Influence of biomaterials on scintigraphic diagnosis of periprosthetic infections. Ceftizoxime-99m technetium model

Abstract Purpose: To compare the influence of two metallic implants in the diagnosis of periprosthetic infection using 99m technetium-labeled ceftizoxime. Methods: Twenty rats were randomly divided into four groups, which received sterile and contaminated titanium and stainless steel implants. After 3 weeks, scintilographic images were obtained using a gamma chamber. Radioactivity counts were obtained for the region of interest (ROI) on the operated and non-operated paws. Results: Groups A, B, and C showed homogenous distribution of the radiopharmaceutical. Hyper uptake was observed in the operated paw from group D. The ROI target count was higher in the two groups with stainless steel implants. Among the control groups, the count was higher in the stainless steel group. Furthermore, among the contaminated groups, the uptake was higher in the stainless steel group, with a significant difference. The target: non-target ratio was significantly lower in the control and contaminated groups with both titanium and stainless steel, but the comparison between control groups and contaminated groups was only significant in the former. The cpm/g observed after a decay of 48h showed statistically significant differences between groups. Conclusion: Different biomaterials used in implants have an influence on the results of scintigraphy with 99mTc-CFT.

Scintigraphic imaging with technetium-99M-labelled ceftizoxime is a reliable technique for the diagnosis of deep sternal wound infection in rats

PURPOSE:To evaluate whether scintigraphy with technetium-99m-labeled ceftizoxime (99mTc-CFT) can differentiate mediastinitis from aseptic inflammation associated with sternotomy.METHODS:Twenty female Wistar rats were randomly distributed into four groups: S (control) -partial upper median sternotomy with no treatment; SW (control) - sternotomy and treatment of sternal wounds with bone wax; SB - sternotomy and infection with Staphylococcus aureus; SWB - sternotomy with bone wax treatment and bacterial infection. Scintigraphy with 99mTc-CFT was performed eight days after surgery and images were collected 210 and 360 min after infusion of the radiopharmaceutical.RESULTS: No animals exhibited clinical signs of wound infection at the end of the experiment, although histological data verified acute inflammatory response in those experimentally infected with bacteria. Scintigraphic images revealed that tropism of 99mTc-CFT to infected sternums was greater than to their non-infected counterparts. Mean counts of radioactivity in bacteria-infected sternal regions (SB and SWB) were significantly higher (p = 0.0007) than those of the respective controls (S and SW).CONCLUSION:Scintigraphy with technetium-99m-labeled ceftizoxime is a method that can potentially detect infection post sternotomy and differentiate from aseptic inflammation in animals experimentally inoculated with S. aureus.

Emergence of decreased susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae in India.

Background. In the past, Neisseria gonorrhoeae has developed resistance to antimicrobial agents used for its treatment. Consequently, extended-spectrum cephalosporins form the mainstay of treatment for gonorrhoea. Methods. Samples from 88 patients attending the sexually transmitted diseases clinics from December 2009 to January 2011 in two referral hospitals in New Delhi were studied. Antimicrobial susceptibility testing was done using the disc diffusion method as per the calibrated dichotomous sensitivity technique against the following antibiotics: penicillin (0.5 i.u.), tetracycline (10 μg), nalidixic acid (30 μg), ciprofloxacin (1 μg), spectinomycin (100 μg), ceftriaxone (0.5 μg) and cefpodoxime (10 μg) (Oxoid UK). Azithromycin (15 μg) (Oxoid, UK) was tested as per the guidelines of the Clinical and Laboratory Standards Institute. Minimum inhibitory concentrations were determined using the Etest for penicillin, tetracycline, ciprofloxacin, ceftriaxone, spectinomycin and azithromycin as per the manufacturer’s instruction (Biomerieux, France). Results. Eighteen isolates of Neisseria gonorrhoeae were obtained. Three of these had decreased susceptibility to ceftriaxone and cefpodoxime by the disc diffusion method. The minimum inhibitory concentrations of ceftriaxone for two isolates were 0.064 μg/ml and for one isolate it was 0.125 μg/ml. Conclusion. Higher minimum inhibitory concentrations to extended-spectrum cephalosporins is of concern as it has been shown to precede treatment failure. This may warrant its use in increased/multiple dosages alone or possibly in combination (dual therapy), thereby complicating effective disease control. Our report is in accordance with earlier reports from different parts of the world. Therefore, a continuous surveillance of antimicrobial resistance is crucial to tailor treatment schedules for Neisseria gonorrhoeae in a particular geographical region.

Pharmacokinetics of cefpodoxime proxetil with special reference to biochemical parameters, tissue residue, and spermatozoa motility in rats.

