Susceptibility of Helicobacter pylori to antibiotics in Chinese patients.

OBJECTIVE: Antibiotic resistance to Helicobacter pylori (H. pylori) has been increasing worldwide. The study aimed to evaluate in vitro susceptibility and resistance patterns to antibiotics in empirical H. pylori eradication regimens, and to determine the optimal antibiotics for treatment. METHODS: H. pylori strains (n =181) were obtained from gastric biopsies of patients with upper gastrointestinal symptoms who underwent esophagogastroduodenoscopy from March to December 2013. The susceptibility of H. pylori strains to amoxicillin (AMX), metronidazole (MTZ), clarithromycin (CLR), amoxicillin-clavulanate (AMC), cephalothin (CEP), cefuroxime (CXM), cefixime (CFM), moxifloxacin (MFX) and minocycline (MNO) was determined. RESULTS: Dual resistance to MTZ + CLR was detected in 48 (26.5%) isolates, MTZ + MFX in 94 (51.9%), and CLR + MFX in 49 (27.1%). Overall, 41 (22.7%) were resistant to MTZ + CLR + MFX. MTZ and CLR resistance rates were significantly associated with the history of H. pylori eradication but there was no significant difference in MFX resistance rates between treated and untreated patients (P = 0.674). No significant relationship was found between antibiotic resistance and patient's gender, age, endoscopic findings, inflammatory severity or gastric atrophy. CONCLUSIONS: AMX, AMC, MNO and cephalosporins, but not MTZ, CLR and MFX, showed good in vitro anti-H. pylori activity. Among cephalosporins, CXM was the most active. H. pylori resistance is higher in patients with previous H. pylori eradication.

Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic murine thigh model of Staphylococcus aureus infection.

AIM: Antofloxacin hydrochloride is a new fluoroquinolone antibiotic with broad-spectrum in vitro activity. Using the neutropenic murine thigh infection model, we defined the pharmacodynamic profile and property of antofloxacin hydrochloride against Staphylococcus aureus. METHODS: Single-dose pharmacokinetic studies of antofloxacin hydrochloride were carried out in thigh infected mice. Therapy was initiated at 2 h postinoculation with 5-640 mg/kg per d fractionated for different dosing regimens. The thighs were removed for bacterial measurement after 24 h of therapy, the best pharmacokinetic/ pharmacodynamic (PK/PD) index correlated with the efficacy was determined by nonlinear regression analysis. A sigmoid E(max) dose-response model was used to estimate the daily dose and AUC(24 h)/MIC (minimal inhibitory concentration) required to achieve a static effect. RESULTS: The PK was linear with similar elimination half-life over the dose range studied. The AUC(24 h)/MIC ratio was the PK/PD parameter that best correlated with efficacy (R(2)=92.3%, 90.8% for the two organisms, compared with C(max)/MIC and T>MIC [%], respectively). The 24 h static dose ranged from 34.3 to 153.7 mg/kg per d for all S aureus strains, the total AUC(24 h)/MIC ratio to achieve bacteriostatic effect varied from 31.7 to 122.5 (mean, 65.7+/-30.6). CONCLUSION: Antofloxacin hydrochloride showed powerful antibacterial activity against the S aureus isolates used in our neutropenic infected mice model. Our data suggested that the AUC/MIC ratio appeared to be most closely linked to the bacterial outcome (R(2)>90%), and a total AUC(24 h)/MIC ratio of 65.7 appears to be the target value to achieve a net bactericidal activity against S aureus, similar to the results of other fluoroquinolones.