POPULATION PHARMACOKINETICS OF CEFPODOXIME IN BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS).

Cefpodoxime proxetil is commonly used to treat cetacean patients with suspected or confirmed bacterial infections; however, pharmacokinetic data are needed to guide proper dosing in these species. Cefpodoxime proxetil is a time-dependent, semisynthetic, third-generation cephalosporin, appropriate for once-daily dosing and U.S. Food and Drug Administration-approved for use in dogs with a broad spectrum of activity including gram-positive and gram-negative species. The objective of this study was to evaluate the population pharmacokinetics of cefpodoxime in bottlenose dolphins (Tursiops truncatus). A sparse-sampling design was used, with serum from dolphins receiving cefpodoxime proxetil at 10 mg/kg orally every 24 h to treat suspected or confirmed bacterial infections. Serum samples (n = 57) from 24 dolphins were analyzed at 12 time points from 0 to 96 h postdose. Serum samples were analyzed using liquid chromatography-mass spectrometry. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment linear models with first order absorption were tested. Covariates including weight, age, and sex were considered for inclusion in the model, and between-subject variability was incorporated. A two-compartment model performed best, where following an oral dose of 10 mg/kg, serum concentration reached a mean maximum concentration of 23.0 µg/ml, mean time to maximum concentration of 5.0 h, and mean half-life of 11.4 h. With daily dosing, accumulation was approximately 18% and steady state was reached by the second dose. Serum protein binding was 82.8% as determined by equilibrium dialysis, similar to plasma protein binding reported in dogs. Based on the population pharmacokinetic model, once-daily oral dosing was systemically absorbed and quickly reached maximum concentrations. The half-life in dolphins appears to be longer than other species studied to date. Given the paucity of antimicrobial pharmacokinetic studies in dolphins, and limited once-daily oral antibiotic options for this species, these data are helpful for clinicians to make informed antimicrobial choices.

Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

OBJECTIVES: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of ß-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. MATERIALS AND METHODS: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of ß-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. RESULTS: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant ß-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). CONCLUSIONS: Despite the frequent association of ESBL genes with inhibitor-resistant ß-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Establishment of epidemiological cut-off values for cefoselis, a new fourth-generation cephalosporin, against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa.

OBJECTIVES: To establish the epidemiological cut-off values (ECOFFs) for cefoselis against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa. METHODS: We collected 2288 non-repetitive clinical isolates from five laboratories throughout four cities in China. The cefoselis MICs and inhibition zone diameters for all isolates were established using the broth microdilution method and the disc diffusion method following EUCAST guidelines. MIC ECOFFs were determined by visual estimation and ECOFFinder software. Zone diameter ECOFFs were set if a high correlation of MICs and inhibition zone diameters was found by Pearson correlation. Zone diameter ECOFFs were finally determined by the visual estimate method. RESULTS: MICs of cefoselis were distributed from 0.008 to >256 mg/L for the four Enterobacterales species and from 0.25 to >256 mg/L for P. aeruginosa. MIC ECOFFs were 0.125 mg/L for E. coli, K. pneumoniae and P. mirabilis, 0.25 mg/L for E. cloacae and 32 mg/L for P. aeruginosa. A high correlation of MICs and zone diameters was observed for all Enterobacterales (|r| > 0.8, P < 0.001) and a relatively high correlation was found for P. aeruginosa (|r| = 0.71, P < 0.001). The zone diameter ECOFF was 24 mm for E. cloacae, E. coli and K. pneumoniae, 26 mm for P. mirabilis and 21 mm for P. aeruginosa. CONCLUSIONS: We determined MIC and zone diameter ECOFFs for cefoselis against four Enterobacterales species and P. aeruginosa. The establishment of ECOFFs for cefoselis provides clinicians with helpful guidance to differentiate WT and non-WT pathogens.

Study of the structure and dynamics at various parts of the antibacterial drug molecule cefpodoxime proxetil.

