Combination Of Fluoroquinolone Research Articles

Is the fluoroquinolone combination necessary for empirical antibiotic regimen in severe community-acquired pneumonia?

ABSTRACT Objectives This study aimed to assess whether superior clinical outcomes can be attained through piperacillin/tazobactam (TZP)+fluoroquinolone (FQ) combination therapy for severe community-acquired pneumonia (CAP) compared to TZP monotherapy. Methods This retrospective study was conducted at a tertiary care hospital in Korea. Adult inpatients diagnosed with pneumonia within 48 hours of hospitalization were included. Severe CAP was defined as a CURB-65 score of ≥ 3 or based on the 2007 guidelines of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) definition. Only patients who received either TZP and FQ combination or TZP as initial empirical therapy were included. Results The final analysis included 145 patients; 57.9% received combination therapy and 42.1% received monotherapy. In the combination therapy group, body mass index (20.67 ± 3.28 vs. 22.26 ± 4.80, p = 0.030) and asthma prevalence (0 vs. 8.3%, p = 0.022) were significantly higher; initial symptoms, clinical severity, and causative pathogens were not significantly different between groups. White blood cell counts (12,641.64 ± 6,544.66 vs. 12,491.67 ± 10,528.24, p = 0.008), and C-reactive protein levels (18.78 ± 11.47 vs. 26.58 ± 14.97, p < 0.001) were significantly higher in the combination therapy group. Clinical outcomes, including all-cause in-hospital mortality rate (26.2 vs. 33.3%, p = 0.358), were not significantly different between the groups. Multivariate analysis identified no significant association between FQ combination and all-cause in-hospital mortality. Conclusion In patients with severe CAP, there were no differences in the clinical outcomes, including mortality, between the TZP and FQ combination therapy and TZP monotherapy. FQ combination was not significantly associated with in-hospital mortality.

Real-world experience of adverse reactions-necessitated rifampicin-sparing treatment for drug-susceptible pulmonary tuberculosis

Rifampicin is an important agent for tuberculosis treatment; however, it is often discontinued because of adverse reactions. The treatment regimen then can be administered as that for rifampicin-resistant tuberculosis, which can be toxic. We retrospectively reviewed 114 patients with drug-susceptible pulmonary tuberculosis who discontinued rifampicin due to adverse reactions during an 18 year period at a tertiary referral center, of which 92 (80.7%) exhibited favorable response. Hepatotoxicity was the leading cause of intolerance. Patients with a favorable response were younger and less likely to have comorbidities. The majority of patients were administered four medications during the intensive phase and three to four during the consolidative phase. For those with a favorable response, the median duration of treatment was 10.2 months and the most common intensive regimen was a combination of isoniazid, ethambutol, pyrazinamide, and fluoroquinolone (25%). The most common consolidation regimen was a combination of isoniazid, ethambutol, and fluoroquinolone (22.8%). Among the patients with a favorable response, two (2.2%) experienced recurrence after a follow-up of 3.4 (interquartile range 1.8–6.8) years. For patients with drug-susceptible pulmonary tuberculosis who do not tolerate rifampicin owing to its toxicity, a shorter regimen may be a useful alternative.

Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case reports and case series

Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study. A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups. The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4. Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms.

Prospects for use of combined antibacterial drugs. Simprazol®: When whole is greater than sum

Today, in the pharmaceutical industry, many manufacturers produce so-called combined drugs containing 2 or 3 or more active ingredients. There are many reviews and studies in the world literature proving that most combinations, in contrast to sequential administration, often have a more pronounced synergistic effect of combined drugs. The use of such therapy increases patient compliance, while at the same time causing positive pharmacokinetic and other effects inherent in the combination, providing the clinician with new opportunities in the treatment of infections. Although the combination of fluoroquinolone and fixed-dose nitroimidazole derivatives is not as widely used in clinical practice, we present a review of Simprazole®, a combination of ciprofloxacin and ornidazole, analyzing the available data on clinical use and possible prospects that new drug.

Empiric Anti-Pseudomonal β-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching.

There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric anti-pseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP. This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019. Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem β-lactam monotherapy and fluoroquinolone combination therapy groups. Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias. In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286). There was no significant difference in 30-day mortality between the two groups (16.8% vs. 18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782-3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups. Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to β-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.

