Fourth-generation Fluoroquinolones Research Articles

Topical Antibiotic Therapy in the Ocular Environment: The Benefits of Using Moxifloxacin Eyedrops.

Moxifloxacin is a fourth-generation fluoroquinolone antibiotic available for ophthalmic use. It inhibits two enzymes involved in bacterial DNA synthesis, covering Gram-positive and Gram-negative pathogens. This spectrum allows for the formulation of self-preserving bottle solutions, while its interesting pharmacological profile is distinguished by efficacy at low tissue concentrations and by an infrequent dose regimen due to its long duration on ocular tissues. This enhances patient compliance, promoting its use in children. The human eye hosts several microorganisms; this collection is called the ocular microbiota, which protects the ocular surface, assuring homeostasis. When choosing an antibiotic, it is appropriate to consider its influence on microbiota. A short dose regimen is preferred to minimize the impact of the drug. Moxifloxacin eyedrops represent an effective and safe tool to manage and prevent ocular infections. As healthcare providers face the complexity of the ocular microbiota and microbial resistance daily, the informed use of moxifloxacin is necessary to preserve its efficacy in the future. In this regard, it is well known that moxifloxacin has a lower capacity to induce resistance (an optimal WPC and MPC) compared to other quinolones, but much still needs to be explored regarding the impact that fluoroquinolones could have on the ocular microbiota.

Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Extensively drug-resistant Pseudomonas aeruginosa: clinical features and treatment with ceftazidime/avibactam and ceftolozane/tazobactam in a tertiary care university hospital center in Portugal - A cross-sectional and retrospective observational study.

Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center. All XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed. One hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDR-PA identification was more frequent in male patients with an average age of 64.3 ± 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p < 0.05), followed by the ones with bacteremia (44.4%, p < 0.05) and those medicated with colistin (39.0%, p < 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower. XDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors' knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal.

Moxifloxacin Treatment for Contact Lens-Related Corneal Ulcer: A Case Report

Introduction : A corneal ulcer is an ophthalmological emergency that can threaten vision. It is characterized by inflammation or infection involving the corneal epithelium and stroma. Prolonged use of contact lenses is more likely to cause corneal ulcers. The purpose of this paper is to report on the management of corneal ulcers.&#x0D; Case Illustration : A 30-year-old female complained of blurred vision, redness, pain, swelling, and sensitivity to light in both eyes for the last two days. She reported falling asleep in her contact lenses two nights before the visit. The patient had compound myopic astigmatism before and her visual acuity was decreased to 3/60 in the right eye and 5/60 in the left eye, examinations showed palpebral edema and conjunctival hyperemia in both eyes. The use of fluorescein in both eyes highlighted the area of the defect. The patient was diagnosed with corneal ulcers. Treatments were Moxifloxacin Eye Drop every hour and Ibuprofen 2x400 mg by intravenous infusion. On the last visit, the corneas were clear with visual acuity 6/15 in both eyes.&#x0D; Discussion : According to the study by Kishor et al., ophthalmic eye drop is the most effective treatment and fourth-generation fluoroquinolones represent the most frequently used strategies in Corneal Ulcer.Conclusion : Antibiotics and analgesics are effective for the management of corneal ulcers in this patient. Education regarding contact lenses is important to prevent the occurrence of corneal ulcers.

Clinical and epidemiological characteristics of multi-drug resistant Enterobacterales isolated from King Fahad Hospital of the University, AlKhobar, Saudi Arabia.

Multi-drug resistant (MDR) Enterobacterales remain a major clinical problem. Infections caused by carbapenem-resistant strains are particularly difficult to treat. This study aimed to assess the clinical and epidemiological characteristics of MDR Enterobacterales isolates. A total of 154 non-repetitive clinical isolates, including Escherichia coli (n = 66), Klebsiella pneumoniae (n = 70), and other Enterobacterales (n = 18), were collected from the Diagnostic Microbiology Laboratory at King Fahad Hospital of the University. Most E. coli isolates were collected from urine specimens (n = 50, 75.8%) and resistance against the third and fourth-generation cephalosporins (ceftriaxone, ceftazidime, cefixime, and cefepime) and fluoroquinolones (ciprofloxacin and levofloxacin) was assessed. Clonal relatedness analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed two clones (E. coli A and B), each comprising two strains. Most K. pneumoniae samples were collected from respiratory specimens (27.1%, 20 samples), and the strains showed overall resistance to most of the antimicrobials tested (54%‒100%). Moreover, clonal-relatedness analysis using ERIC-PCR revealed seven major clones of K. pneumoniae. These findings suggest nosocomial transmission among some identical strains and emphasize the importance of strict compliance with infection prevention and control policies and regulations. Environmental reservoirs could facilitate this indirect transmission, which needs to be investigated.