The structure and dynamics of cefpodoxime proxetil are elucidated by measuring chemical shift anisotropy (CSA) tensor, spin-lattice relaxation time, and local correlation time at twenty-one crystallographically different 13C nuclei sites. The principal components of CSA tensor of cefpodoxime proxetil are extracted by the two-dimensional phase adjusted sinning sideband (2DPASS) cross-polarization magic angle spinning (CP-MAS) solid-state NMR experiment, and the spin-lattice relaxation time is measured by the method outlined by Torchia(T1CP). The local correlation time is calculated by bearing in mind that the spin-lattice relaxation mechanism of 13C nuclei is mainly governed by the CSA interaction and the heteronuclear dipole-dipole interaction. The aminothiazole ring, ß-lactam ring, and dihydrothiazine ring provide stability to the drug molecule and increase the affinity of the drug to penicillin-binding proteins (PBPs) receptors. The principal components of CSA parameters, spin-lattice relaxation time, and local correlation time vary substantially for carbon nuclei residing on these three rings. These signify that not only the electronic environment, but the molecular conformation, and the local dynamics are also altered within the ring. The substitution of the acyl side chain, oxime group, and the aminothiazole ring at the C7 position of the ß-lactam ring enhances the antibacterial activity and the binding affinity of the drug. A huge variation of the spin-lattice relaxation time and local correlation time is observed in those regions. The change in the electron charge distribution and nuclear spin dynamics at different parts of the drug molecule is clear by CSA and spin-lattice relaxation measurements, which will enrich the field "NMR crystallography".

Spray dried nanospheres for inclusion complexes of cefpodoxime proxetil with ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin and methyl-ß-cyclodextrin: improved dissolution and enhanced antibacterial activity.

OBJECTIVE: The aim of the current research was the development hard cellulose capsules containing cefpodoxime proxetil (CEF) (BCS-Class II) encapsulated nanospheres of inclusion complexes with ß-CD, HP-ß-CD and M-ß-CD for efficient antibacterial therapy. SIGNIFICANCE: The reason for this phenomenon is to bring an innovative approach to effective oral antimicrobial therapy with hard cellulose capsules containing spray dried nanospheres of CEF with ß-CD, HP-ß-CD and M-ß-CD by means of increased solubility, dissolution rate and improved antibacterial efficiency with lower oral dose. METHODS: Phase solubility analyses was performed to evaluate the drug/CD interaction, involving the stoichiometry and apparent stability constant. Following the preparation of inclusion complexes by spray-drying method, complexes were characterized for physical, solid-state and microbiological analyses. In vitro dissolution from hard cellulose capsules containing CEF and CEF/ß-CD, CEF/HP-ß-CD and CEF/M-ß-CD complexes were performed. RESULTS: According to AL type phase solubility curves, complexes were formulated as 1:1 molar ratio. The solubility of pure CEF was determined as 0.241 ± 0.002 mg mL-1, the solubility of inclusion complexes increased solubility from 3 to 5 times. The strong host-guest interaction was confirmed for CEF/HP-ß-CD and CEF/M-ß-CD complexes with SEM, DSC, FT-IR and 1H-NMR analyses. Inclusion complexes were more efficient on bacterial cells (2-4 fold) than pure CEF both Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Hard-cellulose capsules filled with inclusion complexes exhibited significantly faster release than unprocessed CEF. CONCLUSION: Hard-cellulose capsules containing CEF/HP-ß-CD and CEF/M-ß-CD complexes appear to be superior alternative to commercially available CEF tablets for effective antibacterial therapy.

Development and characterization of lyophilized cefpodoxime proxetil-Pluronic® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity.

The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and 1H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2-8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f1) and similarity factor (f2). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose.

Antibiotic susceptibility of cultivable aerobic microbiota from the oral cavity of Echis carinatus from Odisha (India).

