibiotic therapy (low-dose CAM) was not necessary in 12 of 41 (29%) patients, while it was prescribed in 29 of 41 (71%). The mean duration of low-dose CAM therapy after FESS was 36 days (range 7 to 122 days;median, 25 days). Patients who received second-line therapy (n = 29) were divided into two groups based on the choice of first-line therapy, a GRNX group (n = 13) and a non-GRNX group (n = 16). Those in the non-GRNX had longer periods of postoperative CAM therapy than those in the GRNX group. Conclusion: GRNX was associated with a shorter duration of low-dose macrolide therapy after FESS, and 29% of patients did not need any low-dose macrolide therapy postoperatively. Therefore, macrolide antibiotics should not be routinely prescribed after FESS.

Impact of an Antimicrobial Stewardship Program Initiative on Antibiotic Optimization in Patients with Gram-Negative Bacteremia

The purpose of this study was to critically evaluate the impact of an institutional blood culture notification protocol called RAIDS （rapid administration of antimicrobials by an infectious diseases specialist） on time to optimization of antimicrobial therapy in hospitalized patients with gram-negative bacteremia. Time to antibiotic optimization was compared in patients with gram-negative bacilli isolated from blood cultures obtained from March-May 2011 （pre-RAIDS） versus March-May 2013 （post-RAIDS）. The results show that patients in the pre-RAIDS study group had a significantly longer time to antibiotic optimization when compared to the post-RAIDS group （median （IQR）, 27.6 （10.8-75.8） h vs. 3.1 （0.8-34.3） h, p = 0.03）. The RAIDS protocol resulted in quicker time to antibiotic de-escalation （pre- vs. post-RAIDS; median （IQR）, 27.6 （10.8-134.5） h vs. 4.3 （1.4-32.6） h, p = 0.03）. There were no differences in clinical outcomes such as clinical cure, microbiological cure, and 30-day mortality between pre-RAIDS and post-RAIDS study groups. Patients in the post-RAIDS arm were more likely to receive appropriate empiric and definitive treatment. Implementation of the RAIDS protocol, which was an ASP （antimicrobial stewardship program） initiative, resulted in quicker time to antibiotic de-escalation and overall treatment optimization. RAIDS reduced the unnecessary use of broad-spectrum antimicrobial in this study population.

Natural History, Outcomes and Antibiotic Treatment for Ventilator-Associated Tracheobronchitis in Critical Ill Patients

We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventilator days. We also examined pathogens, rate of progression from VAT to VAP, and impact of antibiotic therapy for VAT. Data analysis included 234 patients, 100 patients (43%) had at least moderate (+++) bacterial growth in their semi-quantitative endotracheal aspirate (SQ-ETA) cultures. VAT and VAP were each diagnosed in 34 (15%) patients. Staphylococcus aureus was the most common pathogen isolated and had the highest rate of progression from VAT to VAP. Seven (21%) of the 34 patients were diagnosed with VAT that later progressed to VAP in averaged 3 days. Patients diagnosed with VAT had significantly more ventilator days (9 vs 6, p p < 0.001) and hospital days (22 vs 17, p < 0.001). No significant difference was observed in the clinical outcomes of the 25 VAT patients with timely, appropriate antibiotics compared to the 9 VAT patients who did not receive timely appropriate antibiotics. VAT was a risk factor for increased ventilator days, longer length of ICU and hospital stay. The time window from VAT to VAP allowed physicians to identify the pathogens and sensitivity profile needed to treat VAT with appropriate antibiotics. Data from well-designed studies were needed to assess the impact of early, appropriate antibiotic therapy for VAT, the choice of antibiotics, as well as the duration and route of administration.