Bacterial keratitis in a tertiary hospital in São Paulo: a 21-year review of the epidemiological, laboratory, and clinical data.

Infectious keratitis is a sight-threatening condition that is usually an ocular emergency. The visual outcome depends on prompt and accurate clinical management as well as geographic and epidemiological awareness. We conducted a retrospective observational study to define the epidemiological and laboratory profile, as well as the clinical course of bacterial keratitis in a tertiary hospital in São Paulo over 21 years. Information about age, sex, predisposing factors, topical and surgical treatment, visual acuity, ulcers' classification, bacterioscopy, culture, and antibiotic sensitivity tests were collected. This study included 160 patients. The mean age was 65.1±18.4 years and risk factors were identified in 83.1% of the patients. Empirical topical fortified cephalosporin with an aminoglycoside or fourth-generation fluoroquinolone was curative for 66.2% of the cases. The mean treatment duration was 22.5±9 days. The mean variation of visual acuity was -0.25 logMAR, p < 0.001. Culture revealed 64% of Gram-positive bacteria. All Gram-positive bacteria were sensitive to cephalothin, vancomycin, and quinolones. All Gram-negative bacteria were sensitive to gentamicin, tobramycin, amikacin, and ciprofloxacin. These findings reinforce the importance of prompt empirical treatment of severe corneal ulcers with a fortified cephalosporin and aminoglycoside or a fourth-generation fluoroquinolone as there are equally effective. Collected data was insufficient to evaluate resistance of ocular infections over time in this population.

Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin

In this paper, method for enantiomeric purity testing of fourth-generation fluoroquinolone, moxifloxacin hydrochloride, was developed and validated. Exceptional enantioselectivity for this assay was achieved using cyclodextrin type Chiral Stationary Phase (CSP), phenylcarbamate-β-cyclodextrin CSP, and mobile phase consisted of acetonitrile and triethylammonium acetate (TEAA) buffer. Analytical Quality by Design (AQbD) methodology, comprising Design of Experiments (DoE) - Design Space (DS) approach, was used for method development. In order to select appropriate Critical Method Parameters (CMPs), risk assessment was done using combined three step strategy that involved Ishikawa diagram - CNX (Control, Noise and eXperimental) - FMEA (Failure Mode and Effect Analysis). Three CMPs were further selected and investigated in this study: acetonitrile content in the mobile phase (30–50%, v/v), triethylamine content in the TEAA buffer (0.1–1.5%, v/v) and aqueous phase pH (3.5–4.5). Monte Carlo simulations were performed and 3D-DS was computed. One point situated in the center of 3D-DS was selected as working point for method validation, with the following values of CMPs: acetonitrile content in the mobile phase set to 37% (v/v), triethylamine content in TEAA 0.8% and pH value of the aqueous phase set at 4.0. Also, 2D-DS was created (with fixed one factor – pH value of aqueous phase at 4.0) which also gave us confirmation that the selection of working conditions was suitable. The proposed enantioselective method was further on tested for its quantitative robustness, as well as for its suitability for the intended purpose through validation studies.

The ameliorative effects of topical gemifloxacin alone or in combination with clobetasol propionate on imiquimod-induced model of psoriasis in mice.

