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In vitro and in vivo activities of LB10522, a new catecholic cephalosporin.

In vitro activity of LB10522 was compared with those of cefpirome, ceftazidime, ceftriaxone, and cefoperazone against clinical isolates. Against gram-positive bacteria, LB10522 was most active among the compounds tested. It was fourfold more active than cefpirome against methicillin-susceptible Staphylococcus aureus and Enterococcus faecalis. LB10522 was highly effective against most members of the family Enterobacteriaceae tested. Ninety percent of isolates of Escherichia coli, Klebsiella oxytoca, Proteus vulgaris, Proteus mirabilis, and Salmonella spp. were inhibited at a concentration of < or = 0.5 micrograms/ml. These activities were comparable to those of cefpirome. Against Pseudomonas aeruginosa, LB10522 with a MIC at which 90% of the isolates are inhibited of 2 micrograms/ml was 16- and 32-fold more active than ceftazidime and ceftazidime against systemic infections caused by Staphylococcus aureus giorgio, Streptococcus pneumoniae III, Pseudomonas aeruginosa 1912E, Escherichia coli 851E, Proteus mirabilis 1315E, Serratia marcescens 1826E, and Acinetobacter calcoaceticus Ac-54. LB10522 was very resistant to hydrolysis by various beta-lactamases such as TEM-3, TEM-7, SHV-1, FEC-1, and P-99. LB10522 did not induce beta-lactamase in Enterobacter cloacae 1194E, although most of the reference cephalosporins acted as inducers of beta-lactamase in this strain. Time-kill study showed that LB10522, at concentrations of two or four times the MIC, had a rapid bactericidal activity against Staphylococcus aureus 6538p, Escherichia coli 851E, and Pseudomonas aeruginosa 1912E.

Animals↗

Antibiotics with a selective aerobic or anaerobic spectrum have different therapeutic activities in various regions of the colon in interleukin 10 gene deficient mice.

BACKGROUND AND AIMS: Multiple rodent models implicate resident intestinal bacteria in the pathogenesis of chronic immune mediated intestinal inflammation. Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10(-/-)) mice develop colitis, which does not occur in the germ free (GF) state. We investigated whether broad or narrow spectrum antibiotics affect onset and progression of disease in various regions of IL-10(-/-) mice. METHODS: Metronidazole, ciprofloxacin, vancomycin-imipenem (50 mg/kg/day), or water (control) was administered orally before (prevention) or two weeks after (treatment) colonisation of GF IL-10(-/-) mice with SPF bacteria. After four weeks, colonic histology scores and cytokine production by colonic explants were determined. Caecal and colonic contents were collected for quantitative bacterial analysis. RESULTS: In the prevention study, all antibiotics decreased inflammation in the caecum and colon. However, in the treatment study, ciprofloxacin and vancomycin-imipenem decreased caecal inflammation, and reduced Escherichia coli and Enterococcus faecalis concentrations, whereas only vancomycin-imipenem lowered direct microscopic bacterial counts. In contrast, metronidazole and vancomycin-imipenem reduced colonic injury and eliminated anaerobic bacteria, including Bacteroides spp. CONCLUSIONS: Both narrow and broad spectrum antibiotics can prevent disease but treatment of established colitis is more selective. Ciprofloxacin is most effective in the treatment of caecal inflammation, metronidazole preferentially treats the colon, whereas vancomycin-imipenem definitively treats both regions. These results suggest that subsets of aerobic or anaerobic bacteria show regional differences in their capacity to mediate experimental colitis in IL-10(-/-) mice.

Animals↗

Predominance of Gram-negative bacilli and increasing antimicrobial resistance in nosocomial bloodstream infections at a university hospital in southern Taiwan, 1996-2003.

