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In vitro utilization of amylopectin and high-amylose maize (Amylomaize) starch granules by human colonic bacteria.

It has been well established that a certain amount of ingested starch can escape digestion in the human small intestine and consequently enters the large intestine, where it may serve as a carbon source for bacterial fermentation. Thirty-eight types of human colonic bacteria were screened for their capacity to utilize soluble starch, gelatinized amylopectin maize starch, and high-amylose maize starch granules by measuring the clear zones on starch agar plates. The six cultures which produced clear zones on amylopectin maize starch- containing plates were selected for further studies for utilization of amylopectin maize starch and high-amylose maize starch granules A (amylose; Sigma) and B (Culture Pro 958N). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to detect bacterial starch-degrading enzymes. It was demonstrated that Bifidobacterium spp., Bacteroides spp., Fusobacterium spp., and strains of Eubacterium, Clostridium, Streptococcus, and Propionibacterium could hydrolyze the gelatinized amylopectin maize starch, while only Bifidobacterium spp. and Clostridium butyricum could efficiently utilize high-amylose maize starch granules. In fact, C. butyricum and Bifidobacterium spp. had higher specific growth rates in the autoclaved medium containing high-amylose maize starch granules and hydrolyzed 80 and 40% of the amylose, respectively. Starch-degrading enzymes were cell bound on Bifidobacterium and Bacteroides cells and were extracellular for C. butyricum. Active staining for starch-degrading enzymes on SDS-PAGE gels showed that the Bifidobacterium cells produced several starch-degrading enzymes with high relative molecular (M(r)) weights (>160,000), medium-sized relative molecular weights (>66,000), and low relative molecular weights (<66,000). It was concluded that Bifidobacterium spp. and C. butyricum degraded and utilized granules of amylomaize starch.

Amylopectin↗

Studies with cefuroxime: a new beta-lactamase resistant cephalosporin.

28 patients suffering from a variety of bacterial infections have been treated with cefuroxime. 18 were cured and 6 improved during treatment. Side effects were minimal and intramuscular injection was well tolerated. Serum and urine levels well in excess of the MICs of sensitive organisms were obtained using dosages of 750 mg 8 hourly. Biliary excretion was impaired in the presence of obstruction, but adequate bile levels of cefuroxime were observed following relief of the obstruction. Cefuroxime was widely active against gram-negative bacilli and against Streptococcus faecalis, but less active against Bacteroides spp.

Adult↗

Isolation and identification of cheese-smear bacteria inhibitory to Listeria spp.

A newly developed hydrophobic grid membrane method was used to rapidly screen 105 traditional French cheeses for surface smear microorganisms inhibitory to Listeria monocytogenes strain V7. Approximately 125,000 colonies comprising a wide variety of bacteria were examined of which less than 0.1% produced visible zones of inhibition. Isolates possessing antilisterial activity consisted of various strains of Enterococcus faecalis, Staphylococcus xylosus, Staphylococcus warneri and coryneform bacteria, including one orange coryneform resembling Brevibacterium linens. All strains of E. faecalis and the orange coryneform that inhibited L. monocytogenes V7 exhibited strong inhibition against a panel of 21 Listeria strains comprised of L. monocytogenes (14 strains), L. innocua (two strains), L. ivanovii (two strains), L. seeligeri (two strains) and L. welshimeri (one strain). The remaining cheese isolates showed moderate to weak inhibition towards the same set of Listeria strains. Inhibitory substances produced by all strains except the orange coryneform were sensitive to one or more of five proteolytic enzymes tested and were therefore classified as bacteriocin-like inhibitory agents.

Actinomycetales↗

In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin.

