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Modes of inhibition of foodborne non-Salmonella bacteria by selenite cystine selective broth.

Various cell densities of six common foodborne non-Salmonella bacteria were exposed to selenite cystine (SC) Salmonella selective medium. The insensitivity of Pseudomonas aeruginosa and Proteus vulgaris to SC was confirmed. Selenite cystine selective medium was effective against the sensitive bacteria up to certain cell densities, beyond which the bacteria survived. As judged from the minimum cell number required for survival in SC, Staphylococcus aureus was the most sensitive to SC, followed by Bacillus cereus, Escherichia coli and Citrobacter freundii. When sensitive bacteria were grown in SC, they enriched resistant variants which exhibited no or reduced sensitivity to SC. The change in density of sensitive cells after exposure to SC suggested that bacterial sensitivity to SC depended on the efficiency of killing and growth inhibition by SC as well as the fraction of resistant variants in the bacterial population. Since Salmonella samples generally contain unknown numbers and types of sensitive bacteria, it is difficult to predict the effectiveness of their selective inhibition by SC.

Animals↗

A study of the skin flora of spinal cord injured patients.

The skin flora of 11 spinally-injured patients was compared to that of 11 healthy control subjects. The perinea, groins, penile shafts and urethras of the patients were heavily colonized by a range of multi-drug resistant Gram-negative bacilli. Observations on patients from admission for up to 25 days suggest that the Gram-negative bacilli start to colonize the skin 2-3 days after admission. Some species, e.g., Citrobacter diversus and Escherichia coli appear as transient organisms while others such as Enterobacter aerogenes, Serratia marcescens, and Klebsiella pneumoniae seem to become stable skin residents. The relationship of the skin flora to the organisms causing urinary tract infections in these patients was studied.

Bacteriuria↗

The bacterial flora of neonates in intensive care-monitoring and manipulation.

Unlike healthy babies, newborns hospitalized in the neonatal intensive care unit (NICU) are colonized with bacterial flora that reflects their exposure to pathogens in the NICU, not bacterial acquired from mother in the perinatal period. For example, nosocomial Gram-negative bacilli, such as klebsiella, enterobacter, and citrobacter but not Escherichia coli tend to colonize the gastrointestinal tract. Colonization with Gram-negative bacilli generally is a prerequisite for nosocomial infection with these pathogens, but surveillance cultures may not be a cost effective approach to predicting which babies will ultimately become ill. However, screening cultures to detect the emergence of antibiotic-resistant Gram-negative bacilli facilitate containment and guide empiric antibiotic therapy, and surveillance cultures are necessary to detect colonized babies when nosocomial Gram-negative bacilli become epidemic in the NICU. Such cultures are inexpensive and easy to perform if appropriate selective media are used. Surveillance cultures to detect coagulase-negative staphylococci, which numerous investigators claim are increasingly important NICU pathogens, are of little value since colonization is virtually universal in the first week of life. Documentation of colonization with group B streptococci or Staphylococcus aureus also cannot be justified on a routine basis. Screening for methicillin-resistant S. aureus, however, may be indicated since early detection of these strains can limit dissemination in the NICU. Research aimed at restoring colonization resistance with elements of normal bacterial flora or preventing colonization by nosocomial pathogens is in its infancy.

Bacteriological Techniques↗

Infections with gram-negative bacilli in a cardiac surgery intensive care unit: the relative role of enterobacter.

A 7-month prospective survey for cefazolin-resistant Gram-negative bacilli in cardiac surgery patients, receiving cefazolin prophylaxis, showed that 58 (67%) of 87 were colonized with enterobacter, 37 (64%) with citrobacter, 33 (57%) with Pseudomonas aeruginosa, and seven (2%) with Serratia marcescens. About 50% of colonization occurred before cefazolin prophylaxis and was present on admission to the intensive care unit. Typing of strains showed that horizontal transmission accounted for at most 14% of carriage. Cefazolin prophylaxis (and high gastric pH) were associated with increased levels of postoperative colonization, most notably for enterobacter. About 25% of colonization with enterobacter, pseudomonas, and serratia was followed by clinical infection. Enterobacter cloacae was the most common pathogen and pneumonia the most common infection. Infections contributed to eight of 11 deaths; four of the eight involved enterobacter. Potential control measures include eliminating endogenous Gram-negative flora by gut decontamination or at least stemming the increase in level of colonization that occurred after surgery.

