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PubMed2000

[Evaluation of antibiotics by the method of initial bactericidal activity].

Minimum inhibitory concentration (MIC) has been generally used to evaluate the activity of antimicrobial agents. However, there is some discrepancy between clinical efficacy and the MIC value. We studied the relationship between initial bactericidal activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and amikacin (AMK) and the respective MIC values against Pseudomonas aeruginosa PAO1. Initial bactericidal activity was defined as percent reduction of initial bacterial cell concentration (10(6) cells/ml) after 1 hour incubation following addition of antibiotic. The concentration of antibiotic used in this experiment was the blood level of each antibiotic at 3 hours after administration by drip infusion of the usual dose (IPM, PAPM and CAZ were 1 g for 1 hour drip infusion, MEPM was 1 g for 0.5 hours drip infusion and AMK was 200 mg for 1 hour drip infusion, respectively). The antibiotic concentration of IPM, PAPM, MEPM, CAZ and AMK were 8.77 micrograms/ml, 6.37 micrograms/ml, 4.12 micrograms/ml, 12.0 micrograms/ml and 5.18 micrograms/ml, respectively. MICs of IPM, PAPM, MEPM, CAZ and AMK were 2 micrograms/ml, 64 micrograms/ml, 1 microgram/ml, 1 microgram/ml and 2 micrograms/ml, respectively. Initial bactericidal activity of IPM, PAPM, MEPM, and CAZ against P. aeruginosa PAO1 was 98.2%, 86.1%, 48.1%, and 43.4% reduction in bacterial concentration, respectively. AMK shows the strongest initial bactericidal activity with more than 99.9%. The killing speed of IPM was obviously the most rapid among the three carbapenems. The MIC of PAPM was significantly higher than the other antibiotics, and the initial bactericidal activity of PAPM was second to IPM. We can classify antibiotics into two groups based on initial bactericidal activity against P. aeruginosa; one class is antibiotics having rapid initial killing such as AMK, IPM and PAPM, the other is CAZ, MEPM showing slow initial killing.

Amikacin↗

PubMed2001

[In vitro and in vivo activities of panipenem against penicillin-resistant Streptococcus pneumoniae].

Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, > or = 1.56 micrograms/ml) in mice was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), ampicillin (ABPC), and vancomycin (VCM). The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10,693 (serotype 19), into ddY male mice intranasally. Drugs were administered subcutaneously at doses of 0.4, 2, and 10 mg/kg, 18, 26, 42, and 50 hours post-infection. Viable cell counts in the lungs were determined 66 hours post-infection. PAPM/BP showed the greatest efficacy against the infections among tested drugs. MICs of PAPM against PRSP 9601 and 10,693 were both 0.125 microgram/ml, which were superior to those of IPM (0.25 and 0.5 microgram/ml, respectively), MEPM (0.5 and 1 microgram/ml, respectively), CZOP (2 and 1 microgram/ml, respectively), CTRX (both 1 microgram/ml), ABPC (both 4 micrograms/ml), and VCM (0.5 and 0.25 microgram/ml, respectively). These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM. MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of benzylpenicillin, < or = 0.05 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78 microgram/ml), and PRSP, were tested by an agar dilution method. MIC90s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39 microgram/ml; IPM, < or = 0.006, 0.1, and 0.78 microgram/ml; MEPM, 0.05, 0.39, and 1.56 micrograms/ml; and CZOP, 0.2, 0.78, and 6.25 micrograms/ml, respectively. Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP.

Ampicillin↗

PubMed2001

[Pyogenic sacroiliitis in pregnancy].

Pyogenic sacroiliitis is an extremely rare disease in the field of obstetrics and gynecology, and especially for the cases discovered and treated during pregnancy, only five cases can be found in literature. We experienced one case of the disease in which the patient needed urgent hospitalization due to dysbasia caused by fever and pain at the left hip at the 27th week of her pregnancy. The patient was a 31-year-old primipara presenting typical clinical symptoms of pyogenic sacroiliitis along with evidence of severe infection as represented by fever of 39.7 degrees C and CRP of 12.6 mg/dl. She showed a good response to meropenem (MEPM) at 1 g twice a day for 8 days and then at 0.5 g twice a day for 2 days, followed by faropenem (FRPM) at 200 mg three times a day for 12 days, which successfully improved her subjective and objective findings as well as her laboratory test values, resulting in a complete cure. The definitive diagnosis of the disease in the patient was made on the basis of MRI findings, but no pathogen was identified. The patient was found to have marginal placenta previa as a complication, but she had an uneventful trans-vaginal delivery at the 37th week of her pregnancy and left hospital after both she and her baby showed favorable post-delivery progress. The case reported here is the first case of pyogenic sacroiliitis that has ever been discovered and treated during pregnancy in Japan.