During a snake bite, the microbes may get transferred to the bite site and may cause secondary infection along with envenomation. The knowledge on the oral bacterial flora of snakes constitutes information important for snake bite management. The inadequately studied oral microflora of snakes differ geographically, temporally and among the members of the same species. The objective of this study is to determine the pattern of oral bacterial flora of Saw-scaled viper (Echis carinatus) and their susceptibility to antibiotics. Oral swabs were collected from nine healthy Saw-scaled vipers, subjected to microbiological, biochemical and molecular characterization. Additionally, these isolates were subjected to antimicrobial susceptibility testing using ICOSA-20-Plus and ICOSA-20-Minus. A wide range of pathogenic bacteria such as Salmonella arizonae, Pseudomonas stutzeri, Proteus penneri, Alcaligenes faecalis; Citrobacter diversus, C. freundii, Enterococcus faecalis, Bacillus anthracis, Staphylococcus sciuri and Achromobacter xylosoxidans were isolated as new additions to the floral diversity of saw scale viper. Most of the isolates were sensitive towards amikacin, azithromycin, imipenem, ciprofloxacin, gentamicin, ofloxacin, sparfloxacin, tobramycin, levofloxacin, kanamycin, tetracycline, and chloramphenicol while resistant to amoxyclav, cephalothin, cefpodoxime, Co-Trimoxazole, oxacillin and penicillin. The present study revealed that the bacterial flora of the oral cavity of Saw-scaled viper is resistant to many common antibiotics, which are often used for the treatment of snake-bite victims.

Isolation and characterization of Uropathogenic Escherichia coli (UPEC) from red panda (Ailurus fulgens).

BACKGROUND: Disease prevention and control is a significant part in the ex-situ conservation of the endangered red panda (Ailurus fulgens), being bacterial infection is one of the most important health threats to the captive population. To date, studies about the infection caused by Escherichia coli in the red panda are scarce. This study was conducted to determine the cause of death of a captive red panda through clinical symptoms, complete blood count, biochemical analysis, pathological diagnosis and bacterial whole genome sequencing. CASE PRESENTATION: The following report describes a case of a 1.5 year old captive red panda (Ailurus fulgens) that was found lethargic and anorectic. She was moved to the quarantine area for daily treatment with 50 mg of Cefpodoxime Proxetil. During the three-day treatment, she did not eat or defecate, and then died. Clinical hematology revealed the values of neutrophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were significantly higher. Histological analysis demonstrated major pathological damage in the kidneys, liver and lungs, characterized by hyperemia, parenchymal cell degeneration and necrosis and inflammatory cell infiltration which were predominantly neutrophilic. A bacterial strain confirmed as Escherichia coli was isolated post mortem. Whole genome sequencing of the E. coli showed the complete genome size was 4.99 Mbp. PapA, PapC, OmpA, OmpU and other virulence factors which specific to Uropathogenic Escherichia coli (UPEC) were found in the isolate. Among the virulence factors, P pili, type I pili and related factors of the iron uptake system were associated with nephrotoxicity. CONCLUSION: The red panda died of bacterial infection caused by an uropathogenic strain of Escherichia coli. The pathogenic mechanisms of the strain are closely related to the expression of specific virulence genes.

Effects of antibiotics on prevention of infection, white blood cell counts, and C-reactive protein levels at different times in the perioperative period of cesarean section
.

OBJECTIVE: To evaluate the effects of antibiotics on prevention of infection, white blood cell (WBC) counts and C-reactive protein (CRP) levels at different times in the perioperative period of cesarean section. MATERIALS AND METHODS: A total of 486 women undergoing cesarean section were randomly divided into groups A, B, and C (n = 162). Group A was intravenously infused with 250 mL of 0.9% normal saline containing 2 g cefuroxime sodium 30 minutes before surgery within 30 - 45 minutes. Group B was given cefuroxime 30 minutes before surgery and 3 days after surgery, respectively. Group C was given cefuroxime only after returning to ward, once daily for 3 consecutive days. The surgical time, intraoperative blood loss, postoperative hospital-stay length, hospitalization expenditure, maximum body temperature, WBC count and CRP level 3 days after surgery, grade A healing rate of incision at discharge, and incidence of infection were compared. RESULTS: Group A had the shortest postoperative hospital-stay length and lowest hospitalization expenditure (p < 0.05). The maximum body temperature, WBC count and CRP level of group A 3 days after surgery were lowest (p < 0.05). The three groups had similar grade A healing rates of incision (p > 0.05). The postoperative infection rates of groups A and B were similar (p > 0.05), both being significantly lower than that of group C (p < 0.05). CONCLUSION: Single prophylactic use of antibiotics 30 minutes before surgery effectively prevented infection after cesarean section and shortened the hospital-stay length. This method is worthy of clinical promotion due to short duration of antibiotic use and low hospitalization expenditure.