The in vitro antibacterial spectrum of gatifloxacin was compared with those of ciprofloxacin and ofloxacin. Gatifloxacin was two- to four-fold more potent than comparator quinolones against staphylococci, streptococci, pneumococci and enterococci (gatifloxacin MIC90s, < or =1 mg/L, except 4 mg/L against methicillin-resistant Staphylococcus aureus and Enterococcus faecium). Gatifloxacin was two-fold less potent than ciprofloxacin, and the same as or two-fold more potent than ofloxacin against Enterobacteriaceae (MIC90s, 0.06-0.5 mg/L against most members of the Enterobacteriaceae and < or =1 mg/L against Proteus/Morganella spp.). Relative to the comparator quinolones, gatifloxacin was two- to four-fold more potent against Providencia spp., and had good potency against Acinetobacter spp. (MIC90s, 0.25-1 mg/L). Gatifloxacin and ofloxacin had similar anti-pseudomonal potency, with corresponding MIC90s of 4, 8 and 0.25 mg/L for Pseudomonas aeruginosa, Pseudomonas fluorescens and Pseudomonas stutzeri, while ciprofloxacin had two- to eight-fold more potency. The three quinolones were equipotent against Burkholderia cepacia (MIC90s, 8 mg/L), but gatifloxacin was two-fold more potent against Stenotrophomonas maltophilia (MIC90, 4 mg/L). Gatifloxacin was highly potent (MIC90s, 0.03-0.06 mg/L) against Haemophilus influenzae, Legionella spp., Helicobacter pylori and had at least eight-fold better anti-chlamydial and anti-mycoplasma potency (gatifloxacin MIC90s, 0.13 mg/L). The higher quinolone MICs for ureaplasma (MIC90s, 4-8 mg/L) may be due to the acidic pH of the ureaplasma test medium, which antagonizes quinolones. Like other quinolones, gatifloxacin had poor potency against Mycobacterium avium-intracellulare, though it was eight- to 16-fold more potent against Mycobacterium tuberculosis (MIC90, 0.25 mg/L). Of the three quinolones, only gatifloxacin had activity against Bacteroides fragilis and Clostridium difficile. In summary, gatifloxacin is a broad-spectrum 8-methoxy fluoroquinolone that is more potent than ciprofloxacin and ofloxacin against Gram-positive bacteria, chlamydia, mycoplasma, mycobacteria and anaerobes.

Anti-Infective Agents↗

Cloning and sequencing of the low-affinity penicillin-binding protein 3r-encoding gene of Enterococcus hirae S185: modular design and structural organization of the protein.

The clinical isolate Enterococcus hirae S185 has a peculiar mode of resistance to penicillin in that it possesses two low-affinity penicillin-binding proteins (PBPs): the 71-kDa PBP5, also found in other enterococci, and the 77-kDa PBP3r. The two PBPs have the same low affinity for the drug and are immunochemically related to each other. The PBP3r-encoding gene has been cloned and sequenced, and the derived amino acid sequence has been compared by computer-assisted hydrophobic cluster analysis with that of the low-affinity PBP5 of E. hirae R40, the low-affinity PBP2' of Staphylococcus aureus, and the PBP2 of Escherichia coli used as the standard of reference of the high-M(r) PBPs of class B. On the basis of the shapes, sizes, and distributions of the hydrophobic and nonhydrophobic clusters along the sequences and the linear amino acid alignments derived from this analysis, the dyad PBP3r-PBP5 has an identity index of 78.5%, the triad PBP3r-PBP5-PBP2' has an identity index of 29%, and the tetrad PBP3r-PBP5-PBP2'-PBP2 (of E. coli) has an identity index of 13%. In spite of this divergence, the low-affinity PBPs are of identical modular design and possess the nine amino acid groupings (boxes) typical of the N-terminal and C-terminal domains of the high-M(r) PBPs of class B. At variance with the latter PBPs, however, the low-affinity PBPs have an additional approximately 110-amino-acid polypeptide stretch that is inserted between the amino end of the N-terminal domain and the carboxy end of the membrane anchor. While the enterococcal PBP5 gene is chromosome borne, the PBP3r gene appears to be physically linked to the erm gene, which confers resistance to erythromycin and is known to be plasmid borne in almost all the Streptococcus spp. examined.

Amino Acid Sequence↗

Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001-2002: the BSAC Bacteraemia Resistance Surveillance Programme.

