Citrobacter

Mikrobiyol Bul, 1992 Jan, 26(1), 1 - 11
{Typing by isoelectric focusing of beta-lactamase enzymes in Klebsiella and Enterobacter strains resistant to the new beta-lactam antibiotics}; Gur D et al.; Resistance to new generation beta-lactam antibiotics in Gram-negative bacteria is increasing worldwide . This resistance is due to EBS enzymes in Klebsiella spp., and Type-I chromosomal enzymes in Enterobacter spp., Citrobacter, P . aeruginosa, Providencia, M . morganii and S . marcescens . In this study, the types of beta-lactamases in 16 Klebsiella spp . and 15 Enterobacter spp . which are resistant to newer beta-lactam antibiotics was investigated by isoelectric focusing . The results of the study showed that TEM-1 enzymes are prevalent in these isolates . pI (isoelectric point) values and antibiotic susceptibility test results suggest that there are EBS enzymes in Klebsiella spp., and Type-I enzymes in Enterobacter spp . These results have to be supported by further investigations.

Chemotherapy, 1992, 38 Suppl 2, 10 - 7
The threat of resistance to the new oral cephalosporins; Cullmann W; Phenotypic resistance to beta-lactam antibiotics is mainly due to the prevalence of beta-lactamases . The most common enzymes responsible for resistance to aminopenicillins and older (1st generation) cephalosporins are the TEM-1, TEM-2, OXA-1 and SHV-1 enzymes, all of which are plasmid-mediated . The recent development of oral cephalosporins sharing structural features and an antimicrobial spectrum comparable to that of 3rd-generation cephalosporins has provided highly active compounds for the management of outpatient infections . Two principal mechanisms, however, may cause resistance to these new compounds: the overproduction of chromosomally encoded beta-lactamases with predominating cephalosporinase activity, and the recently observed extended-spectrum beta-lactamases . The overproduction of chromosomally mediated beta-lactamases has been observed only in some species (Enterobacter cloacae, Citrobacter freundii, Serratia spp.) which cause mainly nosocomial infections and are therefore of minor importance in outpatients . The extended-spectrum beta-lactamases TEM-3 to TEM-12 and SHV-2 to SHV-7 have been observed in various countries, they derived from the original enzymes by point mutations and occurred in intensive-care units . These enzymes may cause resistance to 3rd-generation cephalosporins including the recently developed orally active compounds . Moderate resistance to cefetamet is observed only in strains producing either the TEM-3 or the TEM-4 enzyme, whereas the prevalence of the other enzymes is of no consequence for the activity of cefetamet . Consequently, cefetamet will not exhibit a marked selection pressure favoring the spread of extended-spectrum beta-lactamase-producing strains.

Arch Microbiol, 1992, 157(5), 471 - 4
Anaerobic malonate decarboxylation by Citrobacter diversus . Growth and metabolic studies, and evidence of ATP formation; Janssen PH et al.; Citrobacter diversus ATCC 27156 was able to grow by decarboxylation of malonate to acetate under strictly anaerobic conditions, in the presence of yeast extract . The growth yield, corrected for growth on yeast extract, was 2.03 g cell dry mass per mol malonate . The addition of malonate to ATP-depleted cell suspensions (less than 0.2 nmol ATP/mg cell protein) resulted in a rapid increase in cellular ATP levels to between 4.5 and 6.0 nmol/mg cell protein . Intact cells decarboxylated malonate at rates of up to 1.5 mumol/min.mg protein . Enzyme assays on malonate-grown cells indicated activation of malonate by an ATP-dependent ligase reaction and by CoA transfer from acetyl-CoA, followed by decarboxylation of malonyl-CoA to acetyl-CoA with subsequent recovery of the invested ATP by substrate level phosphorylation through the activity of acetate kinase . Net ATP synthesis is postulated to be mediated by gradient formation coupled to the decarboxylation of malonyl-CoA . The protonophore CCCP and H(+)-ATPase inhibitor DCCD significantly reduced cellular ATP levels, suggesting a role for proton gradients in the energy metabolism of this strain when growing an malonate . Inhibitors of sodium metabolism or ommission of sodium had no effect on ATP levels or malonate decarboxylation.