Background : Cefpodoxime is a semisynthetic third generation cephalosporin analogue with a relatively broader spectrum of antimicrobial activity against gram negative and gram positive organisms. This is attributed to their somewhat increased resistance to degradation by the betalactamase. Cefpodoxime shows good activity against Klebsiella pneumonia, many members of enterobactericeae and almost all strains of Escherichia coli. It is extensively used in human beings against infections caused by susceptible organisms for a prolonged period and even without its judicious indication. Though various researchers have worked on the pharmacokinetic aspects of the drug, its effects on biochemical parameters and spermatozoa activity are scarcely available in literature. Aim : To determine the oral kinetic ( blood and tissue) after single therapeutic dose of cefpodoxime proxetil (20mg/kg oral bid 7 days) in rats of either sex on tissue half life and certain biochemical parameters such as glucose, hemoglobin, protein, ALT, AST and other parameters like tissue residue, sperm count and spermatozoa motility in male rats. Materials and Methods : For kinetic studies,24 Wister rats of either sex, 3 months of age, (180-210 gm) were used.(Group I-IV; n=6) Blood samples collected from each animal of Group IV through heart puncture at 0 hour to serve as predrug control. All the group (I-IV) received cefpodoxime proxetil 20 mg/kg once orally as a single dose. At the end of 1,4,12 and 24 hour post oral administration, GroupI,II,III and IVwere utilized for kinetic studies. Blood samples were collected from each animal and vital organs viz brain, lung, liver, spleen, kidney and heart were dissected out for drug analysis and determination of weight. For biochemical parameters, tissue residue and spermatozoa motility, twelve male rats were randomly divided into Groups A and B (n=6) Group B received cefpodoxime (20mg/kg orally bid 7 days) while Group A served as control. Biochemical parameters [Blood glucose, protein, Aspartate transaminase(AST), Alanine transaminase(ALT)and hemoglobin] were measured at 0 and 7 th day while sperm count (total,live and dead)and mean organ weight (study and control group) and tissue residue of drug were evaluated at the end of treatment. Absorption of cefpodoxime was observed at 2 hour and reached a maximum at 4 hour and persisted in blood till 24 hour. Elimination half life in lung was highest followed by heart, liver, kidney and spleen while t½ k in plasma was very low suggesting more affinity of cefpodoxime for tissues than blood. Results and Conclusion : Blood glucose, protein, AST and ALT activities were not significantly altered but the hemoglobin level and total and live sperm count decreased significantly in the study group compared to the control group. Residual level of cefpodoxime was highest in liver followed by kidney and other study organs. Therefore, the drug should be used in human beings judiciously and further study on human subjects is warranted.

In vitro study to compare sensitivity of amoxicillin+clavulanic acid and cefpodoxime+clavulanic acid among beta-lactamase positive clinical isolates of gram-positive and gram-negative pathogens.

The present study was carried out to compare the in vitro sensitivity of cefpodoxime + clavulanic acid and amoxicillin + clavulanic acid against 55 Gram-positive and 123 Gram-negative beta-lactamase positive clinical isolates. Micro-organisms isolated from different clinical specimens were tested for beta-lactamase/ESBL by using nitrocefin disc test and for metallo beta-lactamase by using double disc synergy test. A total of 299 (93 Gram-positive and 206 Gram-negative) clinical isolates were tested for beta-lactamase. Among 93 Gram-positive clinical isolates 25 (78.12%) out of 32 coagulase positive S. aureus, 23 (60.52%) out of 38 coagulase negative S aureus, 7 (63.63%) out of 11 enterococci and 0 (0%) out of 12 Strept pneumoniae were positive for beta-lactamase /ESBL. Notably Strept pneumoniae was found to be beta-lactamase/ESBL negative. Among 206 Gram-negative clinical isolates, 25 (69.44%) out of 36 acinetobacter spp, 20 (41.66%) out of 48 Branhamella catarrhalis, 24 (64.86%) out of 37 E. coli, 7 (46.66%) out of 15 H influenzae and 22 (62.85%) out of 35 proteus were positive for beta-lactamase/ ESBL/metallo beta-lactamase. Positive strains were tested for comparative sensitivity to amoxicillin+ clavulanic acid and cefpodoxime+clavulanic acid by Kirby Bauer disc diffusion method. As regards comparative sensitivity among beta-lactamase/ESBL positive Gram-positive strains, 84% and 92% strains of coagulase positive S aureus, 65.21% and 86.95% strains of coagulase negative S. aureus, 83.33% and 100% strains of Strept pneumoniae and 71.42% and 100% strains of enterococci were found sensitive to amoxicillin +clavulanic acid and cefpodoxime + clavulanic acid respectively. Sensitivity to amoxicillin+ clavulanic acid and cefpodoxime +clavulanic acid among beta lactamase/ESBL positive Gram-negative strains of acinetobacter spp, Branhamella catarrhalis, E. coli, H. influenzae and proteus spp were found to be 20% and 28%, 100% and 100%, 50% and 75%, 71.42% and 100%, 50% and 68.18% respectively. This study demonstrated that cefpodoxime +clavulanic acid combination has more potent in vitro activity in comparison to amoxicillin+ clavulanic acid combination against beta-lactamase producing strains of Gram-positive and Gram-negative bacteria. Given this broad spectrum of activity, cefpodoxime+clavulanic acid appears well suited for use in the treatment of a variety of healthcare-associated infections.

