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Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn.

Coagulase-negative staphylococci (CNS) are the leading cause of late-onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety-seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Orebro, Sweden in 1983-1997 were analysed. Twenty-nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed-field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.

Bacterial Typing Techniques↗

Antibodies to bacterial vaccines demonstrating specificity for human choriogonadotropin (hCG) and immunochemical detection of hCG-like factor in subcellular bacterial fractions.

Investigations were done to determine whether vaccines prepared with chemically killed Staphylococcus haemolyticus RU1 and Streptococcus bovis AV46 (bacteria that have been demonstrated to express human choriogonadotropin [hCG]-like material on their surface) elicited antibodies in rabbits with specificity for hCG determinants. In addition, the anatomical locus of the hCG-like factor was determined by separation of bacterial subcellular fractions. The results demonstrated that these bacterial vaccines elicited antibodies immunologically similar to those antibodies produced in response to the whole human trophoblastic hormone, a similarity extending even to cross-reactivity with human luteinizing hormone. The bacterial hCG-like material appeared to be localized in the membranes of the cell wall, and most was present in the soluble membranous and cytoplasmic constituents. Its expression in bacteria was a strain characteristic and not a species characteristic.

Animals↗

Investigation of Staphylococcus strains with heterogeneous resistance to glycopeptides in a Turkish university hospital.

BACKGROUND: The hetero-glycopeptide intermediate staphylococci is considered to be the precursor of glycopeptide intermediate staphylococci especially vancomycin intermediate Staphylococcus aureus (VISA). For this purpose, we aimed to investigate the heterogeneous resistance to glycopeptide and their frequencies in 135 Staphylococcus strains. METHODS: Heterogeneous resistance of Staphylococcus strains was detected by inoculating the strains onto Brain Heart Infusion agar supplemented with 4 mg/L of vancomycin (BHA-V4). Agar dilution method was used for determining MICs of glycopeptides and population analysis profile was performed for detecting frequency of heterogeneous resistance for the parents of selected strains on BHA-4. RESULTS: Eight (6%) out of 135 Staphylococcus strains were exhibited heterogeneous resistance to at least one glycopeptide. One (1.2%) out of 81 S. aureus was found intermediate resistance to teicoplanin (MIC 16 mg/L). Other seven strains were Staphylococcus haemolyticus (13%) out of 54 coagulase negative staphylococci (CoNS). Six of the seven strains were detected heterogeneously reducing susceptibility to vancomycin (MICs ranged between 5-8 mg/L) and teicoplanin (MICs ranged between 32-64 mg/L), and one S. haemolyticus was found heterogeneous resistance to teicoplanin (MIC 32 mg/L). Frequencies of heterogeneous resistance were measured being one in 10(6) - 10(7) cfu/ml. MICs of vancomycin and teicoplanin for hetero-staphylococci were determined as 2-6 folds and 3-16 folds higher than their parents, respectively. These strains were isolated from six patients (7%) and two (4%) of health care workers hands. Hetero-VISA strain was not detected. CONCLUSION: Heterogeneous resistance to glycopeptide in CoNS strains was observed to be significantly more emergent than those of S. aureus strains (vancomycin P 0.001, teicoplanin, P 0.007). The increase MICs of glycopeptide resistance for subpopulations of staphylococci comparing with their parents could be an important clue for recognizing the early steps in the appearance of VISA strains. We suggested to screen clinical S. aureus and CoNS strains, systematically, for the presence of heterogeneously resistance to glycopeptide.

Anti-Bacterial Agents↗

The bacteria responsible for ureolysis in artificial dental plaque.

