Antibiotic Resistance among Fusobacterium, Capnocytophaga, and Leptotrichia Species of the Oral Cavity.

PURPOSE: Antibiotics play an important role in treating periodontal diseases. Due to the effectiveness of antibiotic therapies, their usage in dentistry has significantly increased. The aim of this study focused on the in-vitro susceptibility of different gram-negative oral bacteria species - which are associated with periodontal diseases (Fusobacterium spp., Capnocytophaga spp. and Leptotrichia buccalis) and have different geographical origins (Asia and Europe) - against antimicrobials that are clinically relevant in dental therapy. MATERIALS AND METHODS: A total of 45 strains were tested (29 Fusobacterium spp., 13 Capnocytophaga spp. and 3 L. buccalis) that were either isolated from Chinese patients or were obtained from different strain collections. Their antimicrobial susceptibility to the antimicrobial agents benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, ciprofloxacin, moxifloxacin, clindamycin, doxycycline, tetracycline and metronidazole was tested using the E-Test. Strains with particular resistance to penicillin, clindamycin and metronidazole were further analysed for resistance genes. RESULTS: All tested bacterial isolates were sensitive to amoxicillin, amoxicillin-clavulanic acid, doxycycline and tetracycline, but showed variable sensitivity towards other antibiotics such as benzylpenicillin, ciprofloxacin, moxifloxacin, clindamycin and metronidazole. CONCLUSION: The results of the present study suggest that certain periodontal disease-related bacterial strains can be resistant towards antimicrobial agents commonly used in adjuvant periodontal therapy.

Haemophilus influenzae drug resistance in France from 2017 to 2021: consideration for treatment of otitis media.

OBJECTIVES: Haemophilus influenzae is a prevalent agent of respiratory infections, including acute otitis media (AOM), that lead to high antibiotic prescription and may contribute to the development of bacterial resistance to antibiotics. The objective of this work was to describe and analyse antibiotic resistance of H. influenzae from 2017 to 2021 in France. METHODS: We characterized H. influenzae isolates transmitted to the French national reference centre for H. influenzae between 2017 and 2021. We included all the 608 non-invasive respiratory isolates. Resistance rates to the main antibiotics were described. The relationship between resistance rate, age, and sex of patients and germ serotype was investigated. RESULTS: Isolates were mainly from alveolar lavage (29.3%), expectoration (22.9%), or sputum (15%). Resistance to amoxicillin (61.4%), amoxicillin/clavulanic acid (47.4%), and cefotaxime (39.3%) was high and correlated with the presence of ß-lactamase and/or modifications of the ftsI gene encoding penicillin-binding protein 3. Resistance to sulfamethoxazole/trimethoprim (33.2%) was more moderate. There were no significant differences according to serotype, age, or gender. CONCLUSIONS: The benefit/risk balance of first choice use of amoxicillin and even of amoxicillin/clavulanic acid in AOM is questionable in view of the significant resistance to H. influenzae. The use of sulfamethoxazole/trimethoprim could be an alternative but may still need further evaluation.

Treatment of moderate grade dog bite wounds using amoxicillin-clavulanic acid with and without enrofloxacin: a randomised non-inferiority trial.

BACKGROUND: Dog-to-dog bite wounds are a common veterinary emergency presentation: despite this, there is insufficient information to guide veterinarians on appropriate empirical antimicrobial management. OBJECTIVES: Investigate the effectiveness of amoxicillin-clavulanic acid with and without enrofloxacin in the treatment of moderate grade dog bite wounds (DBW). To describe common pathogens and their antimicrobial susceptibility patterns. MATERIALS AND METHODS: In a single-centre parallel group pragmatic trial, 50 dogs presenting with moderate grade DBW were prospectively randomised to receive amoxicillin-clavulanic acid (group A) or amoxicillin-clavulanic acid and enrofloxacin (group B). Swabs were taken for culture and susceptibility testing at admission. Stabilisation, wound care and surgical debridement were performed at the discretion of admitting clinicians. The primary outcome was complication due to infection at 10 days, with Bayesian inference used to estimate the difference in proportions between treatment groups. RESULTS: Of the 24 dogs in treatment group A, 1 required the addition of enrofloxacin at re-examination. None of the 26 dogs in group B required alteration of antimicrobial coverage. The difference in complication rate due to infection between treatment groups was 4.2%. Twenty-one different organisms were identified: Staphylococcus pseudintermedius, Neisseria spp., Pasteurella multocida and P. canis were the most common. Over 90% of gram-negative and gram-positive isolates were susceptible to amoxicillin-clavulanic acid. Ninety-six percent of gram-negative and 86% of gram-positive isolates were susceptible to enrofloxacin. CONCLUSION AND CLINICAL SIGNIFICANCE: Amoxicillin-clavulanic acid is an appropriate empirical antimicrobial choice for moderate DBW in South East Queensland. Reduced empirical enrofloxacin use will promote antimicrobial stewardship and potentially antimicrobial resistance.