Clostridium difficile infection after antibiotic use.

Every day, patients are prescribed antibiotics to treat infections, and some of these patients will subsequently develop a superinfection with Clostridium difficile. Although the use of antibiotics is a necessary part of modern medical care, clinicians must be judicious with their use and choice of antibiotics to prevent consequences for patients whenever possible.

Levofloxacin versus Cefpodoxime for Antibacterial Prophylaxis in Allogeneic Stem Cell Transplantation.

National guidelines recommend antimicrobial prophylaxis for allogeneic stem cell transplant patients during the pre-engraftment period because of increased infection risk during neutropenia. Fluoroquinolones have demonstrated lower rates of bacteremias and incidence of neutropenic fever, but there is limited evidence in the use of alternative antibacterials such as cefpodoxime. The primary objective of this study is to compare the rates of antibiotic prophylaxis failure between levofloxacin and cefpodoxime in allogeneic stem cell transplant recipients. Secondary objectives include comparing and characterizing number and type of infections, mortality at day 100 post-transplant, and hospitalizations for infectious causes in the first 100 days of transplant. This is a single-center, retrospective chart review of adult patients who received an allogeneic stem cell transplant from matched related and matched unrelated donors and antibacterial prophylaxis with levofloxacin or cefpodoxime from January 1, 2011, to October 1, 2014. A total of 142 patients were evaluated (71 levofloxacin, 71 cefpodoxime). Both levofloxacin and cefpodoxime groups had similar rates of neutropenic fever and antibiotic prophylaxis failure (58% versus 58%, P = NS). There were similar incidences of Clostridioides difficile and Multi-drug resistant (MDR) infections among both levofloxacin and cefpodoxime groups. Rates of infections, hospitalizations, and mortality in the first 100 days were similar among both groups. Cefpodoxime can be used as an alternative to levofloxacin for antibiotic prophylaxis in allogeneic stem cell transplant patients.

Repeated Isolation of Extended-Spectrum-ß-Lactamase-Positive Escherichia coli Sequence Types 648 and 131 from Community Wastewater Indicates that Sewage Systems Are Important Sources of Emerging Clones of Antibiotic-Resistant Bacteria.

Antibiotic resistance in bacteria is an emerging problem globally. Resistant bacteria are found in human and animal microbiota, as well as in the environment. Wastewater receives bacteria from all these sources and thus can provide a measurement of abundance and diversity of antibiotic-resistant bacteria circulating in communities. In this study, water samples were collected from a wastewater pump station in a Norwegian suburban community over a period of 15 months. A total of 45 daily samples were cultured and analyzed for the presence of Escherichia coli Eighty E. coli-like colonies were collected from each daily sample and then phenotyped and analyzed for antibiotic resistance using the PhenePlate-AREB system. During the sampling period, two unique E. coli phenotypes with resistance to cefotaxime and cefpodoxime indicating carriage of extended-spectrum ß-lactamases (ESBL) were observed repeatedly. Whole-genome sequencing of 15 representative isolates from the two phenotypes identified these as two distinct clones belonging to the two globally spread E. coli multilocus sequence types (STs) ST131 and ST648 and carrying blaCTX-M-15 The number of ESBL-positive E. coli strains in the community wastewater pump station was 314 of 3,123 (10%) analyzed E. coli strains. Of the ESBL-positive isolates, 37% belonged to ST648, and 7% belonged to ST131. Repeated findings of CTX-M-15-positive ST648 and ST131 over time indicate that these STs are resident in the analyzed wastewater systems and/or circulate abundantly in the community.

Evaluation of prophylactic antibiotic regimens on recurrence and mortality in spontaneous bacterial peritonitis.

