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[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Aged↗

Overview of a new carbapenem, panipenem/betamipron.

Carbapenems are beta-lactam antibiotics with a broad antibacterial spectrum and a potent bactericidal activity against both aerobic and anaerobic Gram-positive and Gram-negative organisms. They have been widely investigated in the past, and imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP), meropenem (MEPM) and biapenem (BIPM) are presently in clinical use or under trial. Of the carbapenems, imipenem is not readily hydrolysed by microbial beta-lactamase but is hydrolysed to open the beta-lactam ring by DHP-I from kidney and other tissues. In order to achieve greater stability to the enzyme and to prolong the action of the carbapenem in vivo, the co-administration of CS with IPM or the attainment of the chemical construction of the 1-beta methylcarbapenem derivatives in the case of MEPM and BIPM have been performed. However, some difference was found in the DHP-I activity with these carbapenems, but there was no significant difference in the pharmacokinetic parameters: AUC, CLtot, t1/2 and MRT except urinary clearance after administration of these compounds to humans. Considering that MRT as the amount of the antibiotics retained in the body is a clinically important parameter, the structural susceptibility of the carbapenems to the decomposition by DHP-I was suggested to have no clinically meaningful correlation with the pharmacokinetics of these compounds.

Alanine↗

Antibiotic susceptibility of streptococci isolated from blood from neutropenic patients.

MICs were performed on 62 streptococci isolated from the blood of neutropenic patients from 1986 to 1992 using the NCCLS broth microdilution procedure. Species isolated were 43 S. mitis, 6 S.pneumoniae, 5 S.sanguis, 1 S.pyogenes, 1 beta-hemolytic streptococcus of the group G, 1 S.adjacens, 1 S.intermedius, 4 not identified isolates (2 alpha-hemolytic, 1 non-hemolytic and 1 nutritionally variant strains). 26% of all strains were resistant or intermediate to penicillin (MIC 90: 2 mg/l) and 89% to norfloxacine (MIC 90: 32 mg/l). All were susceptible to vancomycin. Among cephalosporins, all strains were susceptible to cefotaxime (MIC 90: 1 mg/l), ceftriaxone (MIC 90: 1 mg/l) and cefepime (MIC 90: 2 mg/l) while 19% were R or I to ceftazidime (MIC 90: 16 mg/l). All were susceptible to imipenem (MIC 90: 0.5 mg/l) and meropenem (MIC 90: 1 mg/l). Among the third generation cephalosporins, ceftazidime--the agent of this class of antibiotics that is most often used for the empirical therapy of febrile episodes in neutropenic patients (in combination but also in monotherapy)--has a high resistance rate as compared to the other compounds.

Bacteremia↗

[Transfer of resistance to new cephalosporins and carbapenems (Imipenem)].

Due to world-wide use of 3rd generation cephalosporins and new beta-lactam antibiotics (imipenem, aztreonam), serious problems emerge caused by the appearance and spread of bacterial strains resistant also to these drugs. While the resistance to ceftazidime, cefotaxime and other "stable" cephalosporins has a transferable character and is plasmid-coded, the resistance to imipenem is transmissible only by bacteriophages. New enzymes in resistant bacteria bind specifically with the metoxyimino moiety of the molecule of these drugs. It is assumed that cephalosporins without the metoxyimino-group (4th generation) and new variants of imipenem (1-methyl-carbapenems, like meropenem and biapenem) will dominate therapy with betalactam antibiotics in the future.

Cephalosporins↗

Susceptibility pattern of Scandinavian Francisella tularensis isolates with regard to oral and parenteral antimicrobial agents.

