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Monitoring antibiotic plasma levels is critical in populations with altered pharmacokinetics, such as critically ill patients in neonatal or adult intensive care units. This study aimed to develop and validate a rapid, reproducible and sensitive liquid chromatography–tandem mass spectrometry assay (LC–MS/MS) for measuring total and unbound concentrations of amoxicillin, ampicillin, ceftazidime, ceftriaxone, ertapenem, fosfomycin and penicillin G in human plasma. The method required 20 and 250 μl sample volumes for measuring total and unbound concentrations, respectively. Sample preparation involved protein precipitation and the addition of an internal standard. Ultrafiltration separated unbound drugs. Method validation covered selectivity, carryover, linearity, accuracy, precision, dilution effects, matrix effects and stability. The LC–MS/MS was performed within a run time of 7.5 min. Calibration curves were linear for ceftazidime and ertapenem (ranges 0.1–50 and 0.05–100 mg/l, respectively) and quadratic for other analytes (0.1–50 mg/l, except for ampicillin: 0.1–20 mg/l; R2 > 0.990). Accuracy was within ±15% of the nominal concentration, and precision did not exceed ±15% (relative standard deviation). Samples showed no significant degradation at the tested temperatures and time points. Clinical applicability was demonstrated in a critically ill neonate. This method with minimal sample volume and short analysis time enables the measurement of total and unbound concentrations of selected antibiotics, and is suitable for routine clinical care and studies. [ABSTRACT FROM AUTHOR]

ABSTRACT In response to the heightened risk of bacterial diseases in fish farms caused by increased demand for fish consumption and subsequent overcrowding, researchers are currently investigating the efficacy and residue management of oxolinic acid (OA) as a treatment for bacterial infections in fish. This research is crucial for gaining a comprehensive understanding of the pharmacokinetics of OA. The present study investigates pharmacokinetics of OA in juvenile rainbow trout. The fish were given a 12 mg kg−1 dose of OA through their feed, and tissue samples were collected of the liver, kidney, gill, intestine, muscle, and plasma for analysis using LC‐MS/MS. The highest concentrations of the drug were found in the gill (4096.55 μg kg−1) and intestine (11592.98 μg kg−1), with significant absorption also seen in the liver (0.36 L/h) and gill (0.07 L/h) (p < 0.05). The liver (0.21 L/h) and kidney (0.03 L/h) were found to be the most efficient (p < 0.05) at eliminating the drug. The study also confirmed the drug antimicrobial effectiveness against several bacterial pathogens, including Shewanella xiamenensis (0.25 μg mL−1), Lactococcus garvieae (1 μg mL−1), and Chryseobacterium aquaticum (4 μg mL−1). The study concludes significant variations among different fish tissues, with higher concentrations and longer half‐lives observed in the kidney and intestine. The lowest MIC value recorded against major bacterial pathogens demonstrated its therapeutic potential in aquaculture. It also emphasizes the importance of understanding OA pharmacokinetics to optimize antimicrobial therapy in aquaculture. [ABSTRACT FROM AUTHOR]

Aims: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment. Methods: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed‐effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic/pharmacodynamic target attainment. The area under the curve/minimal inhibitory concentration ratio of 400–600 mg*h/L was used as target range. Results: Sixteen patients received vancomycin (median gestational age: 41 [range: 38–42] weeks, postnatal age: 4.4 [2.5–5.5] days, birth weight: 3.5 [2.3–4.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1‐compartment model showed the best fit. Vancomycin clearance was 0.17 L/h, lower than literature values for term neonates of 3.5 kg without perinatal asphyxia (range: 0.20–0.32 L/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24 h of treatment. A loading dose of 10 mg/kg followed by 24 mg/kg/day in 4 doses resulted in target attainment. Conclusion: Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model‐informed precision dosing. [ABSTRACT FROM AUTHOR]

Microbial infection is a major medical problem that seriously threatens public health. The abuse of antibiotics that help evolve the emergence of new drug‐resistance mechanisms has led to the wide‐spread and fast expansion of drug‐resistant bacteria, ultimately evolving into superbugs. This significantly impairs the timely and effective treatment of infections, thus threatening global human well‐being. Not all are pessimistic. Nanomaterials have emerged as an innovative choice. Due to their unique physical and chemical properties, superior bactericidal effects, and high biocompatibility, nanomaterials may help eradicate drug‐resistant bacteria to achieve complete remission of infectious diseases. As biological materials, nanomaterials can also improve the efficacy of existing drugs and treatments and even facilitate diagnostic efficiency. In this review, we aim to comprehensively summarize the antibacterial properties of different kinds of nanomaterials and their applications in other spheres related to treating infectious diseases (targeted therapy, phototherapy, vaccine development, and microbial diagnosis). We highlight the latest advances of nanomaterials in treating infectious diseases in different body systems. Finally, we conclude by discussing the weaknesses of currently available materials and unresolved scientific problems, which may provide insights into the development of approved agents that adequately overcome the notorious drug resistance and thereby provide unprecedented discoveries to improve treatments of the most severe bacterial infections. [ABSTRACT FROM AUTHOR]