INTRODUCTION AND OBJECTIVES: Limited data describe current SBP epidemiology and specific secondary SBP prophylactic regimens, leading to variable prescribing practices. This work aims to compare 90-day and one-year SBP recurrence and mortality based on secondary SBP antibiotic prophylaxis regimens. MATERIALS AND METHODS: We performed a retrospective cohort of patients >18 years with an SBP diagnosis from 2010 to 2015 at two academic institutions. Eligible patients had ascitic PMN counts ≥250cells/mm3 or a positive ascitic culture. Patients were compared based on secondary SBP prophylaxis regimens (i.e., daily, intermittent, or no prophylaxis). RESULTS: Of 791 patients with ascitic fluid samples, 86 patients were included. Antibiotic prophylaxis included daily (n=34), intermittent (n=36), or no prophylaxis (n=16). Nearly half of SBP episodes had a positive ascitic fluid culture; 50% were gram-negative pathogens, and 50% were gram-positive pathogens. Daily and intermittent regimens had similar rates of recurrence at 90-days (19.4% vs. 14.7%, p=0.60) and one-year (33.3% vs. 26.5%, p=0.53). Similarly, mortality did not differ among daily and intermittent regimens at 90-days (32.4% vs. 30.6%, p=0.87) or one-year (67.6% vs. 63.9%, p=0.74). When comparing any prophylaxis vs. no prophylaxis, there were no differences in 90-day or one-year recurrence or mortality. CONCLUSIONS: In patients with a history of SBP, our data indicate similar outcomes with daily, intermittent, or no secondary antibiotic prophylaxis. With available data, including ours, demonstrating a changing epidemiology for SBP pathogens, further data is required to determine if traditional approaches to secondary SBP prophylaxis remain appropriate.

Development and validation of RP-HPLC method for simultaneous determination of cefpodoxime proxetil and H2 receptor antagonists in pharmaceutical dosage forms.

A new method on RP-HPLC is devised and validated, as per ICH guidelines, for the synchronous estimation of cefpodoxime proxetil and H2-receptor antagonits that are Cimetidine, Famotidine and Ranitidine. The method is simple, accurate, expeditious, reproducible, robust and precise. Chromatography was done on a C18 (250 x 4.6mm) column with methanol: water as mobile phae in the ratio of 70:30 (v/v), pumped at a flow rate of 1ml/min and pH was maintained using 85% ortho-phosphoric acid at 3. The λ max 240 nm was preferred for UV detection. A good linear relationship was attained, over the concentration ranges of 20-70 µg/ml and 5-30µg/ml, for cefpodoxime proxetil and H2 blockers respectively, with a correlation coefficient of R= 0.9987 to 0.9992. The method was validated and found precised (i.e. intra day and interday analysis) with RSD <2%. LOD and LOQ observations were under 0.4806 to 2.6069µg/ml which proved the method to be sensitive. The method provided satisfactory results of robustness and reproducibility, when validated and applied successfully for analysis of dosage forms.

In vitro Spectroscopic studies on drug interaction of cefpodoxime proxetil and H2 receptor blockers.

One of the relatively advance 3rd generation cephalosporins, cefpodoxime proxetil, is being used all-around. Generally, these are used for the cure of infections allied to urinary and respiratory tract. These cephalosporins have showed a remarkable in vitro activity against many strains of bacteria which are resistant to other orally used active medicinal substances. It is the first oral 3rd generation cephalosporin to be used in the cure of skin infections. The practice of H2 receptor antagonists, concerning lots of treatments recommended in patients with different types of ulcers and allergic urticarial condition, is raising hazards of unwanted secondary outcomes and drug interactions. Learning of in-vitro interaction between cefpodoxime poxetil and H2 blockers (Ranitidine, Famotidine and Cimetidine) were examined applying UV/Visible spectrophotometry and Infrared spectrometry. In the existence of H2 receptor blockers, the cefpodoxime proxetil availability was found to be decreased in vitro only under specific conditions. Furthermore, complexes of Cefpodoxime proxetil-H2 receptor antagonists were manufactured approving the interaction of these drugs. Finally, the above mentioned spectrophotometric techniques were employed to examine the complexes formed (Cefpodoxime proxetil-cimetidine, cefpodoxime proxetil-famotidine and cefpodoxime proxetil-ranitidine).

Antibiotics for recurrent acute pharyngo-tonsillitis: systematic review.