The origin of ureolytic activity in artificial-mouth plaques was established by assessing the contribution to plaque ureolytic activity of the isolated bacteria. To overcome losses of ureolytic activity caused by the unstable presence of urease in oral bacteria, ureolytic bacteria were isolated from an exceptionally active plaque (1 mumol NH3/min per mg protein) in which 63 per cent of the flora was ureolytic. After their ability to metabolize urea was stabilized, 13 ureolytic bacteria remained: seven strains of Streptococcus salivarius, one Streptococcus bovis, two Staphylococcus epidermidis and three Staphylococcus haemolyticus. Their urease activity, measured after growth into stationary phase, was reproducible and strain specific with a 20-fold range within each genus. The mean ureolytic activity of each species, when weighted by its calculated incidence in the original plaque, accounted for 40 per cent of the total plaque ureolytic activity. However, these values for urease levels were only a small fraction of the bacterial ureolytic potential. Urease per mg cell protein measured during the growth cycle of a selected Strep. salivarius, and Staph. epidermidis, varied 10-fold, and reached much higher activities (i.e. 6-8 mumol NH3/min per mg of cell protein) than under the growth conditions that were used to assess the contribution of these species to total plaque ureolysis. Thus urea metabolism in artificial plaque was due mainly to Strep. salivarius, with a small contribution from Staph. epidermidis. The presence of further unidentified species of ureolytic oral bacteria need not be invoked.

Bacteria↗

Spread of clones of multidrug-resistant, coagulase-negative staphylococci within a university hospital.

OBJECTIVE: To detect putative clonal dissemination of multidrug-resistant, coagulase-negative staphylococci (CNS) in a university hospital in northern Sweden. METHODS: All consecutive routine clinical samples from our hospital were screened during two periods (November and December 2001 and September and October 2002) for the presence of multidrug-resistant (defined as resistant to oxacillin, clindamycin, co-trimoxazole, gentamicin, and fusidic acid, but susceptible to vancomycin) isolates of CNS. Genetic similarity between isolates was analyzed using pulsed-field gel electrophoresis (PFGE) and a computer program. RESULTS: Seventy multidrug-resistant isolates from 62 patients were identified, 28 during the 2001 period and 42 during the 2002 period. All isolates except one, which was Staphylococcus haemolyticus, were identified as S. epidermidis. Multidrug-resistant CNS were isolated in samples obtained from 24 different wards. Two subgroups (group A and group B) of S. epidermidis that differed by approximately 40% in PFGE band similarity were identified. Group A consisted of 44 isolates with a PFGE band similarity of greater than 70% that included 6 subgroups consisting of 3 to 16 isolates that expressed a 100% similarity. These isolates were identified during both sampling periods in cultures performed in 18 different wards. A clonal origin could not be excluded for some of the remaining 26 isolates belonging to group B, but none had identical PFGE patterns, suggesting a more diverse origin. CONCLUSION: The results of this study suggest clonal spread of multidrug-resistant CNS within our hospital and that some clones are endemic in the hospital environment.

Adolescent↗

Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels.

Cefdinir is one of the few oral third generation cephalosporins that shows useful activity against nosocomial Gram-positive pathogens. For this reason the anti-staphylococcal potency of the new drug, alone or in combination with other drugs was further characterized. Against penicillin-resistant, oxacillin-susceptible Staphylococcus isolates, cefdinir demonstrated useful in-vitro activity. MIC90 values (in mg/L) were 0.25 for Staphylococcus aureus (30 strains), 0.06 for Staphylococcus epidermidis (24), 0.125 for Staphylococcus hominis (10), 0.5 for both Staphylococcus xylosus (15) and Staphylococcus capitis (11) and 4 for Staphylococcus saprophyticus (10), while Staphylococcus haemolyticus (12) was less susceptible with a MIC90 value of 32. Cefdinir activity was not adversely affected by several variables such as pH, inoculum size or the presence of serum or urine. The new cephem induced a PAE on all isolates studied: with S. aureus the extent of regrowth suppression ranged from 0.8 to 1 h, and with the other species from 0.5 (S. epidermidis) to 4.1 h (S. haemolyticus). Development of resistant strains was rare. At the highest level used (10 x MIC) mutants arose with a frequency of 6 x 10(-8) with S. haemolyticus and 2 x 10(-9) with S. epidermidis. The absence of a paradoxical effect of increasing concentrations of cefdinir on its bactericidal activity was confirmed up to a value of 500-fold the MICs. When cefdinir activity was assessed in association with ciprofloxacin, netilmicin, clarithromycin, fosfomycin, rifampicin, teicoplanin and vancomycin using the chequerboard and time-kill techniques, indifference predominated with all strains and in all combinations. Synergism was detected only in 11 out of a total of 175 tests performed by the chequerboard method. Using the time-kill technique cefdinir reacted synergically in 25 of 126 tests. Antagonism was never observed. S. aureus exposed to sub-inhibitory concentrations of cefdinir failed to grow on mannitol-salt agar and to produce haemolysins, but retained coagulase activity. Penicillinase production was also lost in about 17% of the survivors. Hydrophobicity changes were detected in all species tested with the exception of S. saprophyticus.

