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Antimicrobial Agents and Chemotherapy May 1978Sulfamethoxazole-trimethoprim and three oral cephalosporins, cefaclor, cephalexin, and cephradine, were evaluated in vitro as possible alternatives to chloramphenicol in...
Sulfamethoxazole-trimethoprim and three oral cephalosporins, cefaclor, cephalexin, and cephradine, were evaluated in vitro as possible alternatives to chloramphenicol in the treatment of non-central nervous system infections due to ampicillin-resistant Haemophilus influenzae. Sixty-four isolates of H. influenzae, including 31 beta-lactamase-positive strains, were tested by the agar dilution method. All strains were inhibited by 0.78/0.039 mug sulfamethoxazole-trimethoprim per ml and by 0.78 mug of chloramphenicol per ml. At 6.25 mug/ml, 100, 11, and 3% of all strains were inhibited by cefaclor, cephalexin, and cephradine, respectively. Thus, on the basis of drug concentrations presumably achievable in serum, 100% of strains were susceptible to sulfamethoxazole-trimethoprim, chloramphenicol, and cefaclor. However, a considerable inoculum effect was noted with both beta-lactamase-positive and -negative strains, when tested with sulfamethoxazole-trimethoprim; the minimal inhibitory concentrations of cefaclor were only slightly affected. Also, synergistic effects of sulfamethoxazole-trimethoprim, sulfamethoxazole-erythromycin, and sulfamethoxazole-cefaclor were seen when combinations were tested against both beta-lactamase-positive and -negative strains, as determined by minimal inhibitory concentrations measured by the broth dilution method and by killing curve analyses. These results support further evaluation of these combinations and of cefaclor alone for the treatment of non-central nervous system infections due to H. influenzae.
Topics: Cephalosporins; Cephradine; Drug Combinations; Drug Synergism; Haemophilus influenzae; Microbial Sensitivity Tests; Sulfamethoxazole; Trimethoprim
PubMed: 307367
DOI: 10.1128/AAC.13.5.861 -
American Journal of Veterinary Research May 2010To describe the effects of lithium carbonate on thrombopoiesis in clinically normal dogs and in dogs treated with carboplatin.
OBJECTIVE
To describe the effects of lithium carbonate on thrombopoiesis in clinically normal dogs and in dogs treated with carboplatin.
ANIMALS
18 young adult sexually intact female Beagles.
PROCEDURES
Dogs were assigned to each of 3 treatment groups (6 dogs/group). Group 1 received 150 mg of lithium carbonate (14 to 16 mg/kg), PO, every 12 hours on days 1 through 21. Group 2 received carboplatin (300 mg/m(2), IV) on day 0 and cephalexin (30 mg/kg, PO, q 12 h) on days 14 through 21. Group 3 received lithium, carboplatin, and cephalexin at the aforementioned doses and schedules. Plasma lithium and blood platelet concentrations were measured on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. Number of megakaryocytes in bone marrow specimens and the percentage of large unstained cells and CD34+ mononuclear cells in bone marrow aspirates were determined on days 0, 7, 14, and 21 by manual enumeration, automated hematologic analysis, and flow cytometric immunophenotyping, respectively.
RESULTS
Plasma lithium concentrations ranged from 0.12 to 2.41 mmol/L. All dogs given lithium achieved a concentration within the target interval of 0.5 to 1.5 mmol/L by days 4 to 7. Thrombopoiesis was increased in dogs receiving lithium alone. All dogs given carboplatin developed mild thrombocytopenia. There were no differences between group 2 and group 3 throughout the study.
CONCLUSIONS AND CLINICAL RELEVANCE
Lithium stimulated thrombopoiesis in clinically normal dogs. Lithium administration at the doses and schedules used, with concurrent administration of cephalexin, did not prevent thrombocytopenia induced by carboplatin.
Topics: Animals; Anti-Bacterial Agents; Carboplatin; Cephalexin; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Lithium; Lithium Carbonate; Megakaryocytes; Platelet Count; Thrombocytopenia; Thrombopoiesis; Treatment Outcome
PubMed: 20433382
DOI: 10.2460/ajvr.71.5.555 -
Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.Journal of Negative Results in... May 2017Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs.