The purpose was to determine the current evidence for preferable antibiotic treatment in three common clinical situations with insufficient consensus: Q1: Can antibiotic treatment prevent future attacks of acute pharyngo-tonsillitis (APT) in patients with recurrent APT (RAPT)? Q2: Which antibiotic regimen is preferable in the treatment of APT in patients with RAPT? Q3: Which antibiotic regimen is preferable in the treatment of relapsing APT? Five databases were searched systematically for randomized clinical trials on patients with RAPT with or without current APT or with relapse of APT. Of the unique publications, 643 were found. Five studies addressing Q1 (n = 3) and Q2 (n = 2) met the eligibility criteria. No studies reporting on Q3 were included. Q1: Two studies found that clindamycin and cefpodoxime, respectively, were effective in preventing future APT episodes and in eradicating group A streptococci from the tonsils of RAPT patients. One study found that long-term azithromycin had no effect on the number of APT episodes. Q2: Two studies reported superior clinical and microbiological effects of clindamycin and amoxicillin with clavulanate, respectively, compared to penicillin. The four studies showing superior effects of clindamycin and amoxicillin with clavulanate were assessed to have high risk of bias. Hence, the level of evidence was moderate. There is considerable evidence to suggest that clindamycin and amoxicillin with clavulanate are superior to penicillin with preferable effects on the microbiological flora and the number of future attacks of APT in patients with RAPT. Antibiotic treatment is an option in patients with RAPT, who has contraindications for tonsillectomy.

The performance of a resazurin chromogenic agar plate with a combined disc method for rapid screening of extended-spectrum-ß-lactamases, AmpC ß-lactamases and co-ß-lactamases in Enterobacteriaceae.

A promising means of rapid screening of extended-spectrum-ß-lactamase (ESBL), AmpC ß-lactamase, and co-production of ESBL and AmpC that combines resazurin chromogenic agar (RCA) with a combined disc method is here reported. Cefpodoxime (CPD) discs with and without clavulanic acid (CA), cloxacillin (CX) and CA+CX were evaluated against 86 molecularly confirmed ß-lactamase-producing Enterobacteriaceae, including 15 ESBLs, 32 AmpCs, nine co-producers of ESBL and AmpC and 30 carbapenemase producers. The CA and CX synergy test successfully detected all ESBL producers (100% sensitivity and 98.6% specificity) and all AmpC producers (100% sensitivity and 96.36% specificity). This assay also performed well in screening for co-existence of ESBL and AmpC (88.89% sensitivity and 100% specificity). The RCA assay is simple and inexpensive and provides results within 7 hr. It can be performed in any microbiological laboratory, in particular, in geographic regions in which ESBL, AmpC or co-ß-lactamase-producing Enterobacteriaceae are endemic.

Impact of different organic acids on solubility enhancement of cefpodxime proxetil immediate release tablet and its stability studies.

Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.

Development and validation of HPLC method for the determination of Cefpodoxime Proxetil in human plasma.

A new, simple, accurate, precise and specific method has been developed for the analysis of Cefpodoxime Proxetil in human plasma. The proposed method was developed and validated with the aim to be used in Bioavailability/Bioequivalence studies for quantification of drug in human plasma. The mobile phase components were acetonitrile, methanol, and water in the ratio of 20:50:30. Ortho phosphoric acid was used to adjust at pH5.0. Flow rate and wavelength were kept 1ml/min and 247nm respectively. The column was C-18 HPLC column 5um particle size, L x 1.d. 25cm x4.6mm. (Supelcosil). Retention time of Cefpodoxime Proxetil was found to be 10.967min. The developed method was validated for selectivity, recovery, accuracy, precision, repeatability, reproducibility, stability and linearity in the range of 0.195mcg/ml to 50mcg/ml. The accuracy and Precision of the proposed method were well within the predefined limits i.e. ±15% for all the calibration standards other than LLOQ (Lower Limit of Quantification) where it was well within ±20% of the nominal value. The analytical recovery was always above 89% showing satisfactory recovery. The coefficient of correlation (R2 ) was 0.999. The developed method was found suitable for the estimation of Cefpodoxime Proxetil in plasma.