Psoriasis is a lifelong immune-driven skin condition characterized by excessive epidermal overgrowth and inflammatory cell infiltration. Gemifloxacin is a fourth-generation fluoroquinolone with improved immunomodulatory and anti-inflammatory properties that are believed to possess an attractive role in psoriasis via suppressing the production of cytokines, chemokines, and eosinophil and neutrophil chemotaxis. The aim of this research is to investigate the ameliorative effects of prolonged topical gemifloxacin (GMF) alone and combined with clobetasol propionate (CLO) on an imiquimod (IMQ)-induced mouse model of psoriasis. Forty-eight Swiss albino mice were divided into six groups of eight. All groups except the negative controls got 62.5mg of IMQ 5% topically for 8days. Mice in the control group (controls) got Vaseline instead. Following the induction in the IMQ 5% group, mice in treatment groups CLO 0.05, GMF 1%, GMF 3%, and CLO + GMF obtained clobetasol propionate 0.05%, GMF 1% and 3%, and a combination of both, respectively, for an additional 8days, rendering the experiment 16days long. Our results revealed that gemifloxacin alleviated erythematous, thickened, and scaly psoriatic lesions and inhibited the tissue level of inflammatory cytokines, including interleukin (IL)-8, IL-17A, IL-23, tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). The anti-inflammatory effect also occurred by hindering nuclear factor-kappa B (NF-κB) signaling and reversing histopathological problems. Gemifloxacin acts effectively in mitigating psoriasis-associated lesions and restricting NF-κB-mediated inflammation, recommending gemifloxacin as a promising adjuvant candidate for additional studies on the long-term treatment of autoimmune and autoinflammatory dermatoses like psoriasis.

Prevalence and genetic characterization of clinically relevant extended-spectrum β-lactamase-producing Enterobacterales in the Gulf Cooperation Council countries

IntroductionAmong Gram-negative bacteria (GNB), Enterobacterales (Enterobacterales), such as Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are the most clinically relevant pathogens in healthcare settings. Infections secondary to these pathogens are widely common but multidrug resistance (MDR) in Enterobacterales has become a significant challenge with increased morbidity, mortality, and cost of management. The escalating global prevalence of MDR in Enterobacterales has led to limited treatment options, raising an urgent need for novel antimicrobial therapy(s) and detailed studies exploring underlying resistance mechanisms. In Enterobacterales, the prime antimicrobial resistance mechanism against β-lactam antibiotics is mainly the production of β-lactamases, particularly extended-spectrum β-lactamases (ESBLs). Although the Gulf region is witnessing major challenges from infections secondary to MDR GNB, the extent of the problem has not been fully evaluated. Therefore, this review aims to address the prevalence and genetic characterization of ESBL-producing Enterobacterales in the Gulf Cooperation Council (GCC) countries.MethodsPubMed® (National Library of Medicine, Bethesda, MD, USA) search was conducted, which looked for academic articles discussing the epidemiology of MDR Enterobacterales in the GCC countries, published in the last 5 years.Results and conclusionsIn GCC countries there is a high prevalence rate of MDR Enterobacterales, particularly ESBLs. Prevalence rates of ESBL-producing Enterobacterales among the Enterobacterales in general clinical samples in the GCC region is 21.6%–29.3%, with a slightly higher prevalence rate in intensive care unit patients (17.3–31.3%) and in patients with urinary tract infections (25.2%–31.7%). ESBL carriers have also been noted in the general community. ESBL-producing Enterobacterales from the GCC region show high levels of resistance to ampicillin, aztreonam, third-/fourth-generation cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Intermediate resistance rates are observed against nitrofurantoin, piperacillin/tazobactam, and gentamicin, with increasing resistance observed against tigecycline. The isolates demonstrate low-level resistance to carbapenems, fosfomycin, colistin, and amikacin. Enterobacterales isolates that are concomitant ESBL producers and are carbapenem resistant have been increasingly reported and demonstrate alarmingly increased antibiotic resistance patterns compared with ESBL Enterobacterales. The most prevalent genes for ESBL resistance in the Enterobacterales isolates in the GCC region are: blaCTX-M (subtype group 1) followed by/co-dominated by blaTEM and blaSHV, whereas the most common carbapenem-resistant genes are blaOXA-48 and blaNDM-1.

Moxifloxacin: Physical-chemical and Microbiological Analytical Methods in the Context of Green Analytical Chemistry.

Moxifloxacin (MOX) is a fourth-generation fluoroquinolone used in the form of tablets, infusion solutions and ophthalmic solutions. It does not have a physical-chemical or microbiological analytical method described in an official compendium. However, the literature shows some analysis methods for pharmaceuticals and biological matrices. In this context, the objective is to show the analytical methods present in the literature for the investigation of MOX by physical-chemical and microbiological techniques, as well as discussing them according to the requirements of current pharmaceutical analyses and green analytical chemistry. Among the physical-chemical methods present in the literature for MOX evaluation, 33% are HPLC, 21% are UV-Vis and 17% are capillary electrophoresis. On the other hand, among the microbiological methods, all of them are based on diffusion in agar. There is still scope in the literature to incorporate new and improved analytical methods for MOX evaluation, which adopt the concepts of green and sustainable analytical chemistry, either by using less (or not using) toxic organic solvents, reducing waste generation or even reducing the analysis time according to the intended objectives.