Antibiogram and beta-lactamase genes among cefotaxime resistant E. coli from wastewater treatment plant.

BACKGROUND: The World Health Organization (WHO) recently classified Enterobacteriaceae resistance to third-generation cephalosporin into the group of pathogens with critical criteria for future research. METHODS: A study to assess the antibiogram and beta-lactamase genes among the cefotaxime resistant E. coli (CREc) from a South African wastewater treatment plant (WWTP) was conducted using standard phenotypic and molecular biology characterization methods. RESULTS: Approximate total E. coli (TEc) concentration (log10 CFU/mL) ranged between 5.7 and 6.8 among which cefotaxime resistant E. coli were between 1.8 and 4.8 (log10 CFU/mL) for cefotaxime antibiotic concentration of 4 and 8 mg/L in the influent samples. Effluent samples, heavily influenced by the chlorination had only 0.3 log10 CFU/mL of TEc. Fifty-one cefotaxime resistant isolates were selected out of an overall of 75 isolates, and subjected to a new round of testing, with a follow up of 36 and 48 isolates for both colistin and gentamicin, respectively as guided by initial results. Selected CREc exhibited resistance to amoxicillin-clavulanic acid (35.3%; n = 51), colistin sulphate (76.5%; n = 36), ciprofloxacin (47.1%; n = 51), gentamicin (87.5%; n = 48) and intermediate-resistance to meropenem (11.8%; n = 51). Extended spectrum-beta-lactamase genes detected, viz.: blaCTX-M (52.6%; n = 38) and blaTEM (84.2%; n = 38) and concurrent blaCTX-M + blaTEM (36.8%; n = 38), but no blaSHV was detected. Carbapenem resistance genes, blaKPC-2 (15.8%; n = 38), blaOXA-1 (57.9%; n = 38), blaNDM-1 (15.8%; n = 38) were also detected. Approximately, 10.5 - 36.8% (n = 38) co-occurrence of two or more beta-lactamase genes was detected in some isolates. Out of the selected number (n = 30), 7(23.3%) were enterotoxigenic E. coli (ETEC), 14 (46.7%) were Enteroaggregative E. coli (EAEC), but no enteropathogenic E. coli (EPEC) was detected. CONCLUSION: Resistance to cefotaxime and the presence of a wide range of beta-lactamase genes exposed the potential risks associated with these pathogens via occupational and domestic exposure during the reuse of treated wastewater.

Impact of oral amoxicillin and amoxicillin/clavulanic acid treatment on bacterial diversity and ß-lactam resistance in the canine faecal microbiota.