Adult↗

PubMed2001

[Comparative antibacterial activity of carbapenems against P. aeruginosa (1)].

Comparative antibacterial activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM) and biapenem (BIPM) was determined against 288 clinical isolates of P. aeruginosa collected from various hospitals in 2000. The order of activity by comparison of MIC50/MIC80/MIC90 was: MEPM (1/4/8 micrograms/ml) > BIPM (1/4/16 micrograms/ml) > IPM (2/4/16 micrograms/ml) > PAPM (8/16/32 micrograms/ml). Moreover, the order of activity against 75 strains of P. aeruginosa (MIC of CAZ, AZT was > or = 16 micrograms/ml and MIC of IPM, MEPM was < or = 8 micrograms/ml) by comparison of MIC50/MIC80/MIC90 was: BIPM (1/2/8 micrograms/ml) > or = MEPM (1/4/8 micrograms/ml) > or = IPM (2/2/8 micrograms/ml) > PAPM (8/16/16 micrograms/ml). Judging from both correlation between the MICs of carbapenems and relationship between class C beta-lactamase activity and drug susceptibility of carbapenems, it becomes apparent that carbapenems, especially BIPM and MEPM will be useful for treatment of antipseudomonal cephem resistant pseudomonas infection.

Carbapenems↗

PubMed2002

[Experience of application of meronem in the treatment of severe purulent sepsis in children].

Results of antibacterial therapy with application of meropenem (meronem by firm Astra Zeneca, Great Britain) in 29 childs with severe purulent-septic state, including 5 with toxic peritonitis, in 2--with sepsis, in 3 newborn childs--with esophageal atresia and in 19--with the blood disease (nonhodgkin's lymphoma, an acute lymphoblastic or myeloblastic leucosis, reccurrent of acute lymphoblastic leucosis, nephroblastoma).

Adolescent↗

PubMed2002

[Rapid bactericidal activities of carbapenems against Pseudomonas aeruginosa in simulating human plasma concentrations].

The rapid bactericidal activities of panipenem (PAPM), imipenem (IPM), and meropenem (MEPM) against Pseudomonas aeruginosa were investigated by using in vitro pharmacodynamic model simulating the human plasma concentrations after intravenous drip infusion at 500 mg for 0.5 hours. Against P. aeruginosa PAO1, PAPM and IPM showed rapider reduction in viable cell counts than MEPM at 0.5 hours after exposure. All drugs showed more than 3 log10 reduction in viable cell counts at 2 hours after exposure and bacterial regrowth was not observed throughout 6 hours. The initial bactericidal activities of the drugs against 4 clinical isolates within 1 hour after exposure were also investigated by the same method. Against P. aeruginosa strain 12,475, the 3 drugs showed similar initial bactericidal activity but PAPM and IPM showed stronger initial bactericidal activity than MEPM against the other strains as did against P. aeruginosa PAO1. The morphological change of a strain 12,489, for which the initial bactericidal activities were different largely, after 0.5 hours exposure to simulated drug-concentrations was investigated by scanning electron microscope. PAPM and IPM induced morphological changes in most of the cells and cell lysis and bulge formation. On the other hand, MEPM induced changes of the surface structure of cells and slightly elongated cells, but not cell lysis.

Carbapenems↗

PubMed2002

[Microbiological and clinical studies of Haemophilus influenzae isolated at Kitakyushu Municipal Medical Center from 1996 through 1999].