Adult↗

Potentiation of ferrous sulphate and ascorbate on the microbial transformation of endogenous trimethylamine N-oxide to trimethylamine and dimethylamine in squid extracts.

The levels of trimethylamine N-oxide (TMAO) in the New Zealand (Nototodarus sloani) species of squid extracts were extremely high (above 9200 ppm). When the extracts were incubated for 2 days at 25 degrees C, approximately 60% TMAO was converted to trimethylamine (TMA) and dimethylamine (DMA). This conversion was very low or negligible at 4 degrees C, but was potentiated by the presence of ferrous sulphate (0.014 M) and ascorbate (0.014 M). Citrobacter freundii and Aeromonas hydrophilia were isolated from the extracts. Cultures of these two micro-organisms and of Escherichia coli were active in catalysing the conversion of TMAO to TMA and DMA either in extract or in aqueous solution. Chloramphenicol (0.416 mg/ml) completely inhibited the growth of these micro-organisms and also effectively blocked the conversion of endogenous TMAO to TMA in the extracts. The present findings suggest that gastro-intestinal flora and dietary ferrous salts and ascorbate may play important roles in the conversion of TMAO to TMA and DMA in man following the ingestion of squid and other TMAO-containing seafoods.

Animals↗

The activity and reaction specificity of tyrosine phenol-lyase regulated by monovalent cations.

This work was aimed at studying the effect of monovalent inorganic cations (Li+, Na+, K+, Rb+, Cs+, NH+4) on the catalytic and spectral characteristics of tyrosine phenol-lyase from Citrobacter intermedius. These cations were shown to influence the proportion of the beta-elimination reaction rate to the rate of side transamination reaction. Most of the monovalent cations are non-competitive activators of the beta-elimination reaction; Li+ exerts no effect on the enzyme activity in this reaction; Na+ is an inhibitor of the beta-elimination reaction. The activation of tyrosine phenol-lyase by monovalent cations stems from the creation of an active holoenzyme form (lambda max 420 nm) due to conformational rearrangements of the protein molecule.

Cations, Monovalent↗

Infection and antibiotic therapy in 4000 burned patients treated in Milan, Italy, between 1976 and 1988.

The pathogenic flora, isolated from burn wounds of patients admitted to a burn care unit during the years between 1976 and 1988 were typed and the in vitro susceptibility to antibacterial agents was recorded. Between 1976 and 1988 the general therapeutic approach was changed three times, in congruence with the prevalent nosocomial bacterial resistance. The most frequent isolates were: Pseud. aeruginosa, Staphylococcus aureus, Enterococcus spp., Proteus mirabilis, Escherichia coli, Enterobacter cloacae, Klebsiella spp. and other Enterobacteriaceae, such as Acinetobacter, Citrobacter. The most striking finding was the increase in antibiotic-resistant Enterococcus isolates. Staph. aureus, Klebsiella and E. cloacae showed susceptibility to cephalosporins, imipenem, pefloxacin, vancomycin; Enterococcus susceptibility to pefloxacin and vancomycin, and Pseud. aeruginosa sensitivity to piperacillin, amikacin, tobramycin was generally good. E. coli showed a satisfactory susceptibility on average, and P. mirabilis showed a good sensitivity to piperacillin, cephalosporins, amikacin, tobramycin, aztreonam and imipenem. Thus, the general bacterial flora and susceptibility have remained mostly unchanged over the years, with the conspicuous exception of Enterococcus spp. and E. cloacae, which demonstrated a marked increase in incidence, with a concomitant dramatic decrease in the sensitivity of Enterococcus spp. to antibiotics.

Bacteria↗

Analysis of bacteriuria in patients with burns.

