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[Comparative studies on activities on antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2000). III. Secular changes in susceptibility].

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 1999. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). E. faecalis showed good susceptibility to ampicillin (ABPC) and imipenem (IPM), and the MIC90s were 2 micrograms/ml. Also, E. faecalis showed good susceptibility to vancomycin (VCM). However, the MIC90, which was 2 micrograms/ml between 1992 and 1999, rose to 4 micrograms/ml in patients with complicated UTIs because the strains inhibited at 4 micrograms/ml increased more than before. The low susceptibility of S. aureus to arbekacin (ABK) in complicated UTIs, as shown in 1998 and 1999, recovered in 2000, and no strains inhibited at > or = 4 micrograms/ml were detected. E. coli showed good susceptibility to CTM (MIC90: 0.25-0.5 microgram/ml) and CZOP (MIC90: < or = 0.125 microgram/ml) and was not resistant to those. E. coli also showed good susceptibility to the other drugs except to penicillins. Decreases in susceptibility of E. coli to quinolones, ciprofloxacin (CPFX), and sparfloxacin (SPFX) were observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all drugs did not significantly change in 2000 and was generally good except to penicillins. Although the susceptibility of P. aeruginosa to carbapenems was notable, the MIC90 went up from 4 micrograms/ml to 16 micrograms/ml in complicated UTIs compared with those observed in the previous year.

Anti-Infective Agents, Urinary↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996), III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1996 to May 1997, and the results were compared with those obtained during the same period in earlier years. 1. E. faecalis Among E. faecalis strains, those with high susceptibilities to ampicillin and minocycline appeared to have decreased in the latest study period. 2. S. aureus To almost antimicrobial agents, S. aureus isolated from uncomplicated UTIs showed low susceptibilities. But the MIC50s of those agents for S. aureus from complicated UTIs have changed better state. Particularly, the MIC50s of imipenem and clindamycin were 0.125 microgram/ml or below in the latest period for the first time in our history. 3. E. coli The susceptibilities to piperacillin and quinolones of E. coli isolated from uncomplicated UTIs were better than those isolated from complicated UTIs. 4. Klebsiella spp. The susceptibilities to almost antimicrobial agents of Klebsiella spp. have been better during the latest period, compared to those during period of 1995-1996, but to ofloxacin and ciprofloxacin have appeared to have been lower. 5. P. aeruginosa The susceptibilities to quinolones of P. aeruginosa have been better during the latest period compared those during periods of 1995-1996. But, the susceptibilities to cefozopran, carbapenems and monobactams of P. aeruginosa isolated from complicated UTIs appeared to have been lower. These susceptibility changes should be utilized in determining clinical treatments.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). III. Differences in susceptibilities from previous years].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 11 hospitals during June, 1995 through May, 1996, and the results were compared with those obtained during the same period in earlier years. 1. Macrolide resistant E. faecalis isolated from uncomplicated UTIs during the latest study period appeared to have increased compared to those in previous study periods. More than 50% of the isolated E. faecalis during the latest study period were resistant to macrolide antibiotics, for the first time in our history. 2. No obvious changes were observed through the years for susceptibilities of S. aureus to various antimicrobial agents. Vancomycin (VCM) showed the highest activity against S. aureus, with MICs below 2 micrograms/ml or below. 3. Among E. coli strains, those with low susceptibilities to quinolones appeared to have increased over the years with MIC90 changed from between 0.125 microgram/ml or below and 0.5 microgram/ml in the 1989-1990 period to between 8 micrograms/ml and 128 micrograms/ml in the latest study period. 4. Klebsiella spp. showed higher resistance to most antimicrobial agents during periods of 1993-1994 and 1994-1995, but somewhat lower resistance during period of 1995-1996. No resistant Klebsiella spp. were detected from uncomplicated UTIs during the latest study period. 5. Among P. aeruginosa isolates from complicated UTIs, resistance isolates to gentamicin appeared to be increasing over the years. Resistant strains to quinolones were isolated at lower frequencies during periods of 1991-1994, but higher frequency was observed in the latest period, and MIC50s were between 0.5 and 4 micrograms/ml during 1991-1994, but were 16-32 micrograms/ml during 1995-1996. These susceptibility changes should be utilized in determining clinical treatments.