Profilaktička i terapijska primena antibiotika u kolorektalnoj hirurgiji

Complications in colorectal surgery carry a high risk of morbidity and mortality, prolong hospitalization time and increase treatment costs, and the largest number of postoperative complications is related to surgical site infection (SSI). Antibiotic prophylaxis started in the fifties of the last century and changed with each new antibiotic. The following were used in order: aminoglycosides (1943), macrolides (1952), polymyxins (1958), and cephalosporins (1965). With the discovery of metronidazole in 1970, the prophylactic spectrum was extended to include anaerobic bacteria, which are an indispensable part of the flora in this anatomical region. Due to the nature of the gastrointestinal tract, it was believed that oral antibiotic prophylaxis and mechanical bowel preparation (MBP) could achieve intestinal sterilization and thus ensure a safe surgical intervention. However, studies have shown that MBP did not have an overall beneficial effect on postoperative complications and caused significant patient discomfort, so it was almost abandoned. Today, it is known that about 16% of surgical infections are caused by multiresistant bacteria, and only oral antibiotic prophylaxis is not sufficient to prevent these infections. Namely, in the race between bacterial resistance and the development of new antibiotics, antibiotics are increasingly lagging, and the treatment of complications remains a nightmare for surgeons. For this reason, the prevention of SSI in colorectal surgery is a challenge for 21st-century medicine. In modern surgery, both open and laparoscopic, the first and second generations of intravenous cephalosporins are most often used for prophylactic purposes, as antibiotics of a sufficiently broad spectrum, with favorable pharmacokinetics and rare side effects. New research indicates that in colorectal surgery, the combination of standard intravenous prophylaxis with the addition of an oral antimicrobial the day before surgery is superior when it comes to SSI prevention. However, there are still no clear recommendations on the regimen and type of antibiotics and they should be given in institutional guides and protocols, taking into account the bacterial spectrum in the local environment, as well as resistance, and the availability of appropriate drugs. Therapeutic use of antibiotics is reserved for acute conditions in colorectal surgery and its complications. For therapeutic purposes, more potent antibiotics are used against the expected pathogens, usually a combination of several antibiotics, such as third or fourth-generation cephalosporins, metronidazole, fluoroquinolones, or piperacillin/tazobactam and others. When it comes to the therapeutic use of antibiotics in colorectal surgery, research indicates that the most important thing is to recognize the infection in time and immediately start treatment, correct the therapy according to the causative agent, and also to stop the administration of antibiotics in time, to avoid unwanted complications and already advanced bacterial resistance.

Pharmacokinetic properties of Fluoroquinolones in Comparative Aspect of their effect on Pathogenic microflora

Quinolones and their derivatives of the second to fourth generation (fluoroquinolones) are highly active antimicrobial agents. This research examines pharmacokinetic properties of fluoroquinolones in comparative aspect of their effect on pathogenic. Microflora of conjunctival cavity in children diagnosed with conjunctivitis and dacryocystitis. The study was carried out in 2020 in Ophthalmologic Polyclinics No. 1 (Moscow, the Russian Federation). The group comprised 200 children aged six years who were diagnosed with bacterial conjunctivitis and dacryocystitis. The composition of pathogenic microflora species and the effect of moxifloxacin and other fluoroquinolones on the sensitivity and resistance of microorganisms were analyzed using conjunctival scrapings. The presence of eight species of pathogenic microorganisms in the scrapings has been established. The majority of bacteria detected were gram-positive: St. epidermidis (59%) and St. aureus (21%), p ≤ 0.05. Other types of microorganisms, including gram-negative E. coli, K. pneumonia, and St. saprophycus, were discovered 20 times (p≤0.001 relative to St. epidermidis), 18 times (p ≤ 0.001), and 15 times (p ≤ 0.01) less frequently, accordingly. The levels of bacterial resistance were 13% for moxifloxacin, 16% for levofloxacin, and 21% for ciprofloxacin. Moxifloxacin monotherapy showed a 100% result. After five days of treatment, all patients demonstrated minimal values (0.5 and 0.1 points vs. 3.8 and 4.4 points at the beginning of treatment, p ≤ 0.01) for two parameters (conjunctival hyperemia and sticky eye), the other three parameters were zero. Fourth-generation fluoroquinolone (moxifloxacin) has been shown to be highly effective against gram-positive Staphylococcus aureus bacteria.