Discriminating bacterial adhesion profiles at strain‐specific level is crucial for simulating and predicting infections and persistence, as well as developing more efficient antibacterial therapies. Herein, it is proposed that label‐ and receptor‐free bacterial discrimination can be achieved by dynamic viscoelastic and adhesion monitoring over specified timescales using the quartz crystal microbalance with dissipation monitoring (QCM‐D). Using two closely related E. coli strains, ATCC 8739 and JM109(DE3), it is shown that their viscoelastic and adhesion properties evolve in time through strain‐specific profiles that are clearly distinguishable over a period of 3–4 h. In addition, the viscoelasticity of both E. coli strains shows a strong strain‐specific dependence on the medium ionic strength, allowing to further amplify the differences in the bacterial adhesion signatures. Furthermore, the viscoelastic and adhesion behaviors of the two E. coli strains with two additional bacteria, Citrobacter freundii and Serratia marcescens, are compared. For all four bacteria, distinct viscoelastic profiles and adhesion fingerprints emerge over similar timescales that allow to reliably discriminate the various bacteria. These results and similar studies on other bacteria might have pharmacological benefits, for instance, by highlighting the role of bacterial–substrate adhesion and viscoelastic properties on disease pathogenesis and persistence, toward developing more effective therapies. [ABSTRACT FROM AUTHOR]

Skin infections caused by Panton‐Valentine leukocidin (PVL)‐positive methicillin‐resistant Staphylococcus aureus (MRSA), especially the USA300 clone, have been increasing in Japan. To prevent an epidemic of PVL‐positive MRSA, rapid diagnosis and effective antimicrobial therapy are essential. However, the clinical features of, and antimicrobial efficacy against, these skin infections are not well understood in Japan. Here, we report 10 cases of skin infections caused by PVL‐positive MRSA that presented over a two‐year period in our clinic. Genetic analyses revealed that 90% of the PVL‐positive MRSA strains were identified as USA300 and its related clones. Notably, 70% of the patients had atopic dermatitis (AD) as an underlying disease. Average durations of antimicrobial therapy for AD patients (10.6 weeks) were 2.9‐fold longer than those for non‐AD patients (3.7 weeks). However, all cases were improved by a long‐term course of fosfomycin, minocycline, doxycycline, and/or rifampicin. Our data suggest that AD may be an important risk factor for intractable skin infections caused by PVL‐positive MRSA. [ABSTRACT FROM AUTHOR]

A 3‐year‐old, castrated male mixed‐breed cat presented with an almost 2‐year history of chronic loose stools. On radiography and ultrasound examination, there were two masses in the centre of the abdomen. Contrast‐enhanced computed tomography revealed that the masses were enlarged mesenteric lymph nodes with fluid accumulation. Percutaneous lesion drainage yielded pus‐like fluid. Fluid cytology revealed numerous neutrophils and Gram‐negative rods. Pus culture identified Escherichia coli as the causative organism. Consequently, mesenteric lymph node abscesses were definitively diagnosed. Since computed tomography showed that the abscesses adhered to the surrounding tissues, it was difficult to remove them surgically. With drainage and antimicrobial therapy, the mesenteric lymph nodes gradually decreased in size. However, loose stools persisted. The cat's diet was changed to a hydrolysed diet, and the clinical symptoms improved, suggesting food‐responsive enteropathy. This may be an underlying disease of lymph node abscesses. Lymph node abscesses limited to the mesenteric lymph nodes rarely occur in veterinary medicine, and this is the first report in cats. [ABSTRACT FROM AUTHOR]

Chronic wounds are a considerable health burden with high morbidity and poor rates of healing. Colonisation of chronic wounds by bacteria can be a significant factor in their poor healing rate. These bacteria can develop antibiotic resistance over time and can lead to wound infections, systemic illness, and occasionally amputation. When a large number of micro‐organisms colonise wounds, they can lead to biofilm formation, which are self‐perpetuating colonies of bacteria closed within an extracellular matrix, which are poorly penetrated by antibiotics. Platelet‐rich plasma (PRP) is an autologous blood product rich in growth factors and cytokines that are involved in an inflammatory response. PRP can be injected or applied to a wound as a topical gel, and there is some interest regarding its antimicrobial properties and whether this can improve wound healing. This study aimed to evaluate the in vitro bacteriostatic effect of PRP. PRP was collected from healthy volunteers and processed into two preparations: activated PRP—activated with calcium chloride and ethanol; inactivated PRP. The activity of each preparation against Staphylococcus aureus and Staphylococcus epidermis was evaluated against a control by three experiments: bacterial kill assay to assess planktonic bacterial growth; plate colony assay to assess bacterial colony growth; and colony biofilm assay to assess biofilm growth. Compared with control, both preparations of PRP significantly inhibited growth of planktonic S aureus and S epidermis. Activated PRP reduced planktonic bacterial concentration more than inactivated PRP in both bacteria. Both PRP preparations significantly reduced bacterial colony counts for both bacteria when compared with control; however, there was no difference between the two. There was no difference found between biofilm growth in either PRP against control or against the other preparation. This study demonstrates that PRP does have an inhibitory effect on the growth of common wound pathogens. Activation may be an important factor in increasing the antimicrobial effect of PRP. However, we did not find evidence of an effect against more complex bacterial colonies. [ABSTRACT FROM AUTHOR]

