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In the European Union, the use of veterinary drugs belonging to the A6 group is prohibited in food-producing animals according to Commission Regulation (EU) No. 2010/37. The aim of this study was to improve the analytical control strategy by developing a single method to analyse residues of prohibited pharmacologically active substances in milk. For this, a single method was developed to analyse 16 prohibited pharmacologically active substances belonging to five different substance classes at required or recommended levels: nitroimidazoles at 3 μg kg -1 , nitrofurans at 0.5 μg kg -1 , chloramphenicol at 0.1 μg kg -1 , dapsone at 5 μg kg -1 and chlorpromazine at 1 μg kg -1 . Milk sample preparation started with an acid hydrolysis combined with a derivatisation. These steps were followed by a clean-up consisting of a dispersive solid-phase extraction and a liquid-liquid extraction. Finally, the sample extracts were analysed by liquid chromatography combined with tandem mass spectrometry, operating alternately in the positive and negative mode. The method was fully validated according to Commission Decision 2002/657/EC for bovine milk and additionally validated for caprine milk. The validation proved that the method is highly effective to detect and confirm all 16 substances in bovine and caprine milk and, additionally to quantify 15 of these substances in bovine milk and 13 of these substances in caprine milk. This study resulted in a new multi-class method to detect, quantify and confirm the identity of 16 prohibited pharmacologically active substances belonging to five different substance classes in two types of milk.

Macrolides are critically important antimicrobials for both human and animal health and should be prioritized in risk assessments, as inappropriate use may result in antimicrobial resistance. The antimicrobials erythromycin, oleandomycin, spiramycin, tilmicosin and tylosin were analysed in infant formula samples by HPLC-MS/MS using a validated analytical method based on a modified QuEChERS extraction. The results of the occurrence study were employed to perform a dietary exposure assessment of infants to residues. In a total of 30 analysed samples, 73% contained spiramycin residues and 27%, tilmicosin residues. Calculated daily intakes ranged from 1.47 × 10 -6 to 2.71 × 10 -4 mg kg -1 body weight considering all analytes, representing 0.01-0.59% of acceptable daily intakes. The results of the dietary exposure assessment were all below acceptable daily intakes, indicating low potential health concerns. However, according to Brazilian regulations, infant formulas containing residues of one or more of the investigated analytes were deemed as non-compliant.

Background : Streptococcal Toxic Shock Syndrome (STSS) is a serious condition that can arise from streptococcal postpartum endometritis. It is associated with a substantial increase in mortality rate and can rarely result in multiorgan infarction. Early recognition plays a vital role in patients' outcome. Objective : To report a case of complicated STSS and review the literature for previous case reports of streptococcal postpartum endometritis to determine if STSS diagnostic criteria (published by the Centers for Disease Control and Prevention) were fulfilled. Case presentation : This is a 41-year-old woman who presented 5 days after an uncomplicated vaginal delivery with endometritis complicated by invasive group A β-hemolytic streptococcus (GAS) infection and confirmed toxic shock syndrome. The patient was initially admitted to the critical care unit due to hemodynamic compromise requiring intravenous (IV) fluids, IV antibiotic therapy with penicillin and clindamycin, and IV immunoglobulin therapy. The patient subsequently developed multi-organ infarctions, acute respiratory distress syndrome requiring noninvasive respiratory support, and severe reactive arthritis. Literature review revealed 15 case reports of GAS postpartum endometritis, five met criteria for confirmed STSS. One patient died from severe septic shock leading to cardiopulmonary arrest. Thirteen out of 15 cases of postpartum endometritis occurred after uncomplicated vaginal delivery. Conclusion : STSS is a serious and possibly fatal medical condition that requires early diagnosis and treatment to prevent poor patient outcomes and death. Careful consideration to the patient's postpartum clinical presentation with the implementation of an intradisciplinary approach should be utilized.