BACKGROUND: Aminopenicillins with or without a ß-lactamase inhibitor are widely used in both human and veterinary medicine. However, little is known about their differential impact on the gut microbiota and development of antimicrobial resistance. OBJECTIVES: To investigate changes in the faecal microbiota of dogs treated with amoxicillin or amoxicillin/clavulanic acid. METHODS: Faeces collected from 42 dogs (21 per treatment group) immediately before, during and 1 week after termination of oral treatment with amoxicillin or amoxicillin/clavulanic acid were analysed by culture and 16S rRNA gene sequence analysis. RESULTS: In both groups, bacterial counts on ampicillin selective agar revealed an increase in the proportion of ampicillin-resistant Escherichia coli during treatment, and an increased occurrence and proportion of ampicillin-resistant enterococci during and after treatment. 16S rRNA gene analysis showed reductions in microbial richness and diversity during treatment followed by a return to pre-treatment conditions approximately 1 week after cessation of amoxicillin or amoxicillin/clavulanic acid treatment. While no significant differences were observed between the effects of amoxicillin and amoxicillin/clavulanic acid on microbial richness and diversity, treatment with amoxicillin/clavulanic acid reduced the abundance of taxa that are considered part of the beneficial microbiota (such as Roseburia, Dialister and Lachnospiraceae) and enriched Escherichia, although the latter result was not corroborated by phenotypic counts. CONCLUSIONS: Our results suggest a limited effect of clavulanic acid on selection of antimicrobial resistance and microbial richness when administered orally in combination with amoxicillin. However, combination with this ß-lactamase inhibitor appears to broaden the spectrum of amoxicillin, with potential negative consequences on gut health.

Recurrent urinary tract infections caused by Raoultella planticola after kidney transplant.

Recurrent urinary tract infections are difficult to manage in patients with a history of kidney transplant and may contribute to graft loss. Few cases describe recurrent urinary tract infections due to Raoultella planticola in this population. We describe the management of recurrent urinary tract infections due to R planticola in a kidney transplant recipient and review other case reports of urinary tract infections due to this organism.

Modified Antibiotic Adjuvant Ratios Can Slow and Steer the Evolution of Resistance: Co-amoxiclav as a Case Study.

As antibiotic resistance spreads, developing sustainable methods to restore the efficacy of existing antibiotics is increasingly important. One widespread method is to combine antibiotics with synergistically acting adjuvants that inhibit resistance mechanisms, allowing drug killing. Here we use co-amoxiclav (a clinically important combination of the ß-lactam antibiotic amoxicillin and the ß-lactamase inhibitor clavulanate) to ask whether treatment efficacy and resistance evolution can be decoupled via component dosing modifications. A simple mathematical model predicts that different ratios of these two drug components can produce distinct evolutionary responses irrespective of the initial efficacy. We test this hypothesis by selecting Escherichia coli with a plasmid-encoded ß-lactamase (CTX-M-14), against different concentrations of amoxicillin and clavulanate. Consistent with our theory, we found that while resistance evolved under all conditions, the component ratio influenced both the rate and mechanism of resistance evolution. Specifically, we found that the current clinical practice of high amoxicillin-to-clavulanate ratios resulted in the most rapid adaptation to antibiotics via gene dosing responses. Increased plasmid copy number allowed E. coli to increase ß-lactamase dosing and effectively titrate out low quantities of clavulanate, restoring amoxicillin resistance. In contrast, high clavulanate ratios were more robust-plasmid copy number did not increase, although porin or efflux resistance mechanisms were found, as for all drug ratios. Our results indicate that by changing the ratio of adjuvant to antibiotic we can slow and steer the path of resistance evolution. We therefore suggest using increased adjuvant dosing regimens to slow the rate of resistance evolution.IMPORTANCE As antibiotic resistance spreads, a promising approach is to restore the effectiveness of existing drugs via coadministration with adjuvants that inhibit resistance. However, as for monotherapy, antibiotic-adjuvant therapies can select for a variety of resistance mechanisms, so it is imperative that adjuvants be used in a sustainable manner. We test whether the rate of resistance evolution can be decoupled from treatment efficacy using co-amoxiclav, a clinically important combination of the ß-lactam amoxicillin and ß-lactamase inhibitor clavulanate. Using experimental evolution and a simple theoretical model, we show that the current co-amoxiclav formulation with a high proportion of amoxicillin rapidly selects for resistance via increased ß-lactamase production. On the other hand, formulations with more clavulanate and less amoxicillin have similar efficacies yet prevent the selective benefit of increased ß-lactamase. We suggest that by blocking common paths to resistance, treatment combinations with the adjuvant in excess can slow the evolution of resistance.