Anti-Bacterial Agents↗

Comparative study of hemolytic substances produced by coagulase-negative Staphylococcus strains.

Hemolytic substances H7, H62, and E56, produced by Staphylococcus haemolyticus 7 and 62 and S. epidermidis 56, respectively, were purified. H7 and H62 are probably similar on the basis of their isoelectric focusing profiles in 8 M urea and complete immunological identity as revealed by immunodiffusion with rabbit anti-H7 and anti-E56 sera. For E56, we observed seven bands instead of three in isoelectric focusing and only partial immunological identity with H7 and H62. However, H7 and E56 were similar with regard to the following characteristics: hemolytic spectra against different erythrocytes, kinetics of erythrocyte lysis, heat stability, and inhibition by phosphatidylcholine. E56 was not active at a temperature lower than or equal to 25 degrees C, and its activity increased more rapidly with increased temperature compared with H7. For both substances, the complexes obtained by molecular filtration on Ultrogel AcA54 and the purified peptides by reverse-phase high-pressure liquid chromatography showed some hemolytic activity. These results suggest that a particular association or the presence of a given peptide could enhance the activity.

Chromatography, High Pressure Liquid↗

Stool microflora in extremely low birthweight infants.

AIM: To serially characterise aerobic and anaerobic stool microflora in extremely low birthweight infants and to correlate colonisation patterns with clinical risk factors. METHODS: Stool specimens from 29 infants of birthweight <1000 g were collected on days 10, 20, and 30 after birth. Quantitative aerobic and anaerobic cultures were performed. RESULTS: By day 30, predominant species were Enterococcus faecalis, Escherichia coli, Staphylococcus epidermidis, Enterbacter cloacae, Klebsiella pneumoniae, and Staphylococcus haemolyticus. Lactobacillus and Bifidobacteria spp were identified in only one infant. In breast milk fed (but not in formula fed) infants, the total number of bacterial species/stool specimen increased significantly with time (2.50 (SE 0.34) on day 10; 3.13 (0.38) on day 20; 4.27 (0.45) on day 30) as did quantitative bacterial counts; Gram negative species accounted for most of the increase. On day 30, significant inverse correlations were found between days of previous antibiotic treatment and number of bacterial species (r=0.491) and total organisms/g of stool (r=0.482). Gestational age, birthweight, maternal antibiotic or steroid treatment, prolonged rupture of the membranes, and mode of delivery did not seem to affect colonisation patterns. CONCLUSIONS: The gut of extremely low birthweight infants is colonised by a paucity of bacterial species. Breast milking and reduction of antibiotic exposure are critical to increasing fecal microbial diversity.

Anti-Bacterial Agents↗

Molecular cloning of a 32-kilodalton lipoprotein component of a novel iron-regulated Staphylococcus epidermidis ABC transporter.

Our previous studies identified two iron-regulated cytoplasmic membrane proteins of 32 and 36 kDa expressed by both Staphylococcus epidermidis and Staphylococcus aureus. In this study we show by Triton X-114 phase partitioning and tritiated palmitic acid labelling that these proteins are lipoproteins which are anchored into the cytoplasmic membrane by their lipid-modified N termini. In common with those of some other gram-positive bacteria, these highly immunogenic lipoproteins were released from the bacterial cell into the culture supernatants, with release being promoted by growth of the bacteria under iron-restricted conditions. Immunoelectron microscopy with a monospecific rabbit antiserum to the 32-kDa S. epidermidis lipoprotein showed that the majority of the antigen was distributed throughout the staphylococcal cell wall. Only minor quantities were detected in the cytoplasmic membrane, and exposure of the lipoprotein on the bacterial surface was minimal. A monoclonal antibody raised to the 32-kDa lipoprotein of S. aureus was used in immunoblotting studies to investigate the conservation of this antigen among a variety of staphylococci. The monoclonal antibody reacted with polypeptides of 32 kDa in S. epidermidis and S. aureus and of 40 kDa in Staphylococcus hominis. No reactivity was detected with Staphylococcus lugdunensis, Staphylococcus cohni, or Staphylococcus haemolyticus. The gene encoding the 32-kDa lipoprotein from S. epidermidis has been isolated from a Lambda Zap II genomic DNA library and found to be a component of an iron-regulated operon encoding a novel ABC-type transporter. The operon contains three genes, designated sitA, -B, and -C, encoding an ATPase, a cytoplasmic membrane protein, and the 32-kDa lipoprotein, respectively. SitC shows significant homology both with a number of bacterial adhesins, including FimA of Streptococcus parasanguis and ScaA of Streptococcus gordonii, and with lipoproteins of a recently described family of ABC transporters with proven or putative metal ion transport functions. Although the solute specificity of this novel transporter has not yet been determined, we speculate that it may be involved in either siderophore- or transferrin-mediated iron uptake in S. epidermidis.