Epidemiological and microbiological studies were carried out using 575 strains of Haemophilus influenzae isolated from clinical specimens at Kitakyushu municipal medical center from January 1996 through December 1999. The strains isolated multiply were excluded. The strains of H. influenzae did not increase for 4 years, and were detected more in summer season, peaked in July, and less in winter season. Like the cases of Streptococcus pneumoniae, most (91.8%) of the strains was detected in the specimens from the respiratory tract, and also they were isolated mainly from infants under 4-years old (25.6%) and adults over 65-years old (24.2%) MICs of 7 antimicrobial agents, such as ampicillin (ABPC), sulbactam/ABPC, cefaclor, imipenem, panipenem, meropenem (MEPM), and levofloxacin (LVFX) were determined using broth microdilution methods. Among 575 strains of H. influenzae isolated from clinical specimens, 51 ABPC-resistant strains (8.9%) produced beta-lactamase, and 67 strains (11.6%) were beta-lactamase negative ampicillin resistant H. influenzae. The ABPC-resistant strains existed in 20.5%. Both of MEPM and LVFX showed excellent antimicrobial activity against H. influenzae including ABPC-resistant strains. Four cases of meningitis were reviewed. All of H. influenzae isolated possessed type b capsular antigen. All patients recovered by appropriate antimicrobial treatment. But one adult patient developed serious sequela.

Adult↗

PubMed2002

[In vitro and in vivo antibacterial activities of pazufloxacin mesilate, a new injectable quinolone].

We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results. 1) The MIC50 and MIC90 values of PZFX against clinically isolated Gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively. PZFX showed broad spectrum activity. The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum beta-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron. 2) PZFX showed superior bactericidal activity against S. aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P. aeruginosa to those of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes. 3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P. aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity in a dose-dependent manner against such bacteria. 4) PZFX inhibited both DNA gyrase and topoisomerase IV from S. aureus at nearly the same level. PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase. 5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S. aureus and P. aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder. 6) Intravenous administration of PZFX with high plasma concentration just after administration, showed more excellent therapeutic effect against the rat intraperitoneal infection, than p.o. and s.c. administration.

4-Quinolones↗

PubMed2002

[Investigation on administration method of carbapenems].

Seventy-two women diagnosed as parametritis were enrolled in this study and examined on the effective administration method of carbapenems, imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP) and meropenem (MEPM). The total dosage of each carbapenem was 1.5 g/day, and administration frequency was twice a day (0.75 g x 2) or three times a day (0.5 g x 3). We reviewed the highest body temperature, white blood cell count and CRP value, before treatment and the fourth day after the start of treatment. Three times a day method was statistically superior to twice a day method in the highest body temperature, and CRP value. When we use carbapenem antimicrobial agents, the basis of PK/PD of time above MIC would lead to the increasing clinical effects.

Adult↗

PubMed2003

[Antibacterial activity of biapenem against recent clinical isolates].

Antibacterial activity of biapenem (BIPM) against clinical isolates of 8 species between 2000 and 2002 was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP) and ceftazidime (CAZ). The MICs of biapenem for Gram-positive bacteria were higher than those of IPM/CS and PAPM/BP, equal to those of MEPM and lower than those of CAZ. The MICs of BIPM for Gram-negative bacteria were higher than those of MEPM, equal to those of IPM/CS and PAPM/BP, and lower than those of CAZ. Antibacterial activity of BIPM against Pseudomonas aeruginosa was equal to those of IPM/CS and MEPM and superior to those of PAPM/BP and CAZ. In conclusion, BIPM showed broad antibacterial activity against both Gram-positive and Gram-negative clinical isolates. These results suggest that BIPM is useful for the treatment of various bacterial infections.

Bacteria↗

PubMed2003

[Case report: difficulty in treating one event of Streptococcus pneumoniae meningitis].

Streptococcus pneumoniae is one of the leading causes of acute bacterial meningitis and the emergence of antibiotic resistant pneumococci is an increasing problem worldwide. In this report, a 22-years-old woman was presented with pneumococcal meningitis occurring twice in a 5 months period. After the first meningitis attack, the patient had been vaccinated by 23-valent polysaccharide vaccine but the illness has relapsed. Although S. pneumoniae which was isolated from the patient has been found intermediate resistant to penicillin and susceptible to ceftriaxone by E-test, the patient could be treated only with meropenem. The case has been presented and discussed for ceftriaxone failure in spite of in-vitro susceptibility. On the other hand, this case indicated that vaccination might fail to prevent recurrence.

Adult↗

PubMed2003

[Activity of cephems and carbapenems against clinically isolated Mycobacterium abscessus].