Jpn J Antibiot, 1992 Jan, 45(1), 1 - 11
{Synergistic action of cefodizime with other antimicrobial agents on clinically isolated microorganisms . II . Synergistic action with sisomicin}; Deguchi K et al.; Cefodizime (CDZM) possesses a broad antimicrobial spectrum and a relatively long half life in the blood . In addition, it shows excellent therapeutic efficacies in the treatment of infections in leukopenic animal models, hence it is expected that CDZM may have good efficacies against various infections in immunocompromised hosts . In the meantime, sisomicin (SISO) not only has strong antibacterial activities against Gram-negative rods (GNR), but has relatively low nephrotoxicity and ototoxicity . Thus, we examined antibacterial effectiveness of the combination of CDZM and SISO against clinical isolates in vitro . 1 . Antibacterial effects of CDZM+SISO combination were examined using SISO susceptible strains of Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa . Observations that the combination of the 2 drugs showed FIC indices between less than 0.5-less than 1.0 against most of these strains at SISO concentrations of 1 MIC or sub MIC levels strongly suggested the presence of a synergistic action between the 2 drugs against SISO susceptible strains of GNR . 2 . Of the strains tested, 10% of C . freundii, 6.7% of E . cloacae, 63.3% of S . marcescens, 23.3% of P . vulgaris and 18.0% of P . aeruginosa were found to be resistant to SISO, and little synergistic effect of the 2 drugs was observed against these strains . 3 . As the synergistic effect of the 2 drugs against GNR was observed against SISO susceptible strains including those which were resistant to CDZM, but not against those strains which were resistant to SISO, it seems reasonable to conclude that the appearance of the synergistic effect between the 2 drugs depends on the activity of SISO.

Chemotherapy, 1992, 38(4), 218 - 24
Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity; Nouda H et al.; The affinity of meropenem for various known types of beta-lactamases and its stability to them were tested in comparison with other beta-lactams, including imipenem . Meropenem exhibited a marked stability to all beta-lactamases tested and was only hydrolyzed by Xanthomonas maltophilia beta-lactamase, as were other beta-lactams . This was responsible for the potent antibacterial activities of meropenem against beta-lactamase-producing strains . Meropenem and imipenem had almost the same, relatively high affinity for beta-lactamases; however, they had a lower affinity than clavulanic acid for penicillin beta-lactamases and cefoxitin for cephalosporin beta-lactamases . Meropenem also had higher beta-lactamase inhibitory activity than imipenem . Meropenem inhibited type III (TEM-1), Ia Citrobacter freundii and Ic Proteus vulgaris beta-lactamases in a progressive manner . Meropenem was thought to be a potent inhibitor of various beta-lactamase because of its ability to form stable enzyme-meropenem acyl-complexes . Meropenem generally exhibited a lower induction potential than imipenem against five clinical isolates of C . freundii, Enterobacter cloacae and Pseudomonas aeruginosa, but its induction potential was higher than that of ceftazidime . Meropenem induced beta-lactamases at concentrations above the MIC.

Zh Mikrobiol Epidemiol Immunobiol, 1992, (5-6), 43 - 5
{An increase in the immunogenicity of bacterial antigens under the influence of one of the derivatives of muramyl dipeptide}; Britsina MV et al.; As revealed in animal experiments, glucosaminylmuramyl dipeptide (GMDP), the synthetic analog of muramyl dipeptide, when introduced intraperitoneally in a single injection or orally, exhibits adjuvant activity with respect to Citrobacter 0-antigens, Shigella flexneri and enhances the protective properties of dysentery and pertussis vaccines . The stimulating properties of GMDP depend on its dose, the route of its administration, the time elapsed after its administration, its ratio to the concomitant doses of bacterial antigens and to the dose of the virulent culture used for challenge.

Med Dosw Mikrobiol, 1992, 44(3-4), 97 - 107
{Occurrence of P.fimbrii in strains from selected genera of Enterobacteriaceae}; Jagielski M et al.; This study was aimed at recognition of frequency of occurrence of P fimbriae in strains of Escherichia coli isolated from samples of feces of children with symptoms of diarrhoea and at search of these adhesions in strains representing other than Escherichia genera of Enterobacteriaceae strains . One hundred forty laboratory strains were investigated . They belonged to genus Citrobacter, Enterobacter, Hafnia, Klebsiella, Morganella, Proteus, Providencia, Salmonella, Shigella, and Yersinia . Also were tested 1277 colonies of enteric rods isolated from the MacConkey's medium inoculated with samples of feces from 163 children with symptoms of diarrhoea . Mannose-resistant active hemagglutination test was performed with human group O erythrocytes and guinea pig erythrocytes stabilized with glutaraldehyde . Presence of P fimbriae was detected by the slide latex test with latex covered by P1 glycoprotein . Among 140 laboratory strains of Enterobacteriaceae in 21 strains (3-E . cloaceae, 2-Hafnia, 13-K . pneumoniae, 2-P . rettgeri and in one strains of Providencia) presence of MRHA adhesins was demonstrated . Nine of these strains (2-Hafnia, 5-K . pneumoniae and 2-P . rettgeri) reacted specifically in the latex test . Among 1142 colonies of E . coli isolated from children with symptoms of diarrhoea, 326 colonies belonged to 13 EPEC serotypes . With 118 (36.2%) of EPEC colonies a positive result of MRHA reaction was found with human erythrocytes and 34 (10.4%) with guinea pig erythrocytes . Positive latex test was obtained with 77 (23.6%) colonies . All these colonies possessed MRHA adhesins . Remaining 816 colonies of E . coli strains did not represent microorganisms belonging to serotypes accepted as enteropathogenic . From 112 (13.7%) colonies out of 816 not belonging to EPEC, positive results was obtained in the MRHA test with human erythrocytes and this was the case also with 41 (5.0%) colonies in MRHA reaction with application of guinea pig erythrocytes . The latex test was positive in 65 (7.9%) colonies of E . coli . From remaining 135 colonies other than E . coli, positive result of latex test of presence of P fimbriae was obtained with 54 (40.0%) colonies, including 14 colonies of E . cloacae, 23-K . pneumoniae and 17-K . oxytoca . In all these strains presence of MRHA adhesins was demonstrated . These investigations demonstrated that among EPEC strains significantly more frequently, than not belonging to these serotypes of E . coli, MRHA adhesins, including P fimbriae was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