Objectives: Helicobacter pylori ( H. pylori ) infection caused by antibiotic-resistant strains represents a major public health threat that aggressively promotes gastric cancer progression. Antibiotic resistance evaluation is immensely important to counteract its emergence. Here we merely determine the prevalence of antibiotic resistance in H. pylori isolates and its correlation with cagA motifs and the homB gene. Methods: The antibiotic resistance pattern was investigated on 128  H. pylori isolated strains utilizing the disk diffusion method and study the correlation between it and the presence of pathogenic genes, cagA EPIYA motifs and homB gene, were accurately detected using the PCR. Results: The resistance rates to four antibiotics were 70.1% for metronidazole, 35.5% for amoxicillin, 7.2% for clarithromycin and 8.2% for tetracycline. Resistance phenotypes were separated into two groups, single resistance (63.2%) and multi-resistance (12.5%). The prevalence of cagA -ABCC resistant strains and homB + resistant strains was significantly higher in cancer ( p =  0.04 and p =  0.01, respectively) than those of other diseases. The prevalence of cagA-homB + resistance strains was 21.8% and had a significant correlation with PUD. A significant relationship was observed between amoxicillin resistant rate with ABC- homB ( p =  0.0006). Conclusion: The Resistance rate to selected antibiotics in Shiraz is higher than years ago. The presence of cagA-homB + is associated with antibiotic resistance and also homB can be used as a marker to antibiotic resistance status prediction in H. pylori isolated in this area.

Introduction : Acute bacterial skin and skin structure infection (ABSSSI) represents a major burden for healthcare systems. The increased prevalence of Methicillin-resistant Staphylococcus aureus, combined with the limited availability of microbiologic data when treating ABSSSI, has led to a need for more convenient, less toxic anti-MRSA agents. Recent approvals have added several agents to the antibiotic armamentarium that provide an expanded spectrum of activity and ease of administration compared to older agents. Areas covered : In this review, the authors discuss updated approaches to the management of ABSSSI. They also provide a review of recent FDA approved antibiotics and emerging investigational agents for treatment of ABSSSI. Expert opinion : Several new antibiotic agents have received FDA approval through the revised guidance on ABSSSI clinical trials with advantages of activity against MRSA and ease of administration. In theory, this may translate to reducing the utilization of healthcare resources by allowing for earlier discharge and reducing the need for outpatient parenteral therapy. While the approval of new agents offers the opportunity to improve and simplify treatment of ABSSSI, it is more important now than ever to use these agents in a responsible manner.

Objectives: Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade., Materials and Methods: This population-based study used data from the Swedish Prescribed Drug Register. From July 2005 until December 2014, all regimens that can eradicate H. pylori were identified and evaluated according to patients' age and sex and calendar year of eradication., Results: We identified 157,915 eradication episodes in 140,391 individuals (53.8% women, 42.6% older than 60 years), who correspond to 1.5% of the Swedish population. The absolute number and incidence of eradications decreased over the study period. Overall, 91.0% had one eradication and 0.1% had more than three. Of all eradications, 95.4% followed the recommended regimen, while 4.7% did not. The latter group was overrepresented among individuals aged ≥80 years (7.8%). Amoxicillin and clarithromycin were most frequently prescribed, while metronidazole was rarely used (0.01%). Other prescribed antibiotics were ciprofloxacin (2.4%), doxycycline (1.4%), nitrofurantoin (0.7%), norfloxacin (0.5%) and erythromycin (0.3%)., Conclusions: During the last decade in Sweden H. pylori eradication has been frequently prescribed, but the incidence of eradication has slowly declined. Most eradications followed the recommended regimen, including those occurring after a previous eradication.

Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.

The Evidence Investigator™ system (Randox, UK) is a biochip and semi-automated system. The microarray kit II (AM II) is capable of detecting several compounds belonging to different families of antibiotics: quinolones, ceftiofur, thiamphenicol, streptomycin, tylosin and tetracyclines. The performance of this innovative system was evaluated for the detection of antibiotic residues in new matrices, in muscle of different animal species and in aquaculture products. The method was validated according to the European Decision No. EC/2002/657 and the European guideline for the validation of screening methods, which represents a complete initial validation. The false-positive rate was equal to 0% in muscle and in aquaculture products. The detection capabilities CCβ for 12 validated antibiotics (enrofloxacin, difloxacin, ceftiofur, desfuroyl ceftiofur cysteine disulfide, thiamphenicol, florfenicol, tylosin, tilmicosin, streptomycin, dihydrostreptomycin, tetracycline, doxycycline) were all lower than the respective maximum residue limits (MRLs) in muscle from different animal origins (bovine, ovine, porcine, poultry). No cross-reactions were observed with other antibiotics, neither with the six detected families nor with other families of antibiotics. The AM II kit could be applied to aquaculture products but with higher detection capabilities from those in muscle. The detection capabilities CCβ in aquaculture products were respectively at 0.25, 0.10 and 0.5 of the respective MRL in aquaculture products for enrofloxacin, tylosin and oxytetracycline. The performance of the AM II kit has been compared with other screening methods and with the performance characteristics previously determined in honey.