A detailed analysis of bacteriuria in 148 aged patients with burns was made for a period of 2 years (1991-92), in order to determine the incidence of the urine infections they sustained, the sources and mechanisms of the infections and the impact on the course and outcome of the primary disease. Urine infection was found in 7.6 per cent (46 patients) of all patients treated for burns during the study period; 39.1 per cent were community acquired uroinfection (CAU) and 60.9 per cent were hospital acquired (HAU). In addition there were eight patients with bacteriuria, secondary to a generalized bacterial infection (GBI), and 11 with candiduria associated with massive antibacterial therapy. Leading causes of CAU were the common uropathogens: E. coli, Citrobacter and Proteus sp.; those of HAU were multiresistant hospital strains, characteristic of the Burns Clinic: Pseud. aeruginosa, Klebsiella sp., Acinetobacter sp. and Serratia sp. This study confirmed the role of transurethral catheterizations as factors associated with the development or exacerbation of chronic uroinfections, which increased the chances of non-survival, especially in aged people with concomitant chronic urological, nephrological or other underlying diseases. The causes of death in 20 patients with HAU, CAU, GBI and candiduria were analysed. The need for strict monitoring of burned patients at risk for uroinfection development and the need to take urgent preventive measures is emphasized.

Adult↗

Ceftazidime and amikacin alone and in combination against Pseudomonas aeruginosa and Enterobacteriaceae.

The efficacy of ceftazidime alone and combined with amikacin was studied in a rabbit model simulating closed-space infections at locally neutropenic sites. Six strains of Pseudomonas aeruginosa, and six Enterobacteriaceae (two strains each of Klebsiella pneumoniae and Serratia marcescens and one strain each of Escherichia coli and Citrobacter freundii) in pooled rabbit serum were each inoculated into separate subcutaneous semipermeable chambers. Intramuscular antibiotic therapy was begun 4 hr later with ceftazidime (50 mg/kg) alone and combined with amikacin (15 mg/kg) for Enterobacteriaceae or ceftazidime (100 mg/kg) alone and combined with amikacin (15 mg/kg) for pseudomonads every 6 hr for 16 doses. Amikacin alone was ineffective for all 12 strains. Ceftazidime alone was successful (greater than or equal to 5.5 log10 colony forming units (CFU)/ml decrease from drug-free control) in eliminating five of six Enterobacteriaceae but was not successful against any of the pseudomonads. Ceftazidime plus amikacin was successful against the same five of six Enterobacteriaceae and five of six pseudomonads. The best in vitro tests for the prediction of in vivo outcome were high inoculum (greater than or equal to 7 log10 CFU/ml) susceptibility, checkerboard synergism testing, and conventional inoculum time-kill rates at concentrations of antimicrobials simulating extravascular levels obtained in vivo.

Amikacin↗

BMY-28100, a new oral cephalosporin: antimicrobial activity against nearly 7,000 recent clinical isolates, comparative potency with other oral agents, and activity against beta-lactamase producing isolates.

The antimicrobial activity of BMY-28100 was tested against approximately 7,000 bacterial pathogens in a multicenter, multiphased collaborative investigation. The BMY-28100 spectrum and antimicrobial potency was most similar to that of cefaclor and superior to that of cephalexin among currently available cephalosporins. Species that had greater than or equal to 90% of clinical strains inhibited by BMY-28100 (less than or equal to 8.0 micrograms/ml) were: Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, N. meningitidis, methicillin-susceptible Staphylococcus supp., Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. bovis, serogroup C and G streptococci, Listeria monocytogenes and gm-positive anaerobes. BMY-28100 inhibited 9% more of the 6286 fresh clinical isolates at less than or equal to 8.0 micrograms/ml than cefaclor at the same concentration. BMY-28100 was generally bactericidal, but MICs for some species were markedly increased when an inoculum concentration of 10(7) CFU/ml was used. Strains producing plasmid-mediated beta-lactamases (TEM, OXA, SHV, HMS) were susceptible to BMY-28100, cefaclor, and cefuroxime. BMY-28100 was less active against strains producing chromosomal-mediated beta-lactamases (Types I and IV). BMY-28100 was not hydrolyzed significantly by the tested plasmid-mediated beta-lactamases, but was destroyed by Type I cephalosporinases and Klebsiella K1 enzymes.

Administration, Oral↗

In vitro evaluation of lomefloxacin activity in Colombia.