J Hyg Epidemiol Microbiol Immunol, 1992, 36(4), 419 - 24
Pilot studies on the occurrence of some infectious diseases in two different areas in south Yemen (Aden) (part II . Microbiology); Kopecky K et al.; This paper is the second part of the article dealing with intestinal bacteria . The findings are relatively poor in comparing with the frequency of intestinal protozoa . Among 83 stool specimens taken for bacteriological examination 14 isolations of different bacteria were proved . One S . muenchen was isolated from a 3 year old boy with fever, diarrhoea . Five cases of Alkalescens dispar 05 manit negative and 05 manit positive were identified . Two of these cases were without clinical symptoms . All were males aged 10-17 years . One isolation of E . coli EPEC 086 K6 H11 was in a 10 year-old boy with diarrhoea, four watery stools daily and cramps . Six cases of other E . coli were of different types, all with clinical symptoms . Of them three were males and three females at the age from 3-46 years . One case had a mixed infection of Citrobacter, E . coli and Klebsiella with diarrhoea, about 5 watery stools daily and abdominal pain . The frequency of intestinal bacteria in males was nearly three times higher than in females . The occurrence in age groups 10-20 was almost equal 20.0-22.2%, in 0-4 it was 42.9% and surprisingly low in 5-9 years old--3.4% only.

FEMS Microbiol Lett, 1991 Dec 15, 69(1), 53 - 6
Molecular cloning of the ViaB region of Salmonella typhi; Hashimoto Y et al.; The ViaB region required for Vi antigen production in Salmonella typhi was cloned . The plasmid pGBM124 containing a 14-kb S . typhi chromosomal DNA fragment conferred the ability to produce Vi antigen on Escherichia coli HB101 and ViaB-deleted S . typhi GIFU10007-3 . Tn5 insertion analysis showed that the 14-kb DNA was split into three regions . Region 1 and region 2 are involved in the biosynthesis of Vi polysaccharide . Region 3 is involved in translocation of the Vi polysaccharide to the cell surface . Southern blot hybridization showed that regions 2 and 3 but not region 1, were considerably homologous to the DNA of Vi-positive Citrobacter freundii.

J Chemother, 1991 Dec, 3(6), 343 - 7
Beta-lactamase induction antagonizes beta-lactam susceptibilities in Citrobacter diversus and Enterobacter cloacae clinical isolates; Oliva B et al.; Inducible beta-lactamases were obtained after exposure to several beta-lactams in clinical isolates of Enterobacter cloacae and Citrobacter diversus . Enzyme production was related to the inducer and medium composition . beta-lactamase is able to inactivate only labile compounds, thus generating minimum inhibitory concentrations higher than in the absence of the inducer; imipenem susceptibilities usually were not changed.

Antibiot Khimioter, 1991 Dec, 36(12), 24 - 6
{Microbial colonization and succession in the large intestine of newborn infants during their stay with mothers at the maternity hospital}; Bochkov IA et al.; Formation of microflora in the large intestine of 5-day old infants was studied in one of the Moscow maternity homes . The up-to-date procedures for isolation and identification of aerobic and anaerobic organisms were used in the study and the findings were processed on a computer . In the newborns of the maternity home of the "mother-infant" type there was observed colonization of the large intestine with aerobic and anaerobic organisms . A wave-like dynamics in the formation of the symbiotic microflora was revealed . It reflected the phenomenon of the microbial succession in the infants . The attempts to detect microbial interference between the species colonizing the large intestine showed that it was extremely rare in the 5-day old infants . This was likely the reason of the low intestine resistance to the colonization in the newborns which in its turn defined the frequent colonization of the intestine mucosa with S . aureus and the organisms of the Klebsiella, Enterobacter and Citrobacter group.