Aim: Rapid blood culture pathogen identification facilitated by matrix-assisted laser desorption ionisation time-of-flight and GeneXpert has the potential to improve antibiotic prescribing. This study investigates the impact of these rapid diagnostics on the timeliness of effective and optimal antibiotic prescribing in paediatric patients with bacteraemia.Methods: A single centre retrospective cohort study was performed comparing paediatric bacteraemia cases pre- and post-rapid diagnostic implementation. Primary outcomes were the proportion of cases receiving, and median time to administration of effective and optimal antibiotics from blood culture collection. Secondary outcomes included hospital length of stay, intensive care unit admissions, and all-cause mortality.Results: A total of 255 bacteraemia cases were subject to final data analysis, 129 in the control cohort (pre-implementation of rapid diagnostics) and 126 in the rapid diagnostics cohort. The median time to effective (2.3 vs. 1.8 h, P = 0.20) and optimal therapy (44.4 vs. 39.1 h, P = 0.66) did not differ significantly between the cohorts. There was also no significant difference found in the number of cases reaching effective (120 vs. 116, P = 0.77) and optimal therapy (66 vs. 62, P = 0.76), length of stay (7 vs. 9 days), all-cause mortality (1.6 vs. 1.6%) and number of intensive care unit admissions (20 vs. 15).Conclusion: The implementation of rapid diagnostics, when used in isolation, resulted in no improvement in antibiotic prescribing or patient clinical outcomes. To be effective, rapid diagnostics must be coupled with active real-time antimicrobial stewardship promotion, de-escalation or modification based on early laboratory results. [ABSTRACT FROM AUTHOR]

Background: Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short‐term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized. Methods: To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N = 219) receiving care at our tertiary transplant center with continuous‐flow LVADs placed between August 2007 and July 2019. Results: A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56 years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486 days (range 48‐2287 days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000 days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy. Conclusions: Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression. [ABSTRACT FROM AUTHOR]

Iliopsoas abscess in HD patients is rare. We examined nine HD patients with iliopsoas abscess (six men and five diabetes mellitus cases) treated between 2005 and 2015. Mean age and dialysis vintage at onset were 72 years and 109 months, respectively. Of the nine patients, four had lumbar orthopedic diseases, and two had all components of the classic triad of iliopsoas abscess at onset. All nine patients underwent percutaneous drainage, while seven underwent antimicrobial therapy. The most common pathogenic bacterium was methicillin‐resistantStaphylococcus aureus(MRSA) (n = 5). Four patients had multilocular recurrence on the same side as the initial abscess and did not undergo CT before drainage catheter removal. Five patients died in the hospital, in which three died due to infectious diseases by MRSA. We suggest percutaneous drainage as the first‐line therapy for HD patients with iliopsoas abscess and recommend combining antimicrobial therapy for MRSA, because of poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether catheter replacement is associated with better clinical outcomes in individuals with long‐term urinary catheters. Design: Prospective, noninterventional study. Participants: Individuals (mean age 79.2±11.5) who had had an indwelling urinary catheter for longer than 7 days and a symptomatic urinary tract infection (UTI) (N=315). Measurements: The exposure assessed was replacement of the indwelling urinary catheter within 6 hours. The primary outcome was clinical failure at day 7. We developed a propensity score model for catheter replacement to match participants. Multivariate analysis was conducted to adjust for other risk factors. Results: The catheter was replaced in 98 participants and not in 217. More than half of the participants resided in long‐term care facilities and had high Charlson comorbidity scores. The rate of clinical failure on day 7 was 35.2% (108/306). The 30‐day fatality rate was 30.8% (96/315). We found no statistically significant association between catheter replacement and clinical failure (propensity‐adjusted odds ratio (OR)=0.90, 95% CI=0.50–1.63) or 30‐day fatality (OR=0.76, 95% CI=0.40–1.44). Conclusion: We found no clinical benefit of replacing a long‐term catheter at the onset of the catheter‐associated UTI. Further research is needed through randomized controlled trials. [ABSTRACT FROM AUTHOR]

Abstract: Community‐acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline. [ABSTRACT FROM AUTHOR]