OBJECTIVES: To describe the current patterns of antimicrobial resistance in the major pathogens of bacteraemia in the UK and Ireland, to highlight any unexpected resistance patterns and to act as a reference baseline for future studies. METHODS: In 2001 and 2002, 5092 blood culture isolates were collected by 29 laboratories distributed across the UK and Ireland. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method. RESULTS: Oxacillin resistance was found in 42% of Staphylococcus aureus and 76% of coagulase-negative staphylococci. Streptococci were generally susceptible to beta-lactams, but tetracycline resistance was common (except in Streptococcus pneumoniae) and particularly common among group B isolates (82% resistant). Nine percent of S. pneumoniae had reduced susceptibility to penicillin (MICs 0.12-1 mg/L), but none required >/=2 mg/L for inhibition. High-level gentamicin resistance was seen in 43% of Enterococcus faecalis, often in combination with raised ciprofloxacin MICs (>/=32 mg/L), but these isolates remained susceptible to ampicillin and imipenem. Only linezolid and tigecycline showed in vitro potency against a large proportion of Enterococcus faecium. Vancomycin resistance was restricted to enterococci (20% of E. faecium, 3% of E. faecalis) and a single isolate of coagulase-negative staphylococci (0.2%, MIC of 8 mg/L). Escherichia coli isolates were commonly resistant to amoxicillin (56%) and tetracycline (88%) but remained susceptible to ceftazidime, piperacillin/tazobactam and imipenem. Extended-spectrum beta-lactamases were detected in 2% of E. coli (none in 2001, 3.2% in 2002), 5% of Klebsiella spp. and 8% of Enterobacter spp. Resistance rates of Pseudomonas aeruginosa to ciprofloxacin, ceftazidime, gentamicin, imipenem and piperacillin/tazobactam were between 4% and 7%. Among the newly licensed and developmental agents, there was no resistance to linezolid in Gram-positive organisms. Ertapenem had a wide spectrum, covering Enterobacteriaceae, streptococci and oxacillin-susceptible staphylococci. MICs of tigecycline were low for Gram-positive species and Enterobacteriaceae except Proteeae and Enterobacter spp. CONCLUSION: Antimicrobial resistance among major bloodstream pathogens to those antimicrobials often selected for empirical therapy was relatively uncommon in 2001-2002, usually <10%. An important exception was oxacillin resistance in S. aureus.

Adult↗

Diversity of Salmonella spp. and fungi in northern Greek rivers and their correlation to fecal pollution indicators.

The prevalence and diversity of Salmonella spp., filamentous fungi, and yeasts and their correlation with fecal pollution indicators (total coliforms, fecal coliforms, enterococci) and total heterotrophic bacteria counts were investigated in 95 water samples from the northern Greek rivers Aliakmon and Axios. Salmonella spp. were isolated in 27.4% of the samples and a total of 19 serotypes were identified. The frequency of Salmonella isolation was higher in the Axios (36.8%) than in the Aliakmon (21.0%) river. Significantly (P<0.001) more Salmonella spp. were recovered during warm (41.4%) than cold (5.4%) months. Salmonella-positive samples showed significantly higher counts of total heterotrophic bacteria and coliforms. Filamentous fungi were isolated from 98.9% and yeasts from 17.9% of the samples with respective mean counts of 2.36 x 10(3) and 1.28 x 10(2)cfu/100mL. Totals of 23 genera of filamentous fungi and 3 genera of yeasts were identified. The most frequent filamentous fungi were Penicillium and Aspergillus, while Candida was the most prevalent yeast. A significant (P<0.001) positive correlation of the fecal pollution indicators was demonstrated only for filamentous fungi. The results of this study indicate that these rivers may be potential pathways for human and other animal contamination with Salmonella spp., filamentous fungi, and yeasts, which contribute to the pollution of marine waters and the surrounding environment.

Colony Count, Microbial↗

In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative.