Berl Munch Tierarztl Wochenschr, 1991 Dec 1, 104(12), 409 - 11
{Biochemical properties of avian Citrobacter amalonaticus strains}; Mutlu OF; A report is given on the biochemical properties of C . amalonaticus-strains of avian origin . Some strains show decisive deviations of the "norm", usually established from mammalian strains and details are given in a table . The results are discussed and the strains considered to be avian specific.

Poult Sci, 1991 Dec, 70(12), 2429 - 32
Xylose-lysine-tergitol 4: an improved selective agar medium for the isolation of Salmonella; Miller RG et al.; A study was conducted to evaluate a new selective plating medium for isolating Salmonella using pure bacterial cultures, and poultry environmental specimens containing high numbers of competing enteric bacteria . Xylose-lysine-tergitol 4 (XLT4) agar was found to strongly inhibit Proteus, Pseudomonas, Providencia, and many other nonsalmonellae and to provide good differentiation between Salmonella and Citrobacter . The XLT4 medium significantly improved Salmonella isolation from chicken farm environmental drag-swab samples over the other selective plating media evaluated.

Arch Intern Med, 1991 Dec, 151(12), 2419 - 24
A large nontypical outbreak of Norwalk virus . Gastroenteritis associated with exposing celery to nonpotable water and with Citrobacter freundii; Warner RD et al.; The US Air Force Academy experienced a point-source outbreak of gastroenteritis originally believed to be caused by Salmonella . The overall attack rate was 48% among approximately 3000 cadets and staff . Food-specific attack rates implicated chicken salad . The odds ratio for chicken salad consumption in ill cadets was 10.7 (95% confidence interval: 8.2; 13.8) . The celery component had been exposed to nonpotable water . Citrobacter freundii were statistically associated with consumption of the suspected vehicle and subsequent illness . Most aspects were consistent with the epidemiology of Norwalk gastroenteritis . However, the clinical presentation was not typical of reported outbreaks . One hundred five cadets required intravenous rehydration . Serum samples implicated Norwalk virus as the most probable cause of this outbreak . The Centers for Disease Control (Atlanta, Ga) recently began national surveillance for viral gastroenteritis . All outbreaks of gastroenteritis associated with nonpotable water should be investigated for evidence of viral cause.

J Bacteriol, 1991 Dec, 173(23), 7692 - 4
Presence of 5-methylcytosine in CC(A/T)GG sequences (Dcm methylation) in DNAs from different bacteria; Gomez-Eichelmann MC et al.; The presence of CC(A/T)GG sequences with methylated internal cytosine (Dcm methylation) was determined in DNA from different genera of eubacteria . This methylation was studied by using restriction enzymes EcoRII and BstNI, which cleave unmethylated or methylated CC(A/T)GG sequences . Dcm methylation was only detected in genera of the family Enterobacteriaceae closely related to Escherichia: Shigella, Citrobacter, Salmonella, and Klebsiella.

Antimicrob Agents Chemother, 1991 Nov, 35(11), 2359 - 65
Induction of a class I beta-lactamase from Citrobacter freundii in Escherichia coli requires active ftsZ but not ftsA or ftsQ products; Ottolenghi AC et al.; A possible connection between septation/division and induction of cloned ampC beta-lactamase was investigated . When a ftsZ84(Ts) mutant of Escherichia coli carrying ampR-ampC from Citrobacter freundii was grown at the restrictive temperature (42 degrees C), induction of beta-lactamase by cefoxitin was inhibited by about 80% . Inhibition was virtually complete when a ftsZ84(Ts) mutant of different genetic background was tested . Although somewhat delayed, the induction of beta-lactamase in transformed ftsA(Ts) and ftsQ(Ts) mutants was similar to that observed in wild-type transformants . These results imply that FtsZ is involved in the process of beta-lactamase induction.

J Antimicrob Chemother, 1991 Nov, 28(5), 669 - 76
Selection and characterization of cefepime-resistant gram-negative bacteria; Piddock LJ et al.; The NCTC type strains and four clinical isolates of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, Providencia stuartii and Pseudomonas aeruginosa were exposed, in agar, to cefepime at 3, 5, and 10 x MIC and a breakpoint concentration of 16 mg/L . Mutants were selected at a frequency of approximately 10(-8) that had decreased susceptibility to cefepime and cefpirome, and species-dependent resistance to other beta-lactams . Any putative mutant with a greater than four-fold increase in the MIC was examined to determine its beta-lactamase expression and outer membrane protein (Omp) profile . Mutant strains of P . stuartii and M . morganii lacked an Omp of molecular mass similar to that of OmpF, and were cross-resistant to nalidixic acid . Mutant strains of E . cloacae had derepressed class I beta-lactamase production and lacked an Omp corresponding to OmpF, suggesting that in this species both parameters are necessary for decreased susceptibility . Derepressed beta-lactamases purified from mutant strains of E . cloacae, C . freundii and P . stuartii was able to hydrolyse cefepime, but not as quickly as TEM-10.