Anticancer activity and metabolic alteration in colon and prostate cancer cells by novel moxifloxacin conjugates with fatty acids

The positive and pro-economic trend in the management of cancer treatment is the search for the antineoplastic potential of known, widely used and safe drugs with a different clinical purpose. A good candidate seems to be moxifloxacin with broad-spectrum antibacterial activity, which as the member of the fourth generation fluoroquinolone is known to affect not only bacterial but also eukaryotic DNA topoisomerases, however at high concentration. Due to the fact that the modification of parent drug with lipid component can improve anticancer potential by increasing of bioavailability, selectivity, and cytotoxic efficiency, we evaluated the mechanisms of cytotoxic activity of novel moxifloxacin conjugates with fatty acids and verified metabolic profile in SW480, SW620 and PC3 cell lines.Our study revealed that cytotoxic potential of moxifloxacin conjugates was stronger than free moxifloxacin, moreover, they remained non-toxic to normal HaCaT cells. PC3 were more sensitive to MXF conjugates than colon cancer cells. The most promising cytotoxic activity exhibited conjugate 4m and 16m with oleic and stearic acid reducing viability of PC3 and SW620 cells. Tested conjugates activated caspases 3/7 and induced late-apoptosis, mainly in PC3 and SW620 cells. However, the most pronounced inhibition of NF-κB activation and IL-6 secretion was observed in SW480. Metabolomic analysis indicated influence of the moxifloxacin conjugates on intensity of lipid derivatives with the most successful metabolite profile in PC3. Our findings suggested the cytotoxic potential of moxifloxacin conjugates, especially with oleic and stearic acid can be beneficial in oncological therapy, including their possible anti-inflammatory and known antibacterial effect.

Use of Antimicrobials by Class in Pigs in Germany-A Longitudinal Description Considering Different International Categorisation Systems.

Antimicrobial usage in both human and veterinary medicine is considered one of the main drivers of antimicrobial resistance; its reduction poses a serious challenge. To analyse the associations between usage and resistance, data from monitoring systems and classification of all antimicrobial substances are crucial. In this analysis, we investigated longitudinal data collected between 2013 and 2020 within the Veterinary Consumption of Antibiotics project from pig farms in Germany, including all antimicrobial classes, but focusing on critically important antimicrobials: third- and fourth-generation cephalosporins, fluoroquinolones, macrolides, and polymyxins. Analysing the treatment frequency, we found that a reduction in antimicrobial use in all types of pig production has occurred over time, accompanied by a rising percentage of farms without any usage. The lists of the World Health Organisation, World Organisation for Animal Health, and European Medicine Agency classify different antimicrobial substances as critically important. The vast differences between the respective weighted treatment frequencies allocated to the antimicrobials of main interest reflect the huge impact of the three categorisation systems. We concluded that, with the aim of creating national treatment guidelines supporting veterinarians to make treatment decisions, the list of the European Medicine Agency is the most suitable.