MYCOBACTERIUM HAEMOPHILUM AND CRYPTOCOCCUS NEOFORMANS COINFECTION IN A SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT

Mycobacterium haemophilum and Cryptococcus neoformans are human pathogens in immunocompromised individuals. They exhibit a diversity of cutaneous manifestations and could cause disseminated infections. Herein, we report a Thai female with an underlying disease of systemic lupus erythematous, end stage renal disease and hypertension who was on immunosuppressive therapy and diagnosed with disseminated M. haemophilum and C. neoformans coinfection. She presented with multiple indurated plaques on her back, oedematous plaques on both legs and feet with nodules and ulcers on her right leg. She was diagnosed by skin biopsy, acid-fast staining, real-time polymerase chain reaction, tissue culture and haemoculture. A combination of rifampicin, macrolide, fluoroquinolone, amikacin and co-trimoxazole were used to cure M. haemophilum infection. Cryptococcosis was treated with amphotericin B and flucytosine for 5 weeks, then followed by fluconazole. We aim to report a unique dermatological manifestation, microbiology, histopathology, and treatment of the disease. Successful diagnosis and multiple antimicrobials agents are key managements for Mycobacterium haemophilum infection and Cryptococcosis.

Topical Antibiotic Prophylaxis and Intravitreal Injections: Impact on the Incidence of Acute Endophthalmitis-A Nationwide Study in France from 2009 to 2018.

Background: The dramatic increase in intravitreal injections (IVTs) has been accompanied by a greater need for safer procedures. The ongoing debate about topical antibiotic prophylaxis after IVTs emphasizes the importance of large-scale studies. We aimed to study the role of topical antibiotic prophylaxis in reducing the risk of acute endophthalmitis after IVTs. Methods: Population-based cohort study, in France, from 2009 to 2018, including all French patients receiving IVTs of corticosteroids or anti-VEGF agents. Results: A total of 5,291,420 IVTs were performed on 605,434 patients. The rate of topical antibiotic prophylaxis after IVTs progressively decreased during the study period, with a sharp drop in 2014 (from 84.6% in 2009 to 27.4% in 2018). Acute endophthalmitis occurred in 1274 cases (incidence rate = 0.0241%). Although antibiotic prophylaxis did not alter the risk of endophthalmitis (p = 0.06), univariate analysis showed an increased risk after fluoroquinolone and aminoglycoside prophylaxis. This increased risk was not found in multivariate analysis. However, we observed an increased risk related to the use of fixed combinations of fluoroquinolones and aminoglycosides with corticosteroids (IRR = 1.89; 95% CI = 1.57–2.27%, antibiotics combined with corticosteroids). Conclusion: These results are consistent with the literature. Endophthalmitis rates after IVTs did not decrease with topical antibiotic prophylaxis. The use of a combination of antibiotics and corticosteroids doubles the risk of endophthalmitis and should be avoided. Avoiding antibiotic prophylaxis would reduce the costs and the potential risks of antibiotic resistance.

Toxicity of treatment regimens for drugresistant tuberculosis.

Background. The main factors reducing treatment effectiveness in patients with pulmonary tuberculosis are as follows: the growing drug resistance of mycobacteria, which necessitates the strengthening of chemotherapy regimens, the use of new antimicrobial drugs, as well as poor tolerability of treatment due to the high frequency of adverse drug reactions. Combinations of fluoroquinolones, bedaquiline, and linezolid with traditional anti-tuberculosis drugs are used in new regimens for the treatment of patients with multidrug- and extensively drug-resistant tuberculosis, but the safety of new regimens has yet to be sufficiently studied.The aim was to study the features of toxic effect manifestations of the 5-component antimycobacterial drug complexes in an experiment on rats.Methods. The study was carried out on 64 non-pedigree rats, old females, divided equally into 3 experimental groups and 1 control. Rats of the experimental groups received drug complexes at doses corresponding to therapeutic doses for humans. The complexes’ base components were: moxifloxacin, bedaquiline, linezolid, and capreomycin. The fifth drug in group 1 was prothionamide, in the 2nd — pyrazinamide, in the 3rd — cycloserine. After 14 and 28 days of administration, the clinical picture of intoxication, ECG results, behavioral reactions of rats in the open field test, biochemical blood and urine tests, as well as pathomorphological studies were analysed.Results. Progressive damage to the gastrointestinal tract, liver, kidneys, and central nervous system was observed in rats of all experimental groups. The leading reason of polytoxicity is the nephrotoxic effect caused by capreomycin, to which rats have a high species sensitivity. In group 1, rats were treated with three drugs possessing potential cardiotoxicity; cardiotoxic effect was observed in the form of prolongation of the QT interval on the ECG after 14 days of administration. The most toxic combination of drugs was the one used in rats of the 3rd group, it was enhanced by the addition of neurotoxic cycloserine, which led to the death of more than a third of the animals by the end of the experiment.Conclusion: the use of multicomponent combinations of antimycobacterial drugs, similar in safety profile, increases the risk of developing combined toxic reactions.

