Determination of imipenem, meropenem, panipenem, faropenem concentrations in human plasma by HPLC / 中国药学杂志

OBJECTIVE: To establish a reversed phase HPLC method for the determination of imipenem, meropenem, panipenem, faropenem concentrations in human plasma.

Seven Cases of Decreased Serum Valproic Acid Concentration During Concomitant Use of Carbapenem Antibiotics / 대한진단검사의학회지

Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/ betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.

The Recurrence of Seizure due to Decreased Valproic Acid Level after Administration of Carbapenem / 대한간질학회지

Valproic acid (VPA) is one of the most commonly used antiepileptic drug, but has many drug-drug interactions. A 58-year-old male under the vegetative state has been well controlled with valproic acid (VPA) monotherapy without seizure attacks during the last 6 months. Pneumonia developed and panipenem-betamipron (PAPM-BP) for acinetobacter baumannii was administered. Seizure attacks recurred after 12 days of initiating PAPM-BP. During the maintenance period of PAPM-BP, serum level of VPA was decreased. After the cessation of PAPM-BP, serum level of VPA increased to the previous level without further seizure attacks. PAPM-BP should be cautiously used together with VPA because of possible drug-drug interaction.

Efficacy of Panipenem versus Imipenem against Clinical Isolate of Pseudomonas aeruginosa in a Two-Compartment Artificial Capillary Model / 감염과화학요법

BACKGROUND: Panipenem (PAPM) is a new carbapenem which has an enhanced broad spectrum activity against both gram-positive and negative organisms. However, its activities in vitro against Pseudomonas aeruginosa are still under controversy. The aim of this study was to compare the activity of PAPM with those of imipenem (IMPM) against clinical isolates of P. aeruginosa using in vitro kinetic model and to evaluate the differences according to the quantity of basic amino acid in media. MATERIALS AND METHODS: Using a clinical isolate of P. aeruginosa (SGP14) from blood, an in vitro 2-compartment artificial capillary model based on a dialyzer unit was prepared. Antibiotics were given as a bolus q12 hrs for 48 hrs. Simulated doses and frequencies of PAPM and IMPM were 500 mg q12 hrs as approved by Korea Food and Drug Administration. Muller-Hinton broth (MHB) and minimal broth Davis (MBD) were used as culture media and we divided the experiments into 4 groups [PAPM (MHB), PAPM (MBD), IMPM (MHB), IMPM (MBD)]. At 0, 1, 2, 4, 6, 8, 12, 24, 32, and 48 h, samples were removed from peripheral compartment and viable bacterial counts were measured. RESULTS: The susceptibility of PAPM and IMPM for SGP14 were 64 and 2 ug/mL in MHB and 4 and 2 ug/mL in MBD, respectively. Up until 12 hours, changes in bacterial colony counts were not significantly different (P=0.073) for each group. However among the four groups, PAPM (MHB) showed the least changes compared with PMPM (MBD), IMPM (MBD). The largest decrement of colony during 48 hours was observed with PMPM (MBD), followed by IMPM (MHB) or IMPM (MBD), and PAPM (MHB) in decreasing order (P=0.00). There were no differences between IMPM (MHB) and IMPM (MBD) as for the change in colony counts. CONCLUSIONS: The bactericidal activities of panipenem against the clinical isolate of P. aeruginosa was similar (at 12 h) or superior (at 48 h) to that of imipenem in an in vitro 2-compartment artificial capillary model using minimal broth to simulate human serum drug concentrations.

Efficacy of Panipenem versus Imipenem against Clinical Isolate of Pseudomonas aeruginosa in a Two-Compartment Artificial Capillary Model / 감염과화학요법