1993. Serratia is a rare cause for Infective Endocarditis of the Tricuspid Valve

Abstract Background Serratia marcescens is a Gram-negative motile bacillus that is a facultative anaerobe and non-lactose fermenting. Serratia can be isolated from water, soil, plants, and the intestinal microbiome. Serratia produces a unique Identifying reddish pigment called prodigiosin. Serratia is responsible for only 0.14% of infective endocarditis cases, with a mortality rate of 85%. Methods A 37 YO female with a history of Intravenous heroin abuse was admitted with fevers and dyspnea. Vital signs were BP 76/50, HR 140, RR 26, temp 102 F, and SpO2 98% on room air. She was toxic-appearing. Labs: WBC 26000(4,000 – 11,000 /uL) with 14% bands, Hb 5.6 (12.6 – 17.0 g/dL), PLT 15*10^3(150-372*10^3/uL), creatinine 2.5 (0.50 - 1.60 mg/dL), lactic acid 15.8 (0.5-2.2 mmol/L). We started vancomycin, piperacillin-tazobactam, and norepinephrine for septic shock. A transthoracic echo showed a large mass on the tricuspid valve, and a transesophageal echo depicted it as vegetation. Blood cultures grew Serratia. She underwent excision of anterior and posterior tricuspid valve leaflets with reconstruction and ring annuloplasty. She reported washing her syringes with tab water and reusing them again. Serratia has a predilection for left-side heart valves even in the IVDU population but this patient presented with a tricuspid valve endocarditis. Results Serratia is a rare cause for IE in the ICE study; out of 2.761 definite IE cases identified over five years, only forty-nine instances were due to gram-negative bacilli. Of those, only four cases were due to Serratia. The clinical presentation of Serratia includes constitutional symptoms, new-onset murmur, and cutaneous and neurologic manifestations. Serratia produces multiple pathogenic factors allowing Serratia to result in valvular destruction and perivalvular complications, and distant septic emboli metastasis. Conclusion Serratia is sensitive to third and fourth-generation cephalosporins, monobactams, carbapenems, fluoroquinolones, and aminoglycosides. Treatment is complex due to the production of AmpC B-lactamase, which hydrolyzes third and fourth-generation cephalosporins. The 2005 IDSA suggested a combination of B-lactam and an aminoglycoside for Serratia endocarditis, and these are not guidelines but merely recommendations. Disclosures All Authors: No reported disclosures.

Moxifloxacin embedded p-Sulfonatocalix[6]arene: Multispectroscopic studies to evaluate its in vitro cytotoxicity, antibacterial efficacy, and molecular docking

The rising antibiotic drug resistance is a worldwide issue and has various challenges in new antibiotic drug development. The present study came up with a solution for drug resistance to one the most used antibiotics such as moxifloxacin (Moxi) by supramolecular chemistry. Moxi is a fourth-generation fluoroquinolone drug widely used in respiratory infections. It was encapsulated with p-Sulfontocalix[6]arene (SCX6) and characterized in order to improve its solubility, antibacterial activity and safety. This inclusion complex (M⊂SCX6) was investigated by spectroscopic techniques such as UV–visible, Fluorescence, FT-IR, FE-SEM, HRMS and NMR spectroscopy. The antibacterial study of M⊂SCX6 was evaluated against pathogens S. aureus and E. coli. While, the cytotoxicity study on 3T3-L1 mouse embryonic-fibroblast cell lines and Human RBCs has evaluated the safety of complex M⊂SCX6. Overall, the present study has suggested a novel drug complex with better antibiotic activity and possible therapeutic advantages for tackling antibiotic drug resistance in new drug doses form M⊂SCX6.

Cluster of cases due to Shigella flexneri producing CTX-M-15 in Spain.

The aim of our study was to delineate an outbreak of gastroenteritis caused by Shigella flexneri and affecting sixteen persons between May and June 2014 in Bilbao, Spain. All patients exhibited symptoms after consuming kebab in the same kebab shop.The outbreak is described through the clinical cases, the microbiological and molecular genetic diagnosis, and the epidemiologic investigation. Minimum inhibitory concentrations for ampicillin, amoxicillin plus clavulanic acid, third and fourth generation cephalosporins, carbapenems, monobactams, aminoglycosides, fluoroquinolones, co-trimoxazole, colistin and tigecycline were measured. The S. flexneri strains were screened by PCR for TEM, SHV, CTX-M beta-lactamases and plasmidic AmpCs and aac(6')-Ib gene. Serotyping, pulsed field gel-electrophoresis, conjugation assay, plasmid sizing by S1 enzyme digestion and Southern blot hybridization were accomplished.All the S. flexneri isolates proved to be serotype 2 and produced extended-spectrum beta-lactamase (ESBL). Carbapenems, fluoroquinolones, tigecycline, colistin, and co-trimoxazole remained active antibiotics.All the strains harboured blaCTX-M-15 and blaOXA-1 genes. The strains hosted two high-molecularweight plasmids of 100 and 230 kb, respectively. According to the hybridization assay blaCTX-M-15 was located on the plasmid of 230 kb. The identical pulsotype verified the presence of outbreak.Remarkable, that one of the food handlers has travelled recently to Pakistan, where ESBL-producing Shigella strains had been reported previously. To the best of our knowledge, this is the first outbreak caused by CTX-M-15-expressing S. flexneri in Spain and as well as in Europe.