Anti-Bacterial Agents↗

In vitro fructooligosaccharide utilization and inhibition of Salmonella spp. by selected bacteria.

In vitro experiments were conducted to determine: 1) inhibitory capacities of potential direct-fed microbial bacteria against Salmonella serotypes; and 2) the ability of Bifidobacterium bifidum, Enterococcus faecium, Lactobacillus casei, Lactococcus lactis, Pediococcus sp., and Salmonella spp. to grow in media containing fructooligosaccharides (FOS-50 or FOS pure formulation) as the only carbohydrate source. Thirteen bacteria (two strains of Bacillus coagulans, Bacillus licheniformis, Bacillus subtilis, B. bifidum, E. faecium, two strains of Lactobacillus acidophilus, L. casei, Pediococcus sp., Propionibacterium acidopropionici, P. jensenii, and Propionibacterium sp.) were tested for inhibition of six Salmonella serotypes (S. california, S. enteritidis, S. heidelberg, S. mission, S. senftenberg, and S. typhimurium) using a spot-the-lawn technique. Bifidobacterium bifidum, E. faecium, all lactobacilli, and Pediococcus sp. clearly inhibited growth of all Salmonella serotypes. In the growth experiments, E. faecium, L. lactis, and Pediococcus sp. grew in media with either FOS-50 or the pure formulation of FOS as the sole carbohydrate source. All tested Salmonella serotypes utilized FOS-50 for growth; however growth varied among the serotypes. In contrast, none of the Salmonella serotypes grew in media containing the pure formulation of FOS as the only carbohydrate source.

Animals↗

Treatment of bone and soft tissue infections with teicoplanin.

The use of teicoplanin was evaluated in a group of 33 patients, which included 18 prosthetic infections, seven with osteomyelitis, five skin and soft tissue infections, and three cases of septic arthritis. The bacterial pathogens isolated were 27 isolates of Staphylococcus aureus (methicillin sensitive 18; methicillin resistant 9), Staph. hominis (2), Staph. epidermidis (1), Staph. haemolyticus (2), Enterococcus faecalis (1), Streptococcus pyogenes (1), Peptococcus spp. (1). Eleven patients had polymicrobial infections (Gram-positive plus Gram-negative and/or anaerobic bacteria). In ten cases (nine polymicrobial infections) teicoplanin was used in combination with other antibiotics. Teicoplanin was administered intravenously 400 mg every 24 h in 26 cases, 200 mg every 24 h in six cases and 600 mg every 24 h in one case. The duration of the treatment ranged from 9 to 73 days with a mean of 27.3. Efficacy was evaluable in 30 patients, because in three patients treatment was stopped because of adverse reactions. Cure or improvement was noted in 28 patients (93%). Bacteriological cure occurred in 25 patients (83.3%).

Adolescent↗

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Adolescent↗

In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents.