As part of the worldwide in vitro program to determine the antimicrobial activity of lomefloxacin, our study tested susceptibility of bacterial isolates from hospitals in Medellin, Colombia. A total of 504 bacterial isolates were obtained from patients at three different centers. For Enterobacteriaceae, 0.5 micrograms/ml inhibited 100% of the indole-positive Proteus and Salmonella spp.; 1 microgram/ml inhibited 100% of Shigella and Citrobacter, 2 microgram/ml inhibited 100% of Enterobacter spp., E. coli, Proteus mirabilis, and Serratia marcescens isolates tested. The MIC90 for Klebsiella spp. and Pseudomonas spp. was 4 micrograms/ml. The MIC90 was 4 micrograms/ml for S. aureus and 2 micrograms/ml for S. epidermidis and S. saprophyticus. The MIC90 of Streptococcus spp. were less than or equal to 4 micrograms/ml for all isolates tested. Considering that 97.8% were susceptible to concentrations of less than or equal to 4 micrograms/ml of lomefloxacin, this new quinolone offers potential in the therapy of a variety of systemic infections, especially in patients with multiply resistant pathogens.

4-Quinolones↗

Mechanism of beta-lactamase inhibition: differences between sulbactam and other inhibitors.

Three different types of beta-lactamases--TEM-2 type penicillinase, a typical cephalosporinase of Citrobacter freundii, and a Proteus vulgaris cephalosporinase with broad substrate range--were studied to determine the inactivation and reactivation kinetics for beta-lactamase inhibitors of these enzymes. Sulbactam, cloxacillin sulfone, clavulanic acid, imipenem, and aztreonam were evaluated. On the basis of the kinetic parameters a minimum scheme for the inactivation of these beta-lactamases by each compound was proposed, and the difference in the features of each of these as progressive and competitive inhibitors were evaluated. The relationship between the kinetic parameters and the synergistic effects of the inhibitors in combination with traditional beta-lactam antibiotics on the bacterial strains producing these beta-lactamases was examined. A close relationship between the synergistic effect, expressed as the FIC index, and a proposed parameter, TN x Ki/Km, was demonstrated. The results of this analysis suggest that sulbactam is a beta-lactamase inhibitor applicable to a wide range of beta-lactamase types.

Anti-Bacterial Agents↗

In vitro activity of an oxycephem OCP 9-176 compared with its sulfur analog and other beta-lactams.

OCP 9-176 is an oxycephem antibiotic that contains a 2-aminothiazolyl, carboxypropyl side chain at C-7 and a pyridinium thiomethyl group at C-3. OCP 9-176 was generally twofold less active than its sulfur-containing analog ME 1228 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Providencia stuartii, Proteus vulgaris, and Serratia marcescens. Activity against Enterobacter cloacae and Citrobacter freundii was equivalent. OCP 9-176 was twofold less active than ME-1228 against Pseudomonas aeruginosa and Acinetobacter species. Activity of the two agents was similar against Staphylococcus aureus and Staphylococcus epidermidis. Although OCP 9-176 inhibited E. coli containing TEM-1 and TEM-2, it was less active than ME-1228. Klebsiella organisms with SHV-1 and K-2 beta-lactamases were inhibited, but TEM-3-containing isolates had MICs of 16 micrograms/ml. OCP 9-176 was minimally hydrolyzed by TEM-1, PSE-1, K-1, and P99, and it was a poor inhibitor of P99. Replacement of sulfur with oxygen does not increase the activity of compounds with sulfopyridinium methyl groups at C-3.

Anti-Bacterial Agents↗

In vitro activity of a new cephalosporin ME-1206 compared with other agents.

The in vitro activity of ME-1206, a new aminothiazolyl cephalosporin that can be orally absorbed when converted to an ester, was compared with that of other beta-lactams. ME-1206 inhibited 50% of the Enterobacteriaceae at 2 micrograms/ml, similar to cefotaxime, ceftazidime, and cefixime. It did not inhibit, MIC greater than or equal to 32 micrograms/ml, Enterobacter species or Citrobacter freundii resistant to cefotaxime and ceftazidime, and it was less active than cefotaxime and ceftazidime against Serratia marcescens. Haemophilus influenzae, Neisseria gonorrhoeae, and Moraxella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of ME-1206 inhibited hemolytic streptococci groups A, B, C, and G, MIC90 0.06 micrograms/ml, but it did not inhibit enterococci. Pseudomonas aeruginosa and other pseudomonads were resistant to ME-1206. MICs and MBCs of ME-1206 for susceptible species were within a dilution. ME-1206 was not hydrolyzed by TEM-1 or TEM-2, but was hydrolyzed by TEM-3 and TEM-5. ME-1206 was hydrolyzed by beta-lactamases of Morganella, Proteus vulgaris, and K1 of Klebsiella oxytoca, but minimally by the P99 beta-lactamase of Enterobacter cloacae. ME-1206 is comparable in in vitro activity and beta-lactamase stability to many of the current cephalosporins.