BACKGROUND AND PURPOSE: While nosocomial infections cause substantial morbidity and mortality, the availability of timely and accurate epidemiological information on nosocomial pathogens is essential to the appropriate selection of empirical therapy. This study analyzed nosocomial bloodstream infections (NBSIs) surveillance data to determine trends in the distribution of pathogens and antimicrobial susceptibilities of these pathogens. METHODS: During the period from 1996 to 2003 at National Cheng Kung University Hospital, patients with NBSIs were enrolled in the study, and the ranking of pathogens and status of antimicrobial resistance were determined. RESULTS: From 1996 to 2003, there were 4,038 episodes of NBSIs. The overall incidence was 1.79 episodes per 1,000 inpatient-days. Aerobic Gram-negative bacilli, Gram-positive cocci, fungi, and anaerobes were responsible for 51%, 37%, 10%, and 1.6% of NBSIs, respectively. The 5 leading pathogens were coagulase-negative staphylococci (16% of NBSIs), Staphylococcus aureus (13%), Candida spp. (10%), Acinetobacter baumannii (8%), and Escherichia coli (8%). Oxacillin resistance was found in 90% of coagulase-negative staphylococci and 75% of S. aureus isolates. In contrast to Enterococcus faecalis, in which only 1% of isolates were resistant to ampicillin, 78% of Enterococcus faecium isolates were resistant to ampicillin. The emerging antimicrobial-resistant Gram-negative pathogens included multidrug-resistant A. baumannii, cephalosporin- or fluoroquinolone-resistant E. coli, and extended-spectrum beta-lactamase producing Klebsiella pneumoniae and E. coli. Despite the annual increase in the use of fluconazole, Candida albicans (54%) remained the most common causative pathogen of nosocomial candidemia. CONCLUSIONS: In summary, Gram-negative bacilli predominated among pathogens causing NBSIs and an upsurge in the threat of antimicrobial resistance in our hospital occurred during the 8-year period. Surveillance of the characteristics of NBSIs and antimicrobial resistance patterns, together with appropriate antibiotic and infection control measures, should be reinforced.

Anti-Bacterial Agents↗

Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci.

The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations.

Aminoglycosides↗

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--I. Gram-positive bacteria].

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial susceptibility for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (2,363 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus haemolyticus, Staphylococcus saprophyticus, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, Streptococcus pyogenes, Streptococcus agalactiae, penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate resistant S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP), Streptococcus milleri group and Peptostreptococcus spp. The antibacterial activity of CZOP either against MSSA or MSSE was preferable (MIC90: 2 or 0.5 micrograms/mL) and comparable to those of other cephems. CZOP was also effective on MRSE (MIC90: 16 micrograms/mL) but not on MRSA. CZOP and other cephems had low antibacterial activity against S. haemolyticus (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than those of other cephems, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (32 vs 1-2 micrograms/mL). The antibacterial activity of CZOP against E. faecalis was comparable to that of cefpirome (CPR; MIC90: 16 micrograms/mL) and higher than those of other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, like other drugs. The antibacterial activity of CZOP against S. pyogenes was as potent as those of cefotiam and CPR (MIC90: < or = 0.063 microgram/mL), and, against S. agalactiae, was also preferable (MIC90: 0.125 microgram/mL). CZOP indicated preferable antibacterial activity either against PSSP, PISP, or PRSP (MIC90: 0.25, 1, or 2 micrograms/mL). The antibacterial activity of CZOP against S. milleri group was also preferable, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (4 vs 0.5 micrograms/mL). The antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than those of cefazolin and cefmetazole. The resistance ratio estimated from breakpoint MIC of CZOP was 95.9% in MRSA, 93.5% in PRSP, 63.3% in PISP, 35.8% in S. haemolyticus, 27.9% in E. faecalis, and 13.3% MRSE. Those resistance ratios were comparable to those for cefepime (CFPM), but E. faecalis showed 91.2% for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against these species. In correlation of drug susceptibility, 40.3% of PRSP was not inhibited at breakpoint MIC either CZOP or CFPM while 69.2% at breakpoint MIC either CZOP or ceftazidime. In conclusion, the antibacterial activities of CZOP against the Gram-positive bacteria obtained from the 6-year duration study were consistent with the results from the studies performed until the new drug application approval. A decline in the sensitivities of S. saprophyticus, S. milleri group, PISP, and PRSP to CZOP, however, was suggested.

Carbapenems↗

Changing face of septicaemia and increasing drug resistance in blood isolates.