Synergistic in vitro activity between aztreonam and amoxicillin-clavulanate against Enterobacteriaceae-producing class B and/or class D carbapenemases with or without extended-spectrum ß-lactamases.

Introduction. Carbapenemase-producing Enterobacteriaceae have become a major public health concern over the last decade and treatment options are limited.Aims. We evaluated the synergistic activity of the combination of aztreonam (ATM) and clavulanate for 41 ß-lactam-resistant clinical isolates harbouring class B or/and class D carbapenemases combined or not with extended-spectrum ß-lactamases (ESBLs).Methodology. The MICs of ATM, with and without amoxicillin-clavulanate (AMC), were determined. Time-kill assays were performed for three representative strains.Results. The ATM-AMC combination had a synergistic effect on 34/41 (83 %) isolates. The MIC of ATM, in the presence of clavulanate, was ≤1 mg l-1 for 15/41 (37 %) isolates and ≤4 mg l-1 for 29/41 (71 %) isolates. Synergistic activity was observed for 34/37 (92 %) isolates producing ESBLs and carbapenemases, compared to 0/4 (0 %) for ESBL-negative strains. Complete or partial bactericidal activity was obtained when the MIC of the combination was 0.5 mg l-1 and 1.5 mg l-1 or 8 mg l-1, respectively.Conclusion. The combination of ATM and AMC could be an attractive unconventional treatment for infections due to carbapenemase- and ESBL-producing Enterobacteriaceae.

Leech management before application on patient: a nationwide survey of practices in French university hospitals.

Background: Leech therapy in plastic/reconstructive microsurgery significantly improves a successful outcome of flap salvage but the drawback is a risk of severe infection that results in a drop of the salvage rates from 70-80% to below 30%. We report the results of a national survey conducted in all the French university hospitals to assess the current extent of use of leech for medical practices in the hospital and to investigate maintenance, delivery practices and prevention of the risk of infection. Methods: Data concerning conditions of storage, leech external decontamination, microbiological controls, mode of delivery and antibiotic prophylaxis were collected from all the French university hospitals in practicing leech therapy, on the basis of a standardized questionnaire. Results: Twenty-eight of the 32 centers contacted filled the questionnaire, among which 23 practiced leech therapy, mostly with a centralized storage in the pharmacy; 39.1% of the centers declared to perform leech external decontamination and only 2 centers recurrent microbiological controls of the water storage. Leech delivery was mostly nominally performed (56.5%), but traceability of the leech batch number was achieved in only 39.1% of the cases. Only 5 centers declared that a protocol of antibiotic prophylaxis was systematically administered during leech therapy: either quinolone (2), sulfamethoxazole/trimethoprim (2) or amoxicillin/clavulanic acid (1). Conclusions: Measures to prevent infectious complications before application to patient have to be better applied and guidelines of good practices are necessary.

Staphylococcus saprophyticus: Which beta-lactam?

BACKGROUND: Staphylococcus saprophyticus is resistant to the drugs most often used for the empirical treatment of urinary tract infections (UTI). The adequacy of antimicrobial treatments prescribed for UTI due to S. saprophyticus is not usually questioned. This study described the epidemiology of such infections and assessed the susceptibility of S. saprophyticus to ceftriaxone and amoxicillin-clavulanic acid. METHODS: Methicillin-susceptible S. saprophyticus (MSSS) isolated from clinical samples between November 2014 and July 2016 were included. Clinical data were recorded. The minimum inhibitory concentrations (MICs) of amoxicillin-clavulanic acid and ceftriaxone were measured for these MSSS strains and for 17 randomly selected methicillin-susceptible Staphylococcus aureus (MSSA) strains. RESULTS: Of the S. saprophyticus isolates from urine, 59.5% were associated with a diagnosis of cystitis and 33.3% with pyelonephritis. Sixty percent of S. saprophyticus cystitis cases and 25% of pyelonephritis cases were given an inappropriate antibiotic regimen. The MICs of ceftriaxone ranged from 4 to >32µg/ml for MSSS, and from 1.5 to 4µg/ml for MSSA. CONCLUSIONS: Many UTIs were treated with an empirical antibiotic therapy that was ineffective for S. saprophyticus, revealing that S. saprophyticus is an aetiology that is insufficiently considered in UTI. High MICs for ceftriaxone in MSSS were observed, which raises questions about the use of this antibiotic in UTIs due to S. saprophyticus.