Antibiotic therapy of chronic bacterial prostatitis is more effective considering antibiotic susceptibility of all pathogens isolated

PurposeBecause of the insufficient efficacy of the current treatment of chronic bacterial prostatitis (CBP), it is justified to search for a more effective antibiotic therapy (ABT).Materials and MethodsThis single-centre prospective observational comparative study was conducted in 2012 to 2019 (patients: 60 men with CBP; age: 20–45 y). The clinical examination was performed on admission and at 1, 3, 6, or 12 months. All patients underwent the Meares–Stamey test to obtain expressed prostatic secretion (EPS) and/or post-massage urine (PMU) samples for extended bacteriological examination. The patients were randomly divided into 2 treatment groups (30/30 patients): group I, fluoroquinolones (FQs); group II, a combination of FQs with cephalosporins/macrolides with a treatment duration of 1 month.ResultsPatients of both groups had severe symptomatic CBP with an average duration of 4 years. Twenty-three microorganisms (15 aerobes, 9 anaerobes) were identified in PMU. At 3 months follow-up, a positive clinical effect was noted in both groups, which was significant (p<0.05) only in group II concerning NIH-CPSI questionnaire, leukocyturia, prostate volume, maximum urine flow, and decreased pathospermia. At 6 months follow-up, in group II the frequency of Escherichia coli and Enterococcus spp. decreased significantly. In group I aerobes changed only insignificantly from the initial level, but anaerobes increased significantly. In group II the titers of both, aerobes and anaerobes, were significantly lower (p<0.05) at 6 months follow-up as compared to initial values.ConclusionsABT targeting all taxa in EPS/PMU is a more effective alternative to standard therapeutic regimens for CBP.

Pharmacokinetics and Drug-Drug Interactions of Abacavir and Lamuvudine Co-administered With Antituberculosis Drugs in HIV-Positive Children Treated for Multidrug-Resistant Tuberculosis.

Given the high prevalence of multidrug-resistant (MDR)-TB in high HIV burden settings, it is important to identify potential drug-drug interactions between MDR-TB treatment and widely used nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-positive children. Population pharmacokinetic models were developed for lamivudine (n = 54) and abacavir (n = 50) in 54 HIV-positive children established on NRTIs; 27 with MDR-TB (combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones, and amikacin), and 27 controls without TB. Two-compartment models with first-order elimination and transit compartment absorption described both lamivudine and abacavir pharmacokinetics, respectively. Allometric scaling with body weight adjusted for the effect of body size. Clearance was predicted to reach half its mature value 2 (lamivudine) and 3 (abacavir) months after birth, with completion of maturation for both drugs at 2 years. No significant difference was found in key pharmacokinetic parameters of lamivudine and abacavir when co-administered with routine drugs used for MDR-TB in HIV-positive children.

Combination antibiotic therapy versus monotherapy in the treatment of acute exacerbations of chronic obstructive pulmonary disease: an open-label randomized trial

BackgroundThe role of antibiotics in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations and their effectiveness in combination have not been clearly established. To determine whether using a combination of fluoroquinolones and beta-lactams improves the clinical and microbiological efficacy of antibiotics on day 20 of treatment, we conducted an open-label randomized trial based on clinical outcomes, microbiological clearance, spirometry tests, and signs of systemic inflammation in patients hospitalized with acute exacerbations of COPD.MethodsWe enrolled 139 subjects with COPD exacerbations, defined as acute worsening of respiratory symptoms leading to additional treatment. Patients were divided randomly into two groups: 79 patients using beta-lactam antibiotics alone and 60 using beta-lactam antibiotics plus fluoroquinolones. Clinical and microbiological responses, spirometry tests, symptom scores, and serum C-reactive protein (CRP) levels were evaluated.ResultsClinical success, lung function, and symptoms were similar in patients with or without fluoroquinolone administration on days 10 and 20. Combination therapy was superior in terms of microbiological outcomes and reduction in serum CRP value. Although equivalent to monotherapy in terms of clinical success, the combination showed superiority in terms of microbiological success and a decrease in CRP. The combination therapy group had a higher microbiological success rate with gram-negative bacteria than the monotherapy group with Pseudomonas aeruginosa (100% vs. 33.3%, respectively) and Acinetobacter baumanii (100% vs. 20%, respectively) (P < 0.05).ConclusionsConcomitant use of fluoroquinolone and beta-lactam antibiotics for bacterial infections during COPD exacerbations caused by gram-negative bacteria appear to be effective and should be applied in clinical practice.