Introduction: The wide use of antibiotics both within and beyond the medical territory plays a significant role in the development of resistant bacteria. Therefore, there is a pressing need for the development of effective antibiotics worldwide., Areas Covered: The current analysis report covers the scientific progress in supporting antibiotic patent application and the granted patent literature in China for the last 20 years., Expert Opinion: Among the 2780 patents granted in China last 20 years, β-lactam antibiotics, macrolides, quinolones, aminoglycosides, sulfonamides, glycopeptides and tetracyclines constitute 44.3, 17.4, 13.5, 4.1, 3.8, 3.0 and 2.1% of total patents, respectively. Scientists have faced challenges in developing new antibiotics against increasingly growing types of drug-resistant bacteria, which may causes serious global public health disaster in future. Poor financial investment in antibiotic research has exacerbated the situation. Therefore, new antibiotic patents will be applied continuously. The combination individual β-lactam antibiotics with a β-lactamase inhibitor have been demonstrated clinically beneficial and may suggest a new way for the development of more effective antibiotics in future. Local patent applications of China are stably increasing largely through a dependence on the imitation of Western drugs. The current study may help to better understand the patent situation in China and to invent the more efficient antibiotic therapies.

The treatment of melioidosis currently involves the use of antimicrobials such as ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline. Evaluation of other antimicrobials with activity against the organism continues to be pursued, however, as the causative organism, B. pseudomallei, may not always be susceptible to the above antimicrobials. This study aimed to test the susceptibility of Malaysian isolates of B. pseudomallei against imipenem, meropenem, ertapenem, moxifloxacin and azithromycin. 80 previously stocked clinical isolates collected between 1978 and 2003 from the UMMC, Kuala Lumpur were tested for in vitro susceptibility to these antimicrobials using the E-test minimum inhibitory concentration method. 100% of isolates were sensitive to imipenem and meropenem, 97.5% were sensitive to trimethoprim-sulfamethozaxole, 37.5% to moxifloxacin, and only a minority was sensitive to ertapenem (7.5%). Using breakpoints for Staphylococcus and Haemophilus, 5.0%-6.3% of isolates were sensitive to azithromycin. In conclusion, our findings support the in vitro efficacy of imipenem, meropenem and trimethoprim-sulfamethoxazole against B. pseudomallei. Moxifloxacin, ertapenem and azithromycin cannot be recommended for the treatment of melioidosis; however, further studies are needed to test the efficacy of azithromycin in combination with quinolones.

Acute otitis media (AOM) is treated with antibiotics in the United States, but the changing distribution of bacterial pathogens that cause the disorder can present physicians with several challenges. Most physicians treat AOM empirically, and their treatment choice should target Streptococcus pneumonia, nontypeable Haemophilus influenzae, and Moraxella catarrhalis, as those bacteria are most often isolated in AOM. First-line treatment for new onset AOM remains amoxicillin (80-90 mg/kg/d, divided twice daily). For persistent or recurrent AOM, guidelines recommend high-dose amoxicillin-clavulanate, cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Improved diagnosis and optimizing the choice of therapy by considering in vitro and in vivo efficacy of the different antibiotics will improve patient outcomes. Improved patient outcomes will result in fewer AOM episodes, decreased antibiotic resistance, and reduced direct and indirect health care costs.

Objective: To evaluate the resource consumption and outcomes associated with first-line monotherapy for community-acquired pneumonia, focusing specifically on the use of erythromycin, azithromycin, clarithromycin, and levofloxacin., Study Design: Retrospective managed care database analysis., Patients and Methods: Subjects included patients within a managed care setting over 18 years of age with an initial diagnosis of community-acquired pneumonia from January 1995 to April 2002. Multivariate linear and logistic regression models were used to examine associations with treatment success rates and direct medical costs between antibiotic treatments after controlling for patient demographics and pneumonia risk factors., Main Results: Overall, treatment success rates were high (95.8%), the use of second antibiotics was un common (2.3%), and hospitalizations were infrequent (2.0%) among the 1952 subjects studied. After controlling for patient characteristics and risk factors, significantly lower total costs were associated with erythromycin (92.7% lower, p < 0.001), azithromycin (48.7% lower, p < 0.001), and clarithromycin (21.3% lower, p = 0.015) relative to levofloxacin, with no difference in treatment success between groups. Among newer agents, azithromycin (49.2% lower, p < 0.001) and clarithromycin (21.7% lower, p = 0.013) treatment groups were associated with significantly lower total costs than levofloxacin in the full sample. However, in subjects with a chronic disease score above the sample's mean, only azithromycin was associated with significantly lower total costs (47.9% lower, p < 0.001) relative to levofloxacin., Conclusion: Erythromycin, azithromycin, and clarithromycin were associated with significantly lower total costs than levofloxacin, although treatment success rates did not differ between groups. Following stratification based upon various subset criteria, erythromycin and azithromycin were observed to have significantly lower total costs than levofloxacin. Although these findings may augment clinical guidelines and evidence-based approaches, health plans should consider evaluating their own patient data to see if similar differences exist in their populations.