[A case of coccidioidomycosis in Turkey imported from the United States of America]. / Türkiye'de Amerika Birlesik Devletleri kaynakli bir koksidiyoidomikoz olgusu.

Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is a rare infectious disease except in endemic regions. In this report the third documented imported case of coccidioidomycosis in Turkey was presented. A thirty-year-old male patient was admitted to our hospital with fever and purulent drainage from his chest tube. He had worked in Arizona, USA, until 4 months before this presentation. While in Arizona, he experienced cough and hemoptysis and was diagnosed as pulmonary coccidioidomycosis. He was treated with itraconazole for two months and he had no symptoms for 3 years. He then returned to Turkey and 2 months after his return to Turkey, he was admitted to another hospital in Istanbul with dyspnea and diagnosed as hydro-pneumothorax, and pleural fluid obtained from the inserted chest tube was found to be purulent. One gram of BID amoxicillin-clavulanate was given. Physical examination on admission revealed a purulent drainage on the right side chest tube, a temperature of 38.5°C and decreased breath sounds on the right lung. Piperacillin-tazobactam 3 x 4.5 g intravenous and fluconazole 400 mg intravenous once daily were started. Human immunodeficiency virus test was negative. Gram-negative diplococci and rods, gram-positive cocci and septate hyphae were seen in the Gram stain of his pleural fluid. Pleural fluid culture revealed Moraxella catarrhalis after 24 hours incubation and a mold after 72 hours of incubation. Anti-coccidioidal antibodies were found positive in a titer of 1/2. Hydro-pneumothorax, atelectasis and a 3 mm nodules in the right lung were seen in his thorax CT. The patient's pleural fluid and the culture plates were sent to the Public Health Institute of Turkey, Mycology Reference Laboratory (PHIT-MRL), with a clinical suspicion of coccidioidomycosis. The specimen and plates were submitted to the PHIT-MRL Bio Safety Level-3 laboratory for mycological evaluation. The microscopic examination of 15% KOH preparations of pleural fluid specimens revealed septate hyphae which appear to be in the early stages of forming arthroconidia. The pleural fluid culture grew buff-white coloured colonies with aerial hyphae, which were suspected of being a Coccidioides spp. The strain was identified as C.immitis/posadasii by direct microscopy and culture, and subsequently confirmed by the FDA-approved DNA probe. DNA sequence analysis of the ITS and D1/D2 rDNA regions confirmed the isolate to be C.posadasii species [ITS 100% match to GenBank Accession No. AB232901 (630/630 base pair match), and D1/D2 100% match to GenBank Accession No. AB232884 (617/617 base pair match)]. ITS1 and ITS2 barcode analysis also confirmed the species to be C.posadasii, which is the species endemic in Arizona. Susceptibility testing was performed according to Clinical and Laboratory Standards Institute M38-A2 guidelines in the Fungus Testing Laboratory of the University of Texas Health Science Center at San Antonio and minimal inhibitory concentration values were; 0.125 µg/ml for amphotericin B, posaconazole and voriconazole, 0.5 µg/ml for itraconazole and 8 µg/ml for fluconazole. He had decortication of the pleura and was discharged from hospital after six weeks treatment with intravenous fluconazole which was continued orally for one year. Anti-coccidioidal antibodies were negative after two months of treatment. The patient is currently asymptomatic. The presented case is the third case reported from Turkey and provides additional contribution to the existing literature with regard to the appearance of arthroconidium, which is the unusual hyphal form, instead of the expected spherules in the infected tissue.

Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections and Rationale for Empirical Antibiotic Therapy.