Periprosthetic Infections of the Shoulder Joint: Characteristics and 5-Year Outcome of a Single-Center Series of 19 Cases.

Periprosthetic shoulder infection (PSI) remains a devastating complication after total shoulder arthroplasty (TSA). Furthermore, there is a paucity in the literature regarding its diagnostic and therapeutic management, especially the absence of therapy concepts devised exclusively for PSI. The aim of the presenting study is to examine the characteristics and outcome of patients with PSI who were treated according to well-established algorithms developed originally for periprosthetic joint infection (PJI) of the hip and knee and determine if these algorithms can be applied to PSI. This single-center case series included all patients with a PSI presenting between 2010 and 2020. Recorded parameters included age, sex, affected side, BMI, ASA score, Charlson comorbidity index, preoperative anticoagulation, indication for TSA (fracture, osteoarthritis or cuff-arthropathy), and type of infection (acute or chronic PSI). The outcome was divided into treatment failure or infect resolution. Staphylococcus epidermidis and aureus were the commonest infecting pathogens. Acute PSI was mainly treated with debridement, irrigation, and retention of the prosthesis (DAIR) and chronic cases with two/multiple-stage exchange. The treatment failure rate was 10.5%. C-reactive protein was preoperatively elevated in 68.4% of cases. The mean number of operative revisions was 3.6 ± 2.6, and the mean total duration of antibiotic treatment was 72.4 ± 41.4 days. The most administered antibiotic was a combination of clindamycin and fluoroquinolone. In summary, the data of the current study suggest that therapeutical algorithms and recommendations developed for the treatment of PJI of the hip and knee are also applicable to PSI.

Antimicrobial susceptibility of multidrug-resistant Pseudomonas aeruginosa isolated from drinking water and hospitalized patients in Jordan

Pseudomonas aeruginosa (P. aeruginosa) is an important environmental, opportunistic and nosocomial pathogen with a significant threat to public health. The objectives of this study were to determine the in vitro antimicrobial susceptibility patterns of, and antibiotic drug combinations with synergistic effects against P. aeruginosa isolated from drinking water and hospitalized patients in Jordan. A total of 16 P. aeruginosa isolates were obtained from hospitalized patients and 15 were isolated from bottled drinking water were used in the study. Bacterial isolation and identification was performed using routine microbiological methods and confirmed using PCR technique targeting the 16S rDNA gene. The antimicrobial susceptibility patterns were determined by measuring the minimum inhibitory concentration (MIC) using the 2-fold microdilution method. Synergy interaction between various antimicrobials was determined using the checkerboard method and fractional inhibitory concentration index (FICI). The majority of water isolates were sensitive to gentamicin (93.3%), ticarcillin (86.7%) and ciprofloxacin, levofloxacin, amikacin, colistin, piperacillin, azlocillin, aztreonam, ceftazidime and imipenem (100% each). All water isolates (100%) were resistant to amoxicillin, oxytetracycline and doxycycline (93.3% and 86.7, respectively). For the clinical isolates, all (100%) were sensitive to ceftazidime, 81.3% were sensitive to aztreonam, while 62.5% were sensitive to ciprofloxacin, levofloxacin, gentamicin, amikacin, colistin, piperacillin, ticracillin, azlocillin, and imipenem. All clinical isolates (100%) were resistant to oxytetracycline, doxycycline and amoxicillin. Analysis of the checkerboard synergy assay of multi-drug resistant isolates (n=26) showed significant synergism (P ≤ 0.05) when ciprofloxacin or gentamicin were included in the combination. There were no significant differences in synergistic activity between ciprofloxacin and levofloxacin when combined with other antimicrobial agents of the beta-lactams or aminoglycosides classes. There were no significant differences in the synergistic activities between beta lactams – aminoglycoside and beta lactams – fluoroquinolone combinations. Results of this study indicate an alarming widespread presence of multidrug-resistant P. aeruginosa associated with chronic suppurative infections in hospitalized patients and apparently clean drinking water in Jordan. Treatment of clinical suppurative lesions must be based on culture and in vitro susceptibility testing using potent antimicrobial combinations to avoid emergence of resistant strains and to improve the clinical outcome of treated patients.