METHODS
Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t) (primary outcome), maximum concentration (C), C first time (T), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC), extrapolated to infinity (AUC), or to T of overt drug (AUC), and C/AUC were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range.
RESULTS
Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC, AUC, C, AUC, and C/AUC were within the bioequivalence range, except for ibuprofen C (76.66-98.99), ibuprofen C/AUC (77.19-98.39), and ibuprofen (45.32-91.62) and paracetamol (51.45-98.96) AUC. Out of the 126 individual covert/overt ratios, 2.0-16.7% were outside the +25% range for AUC, 2.0-4.2% for AUC, 25.0-44.9% for C, 67.3-76.7% for AUC, and 45.8-71.4% for T.
CONCLUSIONS
This study couldn't confirm that awareness of drug ingestion modulates its bioavailability. However, it demonstrates the trivial effect of blinding in bioequivalence studies and the extent of bio-variability that would be expected when comparing a drug product to itself.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01501747 (registered Dec 26, 2011).
Topics: Acetaminophen; Adult; Biological Availability; Cephalexin; Cross-Over Studies; Female; Humans; Ibuprofen; Male; Pharmaceutical Preparations; Placebo Effect; Therapeutic Equivalency; Time Factors
PubMed: 28535819
DOI: 10.1186/s12952-017-0075-2 -
Cells Oct 2022This paper presents the genome sequence of a mutant strain ( 4351) and the effect of mutation in lipopolysaccharide biosynthesis on bacterial fitness....
This paper presents the genome sequence of a mutant strain ( 4351) and the effect of mutation in lipopolysaccharide biosynthesis on bacterial fitness. Lipopolysaccharides are the major component of the outer leaflet of the Gram-negative outer membrane. We report here a frameshift mutation of the gene in the genome of 4351. The mutation results in a lack of epimerization of the core heptose while we also found increased thermosensitivity, abnormal cell division, and increased susceptibility to erythromycin and cefalexin compared to the 4303. Comparative genomic analysis supplemented with structural data helps us to understand the effect of specific mutations on the virulence of the bacteria and may provide an opportunity to study the effect of short lipopolysaccharides.
Topics: Cephalexin; Erythromycin; Lipopolysaccharides; Shigella sonnei; Genetic Fitness; Genome, Bacterial; Anti-Bacterial Agents; Carbohydrate Epimerases; Bacterial Proteins; Frameshift Mutation
PubMed: 36291117
DOI: 10.3390/cells11203249 -
The Western Journal of Medicine Jan 1975Penicillin remains the treatment of choice for syphilis, with sustained low blood levels curing virtually all patients having early syphilis and halting disease... (Review)
Review
Penicillin remains the treatment of choice for syphilis, with sustained low blood levels curing virtually all patients having early syphilis and halting disease progression in most patients with symptomatic syphilis. Tetracycline, erythromycin or cephalothin yields similar cure rates for patients with early syphilis who are allergic to penicillin. The efficacy of non-penicillin regimens for the treatment of late syphilis is uncertain. Results of Venereal Disease Research Laboratory (VDRL) or other reagin tests should become negative or remain at very low titer following adequate therapy, although results of Treponema pallidum immobilization (TPI) and fluorescent treponemal antibody-absorbed (FTA-ABS) tests often remain positive.
Topics: Cephalexin; Cephaloridine; Cephalosporins; Chloramphenicol; Drug Hypersensitivity; Erythromycin; Female; Fever; Fluorescent Antibody Technique; Follow-Up Studies; Humans; Neurosyphilis; Penicillin G Benzathine; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Syphilis; Syphilis Serodiagnosis; Syphilis, Cardiovascular; Syphilis, Congenital; Syphilis, Latent; Tetracycline; Treponema pallidum; United States
PubMed: 1089007
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Apr 1985A comparative clinical trial of amoxicillin-clavulanic acid and cephalexin was carried out in 80 women with bacteriuria of pregnancy. Treatment was randomly allocated... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A comparative clinical trial of amoxicillin-clavulanic acid and cephalexin was carried out in 80 women with bacteriuria of pregnancy. Treatment was randomly allocated and consisted of either one tablet of amoxicillin plus clavulanic acid (250 and 125 mg, respectively) three times daily or cephalexin (250 mg) three times daily for 7 days. Overall bacteriological cure rates at 2 weeks were 77% in the amoxicillin-clavulanic acid group and 74% in the cephalexin group. At 6 weeks the respective rates were 76 and 60%. Twenty-five episodes of infection were with ampicillin-resistant strains; cure rates were 82% (2 weeks) and 80% (6 weeks) in the amoxicillin-clavulanic acid group and 85 and 64%, respectively, in the cephalexin group. Differences in cure rates were not statistically significant. No significant difference in the rate of side effects was found. In particular, no toxicity to the fetus was seen which could be ascribed to either drug. Amoxicillin-clavulanic acid would appear to be a safe and effective treatment for bacteriuria of pregnancy.