T-3761, a new quinolone derivative, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.20 to 100 micrograms/ml against gram-positive bacteria, including members of the genera Staphylococcus, Streptococcus, and Enterococcus; 0.025 to 3.13 micrograms/ml against gram-negative bacteria, including members of the family Enterobacteriaceae and the genus Haemophilus; 0.05 to 50 micrograms/ml against glucose nonfermenters, including members of the genera Pseudomonas, Xanthomonas, Acinetobacter, Alcaligenes, and Moraxella; 0.025 micrograms/ml against Legionella spp.; and 6.25 to 25 micrograms/ml against anaerobes, including Bacteroides fragilis, Clostridium difficile, and Peptostreptococcus spp. The in vitro activity of T-3761 against these clinical isolates was comparable to or 2- to 32-fold greater than those of ofloxacin and norfloxacin and 2- to 16-fold less and 1- to 8-fold greater than those of ciprofloxacin and tosulfoxacin, respectively. When administered orally, T-3761 showed good efficacy in mice against systemic, pulmonary, and urinary tract infections with gram-positive and gram-negative bacteria, including quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa. The in vivo activity of T-3761 was comparable to or greater than those of ofloxacin, ciprofloxacin, norfloxacin, and tosufloxacin against most infection models in mice. The activities of T-3761 were lower than those of tosufloxacin against gram-positive bacterial systemic and pulmonary infections in mice but not against infections with methicillin-resistant Staphylococcus aureus. The activities of T-3761 against systemic quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa infections in mice were 2- to 14-fold greater than those of the reference agents.

Animals↗

Characterization of anti-Listeria monocytogenes bacteriocins from Enterococcus faecalis, Enterococcus faecium, and Lactococcus lactis strains isolated from Raïb, a Moroccan traditional fermented milk.

Seventy-four samples of raïb, a Moroccan traditional fermented milk, were screened for their anti-Listeria monocytogenes activity. Nine lactic acid bacteria with antilisterial activity were isolated and identified as Lactococcus lactis [4], Enterococcus faecium [4], and E. faecalis [1]. Antibacterial spectra, determined against 45 target strains, led to the selection of four antibacterial-producing strains, which were further characterized. Their anti-microbial agents, inactivated by one or more proteases, were designed as bacteriocins. Lactococcin R9/2 and R10/1 showed the broadest range of inhibitory action. Anti-bacterial spectra and physico-chemical properties suggest that these bacteriocins were similar to nisin. Enterocin R69 had a specificity of action against Listeria spp., whereas Enterocin R18 had a broad spectrum of activity. Lc. lactis R9/2 and E. faecalis R18 were able to coagulate sterilised UHT milk at 30 degrees C in 24 h and induced a 2 log reduction in L. monocytogenes ATCC 15313 population.

Animals↗

Taxonomy and physiology of probiotic lactic acid bacteria.

The current taxonomy of probiotic lactic acid bacteria is reviewed with special focus on the genera Lactobacillus, Bifidobacterium and Enterococcus. The physiology and taxonomic position of species and strains of these genera were investigated by phenotypic and genomic methods. In total, 176 strains, including the type strains, have been included. Phenotypic methods applied were based on biochemical, enzymatical and physiological characteristics, including growth temperatures, cell wall analysis and analysis of the total soluble cytoplasmatic proteins. Genomic methods used were pulsed field gel electrophoresis (PFGE), randomly amplified polymorphic DNA-PCR (RAPD-PCR) and DNA-DNA hybridization for bifidobacteria. In the genus Lactobacillus the following species of importance as probiotics were investigated: L. acidophilus group, L. casei group and L. reuteri/L. fermentum group. Most strains referred to as L. acidophilus in probiotic products could be identified either as L. gasseri or as L. johnsonii, both members of the L. acidophilus group. A similar situation could be shown in the L. casei group, where most of the strains named L. casei belonged to L. paracasei subspp. A recent proposal to reject the species L. paracasei and to include this species in the restored species L. casei with a neotype strain was supported by protein analysis. Bifidobacterium spp. strains have been reported to be used for production of fermented dairy and recently of probiotic products. According to phenotypic features and confirmed by DNA-DNA hybridization most of the bifidobacteria strains from dairy origin belonged to B. animalis, although they were often declared as B. longum by the manufacturer. From the genus Enterococcus, probiotic Ec. faecium strains were investigated with regard to the vanA-mediated resistance against glycopeptides. These unwanted resistances could be ruled out by analysis of the 39 kDa resistance protein. In conclusion, the taxonomy and physiology of probiotic lactic acid bacteria can only be understood by using polyphasic taxonomy combining morphological, biochemical and physiological characteristics with molecular-based phenotypic and genomic techniques.