A Study of Cutaneous Adverse Drug Reactions and their Association with Autoimmune Diseases at a Tertiary Centre in South-West Rajasthan, India.

Background:Cutaneous adverse drug reactions (CADRs) comprise about 30% of all adverse drug reactions and observed in 2–3% of hospitalized patients by wide variety of offending agents.Aims:To study the clinical patterns, causative drugs and their association with autoimmune diseases in CADR patients.Materials and Methods:A total of 174 CADR patients who presented to the dermatology OPD over a period of 18 months (1 July 2015 to 31 Dec 2016) were considered for the study. Detailed history, clinical examination, hematological, and biochemical investigations were recorded. The venereal disease research laboratory test, HIV (ELISA), and histopathological examination were done wherever indicated.Results:The mean age of the patients with cutaneous drug eruptions was 40.2 years. Most of them (31.0%) were in the age group of 41–50 years. There were 93 (53.4%) males and 81 (46.5%) females with the M:F ratio of 1.5:1. The most common eruption observed was maculopapular rash in 33.3% followed by fixed drug eruption (17.2%) and lichenoid dermatitis' (11.5%). The drugs most commonly responsible for CADRs were antimicrobials (n = 68, 39%) with fixed dose combination of fluoroquinolones with nitroimidazoles (n = 42). We also noticed that a total of 42 patients out of 174 had comorbities in the form of diabetes (n = 27, 15.5%), hypothyroidism (n = 9, 5.1%), rheumatoid arthritis (n = 3, 1.7%), vitiligo (n = 2, 1.1%), and SLE (n = 1, 0.5%).Conclusion:Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be because of the introduction of newer molecules and changing trends in the use of drugs. In our study, a significant relation of CADRs with autoimmune diseases (P value = 0.004) was also observed.

Modern approaches to antibacterial therapy in purulent and necrotic complications of diabetes