Topics: Amoxicillin; Anti-Bacterial Agents; Bacteriuria; Cephalexin; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Female; Humans; Pregnancy; Pregnancy Complications, Infectious
PubMed: 4004191
DOI: 10.1128/AAC.27.4.508 -
Scientific Reports Jul 2017IκBζ, which is encoded by the Nfkbiz gene, is a member of the nuclear IκB family of proteins that act as transcriptional regulators via association with NF-κB....
IκBζ, which is encoded by the Nfkbiz gene, is a member of the nuclear IκB family of proteins that act as transcriptional regulators via association with NF-κB. Nfkbiz-deficient (Nfkbiz ) mice develop spontaneous dermatitis; however, the underlying mechanism has yet to be elucidated. In our study, we found higher skin pathology scores and more serum IgE antibodies and trans-epidermal water loss in Nfkbiz than in Nfkbiz-sufficient (Nfkbiz ) mice. There was also greater expansion of IFN-γ-, IL-17A-, and IL-22-secreting CD4 T cells and of IL-17A-secreting γδ T cells in the skin of Nfkbiz mice than in with Nfkbiz mice. Pyrosequencing analysis showed decreased diversity of resident bacteria and markedly expanded Staphylococcus (S.) xylosus in the skin of Nfkbiz mice. Oral administration of antibiotics including cephalexin and enrofloxacin ameliorated skin inflammation. Topical application of S. xylosus also resulted in the expansion of IL-17A-secreting CD4 T cells along with high levels of pro-inflammatory cytokines and chemokines in the skin of Nfkbiz mice. The expansion of commensal S. xylosus may be one cause of skin dysbiosis in Nfkbiz mice and suggests that the Nfkbiz gene may play a regulatory role in the microbiota-skin immunity axis.
Topics: Adaptor Proteins, Signal Transducing; Animals; CD4-Positive T-Lymphocytes; Cephalexin; Dermatitis; Disease Models, Animal; Enrofloxacin; Humans; Immunoglobulin E; Mice; Nuclear Proteins; Sequence Analysis, DNA; Skin; Staphylococcal Infections; Staphylococcus; Symbiosis
PubMed: 28740238
DOI: 10.1038/s41598-017-05740-z -
Environment International Nov 2019Increasing concentrations of anthropogenic antibiotics and their metabolites in aqueous environments has caused growing concerns over the proliferation of antibiotic...
Increasing concentrations of anthropogenic antibiotics and their metabolites in aqueous environments has caused growing concerns over the proliferation of antibiotic resistance and potential adverse impacts to agro-environmental quality and human health. Photocatalysis using novel engineered nanomaterials such as ZnO nanowires may be promising for removing antibiotics from waters. However, much remains to be learned about efficiency and mechanism for photocatalytic degradation of antibiotics by ZnO nanowires. This study systematically investigated photodegradation of cephalexin using ZnO nanowires under simulated sunlight. The degradation efficiency of cephalexin was substantially increased in the presence of ZnO nanowires especially at circumneutral and alkaline condition (solution pH of 7.2-9.2). The photodegradation followed the first-order kinetics with degradation rate constants (k) ranging between 1.19 × 10 and 2.52 × 10 min at 20-80 mg L ZnO nanowires. Radical trapping experiments demonstrated that hydroxyl radicals (OH) and superoxide radicals (O) predominantly contributed to the removal of cephalexin. With the addition of HCO (1-5 mM) or Suwannee River natural organic matter (SRNOM, 2-10 mg L), the k values were substantially decreased by a factor of 1.8-70 to 1.69 × 10-6.67 × 10 min, probably due to screening effect of HCO or SRNOM sorbed on ZnO nanowires and scavenging of free radicals by free HCO or SRNOM in solution. Combining product identification by mass spectrometry and molecular computation, cephalexin photodegradation pathways were identified, including hydroxylation, demethylation, decarboxylation, and dealkylation. Overall, the novel ZnO nanowires have the potential to be used for removing antibiotics from contaminated waters.