Vancomycin has long been considered the antibiotic of last resort against serious and multi-drug-resistant infections caused by Gram-positive bacteria. However, vancomycin resistance has emerged, first in enterococci and, more recently, in Staphylococcus aureus. Here, the authors attempt to review the prevalence and the mechanisms of such resistance. Furthermore, they focus on strategies that have been developed or are under current investigation to overcome infections caused by vancomycin-resistant strains. Among these are glycopeptide derivatives with higher potency than vancomycin, small molecules that resensitise bacteria to the antibiotic and novel non-glycopeptide antibiotics. These agents are targeted to interfere with protein and/or peptidoglycan (PG) synthesis and integrity or with membrane permeability. Whilst most of these agents are still in clinical or preclinical development, some have entered the clinic and currently represent the only option for treating vancomycin-resistant enterococci (VRE).

There is an urgent need to develop novel classes of antibiotics to counter the inexorable rise of resistant bacterial pathogens. Modern antibacterial drug discovery is focused on the identification and validation of novel protein targets that may have a suitable therapeutic index. In combination with assays for function, the advent of microbial genomics has been invaluable in identifying novel antibacterial drug targets. The major challenge in this field is the implementation of methods that validate protein targets leading to the discovery of new chemical entities. Ligand-directed drug discovery has the distinct advantage of having a concurrent analysis of both the importance of a target in the disease process and its amenability to functional modulation by small molecules. VITA is a process that enables a target-based paradigm by using peptide ligands for direct in vitro and in vivo validation of antibacterial targets and the implementation of high-throughput assays to identify novel inhibitory molecules. This process can establish sufficient levels of confidence indicating that the target is relevant to the disease process and inhibition of the target will lead to effective disease treatment.

The objective of this study was to evaluate antibiotic use in relation to diagnoses and bacteriological findings in a 600-bed Norwegian university hospital. Twelve point-prevalence studies of antibiotic use were conducted between 1996 and 1999. In the point-prevalence studies, 1,096 of 6,588 adult patients (16.6%) used on average 1.25 antibiotics each. Of the patients who received antibiotics, 35% were treated for hospital-acquired infections. Lower respiratory tract and urinary tract infections accounted for more than half of all antibiotic use. Pencillins represented 54% of antibiotic use, cephalosporins 9%, quinolones 6% and antifungal agents 0.7%. The prescribed daily doses for the penicillins were 2-3 times higher than the defined daily doses. Bacteriological samples were obtained from 929 (85%) patients. Compliance with the guidelines was > 90% and was highest when the results of bacteriological samples were positive. Good compliance led to low prevalence of antibiotic use and the use of narrow-spectrum antibiotics.

Infective endocarditis caused by viridans streptococci is a well-described disease. Streptococcus viridans is also an important etiologic agent causing septicaemia in neutropenic patients with haematological diseases. In this study we retrospectively reviewed charts from 111 patients with 121 episodes of viridans streptococci septicaemia during the period 1992-97 for clinical data, presence of endocarditis, subtype and outcome. Forty-seven episodes of S. viridans septicaemia were documented in 45 non-neutropenic patients treated at the Department of Infectious Diseases (Group A). Thirty of these episodes were defined as definite and 9 as possible infective endocarditis, using Duke's critera. Seventy-four episodes of S. viridans septicaemia were identified in 66 patients treated at the Department of Haematology (Group B), only 1 of which fulfilled the criteria for possible infective endocarditis. S. sanguis was the most common subtype (18/47; 38%) in Group A and S. mitis was the major subtype (51/74; 69%) in Group B.

A revised system for antibiotic sensitivity testing in Sweden was proposed in 1977. The new SIR system has been in sue in almost all Swedish routine bacteriological laboratories since 1979. The SIR system implied 2 main changes: 3 sensitivity groups instead of previous 4 and new breakpoints for the sensitivity groups. The new system is presented in comparison with 3 standardized systems currently in use (NCCLS, ICS and DIN systems).