ATP-Binding Cassette Transporters↗

Coagulase-negative staphylococci in very-low-birth-weight infants: inability of genetic markers to distinguish invasive strains from blood culture contaminants.

Selected coagulase-negative staphylococci from the blood of very-low-birth-weight infants in the Neonatal Intensive Care Unit at the Royal Women's Hospital, Melbourne, collected over a 5-year period were examined. Isolates were classified as invasive or contaminants, speciated, typed by pulsed-field gel electrophoresis, and examined for biofilm genes (icaA, icaC, and icaD), adhesion genes (atlE, fbe), and the number of copies of IS256. Of the 24 isolates studied, there were 13 contaminants and 11 invasive isolates. The collection included 15 Staphylococcus epidermidis, eight Staphylococcus capitis, and one each of Staphylococcus warneri and Staphylococcus haemolyticus. Two small clusters of S. epidermidis that belonged to the same molecular type were identified. All S. capitis isolates belonged to the same molecular type or subtype, suggesting that a particular clone was circulating in the unit. There was no significant difference in the species found, the presence of icaA, icaC, icaD, atlE, or fbe, or the number of copies of IS256 between invasive isolates and contaminants. A series of nasal isolates from nonhospitalized adults differed from hospital isolates in the absence of IS256 and the low prevalence of icaC. There was no evidence of IS256-mediated insertion into ica genes as a mechanism of phase variation. These findings suggest that contaminants and invasive isolates derived from the same pool of hospital strains capable of causing sepsis in compromised hosts and that other mechanisms of phase variation exist, apart from IS256 insertion into ica genes.

Biofilms↗

Genomic and food-safety evaluation of Staphylococcus chromogenes in Chinese dairy milk.

Non-aureus staphylococci and mammaliicocci (NASM) cause mastitis and may contaminate milk and dairy products. Milk samples (n&#xa0;=&#xa0;1916) from cows with subclinical or clinical mastitis (SCM and CM, respectively) were collected from 28 large-scale (> 500 lactating cows) Chinese dairy farms. Overall, 999 NASM isolates representing 19 species were identified by MALDI-TOF MS and cpn60 sequencing, with Staphylococcuschromogenes, Mammaliicoccus sciuri and Staphylococcus haemolyticus being most prevalent. Antimicrobial resistance (AMR) was determined with disc diffusion; non-susceptible to penicillin was most common (SCM, 30% and CM, 29%) whereas cefoxitin non-susceptible NASM accounted for 8-10% of isolates; among these, 12.5% carried mecA but none carried mecC. Galleria mellonella was used to assess virulence of 78 strains of S. chromogenes, a dominant species; subsequently, 32 strains, representing higher- and lower-virulence in the Galleria model, were selected for whole-genome sequencing and comparative genomics. S. chromogenes isolates from CM had higher virulence (p&#xa0;<&#xa0;0.05) than those from SCM. The 32 genomes comprised 20 sequence types, indicating high genetic diversity. No robust genomic marker of Galleria virulence phenotype was identified in this selected WGS subset. Acquired resistance genes (n&#xa0;=&#xa0;5) were detected, including a first report of fusC in S. chromogenes; the fusC-positive isolate had an elevated fusidic acid MIC (8&#xa0;mg/L). Although S. chromogenes persisted in milk at 4&#xa0;&#xb0;C, pasteurization (64&#xa0;&#xb0;C for 30&#xa0;min) reduced viable counts to below detection. This study provided new insights into the prevalence, AMR, genomic diversity, and dairy-chain relevance of milk-derived NASM, particularly S. chromogenes. However, the genomic findings were based on an intentionally selected WGS subset and should be interpreted as hypothesis-generating rather than population-representative.

