Infection involves the coexistence of heterodimensional creatures and is influenced by a mutual desire to survive. Viewed by the individual, this is realized by “parenteral digestion” for which the individual develops inflammatory organs along the alimentary canal. Evolutional divergence of mesenchymal cells builds an upper structure of anti-infection strategy by enforcing support of phagocytosis on the older macrophagecentric understructure. Versatile infectious phenomena largely depend on the complexity of the upper structure, in contrast to today's threatening disasters, mostly due to anthropocentric alteration of conventional understructures.

View full abstract

Susceptibility to 7 β-lactam antibiotics, cefepime, cefpirome, ceftazidime, cefoperazone/sulbactam, imipenem and piperacillin (for gram-negatives) or oxacillin (for gram-positives) was studied using a common protocol and method (Etest; AB Biodisk, Sweden) in 22 medical centers. No strains resistant to these β-lactams except for ceftazidime and/or cefpirome were found in oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci. In Escherichia coli, 12.6% of clinical strains were resistant piperacillin, while no strains were observed resistant to other antibiotics. All clinical strains of Klebsiella spp. were susceptible to cefepime and imipenem. Isolates of Enterobacer spp. and Citrobacter spp. were most susceptible to imipenem and cefepime. Isolates of Serratia spp. were more susceptible to imipenem 4.4% resistance, cefepime (5.8%), cefpirome (6.3%), and ceftazidime (6.8%) than other β-lactams tested. Isolates of indole-positive Proteus were more susceptible to cefoperazone/sulbactam (0% resistance), cefepime (0.5%), cefpirome (0.5%), and ceftazidime (3.0%) than other β-lactams tested. Isolates of Pseudomonas aeruginosa were more susceptible to ceftazidime (8.7% resistance) and cefepime (9.1%) than cefoperazone/sulbactam (11.5%), piperacillin (18.5%), imipenem (24.9%), and cefpirome (27.2%). These results clearly indicate that emergence of resistant strains to cefepime is lower than other β-lactam antibiotics tested.

View full abstract

We studied the bactericidal activity of an injectable quinolone, pazufloxacin (PZFX) mesilate, and injectable β-lactams, ceftazidime (CAZ), and imipenem/cilastatin (IPM/CS) against quinolone-and β-lactam-susceptible Escherichia coli (a non-β-lactamase producer) in mixed infection caused by Enterobacter cloacae H-27 (an inducible β-lactamase producer) and E. coli using a rat pouch infection model, with the following results:
1) The bactericidal activity of IPM/CS against E. coli and its concentration in pouches after intravenous administration of 5 mg/kg to rats with the mixed infection were reduced compared to those in single infection with E. coli. Coexistence of the inducible β-lactamase producer affected IPM/CS activity. CAZ concentrations in pouches in the mixed infection model decreased slightly but its activity was reduced compared to those in single infection with E. coli. The coexistence of the inducible β-lactamase producer also affected CAZ activity. No effects were observed in PZFX mesilate.
2) The bactericidal activity of CAZ against E. coli and its concentration in pouches of rats with the mixed infection and with cefmetazole (CMZ) pretreatment to increase β-lactamase activity in pouches were reduced compared to those in single infection by E. coli and in mixed infection without CMZ pretreatment.β-Lactamase induction affected CAZ activity. IPM/CS bactericidal activity decreased compared to that in single infection by E. coli but was similar to that in mixed infection without CMZ pretreatment.β-Lactamase induction did not affect IPM/CS activity. No effects were observed in PZFX mesilate. Piperacillin pretreatment in place of CMZ did not affect CAZ activity.

View full abstract

We studied the bactericidal activity, the development of resistance, and the postantibiotic effect (PAE) using a model simulating the serum level after puzufloxacin (PZFX: free base of PZFX mesilate) drip infusion (d. i.)(0.5g/0.5h) in humans using imipenem/cilastatin (IPM/CS)-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), and compared with those of IPM/CS (0.5g/0.5h d. i.), ceftazidime (CAZ, 1g/1h d. i.), vancomycin (VCM, 0.5g/1h d. i.), and arbekacin (ABK, 0.1g/1h d. i.). In the model with PZFX and CAZ-sensitive P. aeruginosa S-1410, PZFX mesilate showed greater short-term bactericidal activity and bacterial count reduction than CAZ or IPM/CS. In the model with PZFX-intermediately-resistant and CAZ-sensitive P. aeruginosa S-1502, PZFX mesilate showed more rapid bactericidal activity than CAZ or IPM/CS, and PZFX exhibited comparable and superior bacterial count reduction compared to CAZ and IPM/CS. In the model with MRSA F-2341, PZFX mesilate showed greater short-term bactericidal activity and bacterial count reduction than VCM and ABK. After the drug exposure in the simulation model, no change was seen in drug susceptibility in any of the drugs used. After PZFX exposure in the drip infusion model for 0.5h, the PAE exceeded>5.2h for P. aeruginosa S-1410, 0.7h for P. aeruginosa S-1502, and 0.8h for MRSA F-2341.

View full abstract

We studied the clinical efficacy of injectable ciprofloxacin (CPFX) in 14 poor responders to carbapenems and 2 poor responders to injectable third-generation cephems. Efficacy in poor responders to carbapenems was seen in 6 cases and in 2 cases of poor responders to injectable third-generation cephems. Clinical efficacy was 50%(8/16 cases), indicating that injectable CPFX is a highly effective drug in treating poor responders to carbapenems and injeceable third-generation cephems.

View full abstract

A 63-year-old man admitted for persistent cough and sputum was found in detailed examinations to have advanced lung adenocarcinoma (T4 N3 M1, stage IV). One course of combination chemotherapy of cisplatin and paclitaxel was administered. Since grade III nausea developed, they were switched to a combination of carboplatin and TXL, which was administered for 2 coureses. All subjective symptoms were resolved and image findings, particularly ground-glass opacities spreading over the bilateral lung fields, completely disappeared. Cancer recurred about 1.5 months later while he was followed up as an outpatient. None of subsequent chemotherapy regimens were effective. This phenomenon, suggesting tolerance or cross-tolerance of drugs, is now being studied and is considered an important issue in chemotherapy for non-small-cell lung carcinoma.

View full abstract

Intracellular drug susceptibility of Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) replicating in macrophages (MM 6-M Φ s) or type II alveolar epithelial cells (A-549 cells) was compared between organisms adapted to intracellular millieus inside macrophages (I-type) and those extracellularly adapted by passage in 7H9 liquid medium (E-type). We determined parameters, -ΔLog CFU [=Log CFU (-drug)-Log CFU (+drug)] and I/E [-ΔLog CFU (I-type)/-ΔLog CFU (E-type)]. Parameter I/E means the log-unit ratio of the decrease in residual CFU of I-type organisms due to antimicrobial activity of test drugs seen in E-type organisms. This parameter correlates to relative activity of a given drug against I-type organism to its activity against the E-type organism. In most cases of intracellular MTB and MAC inside MM 6-M Φ s, I/E of rifalazil (RLZ), clarithromycin (CAM), and levofloxacin (LVFX) was less than 1.0, indicating that the susceptibility of these organisms to these drugs decreased due to intramacrophage passage of the organisms. In intracellular MTB and MAC inside A-549 cells, results similar to the above were obtained for CAM and LVFX. However, I/E of RLZ was much higher than 1.0 for both MTB and MAC, indicating that the susceptibility of these organisms to RLZ markedly increased after intramacrophage passage of organisms.

View full abstract