Objectives: Debate about whether certain antimicrobial agents traditionally considered vesicants increase the risk of catheter complications has led to uncertainty in venous catheter placement protocols. To understand whether patients requiring home‐based outpatient parenteral antimicrobial therapy (OPAT) should receive peripheral catheters (e.g., midline catheters) versus central venous catheters, and to understand whether certain antimicrobial agents place home‐based OPAT patients at higher risk for catheter complications, we investigated associations between antimicrobial agent(s) and catheter complications. Methods: We performed a prospective cohort study of patients requiring home‐based OPAT discharged from two urban tertiary care academic medical centers, including telephone surveys and chart abstractions. Multivariable Poisson regressions were used to evaluate: (i) associations between antimicrobial agents traditionally considered vesicants, based on pH or osmolarity, and catheter complication rates, and (ii) associations between antimicrobial agent and rates of catheter complications. Results: Vesicant antimicrobials defined using pH or osmolarity criteria were not associated with an increased rate of catheter complications (adjusted incidence rate ratio [aIRR]: 1.63, 95% confidence interval [CI]: 0.89–2.96). Vancomycin was associated with an increased rate of catheter complications, as was daptomycin (aIRR: 2.32 [95% CI: 1.20–4.46] and 4.45 [95% CI: 1.02–19.41], respectively). Staphylococcus aureus infections were also associated with an increased rate of catheter complications (aIRR: 2.13, 95% CI: 1.09–4.19), as were midline catheters (aIRR: 9.44, 95% CI: 2.12–41.97). Conclusions: Our study supports recent guidance identifying vancomycin as a vesicant, among a subset of antimicrobial agents, and removal of pH criteria for identification of vesicants. [ABSTRACT FROM AUTHOR]

Abstract: Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community‐acquired and healthcare‐associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class‐definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de‐escalation or termination of antimicrobial therapy are now important parts of decision‐making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included. [ABSTRACT FROM AUTHOR]

Objectives: Buruli ulcer (BU) is a tropical skin disease caused by infection with Mycobacterium ulcerans, which is currently treated with 8 weeks of streptomycin and rifampicin. The evidence to treat BU for a duration of 8 weeks is limited; a recent retrospective study from Australia suggested that a shorter course of antimicrobial therapy might be equally effective. We studied the outcomes of BU in a cohort of Ghanaian patients who defaulted from treatment and as such received less than 8 weeks of antimicrobial therapy.Methods: A number of days of antimicrobial therapy and patient and lesion characteristics were recorded from charts from a cohort of BU patients treated at Nkawie-Toase hospital between 2008 and 2012. Patients who defaulted from treatment were retrieved, and lesion characteristics and functional limitations were recorded.Results: About 54% of patients defaulted from therapy or wound care. Forty-seven defaulters with follow-up completed had received <56 days of antibiotics. 84% of these patients healed after 32 days or less of antibiotics. There appeared to be an increased rate of healing in smaller lesions; 94% of WHO category I lesions had healed after 32 days or less of antibiotics.Conclusion: Although numbers were small, and a potential for bias exists, our findings suggest that a reduction in the duration of antimicrobial therapy in BU in small, early lesions is feasible. These findings can serve as a basis for future well-designed studies. [ABSTRACT FROM AUTHOR]

Bacterial infections were once a major obstacle to the treatment of acute leukaemia. Improvement in management strategies, including the use of broad-spectrum antibacterial drugs targeting Gram-negative bacteria, has reduced the mortality in neutropenic patients developing blood stream infections and other severe infections. In many countries these achievements are threatened by development of multi-resistant bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. This review addresses the epidemiology, clinical importance and possible management of these multi-resistant organisms. [ABSTRACT FROM AUTHOR]

Objectives To determine whether antimicrobial treatment for suspected urinary tract infections ( UTIs) improves survival in nursing home residents with advanced dementia. Design Prospective cohort study. Setting Thirty-five nursing homes in Boston, Massachusetts. Participants Nursing home residents who experienced at least one suspected UTI over a 12-month period (N = 110); mean participant age 86.4 ± 6.2, 84% female. Measurements Analyses were at the level of the UTI episode. Antimicrobial treatment for each suspected UTI was categorized as none, oral, intramuscular, or intravenous or hospitalization. Survival was calculated from the date of suspected UTI episode until death or last known follow-up date. Covariates included resident and episode characteristics. Cox proportional hazards regression was used to examine the association between treatment group and risk of death after adjusting for covariates. Results Residents experienced 196 suspected UTIs over the follow-up period; 33% (n = 36) died during follow-up. There was no antimicrobial use for 25.0% of the 196 suspected UTIs, oral antimicrobial use in 59.7%; intramuscular antimicrobial use in 9.2%, and intravenous antimicrobial use or hospital transfer in 6.1%. After multivariable adjustment, antimicrobial treatment was not significantly associated with mortality (oral, adjusted hazard ratio for death ( AHR) = 1.09, 95% confidence interval ( CI) = 0.43-2.75; intramuscular, AHR = 0.66, 95% CI = 0.08-5.66; intravenous or hospitalization, AHR = 1.83, 95% CI = 0.44-7.60). Conclusion Although the majority of suspected UTIs that nursing home residents with advanced dementia experienced were treated with antimicrobials, treatment was not associated with survival. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the in vitro susceptibility of Streptococcus agalactiae isolates to oxytetracycline (OTC) and the therapeutic efficacy of the drug against streptococcosis in Nile tilapia. Topics discussed include information on the 29 strains of Streptococcus agalactiae, and the results which suggest that the drug was able to significantly lower the mortalities caused by Streptococcus agalactiae infection in Nile tilapia fingerlings.