Int J Food Microbiol, 1991 Nov, 14(2), 127 - 34
A new plate medium for rapid presumptive identification and differentiation of Enterobacteriaceae; Manafi M et al.; A new selective differential agar medium for rapid presumptive identification of Enterobacteriaceae from water and food samples is described (EMX ID agar) . By a combination of fluorogenic and chromogenic substrates, the medium detects the presence of beta-D-glucuronidase, beta-D-galactosidase, beta-D-xylosidase, tryptophane deaminase and H2S; additionally, cytochrome-oxidase and indole production can be demonstrated . This medium provides an inexpensive means for simple and rapid presumptive identification of E . coli and coliforms and for the differentiation within the Klebsiella-Enterobacter and the Proteus-Providencia-Morganella group . Furthermore, it allows to distinguish between the H2S-positive Enterobacteriaceae Citrobacter freundii, Salmonella spp., S . arizonae, Edwardsiella, Proteus mirabilis, P . vulgaris and some oxidase-positive bacteria.

J Clin Microbiol, 1991 Nov, 29(11), 2385 - 9
Rapid isolation and presumptive diagnosis of uropathogens by using membrane filtration and differential media; Friedman MP et al.; Random urine samples from hospitalized patients (n = 550) and seeded sterile filtered urine samples (n = 730) were used to test a membrane filtration technique, Qualture (Future Medical Technologies International, Inc., West Palm Beach, Fla.), for the detection and identification of uropathogens . Results for each sample were compared with those obtained by the calibrated loop (0.01 ml) method to demonstrate the sensitivity of the method as a screening tool and the specificity of the presumptive diagnosis obtained from the pattern of growth on differential media . The medium was supplied as dehydrated nutrient pads (Sartorius AG, Goettingen, Germany) and was activated by rehydration by the addition of the liquid specimen . With a threshold of 10(4) CFU/ml defining a positive culture, the sensitivity of the Qualture was 100% . At lower levels of bacteriuria, the Qualture was more sensitive than the calibrated loop method . Significant infections were presumptively diagnosed at 4 h by filtration rather than at 24 h on agar medium . The specificity of uropathogen identification ranged from 99% for Enterococcus spp . to 83% for Pseudomonas spp . Citrobacter spp . could not be differentiated from Escherichia coli and Providencia spp . could not be differentiated from Proteus spp., which does not create a therapeutic dilemma . Filtration, isolation, quantitation, and presumptive diagnosis are performed in one step, without subculture . Membrane filtration is a sensitive and rapid technique, with the advantage that it can be used as a collection and transport device without the use of growth inhibitors.

J Bacteriol, 1991 Oct, 173(19), 5964 - 74
Evolution of the ferric enterobactin receptor in gram-negative bacteria; Rutz JM et al.; Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of iron-deficient and replete cell envelopes, 59Fe-siderophore uptake studies, and Western immunoblots and cytofluorimetric analyses with monoclonal antibodies (MAbs), we surveyed a panel of gram-negative bacteria to identify outer membrane proteins that are structurally related to the Escherichia coli K-12 ferric enterobactin receptor, FepA . Antibodies within the panel identified FepA epitopes that are conserved among the majority of the bacteria tested, as well as epitopes present in only a few of the strains . In general, epitopes of FepA that are buried in the outer membrane bilayer were more conserved among gram-negative bacteria than epitopes that are exposed on the bacterial cell surface . The surface topology and tertiary structure of FepA are quite similar in E . coli and Shigella flexneri but differ in Salmonella typhimurium . Of the 18 different genera tested, 94% of the bacteria transported ferric enterobactin, including members of the previously unrecognized genera Citrobacter, Edwardsiella, Enterobacter, Haemophilus, Hafnia, Morganella, Neisseria, Proteus, Providencia, Serratia, and Yersinia . The ferric enterobactin receptor contains at least one buried epitope, recognized by MAb 2 (C . K . Murphy, V . I . Kalve, and P . E . Klebba, J . Bacteriol . 172:2736-2746, 1990), that is conserved within the structure of an iron-regulated cell envelope protein in all the bacteria that we have surveyed . With MAb 2, we identified and determined the Mr of cell envelope antigens that are immunologically related to E . coli FepA in all the gram-negative bacteria tested . Collectively, the library of anti-FepA MAbs showed unique patterns of reactivity with the different bacteria, allowing identification and discrimination of species within the following gram-negative genera: Aeromonas, Citrobacter, Edwardsiella, Enterobacter, Escherichia, Haemophilus, Hafnia, Klebsiella, Morganella, Neisseria, Proteus, Providencia, Pseudomonas, Salmonella, Serratia, Shigella, Vibrio, and Yersinia.