CP-65,207 is a new parenteral penem antibiotic with a broad spectrum that includes gram-positive, gram-negative, and anaerobic microorganisms, with MICs for 90% (MIC90s) of the majority of 1,101 clinical pathogens tested being less than or equal to 1 microgram/ml. The compound was from 10- to 100-fold more active than cefoxitin and broad-spectrum cephalosporins against gram-positive bacteria and anaerobes. CP-65,207 was less active than imipenem for staphylococci, group A streptococci, and Enterococcus faecalis. Against members of the family Enterobacteriaceae, CP-65,207 was in general 100-fold more active than cefoxitin, 5- to 10-fold more active than broad-spectrum cephalosporins, and 2-fold more active than imipenem. Fresh clinical isolates that were resistant to broad-spectrum cephalosporins were highly susceptible to CP-65,207 and imipenem (MIC90, 1 microgram/ml). Isolates of Enterococcus faecalis, Serratia marcescens, and anaerobic Peptococcus spp. had MIC90s of 8, 2, and 3.12 micrograms/ml, respectively. CP-65,207 was not very active against methicillin-resistant staphylococci or Pseudomonas aeruginosa. Killing kinetics showed that against some strains CP-65,207 is rapidly bactericidal at concentrations well below those required to achieve a similar degree of killing with cefotaxime, ceftazidime, and ceftriaxone. CP-65,207 was only slightly susceptible to hydrolysis by type I cephalosporinases and TEM-1, SHV-1, and PSE-2 plasmid-encoded enzymes. It had the highest affinity for penicillin-binding proteins 2, 1A, 1B, and 3 in cell-free preparations of Escherichia coli W-7.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). III. Secular changes in susceptibility].

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined and the results were compared with those obtained between 1991 and 1998. Comparison was made by classifying strains isolated from patients into those with uncomplicated UTIs and those with complicated UTIs (including with or without indwelling catheter). About E. faecalis, increase of low sensitive strains noted in the former year showed a decreasing tendency, however, one strain each with MIC of 4 micrograms/ml to vancomycin (VCM) was detected in patients with both uncomplicated and complicated UTIs. As for S. aureus, many sensitive strains to cephems, imipenem (IPM) and VCM were noted, and each MIC50 was better than that in the former years. S. aureus strains showing low susceptibility to arbekacin (ABK) were detected in patients with complicated UTIs in this year as well as in the former year, and one strain each with MIC of 16 micrograms/ml and 32 micrograms/ml was detected. Susceptibilities of E. coli were effective to all drugs except for penicillins and minocycline (MINO). Decrease of low sensitive strains was also noted in all drugs except for quinolones. Each MIC90 of ciprofloxacin (CPFX) and sparfloxacin (SPFX) in patients with complicated UTIs against E. coli was 3 degrees classes lower than that in patients with uncomplicated UTIs. As for Klebsiella pneumoniae, decrease of low sensitive strains to cephems was noted in patients with uncomplicated UTIs in 1998. In 1999, low sensitive strains decreased also in patients with complicated UTIs, and few were detected. Susceptibilities of K. pneumoniae to quinolones were effective as compared with those in the former years with the MIC80s of 0.125 microgram/ml or below without detection of low sensitive strains. One low sensitive strain of K. pneumoniae with MIC of 8 micrograms/ml was detected for gentamicin (GM). Susceptibilities of P. aeruginosa to carbapenems were notable. The MIC90 of meropenem (MEPM) and IPM was 4 micrograms/ml each which was 2 degrees better than that in 1998. Resistant P. aeruginosa strains to other drugs except for monobactams decreased in 1999.

Anti-Bacterial Agents↗

[Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study].

Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study. Between January and December 2001, we analyzed 80,141 blood cultures by the Bact-Alert system (14,960 FAN aerobics, 3,855 FAN anaerobic, 11,114 standards aerobics, 11,367 standards anaerobic, 12,054 pediatrics and 26,791 FAN pediatrics bottles) and 44.235 series from 27.615 patients at eight hospitals of Buenos Aires city, one of La Plata city and three of the Buenos Aires province. A total of 13,657 blood cultures yielded a positive result. Only 181 of them had been detected as positive between the 5th and 7th day of incubation and only 26 (0.19%) had clinical significance (Staphylococcus aureus 3; coagulase negative staphylococci 2; Enterococcus faecalis 1; Streptococcus pneumoniae 2; Campylobacter spp 1; Escherichia coli 1; Enterobacter cloacae 1; Enterobacteraerogenes 1; Citrobacter freundii 1; Klebsiella pneumoniae 1; Proteus mirabilis 1; Serratia marcescens 4; yeasts 7, including one strain of Cryptococcus neoformans). Of the total of contaminants, 38% were isolated by the anaerobic standard (65% were Propionibacterium spp and 29% coagulase negative staphylococci), 31.2% by the FAN aerobic (33.3% difphteroids and 28.9% Bacillus spp), 11.8% by the pediatric, 9% by FAN pediatric, 8.33% by aerobic standard and 1.4% by FAN anaerobic bottle. Our results show that the prolonged incubation of blood cultures for more than 5 days using the Bact-Alert system is unnecessary.