Background Treatment of sinonasal bacterial biofilms continues to be a challenge in modern rhinology. This study's objective was to assess the safety and efficacy of topically applied Cocktail of S. aureus specific phage (CTSA) alone and in combination with ethylenediaminetetraacetic acid (EDTA) for treatment of Staphylococcus aureus biofilms in vivo. Methods Using a sheep model of sinusitis, frontal sinuses (n = 6 per treatment) were flushed once daily with a CTSA (2 × 106 plaque forming units [PFU]/mL), with or without EDTA (0.075 mg/mL), and compared to a control flush containing saline and heat-inactivated CTSA. Safety was assessed using histology and scanning electron microscopy (SEM) after treatment for 3 days. Efficacy was assessed by quantifying the generation of S. aureus biofilms in the frontal sinuses after 5 days of treatment. Biofilm mass was compared between treatment groups and controls using LIVE/DEAD BacLight staining and confocal scanning laser microscopy to visualize the tissue sections. COMSTAT2 software was used to compute the biofilm mass present on tissue sections. Results Tissue morphology was conserved, with no significant signs of inflammation, when comparing control and test treatments. Furthermore, SEM analysis indicated test treatments were not toxic or damaging to mucosal cilia. COMSTAT2 quantification of biofilm showed a significant reduction in biofilm levels when comparing the control with CTSA ( p = 0.0043), EDTA ( p = 0.0095), and CTSA-EDTA ( p = 0.0022) treatments. Conclusion Results indicate that CTSA and EDTA are safe and efficacious for short-term topical application against S. aureus infection in a sheep sinusitis model, and have the potential to be translated to a clinical setting. [ABSTRACT FROM AUTHOR]

ABSTRACT Photodynamic therapy (PDT) has been considered a feasible alternative for antimicrobial therapy of multidrug-resistant pathogens. However, bacterial response mechanisms against PDT-generated photo-oxidative stress remain largely unknown. Herein, it is shown that the accessory gene regulator Agr is involved in Staphylococcus aureus response to photo-oxidative stress generated by laser-induced PDT with the photosensitizer chlorin e6. Transcriptional profiling revealed that sublethal PDT induces a general stress response and also activates Agr-dependent gene regulation. Moreover, mutant S. aureus lacking Agr function showed hypersusceptibility to two independent PDT conditions with higher energy densities, demonstrating Agr-dependent S. aureus resistance against PDT. [ABSTRACT FROM AUTHOR]

Objectives To describe the presentation of suspected urinary tract infections ( UTIs) in nursing home ( NH) residents with advanced dementia and how they align with minimum criteria to justify antimicrobial initiation. Design Twelve-month prospective study. Setting Twenty-five NHs. Participants Two hundred sixty-six NH residents with advanced dementia. Measurements Charts were abstracted monthly for documentation of suspected UTI episodes to determine whether episodes met minimum criteria to initiate antimicrobial therapy according to consensus guidelines. Results Seventy-two residents experienced 131 suspected UTI episodes. Presenting symptoms and signs for these episodes are mental status change (44.3%), fever (20.6%), hematuria (6.9%), dysuria (3.8%), costovertebral tenderness (2.3%), urinary frequency (1.5%), rigor (1.5%), urgency (0%), and suprapubic pain (0%). Only 21 (16.0%) episodes met minimal criteria to initiate antimicrobial therapy based on signs and symptoms. Of the 110 episodes that lacked minimum criteria to justify antimicrobial initiation, 82 (74.5%) were treated with antimicrobial therapy. Urinalyses and urine culture results were available for 101 episodes, of which 80 (79.2%) had positive results on both tests. The proportion of episodes with a positive urinalysis and culture was similar for those that met (83.3%) and did not meet (78.3%) minimum criteria ( P = .06). Conclusion The symptoms and signs necessary to meet minimum criteria to support antimicrobial initiation for UTIs are frequently absent in NH residents with advanced dementia. Antimicrobial therapy is prescribed for the majority of suspected UTIs that do not meet these minimum criteria. Urine specimens are frequently positive regardless of symptoms. These observations underscore the need to reconsider the diagnosis and the initiation of treatment for suspected UTIs in advanced dementia. [ABSTRACT FROM AUTHOR]