In a retrospective study conducted between January, 2000 and December 2000, 7157 adults and children were studied. Amongst these, 1071 patients had positive blood cultures. Of these, 575 (53.6%) cases were community acquired septicaemia and 486 (46.4%) cases had developed septicaemia of nosocomial origin. Gram negative aerobes accounted for 708 (66.1%) isolates. Amongst them, Klebsiella pneumoniae predominated (23%), followed by Escherichia coli (14%). Acinetobacter spp. emerged as the next common pathogen (9%), followed by Salmonella typhi (5.4%). Staphylococcus aureus (9%) and coagulase negative staphylococci (9%) were the most common gram positive isolates followed by Enterococcus faecalis (4.7%). Antibiotic susceptibility of all these isolates was performed by the modified Stokes' method. Both Klebsiella pneumoniae and Escherichia coli showed alarmingly high resistance to all groups of antibiotics with 70-80% resistance to amoxicillin and cephalexin. Minimum resistance was observed against cefotaxime (23%) and ciprofloxacin (12%). Majority of Enterococcus faecalis were multidrug resistant. Streptococcus pneumoniae exhibited 26% resistance to penicillin. Thus, the study clearly highlights the rising level of drug resistance amongst the bacterial isolates from blood and hence the need to update and formulate newer drug policies.

Adult↗

High prevalence of ceftazidime-resistant Klebsiella pneumoniae and increase of imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. in Korea: a KONSAR program in 2004.

A nationwide antimicrobial resistance surveillance has been conducted since 1997 in Korea. In this study, susceptibility test data generated in 2004 by KONSAR group hospitals were analyzed and compared to those at a commercial laboratory. In hospitals, the rank orders of organisms in 2004 were identical to those in 2003. The most prevalent species was Staphylococcus aureus (20.2%) in hospitals, but Escherichia coli (29.7%) in the commercial laboratory. The proportions of Enterococcus faecium to all isolates of Enterococcus faecalis plus E. faecium were 47.2% in hospitals and 24.9% in the commercial laboratory. The mean resistance rates of significant antimicrobial-organism combinations in hospitals were: oxacillin-resistant S. aureus (68%), oxacillin-resistant (penicillin- nonsusceptible) Streptococcus pneumoniae (68%), vancomycin-resistant E. faecium (25%), cefotaxime-resistant E. coli (14%), ceftazidime- and cefoxitin-resistant Klebsiella pneumoniae (34% and 32%, respectively), and imipenem-resistant Acinetobacter spp. and Pseudomonas aeruginosa (17% and 24%, respectively). In conclusion, oxacillin-resistant staphylococci, expanded-spectrum cephalosporin-resistant K. pneumoniae, and imipenem-resistant Acinetobacter spp. and P. aeruginosa were prevalent in 2004. Increasing trends were observed for vancomycin-resistant E. faecium, cefoxitin- resistant E. coli and K. pneumoniae, and imipenem-resistant Acinetobacter spp. and P. aeruginosa. Certain antimicrobial- organism combinations were also prevalent among the commercial laboratory-tested strains.

Acinetobacter↗

Periodontal microflora of HIV infected patients with periodontitis.

The aim of this study was to determine the microbial profile of periodontal lesions in HIV seropositive patients and to compare it with rapidly progressing periodontal lesions in systemically healthy patients. The subgingival microflora of 20 CDC II, 20 CDC III, 20 CDC IV/V and 20 systemically healthy patients with rapidly progressing periodontitis was examined. Four sites with greatest probing depth in each patient were selected for microbiological sampling. The samples were cultured aerobically and anaerobically for bacterial isolation using selective and non-selective media. Isolates were characterized to species level by conventional biochemical tests and various identification kits. The microflora of periodontitis lesions within the three stages of the HIV infection was similar to that of progressing periodontitis in systemically healthy adults including Campylobacter rectus, Capnocytophaga spp., Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Selenomonas spp. and Peptostreptococcus micros. However, HIV seropositive periodontitis lesions harboured a range of exogenous pathogens rarely associated with common types of periodontitis including Staphylococcus aureus, Enterobacter cloaca, Pseudomonas aeruginosa, Candida albicans, Enterococcus faecalis, Enterococcus avium, Clostridium difficile, Aspergillus fumigatus, Klebsiella pneumoniae and Mycoplasma incognitum. The lack of immune effector and regulatory cells in HIV infected patients could in fact explain the increase of some opportunistic pathogens and the characteristic and rapidly progressing nature of the periodontal disease in these patients.

Journal Article↗

Effects of clindamycin and metronidazole on the intestinal colonization and translocation of enterococci in mice.