Argentina↗

[In vitro and in vivo antibacterial activities of sulopenem, a new penem antibiotic].

The in vitro and in vivo antibacterial activities of sulopenem, a new penem, were evaluated in comparison with imipenem (IPM), meropenem (MEPM), ceftazidime (CAZ) and flomoxef (FMOX). Sulopenem had broad and potent antibacterial spectra against Gram-positive and Gram-negative bacteria, including Enterococcus faecalis, Proteus vulgaris, Morganella morganii, Enterobacter spp. and Citrobacter freundii. Sulopenem showed concentration-dependent bactericidal activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Acinetobacter calcoaceticus. Morphological observation using phase-contrast microscope revealed that sulopenem induced spherical cell formation with E. coli and K. pneumoniae at lower concentrations and bacteriolysis at higher concentrations. Therapeutic efficacies of sulopenem against systemic infections in mice were almost equal to those of imipenem against Streptococcus pneumoniae. While its therapeutic efficacies were superior to those of meropenem, ceftazidime and flomoxef against S. aureus and S. pneumoniae, they were inferior to those of imipenem/cilastatin against S. aureus, K. pneumoniae and A. calcoaceticus.

Animals↗

Antimicrobial susceptibility pattern of blood isolates from a teaching hospital in north India.

Bloodstream infections are associated with significant patient morbidity and mortality worldwide. In this study, we examined antimicrobial susceptibility patterns by reviewing the data on 5,704 blood samples that were collected from patients with fever/sepsis admitted to Government Medical College and Hospital, Chandigarh, India, over a period of 1 year from August 2003 to July 2004. Among the 567 qualifying samples, Pseudomonas aeruginosa (19.75%), Escherichia coli (15.17%), Klebsiella pneumoniae (14.99%), and Salmonella enterica serovar Typhi (12.87%) were the most frequently isolated Gram-negative bacteria other than Citrobacter, Acinetobacter, Proteus, and Enterobacter spp. collectively accounting for 80.96% of the isolates. Staphylococus aureus (13.86%) and Enterococcus feacalis (2.35%) were most frequently isolated Gram-positive bacteria other than other Streptococcus and Staphylococcus spp. collectively accounting for 18% of the isolates. Among the antibiotics used for susceptibility testing of Gram-negative isolates, amikacin showed higher activity (76.61%) against Enterobacteriaceae and ciprofloxacin (65.17%) against non-fermenters. However, cefoperazone + sulbactum showed the highest activity (82.66%) among all Gram-negative isolates. For Gram-positive isolates, vancomycin (100%), ciprofloxacin (89.74%) showed the highest activity against Staphylococcus spp. Combinations of antibiotics are often prescribed as emperic therapy for bacteremia, especially for Gram-negative pathogens. Hence the antibiotic susceptibility patterns of blood isolates reported here may be a useful guide for physicians initiating emperic therapy with antibiotics.

Bacteremia↗

Comparative evaluation of the API 20S and AutoMicrobic gram-positive identification systems for non-beta-hemolytic streptococci and aerococci.