Therapy with appropriate antimicrobial agents is an important component in the management of patients with acute cholangitis and/or acute cholecystitis. In the updated Tokyo Guidelines (TG13), we recommend antimicrobial agents that are suitable from a global perspective for management of these infections. These recommendations focus primarily on empirical therapy (presumptive therapy), provided before the infecting isolates are identified. Such therapy depends upon knowledge of both local microbial epidemiology and patient-specific factors that affect selection of appropriate agents. These patient-specific factors include prior contact with the health care system, and we separate community-acquired versus healthcare-associated infections because of the higher risk of resistance in the latter. Selection of agents for community-acquired infections is also recommended on the basis of severity (grades I-III). Free full-text articles and a mobile application of TG13 are available via . [ABSTRACT FROM AUTHOR]

Objective To document whether presumptive bacterial translocation (PBT) occurs in horses with small intestinal strangulation (SIS). Design Prospective clinical cohort study. Setting University tertiary care facility. Animals Thirty-six adult horses with SIS (clinical cases) and 10 adult horses without gastrointestinal disease (control cases). Interventions Sterile collection and bacterial culture of samples from peripheral venous blood, mesenteric venous blood, mesenteric lymphatic tissue, and intestinal aspirates from horses with SIS and control horses without gastrointestinal disease. Measurements and Main Results Five of 36 (13.8%) horses with SIS had at least 1 sample yield a positive result. Shorter SIS bowel segments were more likely to yield a positive culture result. ( P < 0.01). Two of 10 of control horses had positive culture results with different bacterial species identified compared to horses with SIS. Antimicrobial usage did not influence bacterial culture status ( P = 0.31). There were no differences between culture-positive and culture-negative horses with SIS regarding admission, clinical, or clinicopathologic variables. Conclusions PBT occurs in normal horses and in horses with SIS. Bacterial genera differed between groups. A low incidence of PBT occurs in horses with SIS suggesting postoperative morbidity in some cases may be due to other factors. [ABSTRACT FROM AUTHOR]

Background: We performed bacteriological analysis of bile in acute cholecystitis (AC) patients graded in severity according to the Tokyo guidelines. Methods: We enrolled 163 AC patients in whom bacteriological analysis of bile was performed. Results: Significant differences in age (60 vs. 67 years), body temperature (BT) (37.2 vs. 37.6°C), white blood cell count (13,033 vs. 15,177/mm), and serum C-reactive protein (CRP) (8.9 vs. 16.9 mg/dL) were found between the Mild and Moderate severity groups. The prevalence of bactibilia differed significantly between Mild and Moderate patients (45.3 vs. 67.0%, P = 0.0107); however, there were no significant differences in the bacterial strains, prevalence of antimicrobial resistance, or polymicrobial isolation frequency between the 2 groups. Our local antibiogram revealed that several microorganisms showed higher resistance rates; these were also isolated even in Mild cases. Advanced age, high BT, high serum CRP, and presence of marked local infection were identified as being significantly associated with high risk of bactibilia. Receiver operating characteristic curve analysis indicated the optimal cutoff value of age to be 65 years, of BT to be 37.5°C, and of serum CRP to be 13.4 mg/dL. Conclusion: Adequate broad-spectrum antimicrobial therapy should be administered perioperatively even for Mild patients classified according to the current Tokyo guidelines. These results suggest that more precise severity grades may need to be established, including age and CRP as additional parameters. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: The aim of this longitudinal study was to evaluate the effect of combined treatment on early progressive bone loss around dental implants. Methods: The study sample consisted of 18 implants presenting at 4-6 weeks postplacement with early progressive bone loss. Clinical examination indicated the presence of a fistula in the soft tissue covering the implants in most cases. Defects around the implants were curetted, exposed implant surfaces were mechanically debrided and treated with tetracycline solution, and the defects were filled with bone graft and doxycycline powder. Bioabsorbable membranes were used. Final crowns were placed after 6 months. The patients were followed for an average of 30 months. Results: The surgical sites healed without complication. At the time of loading, the defects were completely restored. At 12 months postloading, there was crestal bone loss to the level of the first thread (average, 1.3 mm). Pocket depths ranged from 3 to 5 mm (average, 3.6 mm) with no bleeding. No further changes were noticed throughout the remaining follow-up visits. All implants were successful according to the criteria proposed by Albrektsson and colleagues. Conclusions: Early detection and treatment of early progressive bone loss around dental implants are the key to saving early failing implants. The author recommends reevaluation visits 4-6 weeks postimplant placement to detect any signs of early failure so that immediate treatment can be undertaken if needed. [ABSTRACT FROM AUTHOR]