Bifidobacterium↗

Comparative in-vitro activity of meropenem against selected pathogens from hospitalized patients in The Netherlands. MASTIN Study Group.

Thirty laboratories evaluated the in-vitro activity of meropenem and 15 commonly used antibiotics against selected microorganisms isolated in 1994-95 from hospitalized patients with serious infections requiring antibacterial treatment. Isolates (2169) from blood, sputum, pus or CSF were included. MICs were determined with Etest and NCCLS breakpoints were used. In general, the MICs of meropenem for Gram-positive isolates were found to be one- to six-fold higher than those of imipenem, except for Enterococcus faecalis. The MIC90 of meropenem for E. faecalis was high (32 mg/L) and distinctly higher than the MIC90 of imipenem (2 mg/L). The MICs of meropenem for Gram-negative isolates were two- to 24-fold lower, with the exception of Acinetobacter spp. Gram-negative fermentative strains, Enterobacter spp. in particular, isolated from patients in intensive care units (ICU) were more resistant to the -lactam antibiotics than those isolated from patients in non-intensive care wards. However, all Enterobacteriaceae, with and without inducible -lactamases, isolated from ICU patients were susceptible to meropenem.

Enterobacteriaceae↗

In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone.

CP-99,219 is a trifluoronaphthyridone with significant antibacterial activity that includes the family Enterobacteriaceae (MICs for 90% of the strains tested [MIC90s], < or = 0.015 to 0.5 micrograms/ml), Moraxella catarrhalis, Haemophilus influenzae, and gonococci (MICs, < or = 0.015 micrograms/ml). Legionella spp. were also CP-99,219 susceptible, with MICs of 0.008 to 0.12 micrograms/ml. CP-99,219 demonstrated activity greater than that of ciprofloxacin, ofloxacin, or enoxacin against Pseudomonas aeruginosa (MIC90, 1 microgram/ml), Xanthomonas maltophilia (MIC90, 2 micrograms/ml), Staphylococcus haemolyticus (MIC90, 0.5 micrograms/ml), Enterococcus faecalis (MIC90, 1 microgram/ml), and pneumococci (MIC90, 0.12 micrograms/ml). Numerous ciprofloxacin-resistant isolates were susceptible to CP-99,219, a new compound showing potential value for further in vivo trials.

Anti-Infective Agents↗

[Clinical laboratory approach to estimating the effective administration dose of imipenem/cilastatin. Evaluation of the disk susceptibility test and its interpretation system].

In vitro activities of imipenem/cilastatin (IPM/CS) against 413 clinical isolates were studied through the evaluation of MICs and the results of disk susceptibility tests. The MICs were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The MIC80s of imipenem (IPM) against Staphylococcus aureus and Staphylococcus epidermidis were 25 and 1.56 micrograms/ml, respectively, showing a bimodal MIC distribution. However, the distribution of MICs against other bacteria studied was of monomodal pattern. Group A Streptococcus, Enterococcus faecalis were inhibited by IPM at dose levels less than 0.025 and 6.25 micrograms/ml, respectively. IPM inhibited Escherichia coli at 0.20 microgram/ml, Klebsiella pneumoniae at 0.39 microgram/ml, Pseudomonas aeruginosa at 3.13 micrograms/ml except one strain showed a MIC of 25 micrograms/ml, Serratia spp. at 3.13 micrograms/ml except one with MIC greater than 100 micrograms/ml, Citrobacter freundii at 0.78 microgram/ml and Enterobacter spp. at 0.39 microgram/ml. Indole (-) Proteus and indole (+) Proteus were inhibited by this drug at levels of 3.13 and 1.56 micrograms/ml, respectively. The reliability of the IPM disk diffusion susceptibility test in quantitative estimation of antimicrobial activities was well demonstrated using commercialized 8 mm diameter Showa disks containing 30 micrograms antibiotic and also disks containing 1-30 micrograms prepared in this laboratory. For the interpretation of the Showa disk susceptibility test, a 4 category system was used. In the 4 category system for Showa IPM disk the following classification of inhibitory zone diameters has been proposed; ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. The results of the test using Showa 30 micrograms disk against various clinical isolates were accurately classified into the 4 groups, showing false positive 8 out of 304 strains (2.6%) and false negative 1 of 304 strains (0.3%). With Showa 30 micrograms disks subclassification of strains with MIC less than 3 micrograms/ml cannot be achieved. In this study, however, the differentiation of strains with MICs less than 1 microgram/ml was made with disks containing 5-10 micrograms, which afforded to set MIC break points at 1 and 3 micrograms/ml. According to current concepts on pharmacokinetics for antibiotics including the penetration of drugs into tissues and inflammatory fluids, serum protein binding of drugs appears to be one of the important determinants of drug distribution in the body. Only free, unbound drug molecules can readily pass through capillary pores into tissue fluids except in the hepato-biliary system.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