The API 20S system (Analytab Products, Plainview, N.Y.) and the AutoMicrobic Gram-Positive Identification system (GPI; Vitek Systems, Hazelwood, Mo.) were evaluated for their capacity to identify the non-beta-hemolytic streptococci and aerococci to the species level. The 20S system identified 86% (six of seven strains) of nonhemolytic group B streptococci, whereas 100% of the same group B streptococcal strains were correctly identified by the GPI system. With both systems 99% (134 of 135 strains) of four species of group D enterococcus strains and 92% (24 of 26 strains) of the Aerococcus spp. strains were identified. The 20S system identified 84% (41 of 49 strains) of three species of group D non-enterococcus strains. The GPI system identified 96% of the same group D non-enterococcus strains. The 20S system identified 84% (190 of 226 strains) of 10 species of viridans streptococci; however, supplemental conventional tests were required to identify 49% (110 of the 226 strains) of the viridans strains to the species level. The GPI system identified 79% of the same viridans streptococci without the need for supplemental tests. Both systems identified 84% (161 of 192 strains) of the seven most commonly occurring viridans Streptococcus spp. The 20S system identified 82% (75 of 92 strains) and the GPI system identified 84% (54 of 64 strains) of Streptococcus pneumoniae.

Bacteriological Techniques↗

In vitro antibacterial activity and beta-lactamase stability of SY5555, a new oral penem antibiotic.

The antibacterial activity of SY5555, a new oral penem antibiotic, was compared with those of cefaclor, cefixime, and cefteram. SY5555 was more active than the comparison agents against methicillin-susceptible Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Citrobacter freundii, Enterobacter cloacae, Morganella morganii, Acinetobacter calcoaceticus, Clostridium spp., and Bacteroides fragilis. Against Providencia spp., Proteus spp., and Haemophilus influenzae, SY5555 was less active than cefixime or cefteram. SY5555 was inactive against methicillin-resistant S. aureus. Enterococcus faecium, Serratia marcescens, Pseudomonas aeruginosa, and Xanthomonas maltophilia, as were the comparison agents. The bactericidal activities of SY5555, cefixime, and cefteram were at or slightly greater than the MICs for clinical isolates of Escherichia coli and Klebsiella pneumoniae. SY5555 was not hydrolyzed by various types of beta-lactamases. However, SY5555 and the comparison agents were hydrolyzed by X. maltophilia (L-1) and P. aeruginosa/pMS354 beta-lactamases, two Bush group 3 beta-lactamases, SY5555 showed a high affinity, as did cefixime and cefteram, for cephalosporinases from C. freundii GN7391 and E. cloacae GN7471 strains. These results suggest that SY5555 may be more specific than existing beta-lactam antibiotics.

Administration, Oral↗

Molecular characterization of a plasmid-borne (pGT633) erythromycin resistance determinant (ermGT) from Lactobacillus reuteri 100-63.

Lactobacillus reuteri 100-63 contains a 9.8 kb plasmid (pGT633) encoding resistance to the macrolide-lincosamide-streptogramin (MLS) type B antibiotics. The restriction endonucleases AccI, BamHI, BclI, EcoRI, EcoRV, HhaI, HindII, HpaI, KpnI, SalI, and SspI were employed to establish a physical map of pGT633. Next, genetic transfer experiments were conducted to establish the host range of pGT633. The results revealed that pGT633 replicated autonomously and encoded constitutive resistance to erythromycin in a variety of bacterial hosts, including Bacillus subtilis BD170, Streptococcus sanguis DL1, Staphylococcus aureus RN4220, and Enterococcus faecalis 19433, as well as several Lactobacillus spp. A 2.2 kb BamHI fragment of pGT633 containing the genetic determinant (ermGT) encoding resistance to erythromycin was cloned into Escherichia coli. Determination of the nucleotide sequence of ermGT revealed a methylase gene 731 bp in length that was highly related (ca. 81% nucleotide and ca. 78% amino acid identity) to the ermC gene from S. aureus plasmid pE194. The leader sequences of ermGT and ermC were identical except for a single base change at nt 51.

Amino Acid Sequence↗

Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases.