Animals↗

In vitro activities of RWJ-54428 (MC-02,479) against multiresistant gram-positive bacteria.

RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria. In a broth microdilution susceptibility test against methicillin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC(90)) of 2 microg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC(90) of 2 microg/ml. RWJ-54428 was active against S. aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, < or = 0.0625 to 1 microg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC(90), 0.5 microg/ml). For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC(90) of 0.125 microg/ml. RWJ-54428 was also active against Enterococcus faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between < or = 0.0625 and 1 microg/ml for ampicillin-susceptible strains and 0.125 and 8 microg/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains of Streptococcus pneumoniae (MIC(90)s, 0.25, 0.125, and < or = 0.0625 microg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae and Moraxella catarrhalis (MIC(90)s, 0.25 and 0.5 microg/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials.

Anti-Bacterial Agents↗

Ampicillin-sulbactam is effective in prevention and therapy of experimental endocarditis caused by beta-lactamase-producing coagulase-negative staphylococci.

Optimal strategies for the prophylaxis and therapy of endocarditis caused by oxacillin-resistant, coagulase-negative staphylococci in patients with native or prosthetic valvular heart disease are not well defined. We compared the in vivo efficacies of ampicillin-sulbactam-based regimens with those of vancomycin-based oxacillin-resistant, beta-lactamase-producing coagulase-negative staphylococcal isolate (Staphylococcus haemolyticus SE220). Ampicillin-sulbactam (100 and 20 mg/kg of body weight, respectively, given intramuscularly in a two-dose regimen) was equivalent to vancomycin (30 mg/kg given intravenously in a two-dose regimen) in its prophylactic efficacy against the coagulase-negative staphylococcal strain (93 and 80%, respectively). The combination of ampicillin-sulbactam plus either rifampin or vancomycin did not enhance the prophylactic efficacy compared with that of ampicillin-sulbactam or vancomycin alone. In the therapy of established aortic valve endocarditis in rabbits caused by this same coagulase-negative staphylococcal strain, animals received 7-day ampicillin-sulbactam-based or vancomycin-based regimens with or without rifampin. All treatment regimens were effective at lowering intravegetation coagulase-negative staphylococcal densities and rendering vegetations culture negative compared with the coagulase-negative staphylococcal densities and vegetations of untreated controls, with ampicillin-sulbactam in combination with rifampin or vancomycin being the most active regimen. However, only the regimen of ampicillin-sulbactam in combination with vancomycin effectively prevented relapse of endocarditis posttherapy after a 5-day antibiotic-free period. For animals receiving rifampin-containing regimens, relapses of endocarditis were associated with the in vivo development of rifampin resistance among coagulase-negative staphylococcal isolates in the vegetation. Ampicillin-sulbactam was highly effective in the prevention of experimental endocarditis caused by a beta-lactamase-producing, oxacillin-resistant coagulase-negative staphylococcal strain. Ampicillin-sulbactam was also efficacious for the therapy of coagulase-negative staphylococcal endocarditis, especially when it was combined with vancomycin to prevent posttherapeutic relapses.

Ampicillin↗

Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin.

Evidence of synergism between combinations of vancomycin and beta-lactam antibiotics against 59 isolates of methicillin-resistant staphylococci (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus) for which vancomycin MICs ranged from 1 to 16 microg/ml were tested by broth microdilution checkerboard, disk diffusion, agar dilution, and time-kill antimicrobial susceptibility tests. The combination of vancomycin and oxacillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxicillin-clavulanate but not for aztreonam. Evidence of synergy correlated directly with vancomycin MICs. The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental endocarditis caused by three clinical isolates of glycopeptide-intermediate-susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in this model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffective for animals infected with HIP5827 or MU50. However, the combination of vancomycin and nafcillin resulted in a mean reduction of 4.52 log10 CFU/g of aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4. 15 log10 CFU/g for animals infected with MU50. Renal abscesses caused by HIP5827 were sterilized significantly better with the combination of vancomycin and nafcillin than by either treatment alone. We conclude that the combination of vancomycin and beta-lactams with antistaphylococcal activity is an effective regimen for the treatment of infections with clinical strains of staphylococci which demonstrate reduced susceptibility to glycopeptides.