BACKGROUND: The causative agent spectrum and resistance patterns of urinary tract infections in children are affected by many factors. AIMS: To demonstrate antibiotic resistance in urinary tract infections and changing ratio in antibiotic resistance by years. STUDY DESIGN: Retrospective cross-sectional study. METHODS: We analysed antibiotic resistance patterns of isolated Gram (-) bacteria during the years 2011-2014 (study period 2) in children with urinary tract infections. We compared these findings with data collected in the same centre in 2001-2003 (study period 1). RESULTS: Four hundred and sixty-five uncomplicated community-acquired Gram (-) urinary tract infections were analysed from 2001-2003 and 400 from 2011-2014. Sixty-one percent of patients were female (1.5 girls : 1 boy). The mean age of children included in the study was 3 years and 9 months. Escherichia coli was the predominant bacteria isolated during both periods of the study (60% in study period 1 and 73% in study period 2). Bacteria other than E. coli demonstrated a higher level of resistance to all of the antimicrobials except trimethoprim-sulfamethoxazole than E. coli bacteria during the years 2011-2014. In our study, we found increasing resistance trends of urinary pathogens for cefixime (from 1% to 15%, p<0.05), amikacin (from 0% to 4%, p<0.05) and ciprofloxacin (from 0% to 3%, p<0.05) between the two periods. Urinary pathogens showed a decreasing trend for nitrofurantoin (from 17% to 7%, p=0.0001). No significant trends were detected for ampicillin (from 69% to 71%), amoxicillin-clavulanate (from 44% to 43%), cefazolin (from 39% to 32%), trimethoprim-sulfamethoxazole (from 32% to 31%), cefuroxime (from 21% to 18%) and ceftriaxone (from 10% to 14%) between the two periods (p>0.05). CONCLUSION: In childhood urinary tract infections, antibiotic resistance should be evaluated periodically and empiric antimicrobial therapy should be decided according to antibiotic sensitivity results.

Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters.

Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.

Determination of minimum biofilm eradication concentrations of orbifloxacin for canine bacterial uropathogens over different treatment periods.

Biofilm formation can cause refractory urinary tract infections (UTIs) in dogs; however, minimum biofilm eradication concentrations (MBECs) of veterinary drugs against canine uropathogens remain to be investigated. In this study, the MBECs of orbifloxacin (OBFX), trimethoprim-sulfamethoxazole (TMS) and amoxicillin/clavulanate (ACV) over different time periods for treatment of canine uropathogenic Escherichia coli (n = 10) were determined. The MBECs of OBFX for other bacterial uropathogens, including Staphylococcus pseudintermedius (n = 5), Pseudomonas aeruginosa (n = 5), Klebsiella pneumoniae (n = 5) and Proteus mirabilis (n = 5) were also determined. Minimum inhibitory concentrations (MICs) were identified for all strains by broth microdilution, and MBECs were determined at 24, 72, and 168 hr using the Calgary biofilm method. The 24 hr MBECs of OBFX, TMS and ACV for the E. coli strains were significantly higher than the MICs (P < 0.05), and the 72 and 168 hr MBECs were significantly lower than those at 24 hr (P < 0.05). In addition, the 24 hr OBFX MBECs for the four other uropathogens were significantly higher than the corresponding MICs (P < 0.05). The 72 and/or 168 hr OBFX MBECs for S. pseudintermedius, K. pneumoniae and P. mirabilis were significantly lower than the 24 hr concentrations (P < 0.05), whereas for P. aeruginosa, no significant difference was found between any of the MBECs (P > 0.05). These data indicate that the administration period and uropathogenic bacterial species are important factors affecting the efficacy of OBFX treatment of biofilm-related UTIs in dogs.

Characteristics of gram-negative urinary tract infections caused by extended spectrum beta lactamases: pivmecillinam as a treatment option within South Dublin, Ireland.