Bacteriophage (phage) therapy involves using phages or their products as bioagents for the treatment or prophylaxis of bacterial infectious diseases. Much evidence in support of the effectiveness of phage therapy against bacterial infectious diseases has accumulated since 1980 from animal model studies conducted in Western countries. Reports indicate that appropriate administration of living phages can be used to treat lethal infectious diseases caused by gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Vibrio vulnificus, and Salmonella spp., and gram-positive bacteria, such as Enterococcus faecium and Staphylococcus aureus. The phage display system and genetically modified nonreplicating phages are also effective for treatment of Helicobacter pylori and P. aeruginosa, respectively. In addition to phage particles per se, purified phage-encoded peptidoglycan hydrolase (lysin) is also reported to be effective for the treatment of bacterial infectious diseases caused by gram-positive bacteria such as Streptococcus pyogenes, S. pneumoniae, Bacillus anthracis, and group B streptococci. All phage lysins that have been studied to date exhibit immediate and strong bacteriolytic activity when applied exogenously. Furthermore, phage-coded inhibitors of peptidoglycan synthesis (protein antibiotics), search methods for novel antibacterial agents using phage genome informatics, and vaccines utilizing phages or their products are being developed. Phage therapy will compensate for unavoidable complications of chemotherapy such as the appearance of multidrug resistance or substituted microbism.

Bacteriophages↗

Value of automatized blood culture systems in the diagnosis of continuous ambulatory peritoneal dialysis peritonitis.

Peritonitis is a common clinical problem that occurs in patients with end-stage renal disease treated by peritoneal dialysis. The aim of this study was to evaluate the value of blood culture systems for the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) peritonitis among 26 samples of peritoneal fluid obtained from patients with the suspicion of CAPD peritonitis. Significant growth was detected in 12 (70.5%) of 17 bacteria-positive samples. The most striking finding was that 8 (66.6%) of these 12 results were obtained only from blood culture bottles. The identified pathogens were methicillin-sensitive coagulase-negative staphylococci (n = 5), alpha-hemolytic streptococci (n = 2), Corynebacterium spp. (n = 2), Escherichia coli (n = 2), and Enterococcus faecalis (n = 1). Using blood culture bottles inoculated with peritoneal fluid at the bedside, rather than submitting the specimen to the laboratory for later processing, is advocated in the prompt diagnosis of CAPD peritonitis.

Ascitic Fluid↗

MC21-A, a bactericidal antibiotic produced by a new marine bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30(T), against methicillin-resistant Staphylococcus aureus.

We previously reported a new marine bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30(T), which produced a bactericidal antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we purified an anti-MRSA substance (MC21-A) from the methanol extract of the cells of P. phenolica O-BC30(T) and analyzed its chemical structure. MC21-A was determined to be 3,3',5,5'-tetrabromo-2,2'-biphenyldiol by spectrometric analyses. Its anti-MRSA activity against 10 clinical isolates of MRSA was comparable to that of vancomycin (MC21-A MICs, 1 to 2 micro g/ml; vancomycin MICs, <0.25 to 2 micro g/ml). This substance was also high active against Enterococcus serolicida, Enterococcus faecium, and Enterococcus faecalis but was less active against Streptococcus spp. A time-kill study also demonstrated that MC21-A was bactericidal and that its killing rate was much higher than that of vancomycin. The postantibiotic effect (PAE) of MC21-A against a clinical MRSA isolate, strain E 31243, was also comparable to that of vancomycin (MC21-A PAEs, 1.46 to 1.65 h; vancomycin PAEs, 0.84 to 1.43 h). However, a lysis experiment demonstrated that this substance failed to lyse MRSA cells. This substance also did not lyse human erythrocytes. A SYTOX Green staining experiment implied that this substance permeabilized the cell membrane of MRSA as its mode of action. When its activities against a hypersensitive Escherichia coli mutant (KO 1489) and wild-type strains were tested, MC21-A exhibited higher levels of activity against the former. Furthermore, MC21-A was not cytotoxic to human normal fibroblast, rat pheochromocytoma, and Vero cells at concentrations up to 50 micro g/ml. These results suggest that MC21-A might be useful as a lead compound in the development of new types of anti-MRSA substances with modes of action different from those of vancomycin and teicoplanin.

Anti-Bacterial Agents↗