FEMS Microbiol Lett, 1991 Sep 15, 67(1), 79 - 84
Cloning and nucleotide sequencing of the gene encoding the beta-lactamase from Citrobacter diversus; Perilli M et al.; The gene coding for the class A beta-lactamase of Citrobacter diversus has been cloned and sequenced . It contains the information for a 294-amino-acid precursor protein, including a 27-residue N-terminal signal peptide . The deduced sequence of the N-terminal portion of the mature protein is in excellent agreement with that determined by microsequencing of the protein and readily explains the pI differences observed between the naturally occurring forms I and II of the enzyme . The sequence of the mature protein exhibits a very high degree of similarity with that of the Klebsiella oxytoca class A beta-lactamase.

J Gen Microbiol, 1991 Sep, 137 ( Pt 9), 2147 - 53
In vitro characterization of intra-generic inhibition of growth in Salmonella typhimurium; Berchieri A Jr et al.; The intra-generic inhibition of bacterial growth observed previously in vivo and in vitro with strains of Salmonella, Citrobacter and E . coli was studied in vitro using S . typhimurium strain F98 . There was complete inhibition of multiplication of S . typhimurium when it was added to stationary-phase broth cultures of different Salmonella serotypes, but only partial inhibition when added to broth cultures of E . coli . The degree of inhibition between different mutants of F98 was affected by the numbers of bacteria of the inhibiting strain, but this was not the only factor, since exponential-phase bacterial cells were less inhibitory than stationary-phase cells . The inhibitory effect was produced at temperatures between 20 degrees C and 40 degrees C . The complete inhibition of growth observed between F98 mutants was abolished by ampicillin, rifampicin and streptomycin, but not by nalidixic acid . Inhibition was also prevented by separating the two cultures by a dialysis membrane . A TnphoA insertion mutant of F98 was produced which did not show inhibition in vitro but was still inhibitory in vivo . It is suggested that this complete inhibition of bacterial multiplication between organisms of the same genus, which is greater than that produced between organisms from different genera, is mediated by a cell surface protein.

J Antimicrob Chemother, 1991 Sep, 28(3), 369 - 75
Characterization of FCE 22101-resistant Enterobacteriaceae and the effect of FCE 22101 upon the activity of anti-pseudomonal beta-lactams for Pseudomonas aeruginosa; Piddock LJ et al.; Twenty-five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia stuartii) were exposed to FCE 22101 in agar containing 3, 5, or 10 x the MIC . Any putative mutant with a greater than or equal to four-fold increase in the MIC was examined for beta-lactamase expression and outer membrane protein (OMP) profile . Mutant colonies were selected at a frequency of 10(-7)-10(-11) with decreased susceptibility to FCE 22101 and other beta-lactams, but after one subculture on antibiotic-free agar the mutants from 13 of the 25 strains reverted to wild-type . Only 19 stable mutants were selected from the other 12 wild-type strains, of which 15 lacked an OMP of similar molecular size to OmpF, and/or a low size OMP of approximately 18 kDa . None of the mutants had a significant alteration in expression of Richmond & Sykes class I beta-lactamase . In a separate section of the study in which 50 strains of Pseudomonas aeruginosa were examined, it was found that FCE 22101, at a concentration of 4 mg/L, induced beta-lactamase expression such that, after 24 h exposure, 24 of the 50 strains had a greater than or equal to four-fold rise in the MIC of several anti-pseudomonal beta-lactams.

Antimicrob Agents Chemother, 1991 Sep, 35(9), 1748 - 52
Pharmacokinetic studies and renal dehydropeptidase stability of the new beta-lactamase inhibitor BRL 42715 in animals; Coleman K et al.; BRL 42715 is a novel, highly potent beta-lactamase inhibitor with good activity against a broad range of beta-lactamases, including the class I enzymes of Enterobacter and Citrobacter spp . (K . Coleman, D.R.J . Griffin, J.W.J . Page, and P.A . Upshon, Antimicrob . Agents Chemother . 33:1580-1587, 1989) . The pharmacokinetics of BRL 42715 were studied following oral and parenteral administration in mice, rats, rabbits, beagle dogs, and cynomolgus monkeys . The elimination half-life (t1/2) of BRL 42715 following intravenous administration was 7 min in rats, 6.2 min in rabbits, 11 min in dogs, and 18 min in cynomolgus monkeys; and interspecies scaling indicated a t1/2 of 31 min in humans . Urinary recovery was 24 to 43% in the three species studied . A linear relationship was observed between the dose and the theoretical concentration in blood at time zero and between the dose and area under the concentration-time curve following intravenous administration to mice . Extravascular dosing in mice, rats, and dogs resulted in an increase in t1/2, suggesting a depot effect . BRL 42715 was absorbed in mice following an oral dose (bioavailability of 0.2), but was not absorbed in rats, dogs, or cynomolgus monkeys to any significant extent . The binding of BRL 42715 in serum was 27 to 38% in mouse, rat, and dog sera but was somewhat higher (68 to 70%) in primate and human sera . BRL 42715 was not readily hydrolyzed by the renal dehydropeptidase enzymes of any of the five species studied.