Topics: Anti-Bacterial Agents; Catalysis; Cephalexin; Kinetics; Nanowires; Photolysis; Rivers; Sunlight; Water Pollutants, Chemical; Water Purification; Zinc Oxide
PubMed: 31437644
DOI: 10.1016/j.envint.2019.105105 -
Communications Biology Feb 2022The peptidoglycan (PG) cell wall provides shape and structure to most bacteria. There are two systems to build PG in rod shaped organisms: the elongasome and divisome,...
The peptidoglycan (PG) cell wall provides shape and structure to most bacteria. There are two systems to build PG in rod shaped organisms: the elongasome and divisome, which are made up of many proteins including the essential MreB and PBP2, or FtsZ and PBP3, respectively. The elongasome is responsible for PG insertion during cell elongation, while the divisome is responsible for septal PG insertion during division. We found that the main elongasome proteins, MreB and PBP2, can be inhibited without affecting growth rate in a quorum sensing-independent density-dependent manner. Before cells reach a particular cell density, inhibition of the elongasome results in different physiological responses, including intracellular vesicle formation and an increase in cell size. This inhibition of MreB or PBP2 can be compensated for by the presence of the class A penicillin binding protein, PBP1B. Furthermore, we found this density-dependent growth resistance to be specific for elongasome inhibition and was consistent across multiple Gram-negative rods, providing new areas of research into antibiotic treatment.
Topics: Cell Count; Cephalexin; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Penicillin-Binding Proteins; Peptidoglycan Glycosyltransferase; Serine-Type D-Ala-D-Ala Carboxypeptidase; Thiourea
PubMed: 35115684
DOI: 10.1038/s42003-022-03056-x -
JCI Insight Apr 2021Proline-glycine-proline (PGP) and its acetylated form (Ac-PGP) are neutrophil chemoattractants generated by collagen degradation, and they have been shown to play a role...
Proline-glycine-proline (PGP) and its acetylated form (Ac-PGP) are neutrophil chemoattractants generated by collagen degradation, and they have been shown to play a role in chronic inflammatory disease. However, the mechanism for matrikine regulation in acute inflammation has not been well established. Here, we show that these peptides are actively transported from the lung by the oligopeptide transporter, PEPT2. Following intratracheal instillation of Ac-PGP in a mouse model, there was a rapid decline in concentration of the labeled peptide in the bronchoalveolar lavage (BAL) over time and redistribution to extrapulmonary sites. In vitro knockdown of the PEPT2 transporter in airway epithelia or use of a competitive inhibitor of PEPT2, cefadroxil, significantly reduced uptake of Ac-PGP. Animals that received intratracheal Ac-PGP plus cefadroxil had higher levels of Ac-PGP in BAL and lung tissue. Utilizing an acute LPS-induced lung injury model, we demonstrate that PEPT2 blockade enhanced pulmonary Ac-PGP levels and lung inflammation. We further validated this effect using clinical samples from patients with acute lung injury in coculture with airway epithelia. This is the first study to our knowledge to determine the in vitro and in vivo significance of active matrikine transport as a mechanism of modulating acute inflammation and to demonstrate that it may serve as a potential therapeutic target.
Topics: Acute Lung Injury; Animals; Anti-Bacterial Agents; Biological Transport, Active; COVID-19; Cefadroxil; Cells, Cultured; Chemotactic Factors; Chemotaxis, Leukocyte; Disease Models, Animal; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Inflammation; Mice; Oligopeptides; Proline; Symporters
PubMed: 33830084
DOI: 10.1172/jci.insight.140750