The intestinal colonization and translocation of enterococci was studied in mice treated intramuscularly with metronidazole or clindamycin, with or without oral streptomycin. Treatment with metronidazole resulted in selective elimination of strictly anaerobic cecal bacteria, with a 100-fold increase in the numbers of aerobic and facultative gram-negative bacilli and a 10,000-fold increase in the numbers of aerobic and facultative gram-positive species. Clindamycin had a similar effect on the cecal flora except that the numbers of aerobic and facultative gram-positive bacteria decreased at least 10-fold. The predominating gram-positive species in the cecal flora or metronidazole-treated mice was an enterococcus, but this organism could not be recovered from the ceca of clindamycin-treated mice. Translocating bacteria (primarily gram-negative enteric bacteria) were recovered from the mesenteric lymph nodes of the majority of mice given metronidazole or clindamycin. Gram-positive bacteria were not recovered from the mesenteric lymph nodes of 20 clindamycin-treated mice, whereas 26% of 19 metronidazole-treated mice had translocating enterococci. With addition of streptomycin to the metronidazole and clindamycin regimens, mice treated with metronidazole-streptomycin became colonized predominantly with an enterococcus, and this was the only translocating species recovered from 13% of 23 mice; however, enterococci could not be detected in the ceca of clindamycin-streptomycin-treated mice, and Bacillus spp. were recovered from the mesenteric lymph nodes of 8% of 24 mice, reflecting the composition of the cecal flora. The apparent elimination of enterococci from the ceca of clindamycin and clindamycin-streptomycin-treated mice was inconsistent with the observation that the average (n=6) peak levels of clindamycin in blood and ceca were 25 and 21 microgram/ml, respectively, whereas the in vitro MIC was 128 microgram/ml. However, this apparent in vivo activity of clindamycin against enterococci was not evident in mice given 10(9) oral enterococci; the concentrations of cecal enterococci in both clindamycin-streptomycin- and metronidazole-streptomycin-treated mice were 10(10) to 10(11) enterococci per g, with translocating enterococci recovered from approximately half of these antibiotic-treated mice. Thus antibiotic therapy with metronidazole, clindamycin, metronidazole-streptomycin, and clindamycin-streptomycin resulted in a wide variation in the cecal population levels and translocation frequencies of enterococci. This variation appeared to be related to the discrepancy between the in vivo and in vitro activities of clindamycin against enterococci.

Animals↗

Verifying apple cider plant sanitation and hazard analysis critical control point programs: choice of indicator bacteria and testing methods.

The objectives of this study were (i) to evaluate the survival of coliforms, Escherichia coli, and enterococci in refrigerated apple cider; (ii) to develop simple and inexpensive presumptive methods for detection of these bacteria; (iii) to perform a field survey to determine the prevalence of these bacteria on apples and in apple cider; and (iv) based on our results, to recommend the most useful of these three indicator groups for use in verifying apple cider processing plant sanitation and hazard analysis critical control point (HACCP) programs. Eight of 10 coliform strains (5 E. coli, 1 Enterobacter aerogenes, and 2 Klebsiella spp.) inoculated into preservative-free apple cider (pH 3.4, 13.3(o) Brix) survived well at 4 degrees C for 6 days (< or = 3.0 log10 CFU/ml decrease). Of 21 enterococci strains (Enterococcus faecalis, E. faecium, and E. durans), only 2 E. durans and 3 E. faecium strains survived well. Simple broth-based colorimetric methods were developed that detected the presence of approximately 10 cells of coliforms or enterococci. In three field studies, samples of unwashed apples (drops and picked), washed apples, and freshly pressed cider were presumptively analyzed for total coliforms, E. coli, and enterococci using qualitative and/or quantitative methods. Drop apples were more likely than picked apples to be contaminated with E. coli (26.7% vs. 0%) and enterococci (20% vs. 0%). Washing had little effect on coliform populations and in one field study was associated with increased numbers. Total coliform populations in cider ranged from < 1 CFU/ml to > 738 most probable number/ml, depending on the enumeration method used and the sample origin. E. coli was not recovered from washed apples or cider, but enterococci were present on 13% of washed apple samples. The qualitative coliform method successfully detected these bacteria on apples and in cider. Based on its exclusively fecal origin, good survival in apple cider, and association with drop apples, we conclude that E. coli is the most useful organism for verifying apple cider sanitation and HACCP programs.