Infection, 1991 Sep-Oct, 19(5), 363 - 9
In vitro activity of cefpodoxime and ten other cephalosporins against gram-positive cocci, Enterobacteriaceae and Pseudomonas aeruginosa, including beta-lactamase producers; Wiedemann B et al.; Cefpodoxime, the deesterified part of the orally available cefpodoxime proxetil, is active against most Enterobacteriaceae with MIC50 of 0.06 to 2 mg/l . Only Enterobacter cloacae and Citrobacter freundii strains show MIC50 of 4 mg/l . Coagulase negative staphylococci have a MIC50 of 2, while Staphylococcus aureus strains have a MIC of 4 mg/l . In comparison to other orally available cephalosporins cefpodoxime is slightly less active than cefixime and cefotiam against gram-negative bacteria but more active than cefuroxime, cefaclor, and cephalexin . Against staphylococci the activity of cefpodoxime is comparable to that of cefotiam and cefuroxime and superior to cefaclor and cephalexin, while cefixime does not have sufficient activity against these species . Like all cephalosporins cefpodoxime has no activity against enterococci.

Diagn Microbiol Infect Dis, 1991 Sep-Oct, 14(5), 435 - 41
Oral ofloxacin therapy of infections due to multiply-resistant bacteria; Scully BE et al.; 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.

Diagn Microbiol Infect Dis, 1991 Sep-Oct, 14(5), 425 - 34
In vitro activity evaluations of cefdinir (FK482, CI-983, and PD134393) . A novel orally administered cephalosporin; Briggs BM et al.; 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.

Diagn Microbiol Infect Dis, 1991 Sep-Oct, 14(5), 417 - 24
In vitro activity of a new cephalosporin ME-1206 compared with other agents; Chin NX et al.; 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.

Mol Biol Evol, 1991 Sep, 8(5), 654 - 68
Temporal and topological clustering of diverged residues among enterobacterial dihydrofolate reductases; Garvin LD et al.; The complete nucleotide and encoded amino acid sequences were determined for the dihydrofolate reductase (DHFR) from the bacteria Enterobacter aerogenes and Citrobacter freundii . These were compared with the closely related Escherichia coli DHFR sequence . The ancestral DHFR sequence common to these three species was reconstructed . Since that ancestor there have been seven, nine, and one amino acid replacements in E . coli, E . aerogenes, and C . freundii, respectively . In E . coli, five of its seven replacements were located in the beta-sheet portion of the protein, and all seven were located in a single restricted region of the protein . In E . aerogenes, all nine of its replacements were located within surface residues, with five clustered in a region topologically distinct from the E . coli cluster . The replaced side chains are sometimes in direct contact but more often are separated by an intervening side chain . It is argued that the temporal clustering of replacements is typical for the evolution of most proteins and that the associated topological clustering gives a picture of how evolutionary change is accommodated by protein structure.

J Antimicrob Chemother, 1991 Aug, 28(2), 209 - 19
beta-Lactamase expression and outer membrane protein changes in cefpirome-resistant and ceftazidime-resistant gram-negative bacteria; Piddock LJ et al.; Twenty-five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia stuartii) and five strains of Pseudomonas aeruginosa were exposed to various concentrations of cefpirome or ceftazidime in agar . Mutants with a greater than four-fold increase in the MIC were examined for changes in beta-lactamase expression and outer membrane protein (OMP) profile . Both agents selected mutants with decreased susceptibility to the selecting antibiotic and other beta-lactams at a frequency of 10(-7)-10(-8) . The MICs of all beta-lactams were higher for the resistant mutants of E . cloacae and P . aeruginosa than for the other species . Both agents selected mutants expressing derepressed class I beta-lactamase, but this was more common with ceftazidime . Only a few mutants of P . aeruginosa and E . cloacae had an MIC of cefpirome that was above the recommended breakpoint concentration . Some mutant strains of Enterobacteriaceae lacked an OMP of molecular size similar to OmpF, but the MIC of cefpirome was below the breakpoint concentration for all these strains.