Antibacterial spectrum of a novel des-fluoro(6) quinolone, BMS-284756.

The in vitro spectrum of a novel des-fluoro(6) quinolone, BMS-284756, was compared with those of five fluoroquinolones (trovafloxacin, moxifloxacin, levofloxacin, ofloxacin, and ciprofloxacin). BMS-284756 was among the most active and often was the most active quinolone against staphylococci (including methicillin-resistant strains), streptococci, pneumococci (including ciprofloxacin-nonsusceptible and penicillin-resistant strains), and Enterococcus faecalis. BMS-284756 inhibited approximately 60 to approximately 70% of the Enterococcus faecium (including vancomycin-resistant) strains and 90 to 100% of the Enterobacteriaceae strains and gastroenteric bacillary pathogens at the anticipated MIC susceptible breakpoint (</=4 microg/ml). Against the nonfermenters, BMS-284756 inhibited 90 to 100% of Pseudomonas fluorescens, Pseudomonas stutzeri, Stenotrophomonas maltophilia, Flavobacterium spp., and Acinetobacter spp. and 72% of Pseudomonas aeruginosa strains at 4 microg/ml. Against anaerobic bacteria, BMS-284756 was among the most active, inhibiting essentially all strains tested. It had very low MICs against the fastidious and atypical microbial species, in particular against mycoplasmas or ureaplasmas, Borrelia burgdorferi, chlamydia, and gonococci. These results indicate that with its broad antibacterial spectrum, BMS-284756 should be evaluated clinically for the treatment of community and nosocomial infections.

Anti-Infective Agents↗

Generation of auxotrophic mutants of Enterococcus faecalis.

A 22-kb segment of chromosomal DNA from Enterococcus faecalis OG1RF containing the pyrimidine biosynthesis genes pyrC and pyrD was previously detected as complementing Escherichia coli pyrC and pyrD mutations. In the present study, it was found that the E. faecalis pyrimidine biosynthetic genes in this clone (designated pKV48) are part of a larger cluster resembling that seen in Bacillus spp. Transposon insertions were isolated at a number of sites throughout the cluster and resulted in loss of the ability to complement E. coli auxotrophs. The DNA sequences of the entire pyrD gene of E. faecalis and selected parts of the rest of the cluster were determined, and computer analyses found these to be similar to genes from Bacillus subtilis and Bacillus caldolyticus pyrimidine biosynthesis operons. Five of the transposon insertions were introduced back into the E. faecalis chromosome, and all except insertions in pyrD resulted in pyrimidine auxotrophy. The prototrophy of pyrD knockouts was observed for two different insertions and suggests that E. faecalis is similar to Lactococcus lactis, which has been shown to possess two pyrD genes. A similar analysis was performed with the purL gene from E. faecalis, contained in another cosmid clone, and purine auxotrophs were isolated. In addition, a pool of random transposon insertions in pKV48, isolated in E. coli, was introduced into the E. faecalis chromosome en masse, and an auxotroph was obtained. These results demonstrate a new methodology for constructing defined knockout mutations in E. faecalis.