Background. The incidence of purulent and necrotic complications (PNC) in patients with diabetes mellitus (DM) is 3 times higher than in people without diabetes, and the duration of treatment is 2 times longer. The reasons for this include loss of sensitivity, which increases the risk of injury; autonomic neuropathy with the formation of skin cracks, which increase the likelihood of infection; motor neuropathy with the development of keratoses and deformities; disorders of the circulation (in both main arteries and in microcirculation).&#x0D; Objective. To describe modern approaches to antibacterial therapy (ABT) in PNC of DM.&#x0D; Materials and methods. Analysis of literature data on this topic; own research. The study involved 149 patients with diabetic foot who underwent 198 surgeries. 75 patients were admitted with diabetes decompensation. Main group patients (n=45) were prescribed a balanced infusion (Gekodez, Xylate, Gluxyl) and ABT (Leflocin 750, Linelid, Brakson (all medication produced by “Yuria-Pharm”) according to the indications), and the control group patients (n=30) ere prescribed standard infusion therapy and ABT.&#x0D; Results and discussion. In diabetes, purulent infection leads to decompensation of carbohydrate metabolism, and the latter, in turn, worsens the course of purulent infections. 1 ml of pus inactivates 12-15 U of insulin (endogenous or exogenous). The main types of PNC in patients with diabetes include purulent and inflammatory diseases of the skin and adipose tissue, mastitis, parotitis, arthritis, pleurisy, peritonitis, paraproctitis, diabetic foot syndrome (DFS). DFS is a specific symptom complex of foot lesions in diabetes. Its pathogenesis is based on the diabetic micro- and macroangiopathy, peripheral neuropathy of the lower extremities, and osteoarthropathy. There are 3 clinical forms of DFS: neuropathic and infected, ischemic and gangrenous, and mixed. Each hour 55 amputations of the lower extremities are performed globally due to DFS. The main treatment for patients with stage III-V DFS is surgery, which should be supplemented with ABT. The initial empirical ABT should affect the full range of potential pathogens. A combination of several antibiotics with a synergistic effect is used; correction is performed in 72 hours after receiving the results of microbiological examination. For infections that do not threaten limb amputation, fluoroquinolones, lincosamides, cephalosporins of the first generation are prescribed. In case of infections that threaten limb amputation, it is advisable to prescribe fluoroquinolones in combination with lincosamides, ampicillin/sulbactam, cephalosporins of the second generation; with the addition of metronidazole. For life-threatening infections, tienams, vancomycin + aztreonam + metronidazole, clindamycin + ampicillin/sulbactam are prescribed. In addition to the antibacterial power of the drug, its ability to penetrate into the infection focus has a great impact. It was shown that when 750 mg of levofloxacin was administered 120-150 min before necrectomy, its concentration along the cut-off line exceeded the minimum inhibitory concentration for 90 % of bacteria. The advantages of fluoroquinolones also include a high degree of bactericidal activity, a wide range of antimicrobial action, and a long half-life. After fluoroquinolones intake, a kind of “sugar crisis” can occur with changes in blood glucose levels. Its mechanism is still unclear. 80 % of all cases of impaired glucose homeostasis on the background of fluoroquinolones occur with the use of gatifloxacin. Leflocin (“Yuria-Pharm”) is a third-generation fluoroquinolone that has the least effect on carbohydrate metabolism among all drugs in its class. At a dose of 750 mg Leflocin can be used once a day. Staphylococcus aureus is the leading pathogen in DFS. The prevalence of its methicillin-resistant strains is increasing and currently is about 15-30 %. Linezolid (Linelid, “Yuria-Pharm”) – a synthetic antibiotic used to treat severe infectious processes caused by gram-positive bacteria resistant to other AB – is the drug of choice in case of detection of such strains. Linezolid provides effective concentrations in the inflammatory focus in DFS. If the DFS infection is caused by gram-negative bacteria, it is advisable to prescribe tobramycin (Brakson, “Yuria-Pharm”) – a natural aminoglycoside of the third generation for parenteral and local treatment. According to the results of our own study, combined infusion therapy and ABT was accompanied by significantly fewer cases of loss of consciousness than standard treatment (4.2 % vs. 10.8 %; p=0.025), acute renal failure (4.72 % vs. 10 %; p=0.031), the average score of pain on a visual-analog scale (3.12 vs. 4.25 points; p=0.042), the duration of inpatient treatment after surgery (25.8 vs. 36.1 days; p=0.029).&#x0D; Conclusions. 1. Modern ABT in patients with DM and PNC should be comprehensive and affect the main links in the pathogenesis. 2. The choice of antibiotic should be made taking into account the degree of penetration of the drug into the focus of the pathological process and the sensitivity of microorganisms. 3. In case of PNC of DFS it is reasonable to use Leflocin (gram-positive flora), Linelid (methicillin-resistant staphylococcus), Brakson (gram-negative flora).

Contamination of hen manure with nine antibiotics in poultry farms in Ukraine

The problem of processing, use and utilization of poultry manure contaminated with antibiotics remains unsolved not only Ukraine but around the world, and theatment and prevention of highly contagious infectious diseases among birds requires antibacterial medication use. By liquid chromatography, 293 hen manure samples of 12 Ukrainian industrial flocks of poultry farms were studied. The residual content of 9 antibiotics in the hen manure was found, including 38.2% of tetracycline preparations (doxycycline, oxytetracycline, tetracycline and chlortetracycline), fluoroquinolone (enrofloxacin and norfloxacin) including combinations of incompatible tetracyclines and fluoroquinolones, broad-spectrum penicillins (amoxicillin), fenicols (florfenicol), macrolides (tylosin) and one sulfanilamide preparation (sulfametazine). The most common antibiotics in hen manure of Ukrainian industrial flocks of poultry farms are the antibiotics of the tetracycline group, the main one being doxycycline. A high correlation was determined between the release of doxycycline with eggs and hen manure after the preparation was used perorally in preventive and therapeutic doses. Time of complete excretion of doxycycline from the hen body at the preventive dose (50 mg/L of water for 7 days) was 14 days for manure, 8 days for eggs, following its withdrawal, and at the therapeutic dose (100 mg/L of water for 7 days ) – 20 days for manure, and 9 days for eggs, following its withdrawal. The perspective of using the obtained data about the duration of excretion of doxycycline with hen manure consists in confirmation of the time of the antibiotic’s excretion with manure following its use for preventive or therapeutic purpose, which will help in controlling it as a source of environmental pollution. The time of doxycycline excretion from the body of hens with eggs and manure may be used practically by professionals in veterinary medicine in the case of prescribing or replacing antibiotics for treatment of infectious diseases of poultry to prevent the combination of incompatible preparations in the body and manure. The obtained experimental data may form the basis for the development of national regulations on the processing, usage and utilization of manure of hens under treatment with antibiotics.