BACKGROUND: Panipenem (PAPM) is a new carbapenem which has an enhanced broad spectrum activity against both gram-positive and negative organisms. However, its activities in vitro against Pseudomonas aeruginosa are still under controversy. The aim of this study was to compare the activity of PAPM with those of imipenem (IMPM) against clinical isolates of P. aeruginosa using in vitro kinetic model and to evaluate the differences according to the quantity of basic amino acid in media. MATERIALS AND METHODS: Using a clinical isolate of P. aeruginosa (SGP14) from blood, an in vitro 2-compartment artificial capillary model based on a dialyzer unit was prepared. Antibiotics were given as a bolus q12 hrs for 48 hrs. Simulated doses and frequencies of PAPM and IMPM were 500 mg q12 hrs as approved by Korea Food and Drug Administration. Muller-Hinton broth (MHB) and minimal broth Davis (MBD) were used as culture media and we divided the experiments into 4 groups [PAPM (MHB), PAPM (MBD), IMPM (MHB), IMPM (MBD)]. At 0, 1, 2, 4, 6, 8, 12, 24, 32, and 48 h, samples were removed from peripheral compartment and viable bacterial counts were measured. RESULTS: The susceptibility of PAPM and IMPM for SGP14 were 64 and 2 ug/mL in MHB and 4 and 2 ug/mL in MBD, respectively. Up until 12 hours, changes in bacterial colony counts were not significantly different (P=0.073) for each group. However among the four groups, PAPM (MHB) showed the least changes compared with PMPM (MBD), IMPM (MBD). The largest decrement of colony during 48 hours was observed with PMPM (MBD), followed by IMPM (MHB) or IMPM (MBD), and PAPM (MHB) in decreasing order (P=0.00). There were no differences between IMPM (MHB) and IMPM (MBD) as for the change in colony counts. CONCLUSIONS: The bactericidal activities of panipenem against the clinical isolate of P. aeruginosa was similar (at 12 h) or superior (at 48 h) to that of imipenem in an in vitro 2-compartment artificial capillary model using minimal broth to simulate human serum drug concentrations.

In Vitro Activities of Panipenem against Clinical Isolates of Aerobic and Anaerobic Bacteria / 감염과화학요법

BACKGROUND: Panipenem is a carbapenem antimicrobial agent which has been shown to have broad-spectrum activities against various aerobic and anaerobic bacteria. In this study, in vitro activities of panipenem against recent clinical isolates of aerobic and anaerobic bacteria were determined. METHODS: Aerobic and anaerobic bacteria were isolated in 2001 and in 2000-2001, respectively, from a tertiary-care hospital patients. Antimicrobial susceptibility was tested by the NCCLS agar dilution method. RESULTS: MIC90s of panipenem were:similar to those of imipenem for aerobic gram-positive cocci and Enterobacteriaceae; slightly lower than those of meropenem for gram-positive cocci, but slightly higher for Enterobacteriaceae; slightly higher than imipenem for A. baumannii, but similar for anaerobic bacteria. CONCLUSION: MIC90s of panipenem were similar to those of imipenem for aerobic and anaerobic bacterial isolates, which frequently involve respiratory, urinary, intraabdominal and wound infections. When imipenem breakpoints are applied to interpret panipenem susceptibilities, panipenem can be considered useful for the treatment of various infections, including nosocomially acquired ones.

In Vitro Activities of Panipenem against Clinical Isolates of Aerobic and Anaerobic Bacteria / 감염과화학요법

BACKGROUND: Panipenem is a carbapenem antimicrobial agent which has been shown to have broad-spectrum activities against various aerobic and anaerobic bacteria. In this study, in vitro activities of panipenem against recent clinical isolates of aerobic and anaerobic bacteria were determined. METHODS: Aerobic and anaerobic bacteria were isolated in 2001 and in 2000-2001, respectively, from a tertiary-care hospital patients. Antimicrobial susceptibility was tested by the NCCLS agar dilution method. RESULTS: MIC90s of panipenem were:similar to those of imipenem for aerobic gram-positive cocci and Enterobacteriaceae; slightly lower than those of meropenem for gram-positive cocci, but slightly higher for Enterobacteriaceae; slightly higher than imipenem for A. baumannii, but similar for anaerobic bacteria. CONCLUSION: MIC90s of panipenem were similar to those of imipenem for aerobic and anaerobic bacterial isolates, which frequently involve respiratory, urinary, intraabdominal and wound infections. When imipenem breakpoints are applied to interpret panipenem susceptibilities, panipenem can be considered useful for the treatment of various infections, including nosocomially acquired ones.