Beverages↗

[Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method].

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

Isolation and characterization of two bacteriocins produced by Enterococcus faecium strains inhibitory to Listeria monocytogenes.

A total of 4000 bacterial strains were isolated from milk, cheese and from different samples taken on the farm (silage, faeces) and screened for their antimicrobial activity against Listeria monocytogenes. Only eight of the almost 4000 strains exhibited inhibitory activity in the cell-free supernatant fluid. Two different Enterococcus strains (RZS C5 and RZS C13) were chosen for further study. Plasmid profile analysis of both revealed that RZS C5 contained a 4 kb plasmid while RZS C13 contained a 23 kb plasmid. The inhibitory compounds were proteinaceous and active against all Listeria spp. tested while most of the lactic acid bacteria were insensitive. Weak inhibition was also detected against Clostridium perfringens and some Bacillus spp. Cross-inhibition tests showed different profiles. The bacteriocins were heat-resistant and were very stable during storage, especially at low pH values. Their molecular weight was estimated at +/- 3.0 kDA. Addition of 200 AU/ml of bacteriocin resulted in an initial rapid decrease of the number of viable L. monocytogenes cells followed by slower a logarithmic decrease.

Animals↗

[HR 810 (cefpirome). Experimental evaluation of the in vitro and in vivo antibiotic activity of a new amino-2-thiazole methoxy- imino cephalosporin].

HR 810 or cefpirome is a new amino thiazole cephalosporin whose specific characteristic is a cyclopentenopyridinium group in position 3 of the cephem nucleus. This structure is responsible for a broad spectrum of activity, covering Enterobacteriaceae, including cephalosporinase-producing Enterobacter spp. and Citrobacter spp., Staphylococcus aureus, Pseudomonas aeruginosa and group D Streptococci.

Animals↗

Comparative study of new benzenesulphonamide fluoroquinolones structurally related to ciprofloxacin against selected ciprofloxacin-susceptible and -resistant Gram-positive cocci.

The in vitro activities of benzenesulphonamide fluoroquinolones (BSFQs) I-III, new fluoroquinolones with a p-substituted benzenesulphonyl moiety attached to the C(7) piperazinyl ring of ciprofloxacin, were assessed in comparison with those of N-sulfanilylpiperazinyl fluoroquinolone (NSFQ)-105 and ciprofloxacin for 133 Gram-positive clinical isolates. NSFQ-105 and BSFQ-I were the most active drugs. They were 16- to 64-fold more active than ciprofloxacin against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, including ciprofloxacin-resistant strains, and Streptococcus pneumoniae (eight- to 32-fold). A high degree of correlation was found between the MICs of the new compounds and ciprofloxacin for Staphylococcus spp. and E. faecalis. Staphylococci and enterococci exhibit cross-resistance to BSFQs and ciprofloxacin.

Anti-Infective Agents↗

Microbiology of indwelling central intravascular catheters.

Indwelling central-line catheters (n = 502) from 362 patients in intensive care units were analyzed prospectively. The skin site, 6-cm-distal and -proximal subcutaneous segments of the catheter, exudates, and blood were cultured. Semiqualitative roll plate cultures of the catheter segments were followed by broth cultures and examined for 72 h. All isolates were identified, and susceptibilities were determined. Line infections, defined clinically, yielded 22 different microbial species; 10 different species were recovered from colonized lines. Of the Staphylococcus epidermidis isolates recovered, 39% occurred singly and 21% occurred in combination with other microorganisms; Enterococcus faecalis, S. hominis, and Pseudomonas aeruginosa were next in frequency of isolation. Line infections also yielded other staphylococci, viridans group streptococci, several members of the family Enterobacteriaceae, acinetobacters, anaerobic bacteria, Candida spp., and Aspergillus fumigatus. While S. epidermidis was also the most frequent isolate among the line colonizers, different species and different frequencies of isolation were found among this group. The study showed that the distal catheter segment broth culture was the best predictor of clinical line infections; in addition, gram-negative bacteria were isolated only from the catheters of patients with overt infections.

Bacteria↗

Two investigational glycylcyclines, DMG-DMDOT and DMG-MINO. Antimicrobial activity studies against gram-positive species.