Base Sequence↗

Comparative synergistic activity of netilmicin-piperacillin versus gentamicin-piperacillin.

The synergistic action of the combination netilmicin-piperacillin in comparison to gentamicin-piperacillin was studied in 206 clinical isolates of staphylococci, enterococci, Enterobacteriaceae and Pseudomonas aeruginosa by means of the checkerboard technique. Overall, netilmicin-piperacillin acted synergistically against 31% and gentamicin-piperacillin against 14% of the 206 strains. In particular, synergism was more frequently observed with netilmicin-piperacillin against Escherichia coli, Citrobacter spp., indole-positive Proteus spp. and Pseudomonas aeruginosa. Synergy was uncommon with either combination against enterococci, Staphylococcus epidermidis and Serratia spp. Only partial synergy or indifference was seen with both combinations against Klebsiella spp. The interaction of netilmicin would appear to be superior to that of gentamicin in combination with piperacillin.

Bacteria↗

Activity of meropenem, against gram-positive bacteria.

A new carbapenem antibiotic, meropenem, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative, methicillin-susceptible staphylococci equally well. Among the comparative antimicrobials examined, only N-formimidoyl-thienamycin (imipenem) was two to four times more active than meropenem. Compared with vancomycin or methicillin, meropenem was 10-20 times more active. Strains of 11 species of streptococci were highly susceptible to meropenem; the geometric mean MICs of the drug for these species ranged from 0.01 to 0.04 mg/l. The agent, however, only had moderate activity against Enterococcus faecalis (mean MIC 5 mg/l) and Ent. faecium (mean MIC 11.6 mg/l). Among Corynebacterium jeikeium, strains were encountered that showed susceptibility to meropenem but resistance to imipenem and other beta-lactams. Strains of other corynebacteria, Rhodococcus equi, Erysopelothrix rhusiopathiae, Listeria monocytogenes, and Bacillus spp. all were highly susceptible to meropenem (mean MICs 0.04-0.17 mg/l). Although methicillin-resistant staphylococci were inhibited by concentrations of 1-2 mg/l of meropenem in agar dilution tests, such strains showed heteroresistance in population studies, as is typical for all beta-lactam antibiotics. In addition, the biochemical correlate of methicillin-resistance, penicillin-binding protein 2', showed low affinity for meropenem, similar to that for imipenem. Meropenem was as bactericidal as imipenem and comparative bactericidal antimicrobials in killing-curve experiments. Strains of Ent. faecium, C. jeikeium, and L. monocytogenes were killed at a slower rate than streptococci or staphylococci.

Bacterial Proteins↗

A comparison of antimicrobial resistance rates in Gram-positive pathogens isolated in the UK from October 1996 to January 1997 and October 1997 to January 1998.

Rates of resistance for two consecutive years for 28 centres (10 Teaching, nine Associate Teaching and nine District General hospitals) in the UK were compared. Combined rates of resistance for each of the hospital types of Staphylococcus aureus to methicillin revealed an increase in the rate of resistance in Teaching hospitals (12.5% year 1, 23.5% year 2), but, for Associate Teaching and District General hospitals rates fell (Associate Teaching 19.1% year 1, 11.9% year 2; District General 16.5% year 1 and 11.3% year 2). Using conventional methodology to determine MICs, no strain was considered to have reduced susceptibility to vancomycin. Among coagulase-negative staphylococci, increased resistance was observed for Staphylococcus epidermidis to rifampicin, for Staphylococcus haemolyticus to clindamycin, for Staphylococcus saprophyticus to penicillin and for Staphylococcus spp. to clindamycin, methicillin and rifampicin. For Streptococcus pneumoniae an upward trend in low-level resistance to penicillin was observed (18 of the 28 centres), however, for high-level resistance the trend was in the opposite direction (only four centres showed an increase). For Enterococcus faecalis there was a trend to a fall in levels of resistance, the only exception being an increase in high-level gentamicin resistance (10.5% year 1, 15.1% year 2, P = 0.0388). For Enterococcus faecium rates of resistance were not significantly different except for increases in resistance to nitrofurantoin and rifampicin.

Anti-Bacterial Agents↗