Some recently introduced antimicrobial agents have only been incompletely evaluated for use in Francisella tularensis infections. The present study evaluated the susceptibility pattern of Scandinavian human, rodent, and hare F. tularensis isolates with respect to a selection of traditional as well as recently introduced antimicrobial agents. All strains were resistant to the following beta-lactams: penicillin, cephalexin, cefuroxime, ceftazidime, aztreonam, imipenem, and meropenem with minimal inhibitory concentrations > 32 mg/l. Against macrolides, a mixed susceptibility/resistance pattern appeared. All strains were susceptible to gentamicin, chloramphenicol, doxycycline, and four quinolones. Since the quinolones showed the lowest MIC values, and in addition give a good intracellular penetration, we conclude that future drugs to consider against tularemia should definitely include this group of antibiotics. The outpatient mode of antibiotic treatment is especially relevant as the Scandinavian variant of F. tularensis infection is nonlethal, usually pustuloglandular, and not septicemic. Therefore, oral drugs must be sought, and the quinolone group also satisfies this requirement.

Administration, Oral↗

Evidence for antibiotic-mediated endotoxin release as a contributing factor to lethality in experimental gram-negative sepsis.

Endotoxic lipopolysaccharide (LPS) is a major constituent of the outer membrane of the Gram-negative microbe. Following its release from the bacterium, LPS serves as a potent proinflammatory stimulus by interacting with humoral and cellular mediator systems to stimulate production of an array of inflammatory molecules. Cell-wall active antibiotics are known to promote endotoxin release. To assess the contribution of antibiotic-induced endotoxin release in the pathogenesis of Gram-negative sepsis, we have developed several experimental models in which mice have been pretreated with various agents to make them sensitive to Gram-negative (E. coli, pseudomonas) infection and/or the lethal effects of endotoxin. For the former, both cyclophosphamide (which renders mice neutropenic) and the reversible hepatotoxin D-galactosamine (D-gal) have been used. D-gal also sensitized mice to the lethal effects of LPS. Infected mice treated with cell-wall active antibiotics are protected approximately five- to 10-fold (as assessed by increases in LD50) if they are sensitive to LPS lethality (D-gal treatment) but 500-fold if they are resistant to LPS lethality. Importantly, different antibiotics that have been documented to cause different amounts of endotoxin release in vitro also differ in their protective efficacy in vivo. Thus, imipenem, which causes relatively low endotoxin release, is significantly more protective (8-fold) than ceftazidime or meropenem (3-fold, P < 0.005) under conditions of equivalent MICs. Lethality data correlate well with circulating levels of interleukin-6 (Il-6) in vivo and with induction of Il-6 in ex vivo studies in which anticoagulated mouse blood is incubated with bacteria and antibiotics. Finally, antiendotoxin agents manifest additional levels of protection in vivo under conditions in which antibiotics alone are not protective. Collectively, these results strongly implicate antibiotic-induced endotoxin release as a significant contributing factor in experimental Gram-negative sepsis.

Animals↗

Susceptibilities to 23 antimicrobial agents and beta-lactamase production of blood culture isolates of Acinetobacter sp in Hong Kong.

The susceptibility of 140 Acinetobacter spp. isolated from blood cultures of patients from the Prince of Wales Hospital, Hong Kong, from 1990 to 1994 to 23 antimicrobial agents was studied by an agar dilution method. Resistance to most of the beta-lactams, aminoglycosides and fluoroquinolones tested was high, being 11%-92%. Only amikacin, imipenem and meropenem were reliably active against this organism. Most of the isolates produced cephalosporinases with very high pIs while 33% produced beta-lactamases with pI ranges of 5.2-8.7.

Acinetobacter↗

[In vitro susceptibility testing of 446 clinical isolates of gram-positive bacteria to new quinolones, carbapenems and cephalosporins].

OBJECTIVE: To assess the in vitro susceptibility of gram-positive bacteria isolated in the São Paulo Hospital against five fluoroquinolones, three carbapenems and three cephalosporins. MATERIALS AND METHOD: Susceptibility was tested in 77 isolates of streptococci, 38 enterococci, 25 S. aureus and 91 S. epidermidis. The strains were isolated in the São Paulo Hospital in June and July of 1992. The susceptibility testing was performed by broth microdilution according to the procedure described by the national committee for Clinical Laboratory Standards (NCCLS). The antimicrobial agents tested were: ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin (formerly OPC 17116), DU-6859, imipenem, meropenem, biapenem, ceftazidime, cefepime and FK-037. RESULTS: The best in vitro activity was demonstrated by the new fluoroquinolones, especially DU 6859. Among the commercially available compounds, the fluoroquinolones ciprofloxacin and ofloxacin (81% susceptibility) and the carbapenem imipenem (74% susceptible) were the most active compounds. The highest resistance rates were shown by enterococci and oxacillin-resistant staphylococci. CONCLUSIONS: The results of the present study showed that the in vitro activities of the new carbapenems are similar to that of imipenem and the fourth generation cephalosporins are more active than ceftazidime against gram-positive bacteria. In addition, the newer fluoroquinolones were four to sixteen-fold more active than that showed by the commercially available compounds of this class, especially against enterococci and oxacillin-resistant staphylococci. These results indicate that these newer fluoroquinolones should be further evaluated in clinical trials.