BACKGROUND: The prevalence of urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. This pilot study aimed to assess the viability of pivmecillinam as a therapeutic option in a Dublin cohort of mixed community and healthcare origin. METHODS: A prospective measurement of mean and fractional inhibitory concentrations of antibiotic use in 95 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae was carried out. 36 % patients were from general practice, 40 % were admitted to hospital within south Dublin, and 25 % samples arose from nursing homes. EUCAST breakpoints were used to determine if an isolate was sensitive or resistant to antibiotic agents. RESULTS: Sixty-nine percent of patients (N = 66) with urinary ESBL isolates were female. The mean age of females was 66 years compared with a mean age of 74 years for males. Thirty-six percent of isolates originated from primary care, hospital inpatients (26 %), and nursing homes (24 %). The vast majority of ESBL isolates were E. coli (80 %). The E tests for mecillinam and co-amoxiclav had concentration ranges from 0.16 mg/L up to 256 mg/L. The mean inhibitory concentration (MIC) of mecillinam ranged from 0.25 to 256 mg/L, while co-amoxiclav MICs ranged from 6 to 256 mg/L. The percentage of isolates resistant to mecillinam and co-amoxiclav was found to be 5.26 and 94.74 % respectively. CONCLUSIONS: This is the first study exploring the use of pivmecillinam in an Irish cohort and has demonstrated that its use in conjunction with or without co-amoxiclav is an appropriate and useful treatment for urinary tract infections caused by ESBL-producing organisms.

Role of age and sex in determining antibiotic resistance in febrile urinary tract infections.

OBJECTIVES: To identify the age- and sex-specific antimicrobial susceptibility patterns of Gram-negative bacteria (GNB) in outpatient febrile urinary tract infections (UTIs) in Korea. METHODS: A total 2262 consecutive samples collected from patients aged 1-101 years with febrile UTIs, during the period January 2012 to December 2014, were analyzed in this multicentre, retrospective cohort study. RESULTS: The sensitivities to cefotaxime and cefoxitin were over 85% for females but under 75% for males. Sex played an important role in the susceptibility of GNB to cefotaxime (p<0.001) and cefoxitin (p<0.001). The sensitivity to ciprofloxacin (age >20 years) was under 75% in both sexes, and was not influenced by sex (p=0.204). Age distributions of the incidences of resistance to cefotaxime, cefoxitin, and ciprofloxacin (age >20 years) were similar to the age distribution of the incidence of GNB, which indicates that the resistance patterns to these drugs were not affected by age (Kolmogorov-Smirnov test, female/male: p=0.927/p=0.509, p=0.193/p=0.911, and p=0.077/p=0.999, respectively). CONCLUSIONS: Age is not a considerable factor in determining the antibiotic resistance in febrile UTIs. Ciprofloxacin should be withheld from both sexes until culture results indicate its use. Second- or third-generation cephalosporins such as cefoxitin and cefotaxime can be used empirically only in females.

Antimicrobial Susceptibility and Characterization of Virulence Genes of Enterococcus faecalis Isolates from Teeth with Failure of the Endodontic Treatment.

INTRODUCTION: The aim of this study was to investigate the prevalence of virulence factors and the antimicrobial resistance of Enterococcus faecalis isolates of teeth with failure of the endodontic treatment. METHODS: Twenty root canal samples were collected from teeth with apical periodontitis. E. faecalis was firstly identified based on phenotypic features and then by 16S ribosomal RNA gene sequencing. The antimicrobial susceptibility was determined by the minimum inhibitory concentration (MIC) of amoxicillin, amoxicillin + clavulanate, azithromycin, benzylpenicillin, ciprofloxacin, clindamycin, chloramphenicol, doxycycline, erythromycin, gentamicin, metronidazole, moxifloxacin, rifampicin, tetracycline, and vancomycin using the E test method. Virulence factors (ace, asa, asa373, cylA, efaA, esp, and gelE) were detected by polymerase chain reaction assay. RESULTS: Amoxicillin + clavulanate was effective against all strains. Intermediate and total resistance was found against the majority of the tested antimicrobials. The susceptibility of some microorganisms to some antimicrobial agents changed according to the evaluation time. MIC50 and MIC90 also varied according to the evaluation time. In relation to the virulence factors of the E faecalis isolates, ace was detected in 100% of the strains, asa (60%), asa373 (15%), efaA (95%), esp (70%), and gelE (75%), whereas cylA was not detected. CONCLUSIONS: It was concluded that E. faecalis isolates from persistent endodontic infections showed varied degrees of intermediate/total resistance to several antimicrobial agents, with amoxicillin + clavulanate being the most effective agent. Moreover, the strains showed different patterns for virulence gene detection.