Animals↗

Adhesion of bacteria to stainless steel and silver-coated orthopedic external fixation pins.

Bacterial adhesion to silver-coated orthopedic external fixation pins was compared with stainless steel controls in an in vitro study. Using five bacterial isolates from wound infections, the silver coating was found to reduce adhesion for Escherichia coli, Pseudomonas aeruginosa, and two strains of Staphylococcus aureus while the converse applied for Staphylococcus haemolyticus. When placed in human serum, both surfaces were conditioned to a similar extent with serum proteins; this conditioning lead to further reductions in bacterial adhesion, ultimately approaching similar levels for both stainless steel and silver-coated samples.

Bacterial Adhesion↗

Comparative in vitro activity of cefpirome and cefepime, two new cephalosporins.

In in vitro tests the broad-spectrum cephalosporins cefpirome and cefepime were highly active against Enterobacteriaceae, although often less so against strains resistant to amoxicillin-clavulanate and ticarcillin-clavulanate, and against most strains of Acinetobacter spp. and Aeromonas hydrophila. They were also active against Pseudomonas aeruginosa, although strains with non-plasmid mediated beta-lactam resistance were sometimes less sensitive. Other Pseudomonas spp. varied in their sensitivity. Both agents were highly active against Haemophilus influenzae, but beta-lactamase-producing Branhamella catarrhalis were somewhat less sensitive. Neisseria gonorrhoeae were susceptible, although non-beta-lactamase producing penicillin-resistant strains had higher MICs. Gardnerella vaginalis was also susceptible and Campylobacter coli/jejuni usually susceptible. Both antibiotics had good activity against Staphylococcus aureus and coagulase-negative staphylococci except for methicillin-resistant strains and Staphylococcus haemolyticus which were of borderline sensitivity. All streptococci were sensitive, with the exception of highly penicillin-resistant pneumococci and enterococci against which cefpirome had greater activity than cefepime. Both antibiotics had little useful activity against the Bacteroides fragilis group or Bacteroides oralis group but were active against most other anaerobes. Clostridium difficile and some other Clostridium species were resistant.

Anti-Bacterial Agents↗

In vitro evaluation of E-4695, a new fluoro-naphthyridine.

Compound E-4695, a C-7 azetidinyl fluoro-naphthyridine, was compared to six structurally related quinolones and was generally two- to four-fold more active than ciprofloxacin. E-4695 was particularly active against Staphylococcus aureus (MIC90 0.06 mg/l), Staphylococcus haemolyticus (MIC90 0.5 mg/l), Klebsiella spp. (MIC90 less than or equal to 0.015 mg/l), Serratia marcescens (MIC90 0.06 mg/l), Acinetobacter spp. (MIC90 less than or equal to 0.015 mg/l), Pseudomonas aeruginosa (MIC90 0.5 mg/l), Xanthomonas maltophilia (MIC90 0.5 mg/l), and Neisseria gonorrhoeae (MIC90 less than or equal to 0.001 mg/l). This new quinolone-like drug requires further investigations to confirm these promising in vitro findings.

Anti-Bacterial Agents↗

In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial isolates from neutropenic cancer patients.

The in vitro activity of FK-037, a novel parenteral cephalosporin, was compared to that of ceftazidime, aztreonam and piperacillin (agents often used in empiric regimens in cancer patients) against recent bacterial isolates from patients with cancer. FK-037 was either equal to or 2 to 16-fold more active than the comparative agents against members of the Enterobacteriaceae. It was also active against Acinetobacter spp., Aeromonas spp., Pseudomonas aeruginosa, and other Pseudomonas spp. Xanthomonas maltophilia and Alcaligenes denitrificans were relatively resistant to all four agents. FK-037 was also 4 to 16-fold more active against most gram-positive organisms (including some methicillin-resistant staphylococci) than was ceftazidime. Enterococcus spp., Listeria monocytogenes and Staphylococcus haemolyticus were relatively resistant to FK-037 and ceftazidime. Overall, FK-037 has a broad antimicrobial spectrum that includes the majority of gram-positive and gram-negative isolates.

Aztreonam↗