DMG-DMDOT (CL-331,002 OR CL-331,928) and DMG-MINO (CL-329,998 or CL-344,677) are two new semisynthetic tetracyclines called glycylcyclines, with a broad spectrum of activity and includes Enterobacteriaceae, Gram-positive cocci, JK diphtheroids, and Bacillus cereus. Potent activity was demonstrated against all Streptococcus spp. strains [minimum inhibitory concentrations] (MIC90S) 0.06-0.25 micrograms/ml) and staphylococci (oxacillin susceptible ans resistant; MIC90S 0.12-2 micrograms/ml). Both glycylcyclines (MIC90, 0.06 micrograms/ml) were more potent than minocycline (MIC90 8 micrograms/ml) against Enterococcus faecium, many of which were vancomycin resistant (116 strains). Organisms with minocycline MICs at > or = 8 micrograms/ml (Staphylococcus aureus, enterococci, beta-hemolytic streptococci, and pneumococci) had glycylcycline MIC results ranging from 0.06 to 0.5 micrograms/ml (e.g., apparent use against existing tetracycline-resistance phenotypes). Drugs in this class appear promising for therapy of infections caused by Gram-positive species now testing resistant to contemporary antimicrobial agents, and further development of compounds in this class is encouraged.

Anti-Bacterial Agents↗

Characterization of a bacteriocin produced by Enterococcus faecium GM-1 isolated from an infant.

AIM: To partially characterize the bacteriocin produced by the GM-1 strain of Enterococcus faecium, isolated from the faeces of a newborn human infant. METHODS AND RESULTS: The bacteriocin produced by E. faecium GM-1 showed a broad spectrum of activity against indicator strains of Escherichia coli, Staphylococcus aureus, Vibrio spp., Salmonella typhimurium, Listeria monocytogenes, Lactobacillus acidophilus, and Streptococcus thermophilus. Treatment of the GM-1 bacteriocin with proteolytic enzymes reduced its inhibitory activities. The bacteriocin was stable at 100 degrees C for 20 min and displayed inhibitory activity at neutral pH. The optimal production of bacteriocin from E. faecium GM-1 was obtained when the culture conditions were pH 6.0-6.5 and 35-40 degrees C. The inhibitory activity of the bacteriocin was not substantially changed by the use of different carbon sources in the media, except when galactose was substituted for glucose. The use of a sole nitrogen source caused a decrease in inhibitory activity. A bacteriocin gene similar to enterocin P was identified from the total DNA of E. faecium GM-1 by PCR and direct sequencing methods. CONCLUSION: E. faecium GM-1, which was isolated from the faeces of a newborn baby, produces an enterocin P-like bacteriocin with inhibitory activity against Gram-positive and Gram-negative bacteria, including food-borne pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: E. faecium GM-1, isolated from infant faeces, produces a new bacteriocin that is similar to enterocin P. This bacteriocin is heat stable and has a broad antibacterial spectrum that includes both Gram-positive and Gram-negative bacteria.

Amino Acid Sequence↗

Post-surgical enterococcal meningitis: clinical and epidemiological study of 20 cases.

Enterococcal post-surgical meningitis is an uncommon disease. 20 episodes of nosocomial post-surgical enterococcal meningitis diagnosed between 1994 and 2003 were retrospectively studied. During the period of study 20 cases of post-surgical enterococcal meningitis (60% female, mean age 55+/-18 y, range 16-78 y) were reviewed. The mean time between admission at the hospital and surgery was 26 (SD = 15) d (range 7-61 d). The most frequent underlying diseases were: intracerebral haemorrhage (55%), brain neoplasms (25%), head trauma (15%) and hydrocephalus (5%). 11 patients had previously received antibiotic treatment. The isolates identified were Enterococcus faecalis (n = 18) (90%), E. faecium (1) and E. durans (1). 11 patients had polymicrobial infections. The treatment most frequently used was vancomycin alone or with other antibiotics (11). In 5 patients intrathecal vancomycin (20 mg/d) was also added. The mortality rate was not different in intrathecally treated patients. Cerebrospinal fluid (CSF) devices were removed in 8 patients. Four patients died due to the infection. Mortality was significantly associated with lack of removal of the CSF devices (p = 0.04). Enterococcal spp. are a cause of nosocomial meningitis associated with neurosurgical procedures and the presence of neurological devices.

Adolescent↗