Carbapenems↗

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

Ampicillin↗

Susceptibilities of 97 strains of Xanthomonas maltophilia to antibiotics and the effect of beta-lactamase inhibitors.

An agar dilution technique and the 'E' test were used to compare the antimicrobial activities of ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, meropenem, biapenem, imipenem, levofloxacin, ofloxacin, ciprofloxacin, ceftazidime and cefepime against 97 clinical isolates of Xanthomonas maltophilia. Intermediate susceptibility breakpoints for members of the family Enterobacteriaceae were used. Results were analysed as minimum inhibitory concentrations for 50 and 90% of the strains tested and as percentages of strains susceptible at the breakpoint. Good correlation between the two techniques was observed, with ticarcillin-clavulanate clearly the most active agent by both methods with 64 to 66% followed by levofloxacin with 63 to 65% of the strains being susceptible. Biapenem and imipenem showed weak activity with none of the strains being susceptible. Ceftazidime had better activity than cefepime when they were compared by the two methods. There was no significant difference in the results between the two susceptibility techniques used.

Anti-Bacterial Agents↗

[Occurrence and susceptibility of hospital strains producing enzymes with a wide spectrum of substrate profiles].

In connection with more and more frequent occurrence of extended spectrum beta-lactamases an effort has been made to detect their presence in the biological materials coming from the patients of different wards of Mining Hospital in Sosnowiec from January to September 1995. Among 38 diagnostic materials, from which the strains in question were isolated, the following materials have been examined: bronchial lavage (52.6%), surgical wounds (18.4%), urines (15.8%) and others (13.2%). The examined diagnostic materials came from Intensive Care Unit (87.0%), Casualty and Orthopaedic Surgery Clinic (5.0%) and General Surgery Clinic (3.0%). The most frequently isolated microorganisms were Klebsiella pneumoniae. (47.4%), Serratia marcescens (36.8%), Enterobacter cloacae (10.5%) and others (5.3%). Half of the examined strains constituted those producing extended spectrum beta-lactamases and probably possessing an extra resistance mechanism: (Serratia marcescens--74%, Enterobacter cloacae--21%, Enterobacter aerogenes--5.0%) and 50% were those producing extended--spectrum beta-lactamases. (Klebsiella pneumoniae--95%, Escherichia coli--5%). Susceptibility of the examined strains to anti-microbial antibiotics was diverse. Full susceptibility of the analysed strains has been observed exclusively in case of Karbapenems (Imipenem, Meropenem and Cefamycyn). In case of beta-lactamase with beta-lactamase inhibitor combinations susceptibility was diverse and dependent on the species of the examined microorganism.

Body Fluids↗

Emergence of antimicrobial resistance in community-acquired pulmonary pathogens.

Antibiotic resistance to the common respiratory tract pathogens is increasing worldwide. Penicillin-resistant pneumococci are of particular concern. Most strains of penicillin-resistant Streptococcus pneumoniae have intermediate resistance to penicillin, and highly resistant strains are rare at present. Careful selection of antibiotics with low resistance potential and excellent activity against highly penicillin-resistant pneumococci (ie, cefotaxime, ceftriaxone, cefepime, cefprozil, doxycycline, levofloxacin, sparfloxacin, and meropenem) is the best current strategy to delay or increase the emergence of highly penicillin-resistant strains of S pneumoniae.

Anti-Bacterial Agents↗

[Current antimicrobial drugs].