Detection of extended spectrum beta-lactamase production in clinical isolates of Klebsiella spp.

BACKGROUND & OBJECTIVE: Clinical laboratories need to develop quick screening methods for detection of extended spectrum beta-lactamase (ESBL) producing strains, so that the appropriate medication can be started without delay. In this study, we report the screening sensitivity of four representative antimicrobial agents i.e., cefpodoxime, cefotaxime, ceftazidime and aztreonam, commonly used for ESBL detection in Klebsiella spp. METHODS: A total of 100 clinical isolates of Klebsiella spp. from the cases of neonatal septicaemia at a tertiary care hospital from north India, were screened for ESBL production by Kirby- Bauer's disc diffusion (cefpodoxime, cefotaxime, ceftazidime and aztreonam) and minimum inhibitory concentration (MIC) test by agar dilution methods. Confirmation was done by double disc method. RESULTS: Results showed that 58 of the 100 isolates tested were ESBL positive by confirmatory test and cefpodoxime was more efficient ESBL screening antimicrobial agent than ceftazidime, cefotaxime and aztreonam. INTERPRETATION & CONCLUSION: Using the standard disk diffusion as screening test for identifying ESBL producers, cefpodoxime was found to be the most efficient antimicrobial agent in screening isolates as potential ESBL producers followed by ceftazidime in Klebsiella spp. isolates.

Actividad comparativa in vitro de cefpodoxima en relación a otros antibióticos de uso frecuente, frente a patógenos respiratorios, urinarios y de infecciones de partes blandas / Activity of cefpodoxime against pathogens causing respiratory, urinary or soft tissue infections

Background: Cefpodoxime is a new antimicrobial in the Chilean market, recommended for treatment of respiratory and urinary tract infections. Aim: To study the susceptibility of common pathogens isolated from Chilean patients to cefpodoxime and other antimicrobials. Material and methods: The in vitro activity of cefpodoxime, expressed as Minimal Inhibitory Concentration, was studied in 331 S pneumoniae, H influenzae, M catarrhalis, E coli, S aureus and S pyogenes strains, isolated between 2000 and 2004 from respiratory, urinary and soft tissue infections, respectively. Results: Eleven percent of S pneumoniae isolates were resistant to penicillin, 11% were resistant to cefuroxime and 10% to cefpodoxime. All H influenzae isolates were susceptible to cefpodoxime. No H influenzae isolates were resistant to second or third generation cephalosporines. Four percent of H influenzae isolates were resistant to ampicillin by ß-lactamase production. In contrast 81% of M catarrhalis strains were resistant to ampicillin. Six percent of E coli isolates were resistant to cefpodoxime, 9% to cefuroxime, 11% to cefadroxile and 50% to ampicillin or trimethoprim/sulphamethoxazole. Cefpodoxime was the most active antimicrobial against S pyogenes. Conclusions: Cefpodoxime, recently introduced in Chile, is a good alternative for the treatment of common respiratory and urinary tract infections.

Cefpodoxime - utility in respiratory tract infections and typhoid fever.

Cefpodoxime is a oral third generation cephalosporin active against most of gram positive and gram negative bacteria except Pseudomonas, B. fragilis and Entrococcous. Clinical studies have confirmed efficacy of cefpodoxime in acute otitis media, sinusitis and tosillopharyngitis. Twice daily administration and safety profile increases compliance and decreases failure rate. It has a role as switch over therapy from intravenous ceftriaxone in serious respiratory tract infections (RTIs). In areas where common respiratory pathogens show decreased sensitivity to penicillins and macrolides cefpodoxime can be used as empirical first line therapy in respiratory tract infections. It seems to be a promising molecule in pediatric typhoid fever because of its excellent activity against Salmonella species but clinical trials are limited.