Amikacin↗

In vitro activity evaluations of cefdinir (FK482, CI-983, and PD134393). A novel orally administered cephalosporin.

Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections.

Cefdinir↗

Oral ofloxacin therapy of infections due to multiply-resistant bacteria.

We determined the efficacy and safety of orally administered ofloxacin, 400 mg twice daily, in the treatment of infections due to multiply-resistant bacteria. Patients (n = 99) were treated for 84 infections in 82 patients evaluable for efficacy with a bacteriologic response of 71%. Organisms treated included Pseudomonas aeruginosa (39), Staphylococcus aureus (11), Serratia marcescens (9), Enterobacter species (7), five each of Escherichia coli, Citrobacter, Salmonella, Klebsiella, and other organisms. The overall clinical responses was 89%: 28 (90%) of 16 osteomyelitis, 10 (83%) of 12 urinary tract infections, and three of three bacteremias. Insomnia occurred in 27% and responded to dose reduction. Resistance of P. aeruginosa to ofloxacin developed in 15% of isolates. No hepatic, renal, or hematologic toxicity developed in spite of long therapy, 283 days. Ofloxacin was an effective therapy for lower respiratory, urinary, bone, and soft tissue infections due to multiply-resistant Gram-negative bacteria and is effective for selected Staphylococcus aureus infections.

Administration, Oral↗

Antimicrobial effects of the combination of ceftibuten and an orally absorbed penem SCH 29482.

Ceftibuten is a new beta-lactamase-stable 3-aminothiazolyl cephalosporin that lacks activity against staphylococci and group-B streptococci. We determined the effect of the combination of ceftibuten with SCH 29482, an orally absorbed penem. The combination of the two agents was additive for 25% or indifferent for 57% of the Gram-positive species, Haemophilus, and Moraxella tested with a mean fractional inhibitory concentration (FIC) index of 0.75. The combination of ceftibuten and SCH 29482 was also indifferent for Bacteroides fragilis and other Bacteroides species, all of which were inhibited by less than or equal to micrograms/ml of SCH 29482. Antagonism of the combination was found for 80% of Serratia marcescens and for 30% of Citrobacter freundii and Enterobacter cloacae. Overall, the combination of ceftibuten and SCH 29482 at concentrations that can be achieved in serum after ingestion of 400 and 50 micrograms/ml, respectively, provided antibacterial activity against most Gram-positive aerobic and anaerobic species that cause upper respiratory, intraabdominal, and urinary infections.

Anti-Bacterial Agents↗

Use of a commercial double-test tablet (Rosco PGUA/indole) for screening of Escherichia coli.

A commercial double-test tablet (Rosco PGUA/indole) for detection of beta-glucuronidase (beta-GUR) activity and indole production was evaluated on a collection of 393 isolates of Enterobacteria. Both beta-GUR and indole were positive on 96.6% of Escherichia coli strains. beta-GUR, only, was also detected in 25 Shigella spp., four Enterobacter cloacae, eight Citrobacter freundii, and five Salmonella enteritidis strains, none of which were indole producers. An additional 261 consecutive clinical isolates of oxidase-negative nonswarming Gram-negative bacilli were studied in a parallel comparative field trial against conventional identification methods. For 200 strains, the standard method and PGUA/indole test were performed from the primary culture plate. The remaining 61 (23.4%) required subculture before testing. Sensitivity, specificity, positive predictive value, and negative predictive value of PGUA/indole test in the screening for E. coli were, respectively, 94.1%, 100%, 100%, and 87.1%. In our experience, PGUA/indole test is a rapid, precise, simple-to-perform, and economical method for screening E. coli. However, the need for a large inoculum may limit its application on primary cultures.

Bacteriological Techniques↗