In the past few years several new antibiotics became available, but no major inventions as to new treatment strategies were made. There are a few new broad-spectrum antibiotics for the intravenous route like piperacillin-tazobactam, the carbapenem meropenem and the fourth-generation cephalosporins. cefepime and cefpirome. New oral antibiotics include the third-generation cephalosporins ceftibuten, cefetamet and cefpodoxime and the macrolides clarithromycin and azithromycin. The last two have the great advantage of less frequent dosing and fewer side effects than erythromycin. Of the two new quinolones, sparfloxacin and trovafloxacin, trovafloxacin is the more promising. In the treatment of Gram-positive infections the glycopeptide teicoplanin became available and the combined derivatives quinupristin-dalfopristin may prove valuable in the future.

Anti-Bacterial Agents↗

Differential release of endotoxin from Pseudomonas aeruginosa treated with beta-lactam antibiotics and its effect on the lethal activity.

The relationship between the level of endotoxin released from Pseudomonas aeruginosa by exposure to beta-lactam antibiotics and the lethal activity against D-galactosamine (D-GalN)-sensitized mice was examined. In vitro treatment of P. aeruginosa with imipenem (IPM) exclusively caused low-level release of free endotoxin, which was not lethal for D-GalN-sensitized mice. Treatment with other beta-lactam antibiotics, such as ceftazidime (CAZ), meropenem (MEPM) and cefozopran (CZOP) caused high-level release of free endotoxin and it exhibited the lethal action against D-GalN-sensitized mice. This study demonstrated close association of free endotoxin released by antibiotic treatment with the lethal activity.

Animals↗

In vitro antibacterial activity and beta-lactamase stability of the new carbapenem SM-7338.

The in vitro activity of the new carbapenem SM-7338 was tested in comparison with imipenem, ceftazidime, cefotaxime, flomoxef, cefuzonam and cefmetazole against 2850 clinical bacterial isolates. SM-7338 showed good activity against a broad spectrum of gram-positive and gram-negative bacteria. SM-7338 was very active against gram-negative bacteria, inhibiting all Enterobacteriaceae, except 25% of Serratia marcescens isolates, at a concentration of 0.78 mg/l. SM-7338 inhibited the majority of Pseudomonas spp. at concentrations of less than or equal to 3.13 mg/l, its activity being twofold higher than that of imipenem. However, the activity of SM-7338 against gram-positive cocci was about one-fourth that of imipenem. Against anaerobes, SM-7338 also had the best activity of the beta-lactams tested. The compound was inactive against methicillin-resistant staphylococci, Enterococcus faecium, Xanthomonas maltophilia and Flavobacterium spp., as were the other beta-lactams. SM-7338 was quite stable in the presence of various types of beta-lactamase, but was hydrolyzed by Xanthomonas maltophilia beta-lactamase, as was imipenem. This high degree of stability was responsible for the potent activity of SM-7388 against beta-lactamase-producing species such as Enterobacter cloacae, Citrobacter freundii and Proteus vulgaris. SM-7338 also showed bactericidal activity against clinical isolates at the MIC or at concentrations slightly above the MIC.

Anti-Bacterial Agents↗

Aspirin treatment for neonatal infectious endocarditis.

We describe a term female neonate with Serratia marcescens endocarditis. Despite adequate antibiotic therapy for 8 days, the bacteremia persisted and there was an increase in vegetation size. Treatment with aspirin was initiated, with resolution of the bacteremia and a gradual decrease in vegetation size. We conclude that in neonatal endocarditis, aspirin may be beneficial additional treatment.

Anti-Bacterial Agents↗

A new modeling approach to the effect of antimicrobial agents on heterogeneous microbial populations.

We develop a mathematical framework to model the dynamics of the effect of antimicrobial agents on heterogeneous microbial populations of distributed antimicrobial resistance. Our framework uses the concept of cumulants of a distribution. Simplifications that result in easily usable approximation tools are presented. A case study on experimental data exemplifies shortcomings of standard methods and the usefulness of the proposed approach. Suggestions for future development are made.

Algorithms↗