Camellia sinensis Ameliorates the Efficacy of Last Line Antibiotics Against Carbapenem Resistant Escherichia coli.

Aquo-ethanolic extract of Camellia sinensis (PTRC-31911-A), standardized using Fourier transform infrared analysis, was found to have seven common functional groups in comparison with pre-identified marker compound 'quercetin'. Phyto-chemical quantitation analysis revealed the presence of 10.65 µg/mg of flavonoids. The bioactivity fingerprint profile of PTRC-31911-A includes IC50 (Hydroxyl radical site specific scavenging) = 11.36 ± 0.5 µg/mL, IC80 (Hydroxyl radical non-site specific scavenging) = 26.44 ± 0.5 µg/mL and IC50 (Superoxide ion scavenging) = 10.141 ± 0.5 µg/mL. The drug combination analysis of PTRC-31911-A with five third-line antibiotics was carried out against carbapenem-resistant Escherichia coli. The analysis of combination of PTRC-31911-A (6.25-1000 µg/mL) and antibiotics (6.25-1000 µg/mL) revealed synergistic behaviour (fractional inhibitory concentration indices < 1) with tigecycline, ertapenem, meropenem, colistin and augmentin. The lead combination of PTRC-31911-A + ertapenem or meropenem showed maximum augmentative potential at 50 and 100 µg/mL, respectively, with nearly five-fold decrease in minimum inhibitory concentrations as compared with respective antibiotics alone. The synergistic effects implied that the antibacterial combinations of PTRC-31911-A and ertapenem, meropenem, colistin, tigecycline or augmentin would be more effective than a single monotherapy with either of the antibacterial agent.

Laser receptive polyelectrolyte thin films doped with biosynthesized silver nanoparticles for antibacterial coatings and drug delivery applications.

We report a simple method to fabricate multifunctional polyelectrolyte thin films to load and deliver the therapeutic drugs. The multilayer thin films were assembled by the electrostatic adsorption of poly (allylamine hydrochloride) (PAH) and dextran sulfate (DS). The silver nanoparticles (Ag NPs) biosynthesized from novel Hybanthus enneaspermus leaf extract as the reducing agent were successfully incorporated into the film. The biosynthesized Ag NPs showed excellent antimicrobial activity against the range of enteropathogens, which could be significantly enhanced when used with commercial antibiotics. The assembled silver nano composite multilayer films showed rupture and deformation when they are exposed to laser. The Ag NPs act as an energy absorption center, locally heat up the film and rupture it under laser treatment. The antibacterial drug, moxifloxacin hydrochloride (MH) was successfully loaded into the multilayer films. The total amount of MH release observed was about 63% which increased to 85% when subjected to laser light exposure. Thus, the polyelectrolyte thin film reported in our study has significant potential in the field of remote activated drug delivery, antibacterial coatings and wound dressings.

[Infectious exacerbation of chronic obstructive pulmonary disease: prospects for high-dose levofloxacin therapy].

This open comparative randomized study of efficacy, safety, and pharmacoeconomic characteristics of hilifox-750 (750 mg daily for 5 days) and amoxiclav 2X (875/125 mg twice daily for 10 days) included 60 patients with chronic obstructive pulmonary disease (COPD). Duration of the study was 6 months. Medians of age and smoking index in the group treated with hilifox-750 were 63.5 yr (59, 67) and 30 packs/yr (15, 60) respectively. The treatment reduced cough, apnea, sputum volume and pyoptysis with comparative rates of normalization of body temperature and peripheral leukocyte counts in both groups. Helifox-750 promoted decrease in coughing and apnea within the first three days of therapy. 28 (93%) and 26 (87%) patients recovered by day 4 of helifox and amoxiclav therapy (F-test p = 0.67). Both drugs showed comparable bacteriological efficacy. They were not different in terms of side effect frequency that were mild, resolved spontaneously and did not require withdrawal of therapy. Helifox had advantages over amoxiclav in that it reduced duration of antibacterial therapy to 5 days and of temporary incapacity to 12 days (vs 14); moreover, it needs to be taken only once daily.