Toxic Megacolon – the Complication of an Infection with Clostridium difficile after an Odontogenic Abscess. Case Presentation

Abstract Background: Clostridium difficile (CD) is the major cause of nosocomial antibiotic-associated infections, having as main manifestation diarrhea and life-threatening inflammation of the colon. Surgery may be necessary in up to 80% of patients due to the frequent complications associated with this condition. The mortality rate of this devastating disease could reach 50% even after proper treatment. Case report: We report a case of a 24-year-old female who was admitted with clinical signs of an odontal inflammatory process. After repeated surgical treatments and antibiotic therapy, she presented acute abdominal pain on the 14th postoperative day. The explorative laparotomy was negative. Clostridium difficile was isolated from her stool, and she was transferred to the Department of Infectious Diseases. After a few days without any favorable clinical outcome, she was transferred to the intensive care unit (ICU), where she developed acute respiratory distress syndrome. Despite the immediate surgical intervention and ICU care, she died within 15 days after admission. Conclusions: CD infection is considered a complication of antibiotic treatment, having as main cause the combination of fluoroquinolones with antisecretory drugs. In the first phase, the changes of the colon can be minimal with the manifestation of a false acute surgical abdomen, but toxic colon can develop in evolution, leading to multi-system organ failure and death.

Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2

Polymyxin B (PB), as the last-line of defense against multidrug-resistant Gram-negative bacteria, has caused resistance to P. aeruginosa recently. Fortunately, synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance. Here, we performed a screen of 970 approved drugs synergized with PB against the P. aeruginosa DK2, which is severely resistant to PB, MIC = 512 μg/mL. Encouragingly, we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint (2 μg/mL). Especially, gemifloxacin achieved the highest synergistic effect with PB, leading to a 4096-fold MIC reduction (reduced from 512 μg/mL to 0.125 μg/mL). Furthermore, synergistic effect was also observed in the combination of gemifloxacin and colistin. Finally, outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes for P. aeruginosa which partly explained the synergy mechanism. These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections.

Moraxella species: infectious microbes identified by use of time-of-flight mass spectrometry.

To report the clinical manifestations, identification, antimicrobial susceptibilities, and treatment outcomes of ocular infections caused by Moraxella species. Retrospective study. The medical records of all patients treated at the Departments of Ophthalmology of the Ogaki Municipal Hospital and the Gifu University Graduate School of Medicine for ocular infections caused by Moraxella species between January 2011 and June 2017 were examined. The stored Moraxella species isolated from ocular samples were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), molecular identification, and the biochemical properties. Sixteen eyes of 16 patients were treated for Moraxella ocular infections. The patients' median age was 72 years. A predisposing systemic or ocular condition was identified in 15 of the patients. Nine of the patients developed keratitis; four, conjunctivitis; and three, blebitis. M lacunata (6 eyes), M catarrhalis (6), M nonliquefaciens (3), and M osloensis (1) were identified by MALDI-TOF MS. All isolates were sensitive to levofloxacin, tobramycin, ceftazidime, ceftriaxone, and cefazolin. Twelve patients with keratitis or blebitis were treated with various topical antimicrobial combinations, and systemic antibiotics were used in 10 of the 12 patients. The mean time for the complete closure of the epithelial defects with keratitis was 24 days. The visual outcomes after treatment were favorable except in 1 keratitis patient who underwent enucleation. The use of duo-therapy with a combination of fluoroquinolone and cefmenoxime should be considered in cases nonresponsive to monotherapy, such as keratitis and bleb-associated infections. MALDI-TOF MS is useful for the identification of Moraxella to the species level.

Fluorinated 1,3-benzothiazin-4-ones containing fluoroquinolone fragment

We have developed an efficient synthetic approach to potential antibacterial agents with double mechanism of action through the combination of antibacterial fluoroquinolones with 1,3-benzothiazin-4-ones.