Clavulanate tablets

6– 12, 25 In thigh and lung infection models in neutropenic mice, Craig et al . have shown that the t > MIC for ?-lactam antibiotics against S.

pneumoniae needed to be approximately 40–50% of the dosage interval in order to achieve a 90–100% survival of the mice after 4 days of treatment.

When the t > MIC was ?20%, the mortality was almost 100%. 11 In another study by Andes & Craig, renal impairment was induced in neutropenic mice to simulate the human pharmacokinetics of amoxicillin.

pneumoniae with different

amoxicillin

studied

With a simulated dose of 500 mg (even though t > MIC was 1–1.5 h less than in humans) they found killing of strains with MICs up to 2 mg/L. 10 In this study, they also found that the differences between the extent of killing for amoxicillin and co-amoxiclav at the end of 24 h of therapy were insignificant.

10 In another study, Woodnutt & Berry used a rat pneumonia model.

pneumoniae with different amoxicillin MICs (2, 4 and 8 mg/L) and could show a significant reduction in bacterial counts in the lungs when concentrations of co-amoxiclav in plasma were above the MIC for at least 34% of a 24 h dosing interval. Concerning clinical trials, Craig & Andes compiled data retrospectively that included patients with otitis media caused by S. influenzae , where the microbiological efficacy was followed by repeated tympanocenteses.

They found that an increased time that free serum levels were above the MIC (calculated from published serum pharmacokinetic data in paediatric populations) correlated with an increased bacteriological eradication of the infecting pathogens. To achieve an 80–85% bacteriological cure rate of both cephalosporins and penicillins against the two pathogens, a time above the MIC of 50% and 40%, respectively was required.

have published data on bacterial eradication in the treatment of sinusitis, and found the same figures for t > MIC as with otitis media.

This in vitro kinetic model provides a valuable tool to compare the antibacterial effects of different antibiotics, however, like other in vitro PK/PD models, the model more closely mimics the effects in an immunocompromised host as the synergic effects of the host are not taken into account. The pharmacokinetically enhanced amoxicillin 2000 mg twice daily formulation was more effective than any of the other formulations tested, achieving substantially better eradication rates against S.

pneumoniae isolates

with

However, with the interplay of the host's immune system, this reduction could provide some advantage over standard co-amoxiclav formulations in the clinic.

Multicenter, Open-Label, Randomized Study to Compare the Safety and Efficacy of Levofloxacin versus Ceftriaxone Sodium and Erythromycin Followed by Clarithromycin and Amoxicillin- Clavulanate in the Treatment of Serious Community-Acquired Pneumonia in Adults. Kahn, Multicenter, Open-Label, Randomized Study to Compare the Safety and Efficacy of Levofloxacin versus Ceftriaxone Sodium and Erythromycin Followed by Clarithromycin and Amoxicillin- Clavulanate in the Treatment of Serious Community-Acquired Pneumonia in Adults, Clinical Infectious Diseases , Volume 38, Issue Supplement_1, January 2004, Pages S16–S23, https://doi.org/10.1086/378406. This randomized, multicenter, phase IV, comparative trial, which was designed to show equivalence, compared the efficacy of levofloxacin with that of a ?-lactam-macrolide combination in the treatment of 269 seriously ill patients with community-acquired pneumonia. Patients were randomly assigned to 1 of 2 treatment arms: (1) levofloxacin, 500 mg intravenously, followed by oral administration, every 24 h for 7–14 days, or (2) ceftriaxone sodium, 1–2 g intravenously or intramuscularly every 24 h, with erythromycin, 500–1000 mg intravenously every 6 h, and then switched to amoxicillin-clavulanate, 875 mg orally twice daily, with clarithromycin, 500 mg orally twice daily for 7–14 days. Among patients evaluable for clinical efficacy, 89.5% of levofloxacin-treated patients (85 of 95 patients) and 83.1% of comparator-treated patients (74 of 89 patients) achieved clinical success (a cure or an improved condition). Both levofloxacin and the comparator were safe and well tolerated, with gastrointestinal disorders being the most common adverse event in both groups. Levofloxacin was as efficacious as the?-lactam-macrolide combination in the treatment of seriously ill patients with community-acquired pneumonia. Community-acquired pneumonia (CAP) continues to be a prevalent infection, with an estimated 4 million cases occurring each year in the

United

Among Americans ?65 years old, pneumonia is the fifth leading cause of death [ 2].

Standard empirical therapy for patients admitted to the general hospital ward includes the use of broad-spectrum antibacterial agents, which, in many cases, includes a second- or third-generation cephalosporin combined with a macrolide. However, alternative therapies that provide similar antibacterial coverage may also be appropriate. Levofloxacin is a fluoroquinolone that is indicated for the treatment of severe CAP, including CAP due to penicillin-resistant Streptococcus pneumoniae and Legionella

pneumophila

The present study examines the safety and efficacy of levofloxacin monotherapy, compared with the safety and efficacy associated with the combination of a ?-lactam and amacrolide, for the treatment of seriously ill patients with CAP. Adult patients with signs and symptoms of CAP who met ?3 American Thoracic Society criteria for in patient treatment were included in the study [ 3]. In addition, all patients included in the study required mechanical ventilation or had ?2 of the following: fever (oral temperature, ?39°C) or hypothermia (oral temperature, ?35.5°C), arespiratory rate of >30 breaths/min, systolic hypotension (systolic blood pressure, 4]. Repeat assessments were to be done on study days 2–4, at

5–7

Each study patient provided a sputum specimen for Gram stain and culture.

Acceptable specimens included deep expectorated or suctioned sputum; transtracheal aspirates; bronchial brushings, washings, and biopsy samples; and pleural fluid.

Two sets of blood samples for culture were obtained at admission.

If blood cultures performed at the time of admission yielded positive results, the cultures were repeated at subsequent visits. Testing for a typical pathogens at baseline included serologic testing for L. pneumophila, Chlamydia pneumoniae , and Mycoplasma pneumoniae; culture of respiratory fluids for L. pneumophila; culture of nasopharyngeal samples for C. Inclusion of a typical pathogens on the basis of serological findings was based on the following standard laboratory criteria: for L. pneumophila , a single IgM or IgG ELISA titer of >1:256 or a 4-fold increase or decrease in the titer at follow-up 3–4 weeks after therapy (5–6 weeks after study admission); for C.

pneumoniae , a 4-fold increase or decrease in the microimmunofluorescence IgM or IgG titer at follow-up 3–4 weeks after therapy (5–6 weeks after study admission); and, for M.

pneumoniae , either a single IgM ELISA titer of >1:16 or a 4-fold increase or decrease in the

titer

weeks

The results for

each

expanded

“Cure” was defined as resolution of pretreatment clinical signs and symptoms and no further requirement for antimicrobial therapy for CAP.

“Improvement” was defined as clinical findings that subsided significantly, albeit with incomplete resolution of clinical evidence of infection in a subject who required no further antimicrobial therapy for CAP.

“Failure” (i.e., presumptive microbiological failure [final culture not obtained]) was defined as no apparent response to therapy or as an incomplete response requiring additional antimicrobial therapy for CAP.

The secondary efficacy variables included the microbiological response, according to pathogen, at the test-of-cure visit; transition in signs and symptoms during therapy; and clinical response at the visit that occurred 1 month after therapy for patients considered to have clinical success at the test-of-cure visit.