Since the early development of antibiotics, antimicrobial resistance has continued to emerge as a formidable adversary in the fight against infectious disease. Once an issue confined to hospitals, antibiotic resistance has now invaded communities, targeting not only the immunocompromised patient, but also those who are immunocompetent. To stem this crisis, researchers have developed more powerful and more costly antibiotics, which have only complicated the resistance problem. Education of the patient and the prescriber, as well as antimicrobial stewardship programs, are necessary to avert a global antibiotic resistance catastrophe. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the predictive value of relevant clinical and laboratory parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates with suspected late-onset sepsis (LOS).Methods: NICU neonates were prospectively followed for septic events. One hundred and eleven neonates developed 148 suspected septic events beyond 3 d of age. We recorded the clinical signs and laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus-specific PCR, microbiological data, and empiric antimicrobial therapy.Results: Variables significantly associated with subsequently confirmed LOS included hypotension (relative risk (RR) = 5.6, 95% CI 3.29-9.53), mechanical ventilation (RR = 2.46, 95% CI 1.24-4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR = 5.13, 95% CI 2.54-10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32-6.15), and small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03-4.38). PCT was not significantly associated with LOS. For detection of staphylococcal bacteremia, Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%, positive predictive value 53.3%, and negative predictive value 95.4%.Conclusion: Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status at onset of sepsis are significant predictors of proven neonatal LOS. Staphylococcus-specific PCR might be of value in ruling out staphylococcal sepsis. [ABSTRACT FROM AUTHOR]

The article focuses on the topics discussed in the symposium, Scientific Basis for Tissue-Directed Antimicrobial Therapy, held on July 21 and 22, 2005 in Boston, Massachusetts. Discussions focused on the reevaluation of approaches to antimicrobial therapy. Panelists also considered the factors when characterizing the tissue-directed antimicrobial therapy. Measures to address the issues and challenges faced by infectious disease specialists were also discussed.

Periodontitis may be viewed as an infectious disease with a number of specific characteristics. Pathogens of the subgingival microbiota can interact with host tissues even without direct tissue penetration. Hence, antimicrobial agents must be available at a sufficiently high concentration not only within the periodontal tissues, but also outside, in the environment of the periodontal pocket. The subgingival microbiota accumulate on the root surface to form an adherent layer of plaque with the characteristics of a biofilm. Several mechanisms, such as diffusion barriers, and selective inactivation of agents lead to an increased resistance of bacteria in biofilms. Mechanical supragingival plaque control is indispensable to prevent the re-emergence of periodontal pathogens and the re-establishment of a biofilm in treated sites. Since specific features have important implications for the use of antimicrobial agents in periodontal therapy, extrapolations from experiences made in the therapy of other infections are only partially valid. The ultimate evidence for the efficacy of systemic or local chemotherapy must be obtained from treatment studies in humans with adequate follow-up. [ABSTRACT FROM AUTHOR]

AbstractBackground, aims: Between 4 and 8% of periodontitis patients are reported to respond poorly to conventional therapy. In these cases, adjunctive use of systemic antibiotics might be a reasonable therapeutic approach. The purpose of this study was to evaluate the effects of systemic amoxicillin/clavulanate as adjunct to periodontal surgery on the predominant subgingival microorganisms in patients not responding to mechanical therapy. Furthermore, the bacterial susceptibility to amoxicillin/clavulanate was analyzed before and after therapy in order to assess the clinical validity of pre-therapeutic susceptibility testing. Methods: In 10 periodontitis subjects with no subgingival detection of Actinobacillus actinomycetemcomitans, the predominant subgingival organisms were identified using the identification system Rapid ID 32 A as well as antibiotic susceptibility was tested utilizing the E test. Results: Porphyromonas gingivalis and Prevotella oralis were detected in 7/10 subjects and could no more recovered after therapy. Fusobacterium nucleatum and Peptostreptococcus micros were present in 5/10 patients before treatment, but could be detected in 6/10, resp. 3/10 after therapy. In 4/10 subjects harboring F. nucleatum and in 3/10 with P. micros, those organisms were not targeted by amoxicillin/clavulanate, although post-treatment testing revealed their alleged susceptibility (MICs varied from 0.023 to 0.032 μg/ml, resp. from 0.125 to 2.0 μg/ml). Conclusions: The results of this study suggest that the outcomes of conventional methods of susceptibility testing have to be interpreted very carefully when being used for treatment of plaque-related diseases. Furthermore, since the endpoint of systemic antibiotic treatment as adjunct to conventional therapy is elimination of F. nucleatum or P. micros in patients harboring these organisms, the use of amoxicillin/clavulanate appears not to be justified. [ABSTRACT FROM AUTHOR]

Introduction: Upper respiratory tract infection (URTI) is a common health problem among patients attending primary health care (PHC) clinics (Kuyvenhoven et al. 1993; Khattab et al. 1997) and sore throat is one of the most common presenting symptoms in PHC clinics. It imposes a heavy burden on resources and time and results in the prescription of an oral antibiotic in 20% to 90% of cases (Kuyvenhoven et al. 1993; Carr et al. 1994). Two-thirds of all antimicrobial drugs prescribed by Dutch PHC physicians, for example, are prescribed for URTI (Kuyvenhoven et al. 1993). PHC physicians prescribe antibiotics for sore throat for different reasons, including the ?prevention of complications (e.g. rheumatic fever, glomerulonephritis, sinusitis, otitis media, etc.), the relief of symptoms and for psychosocial ?reasons (Little & Williamson 1994). The majority of PHC physicians working in Saudi Arabia are expatriates contracted from outside the Kingdom. These colleagues come with varied backgrounds and attitudes to prescribing. A minority of patients presenting with sore throat have acute tonsillitis and only one-third appeared to harbour Group A b-haemolytic streptococci (GABHS), including carriers (Dangnelie et al. 1996). Thus a large number of patients may be unnecessarily exposed to risk of antibiotics and development of resistance with a concomitant drain on the health budgets. Furthermore, it is common for broad-spectrum antibiotics, particularly amoxycillin, to be chosen, despite consistent advice that penicillin or erythromycin are still the most appropriate antibiotics for sore throat of bacterial origin (Fry 1993).Local studies that have evaluated the presentation and management pattern of such problems in PHC clinics in Saudi Arabia are rare. This study was initiated to address the following research questions:1 What is the pattern of presentation and management of sore throat in PHC clinics?2 Could clinical presentation guide us in the initiation of... [ABSTRACT FROM AUTHOR]