To screen effective useful drugs for disease due to M. abscessus, we determined MIC of 3 cephems [ceftazidime (CAZ), cefoxitin (CFX), flomoxef (FMOX)] and 3 carbapenems [imipenem (IPM), panipenem (PAPM), meropenem (MEPM)] for 8 strains of clinically isolated M. abscessus by micro-dilution method using MGIT system. In all the 8 strains, MICs of CAZ are higher than 32 micrograms/ml. MIC50, MIC90, MIC range of CFX are 32 micrograms/ml, > 32 micrograms/ml and 16- > 32 micrograms/ml respectively, and for FMOX, 16 micrograms/ml, 32 micrograms/ml and 16-32 micrograms/ml; for IPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml; for PAPM, 4 micrograms/ml, 16 micrograms/ml and 4-16 micrograms/ml; for MEPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml. From this study, it is concluded that FMOX, IPM, PAPM and MEPM can be clinically useful drugs in the treatment of the disease due to M. abscessus.

Carbapenems↗

PubMed2003

Community-acquired bacteremic cellulitis caused by Acinetobacter baumannii.

Acinetobacter baumannii is rarely encountered as a pathogen causing community-acquired skin and soft tissue infection. A 79-year-old man had a fever for 3 days accompanied by pain and swelling over the left leg around an old scar caused by a dog bite 10 years ago. Two sets of blood cultures and a wound culture all yielded A. baumannii. The patient's condition deteriorated initially but recovered completely after 3 weeks of meropenem treatment. This case suggests that A. baumannii should be included among pathogens with the potential to cause complicated skin infection in the community.

Acinetobacter Infections↗

PubMed2004

[Meningitis due to Pseudomonas stutzeri: a case report].

Pseudomonas stutzeri is a saprophytic microorganism that rarely causes severe infections. In this report, a 28 days old male patient with meningomyelocele at birth was presented. The patient was admitted to the hospital with fever, and diagnosed as meningitis on the basis of physical examination and leukocytosis (blood: 16.380/mm3, cerebrospinal fluid (CSF): 130/mm3; 90% PMNL). Following diagnosis ceftriaxone therapy was started led to improvement in clinical and laboratory findings. However on the 20th day, the clinical signs and symptoms became worse, and the patient was diagnosed to develop a second meningitis attack by laboratory examination of CSF. P. stutzeri was isolated from the CSF culture, and the isolate was found to be resistant to ceftriaxone. Upon this result the therapy has changed to meropenem. On the 5th day of the therapy, the patient has slightly improved and he was discharged due to the wishes of his parents, however he died two days after discharge. This first case of P. stutzeri meningitis in neonates was presented to withdraw attention to this clinical entity.

Anti-Bacterial Agents↗

PubMed2004

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated at Kochi Municipal Central Hospital in the last 3 years].

Antimicrobial susceptibility of Pseudomonas aeruginosa isolated at Kochi Municipal Central Hospital between 2001 and 2003 was assessed according to the NCCLS interpretive criteria. 1. The piperacillin-susceptible rate was 92.9%. 2. Among cephem antibiotics, the ceftazidime-susceptible rate was the highest (96.0%). 3. As for aminoglycosides, susceptibility to tobramycin and amikacin remained with a susceptible rate of 93.2% and 94.8%, respectively. 4. The carbapenem-susceptibility remained high. The susceptible rate for meropenem (94.1%) was higher than that for imipenem (88.3%). 5. Acquisition of resistance was observed in urinary isolates. Four multi-drug resistant P. aeruginosa, which are resistant to all of imipenem, amikacin and ofloxacin were isolated in this study and all were isolated from urine. 6. Of 388 isolates, 34 isolates were resistant to imipenem, but no positive isolate was found in screening of metallo-beta-lactamase-producing bacteria.

Amikacin↗

PubMed2004

[Antibiotic susceptibility and occurrence of ESBL in Pseudomonas aeruginosa strains isolated from different clinical specimens].