Physico-chemical parameters for the assembly of moxifloxacin hydrochloride and cetyltrimethylammonium chloride mixture in aqueous and alcoholic media

The aggregation behavior of the mixture of cetyltrimethylammonium chloride (CTAC), a cationic surfactant, and moxifloxacin hydrochloride (MFH), a fourth-generation fluoroquinolone antibiotic drug, has been studied using the conductivity technique in aqueous and alcoholic (EtOH, 1-PrOH, and 2-BuOH) media. The study was performed at several temperatures between 298.15 and 323.15 K at 5 K intervals. The assembly has been characterized by evaluating the micellar parameters, such as the critical micelle concentration (CMC) and the counter ion binding (β), of the CTAC + MFH mixture. The values of the CMC for the assembly of the CTAC + MFH mixture were reliant on the composition of alcohols in the mixed solvents and the temperature. The CMC values of the CTAC + MFH mixture increased with increasing temperature; that is, assembly was delayed by increased temperature. The micellization of the CTAC + MFH mixed system was delayed in alcoholic media. The observed -ΔGm0 values for the association of the CTAC + MFH mixed system demonstrated a spontaneous aggregation process under all study conditions. Based on the -ΔHm0 and +ΔSm0 values, the association of the CTAC + MFH mixture is exothermic and the interaction forces acting between the CTAC and MFH species are hydrophobic, ion–dipole, and electrostatic interactions. The transfer properties and enthalpy–entropy compensation were also assessed and described comprehensively.

Evaluation of growth and antioxidant responses of freshwater microalgae Chlorella sorokiniana and Scenedesmus dimorphus under exposure of moxifloxacin

As one of the fourth-generation fluoroquinolone antibiotics, moxifloxacin (MOX) has been frequently released to the aquatic environment, threatening local organisms. However, researches on its ecotoxicity to aquatic organisms are still limited. This study analyzed effects of MOX on the growth, photosynthesis and oxidative stress of two common types of freshwater microalgae, Chlorella sorokiniana and Scenedesmus dimorphus. The 96 h-EC50 values of MOX for C. sorokiniana and S. dimorphus were 28.42 and 26.37 mg/L, respectively. Although variations of specific indicators for photosynthetic fluorescence intensity were different, photosystems of two types of microalgae were irreversibly damaged. The malondialdehyde content and superoxide dismutase of C. sorokiniana and S. dimorphus evidently increased, indicating that the exposure of MOX caused serious oxidative stress. Chlorophyll a, b and carotenoids contents of C. sorokiniana increased, probably resulting from the resistance to oxidative stress, whereas they were inhibited due to oxidation damage as for S. dimorphus. Risk quotients (RQs) of MOX for C. sorokiniana and S. dimorphus in wastewater were 7.882 and 8.495, respectively, which demonstrated that MOX had a considerable risk to aquatic environment, especially in the context of its increasing use in practice.

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation.

Bacterial conjunctivitis significantly impacts public health, including more than one-third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it has a high incidence of bacterial resistance to the antibiotics commonly used for treatment. Among the most recent antibiotics, besifloxacin is a fourth-generation fluoroquinolone antibiotic indicated exclusively for topical ophthalmic use. Due to its importance in treating bacterial conjunctivitis and its low solubility in water, limiting its efficacy, a nanotechnology-based drug delivery preparation was developed to overcome this hurdle. Besifloxacin nanocrystals were prepared by small-scale wet milling and response surface methodology, using Povacoat® as a stabilizer. The particle’s average hydrodynamic diameter (Z-ave) was approximately 550 nm (17 times smaller than raw material), with a polydispersity index (PdI) of less than 0.2. The saturation solubility increased about two times compared to the raw material, making it possible to increase the dissolution rate of this drug substance, potentially improving its bioavailability and safety. The optimized preparation was stable under an accelerated stability study (90 days). The Z-ave, PZ, PdI, and content did not alter significantly during this period. Furthermore, the 0.6% m/m besifloxacin nanocrystals at the maximum dose and the Povacoat® stabilizer did not show toxicity in Galleria mellonella larvae. The innovative ophthalmic preparation minimum inhibitory concentration (MIC) was 0.0960 µg/mL and 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy. Therefore, besifloxacin nanocrystals revealed the potential for reduced dosing of the drug substance, with a minor occurrence of adverse effects and greater patient adherence to treatment.