Sites affected with adult periodontitis were observed for 3 months to compare their clinical and microbiologic responses to (1) a single 2 g dose of metronidazole, (2) scaling and root planing, or (3) no treatment. 2 sites with probing depths ≥ 5 mm in each of 18 female subjects (6 in each treatment group) were evaluated clinically (plaque and bleeding indices, probing depth, attachment loss) and microbiologically (%s of cocci, motile rods, non-motile rods and spirochetes, and of obligate anaerobic colony-forming units, black-pigmented Bacteroides, Fusobacterium and Actinobacillus actinomycetemcomitans in subgingival plaque). No significant differences in these variables existed between the 3 groups at baseline. The no-treatment (control) group showed no substantial clinical or microbiologic changes during the study. After 1 month, scaling and root planing had effected significant clinical improvement and significant shifts in the subgingival flora to a pattern more consistent with periodontal health; these changes were still evident at 3 months. In contrast, 1 month after metronidazole, there was some clinical improvement and a significant increase in cocci and a decrease in motile rods, but at 3 months these changes were no longer evident. The results show that the benefits of scaling and root planing are sustained for at least 3 months. However, the benefits of a single 2 g dose of metronidazole are both few and transient, indicating that this regimen, while effective against anaerobic infections in other organ systems, is not clinically or microbiologically effective in the treatment of adult periodontitis. [ABSTRACT FROM AUTHOR]

Local delivery of antimicrobials has been investigated as a possible method for controlling and treating periodontal disease. A number of anti- microbial agents have been studied both as adjunctive therapies with scaling and root planing and as stand-alone chemotherapies. More recent investigations have focussed on the delivery of antimicrobials in sustained-release formulations designed to maintain effective concentrations of drug within the periodontal pocket. This article provides an overview of the development of the use of locally- delivered metronidazole in periodontal therapy and the current state-of-the-art of the technique. It is concluded that treatment with local delivery of metronidazote seems to be as effective as scaling and root planing in untreated as well as in recall subjects. However, there are reasons to suggest that local delivery of intronidazole should not be used as a substitute for conventional treatment of periodontal disease, since side-effects of long-term use and repeated use are not known. The antibiotic regimen should preferably be used as an adjunct to surgical and non-surgical therapy. [ABSTRACT FROM AUTHOR]

Rhinosinusitis is a common children’s disease. Most cases are acute, follow an episode of common cold, and are the consequence of a superimposed bacterial infection. If mild, they are characterized by the persistence of signs and symptoms of upper respiratory tract disease for more than 10 days; if severe, they involve fever and a purulent nasal discharge, and can cause a substantial decline in general health. Recurrent acute or chronic cases are usually diagnosed in children with predisposing factors, such as recurrent respiratory tract infections, allergic rhinitis, cystic fibrosis, immunodeficiency, ciliary dyskinesia, anatomic abnormalities or reflux. Therapy is based on antibiotics, administered orally in mild, and intravenously in severe cases. On the basis of recently highlighted antibiotic resistances and the possibility of spontaneous resolution, experts agree in considering amoxicillin the drug of choice for mild cases, and an antibiotic capable of overcoming all possible resistance for severe cases. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a treatment by combining light and a photosensitizer to generate reactive oxygen species (ROS) for cellular damage, and is used to treat cancer and infectious diseases. In this review, we focus on recent advances in design of new photosensitizers for increased production of ROS and in genetic engineering of biological photosensitizers to study cellular signaling pathways. A new concept has been proposed that PDT‐induced acute inflammation can mediate neutrophil infiltration to deliver therapeutics in deep tumor tissues. Combination of PDT and immunotherapies (neutrophil‐mediated therapeutic delivery) has shown the promising translation of PDT for cancer therapies. Furthermore, a new area in PDT is to treat bacterial infections to overcome the antimicrobial resistance. Finally, we have discussed the new directions of PDT for therapies of cancer and infectious diseases. In summary, we believe that rational design and innovations in nanomaterials may have a great impact on translation of PDT in cancer and infectious diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Infectious DiseaseNanotechnology Approaches to Biology > Nanoscale Systems in Biology [ABSTRACT FROM AUTHOR]