The aim of this study was to evaluate the drug susceptibility of 132 P. aeruginosa strains isolated from patients hospitalized in SPSK University Hospital in Bialystok. The isolates were obtained from clinical specimens over an 11-month period in 2001 and 2002. All the strains were identified in automatic ATB system using API 20 NE strips, and their susceptibility to antibiotics was tested by standard disc-diffusion method and agar dilution method. The minimal inhibitory concentration (MIC) was determined for five antibiotics: piperacillin, amikacin, ceftazidime, imipenem and ciprofloxacin. The majority of strains were susceptible to ceftazidime (91.7%), piperacillin combined with tazobactam (85.6%), amikacin (80.3%), meropenem and imipenem (81.8%). Many of our strains were resistant to cefotaxime (73.5%), ticarcillin (53%) and ciprofloxacin (48.5%). Also, the trial was undertaken to detect strains producing extended-spectrum beta-lactamases (ESBL) and inducible beta-lactamases (IBL) among P. aeruginosa rods isolated from different specimens. ESBL-producing strains were detected with double disc test (DDST) and combination double disc (CD) test. Clavulanate was applied as the inhibitor of these beta-lactamases. Strains producing ESBL were not found. On the other hand, as many as 127 P. aeruginosa strains (96.2%) produced inducible beta-lactamases (IBL).

Amikacin↗

PubMed2005

Serratia marcescens bacteremia at a medical center in southern Taiwan: high prevalence of cefotaxime resistance.

Antimicrobial resistance of isolates and risk factors for mortality were retrospectively investigated in 71 adult patients with Serratia marcescens bacteremia. During the 4-year study period, 78 clinically significant episodes of S. marcescens bacteremia occurred in 71 patients. The mean age of the patients was 65 years (range, 25-86 years) with a male predominance (45 patients, 63%). Most of the bacteremic episodes were nosocomial (78%), and 34% were polymicrobial. The overall mortality rate within 2 weeks after the onset of bacteremia was 41%. The presence of malignancy and critical illness at initial presentation were independent risk factors for mortality. By disk susceptibility test, 72 isolates were resistant to cefotaxime (92%) but susceptible to ceftazidime (99%). All isolates were susceptible to meropenem. Among the 47 patients with monomicrobial S. marcescens bacteremia, the mortality rate within 5 days of onset in patients receiving appropriate empirical antimicrobial therapy was lower than that in patients receiving inappropriate therapy although this difference was not significant (14% vs 28%, p = 0.27). Among the patients with cefotaxime-resistant but ceftazidime-susceptible S. marcescens bacteremia treated with ceftazidime, 6 of 7 patients (86%) survived for more than 2 weeks, suggesting the potential effectiveness of ceftazidime in the treatment of cefotaxime-resistant Serratia infections. Further clinical studies are required to delineate the clinical role of ceftazidime therapy for infections caused by S. marcescens with this resistant phenotype.

Adult↗

PubMed2005

[A preliminary study of the administration of carbapenem antibiotics in sepsis patients on the basis of the administration time].

UNLABELLED: It is important to take into consideration the duration for which the plasma concentration of the drug is higher than the Minimal Inhibitory Concentration during treatment with carbapenem antibiotics, because the antibiotics are time-dependent drugs. A preliminary study of the administration of carbapenem antibiotics on the basis of the pharmacokinetics/pharmacodynamics (PK/PD) was conducted. SUBJECTS: Ten patients with intraabdominal infection. METHODS: The patients were divided into two groups: the first group was assigned to administration of a carbapenem antibiotic (meropenem) at a daily dose of 0.5 g in 3 divided doses, each dose by intravenous infusion over 3 hours (Group 3 H), and the other group was assigned to administration of each dose over 30 minutes (Group 30 M). The body temperature (BT), white blood cell count (WBC), serum C-reactive protein (CRP) level, and the systemic inflammatory reactive syndrome (SIRS) score before and 96 hours after the drug administration were compared between Group 3 H and Group 30 M. RESULTS: There were 5 patients (mean age, 67.4+/-14.6 years) in Group 3H and 5 patients (mean age, 60.0+/-12.8 years) in Group 30 M. The evaluated parameters (BT, WBC, CRP, SIRS score) before the drug administration in Groups 3 H and 30M were not significant. Group 3 H showed significant decreases in the SIRS scores at 96 hours after the drug administration, however, there were no significant differences in the BT, WBC or CRP between the two groups. DISCUSSION: Group 3 H showed early improvement in the SIRS scores. Administration of carbapenem antibiotics based on the PK/PD is important, and requires further studies.

Abdomen↗