Eur J Clin Microbiol Infect Dis, 1991 Aug, 10(8), 676 - 82
In vitro activity of cefcanel versus other oral cephalosporins; Chin NX et al.; Cefcanel is a new orally absorbed cephalosporin . Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against gram-positive and negative aerobic and anaerobic bacteria . Cefcanel had excellent activity against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, MIC90 1 micrograms/ml, superior to the other oral cephalosporins . However, methicillin-resistant staphylococci were resistant, MIC greater than or equal to 16 micrograms/ml . Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.015-1 micrograms/ml, concentrations comparable to other cephalosporins . Clostridium spp . were inhibited by 0.25 micrograms/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were greater than 64 micrograms/ml for Bacteroides spp . The MIC90 for Moraxella catarrhalis was 1 micrograms/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime . Escherichia coli and Klebsiella pneumonia which were high beta-lactamase producers were resistant, MICs greater than 64 micrograms/ml, and 50% of Enterobacter cloacae and Citrobacter freundii were resistant . Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases . Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of greater than or equal to 16 micrograms/ml . Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibited Haemophilus influenzae carrying TEM-1.

Eur J Clin Microbiol Infect Dis, 1991 Aug, 10(8), 669 - 75
In vitro activity of Ro 09-1428 compared to other cephalosporins; Chin NX et al.; The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gram-negative organisms . Ro 09-1428 inhibited group A streptococci at less than or equal to 0.12 micrograms/ml, and group B, C and G streptococci and Streptococcus pneumoniae at 0.5 micrograms/ml, whereas for Staphylococcus aureus Ro 09-1428 had MICs of 8-16 micrograms/ml similar to ceftazidime and E-1040 . Against Pseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at less than or equal to 0.12-2 micrograms/ml, and inhibited ceftazidime-resistant isolates . The majority of Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella and Shigella were inhibited by less than or equal to 0.5 micrograms/ml as with the other cephalosporins . For most Citrobacter freundii and Enterobacter cloacae Ro 09-1428 had higher MICs of 4-16 micrograms/ml; most ceftazidime-resistant isolates of these species were resistant . Anaerobes, enterococci and Listeria monocytogenes were resistant to Ro 09-1428 . Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2, Staphylococcus aureus PC-1, Moraxella catarrhalis Bro-1, Enterobacter P-99, Pseudomonas aeruginosa Sabath-Abraham or Klebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9 . Ro 09-1428 was markedly less active at an acid pH.

J Infect Dis, 1991 Jul, 164(1), 195 - 8
Antibacterial activity of crotalid venoms against oral snake flora and other clinical bacteria; Talan DA et al.; Despite heavy oral and fang contamination of crotalid species with a wide variety of potentially pathogenic bacteria, crotalid envenomation is associated with a low incidence of bacterial infection . Minimal inhibitory and bactericidal concentrations of venoms from three crotalid species were determined against six aerobic and eight anaerobic reference and oral crotalid microorganisms . All anaerobic isolates were resistant to greater than 20,480 micrograms/ml, whereas variable activity (range, 5-20,480 micrograms/ml) was observed for aerobic strains . Further studies against other aerobic clinical isolates demonstrated that venom had the greatest activity (MIC, less than or equal to 80 micrograms/ml) against staphylococci, Pseudomonas aeruginosa, and Enterobacter, Citrobacter, Proteus, and Morganella species . Inhibitory activity was lost with prolonged incubation for many gram-negative species . Crotalid venoms are broadly active against aerobic gram-negative and -positive bacteria . This activity may play a role in the low incidence of infection after envenomation injuries.

Jpn J Surg, 1991 Jul, 21(4), 376 - 80
The influence of clinical use of antibiotics and the sensitivity of strains isolated from postoperative infections--a comparison of nosocomial pathogens with strains isolated from the bacterial flora of patients; Takesue Y et al.; In the present study, we investigated how the recent clinical use of antibiotics have altered the antibiotic susceptibility of strains isolated from postoperative infections, especially Gram-negative rods . For Pseudomonas aeruginosa, serogroup E strains accounted for about 20 per cent of postoperative infections, but were unable to be isolated from either the feces of patients on admission or from the appendix contents of patients with appendicitis . It therefore appeared that serogroup E strains were responsible for the nosocomial infections in our department . The strains of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa serogroup E, which we assumed to be nosocomial pathogens, acquired a high level of resistance to antibiotics soon after third-generation cephems became widely used . On the other hand, the antibiotic susceptibility of Enterobacter cloacae, Citrobacter freundii, and the serogroups of Pseudomonas aeruginosa other than E, which were considered to originate from the bacterial flora of patients, did not vary throughout the several years of the study period.

Mol Microbiol, 1991 Jul, 5(7), 1715 - 25
Purification and mutant analysis of Citrobacter freundii AmpR, the regulator for chromosomal AmpC beta-lactamase; Bartowsky E et al.; AmpR, the transcriptional regulator for the Citrobacter freundii ampC beta-lactamase gene, was purified . The purified AmpR had DNA-binding activity, the same molecular mass (32 kDa) on sodium dodecyl sulphate/polyacrylamide gel electrophoresis as previously described, and N-terminal sequencing of the first 15 amino acids was in agreement with that predicted from the nucleotide sequence . Two mutants were isolated that abolish DNA-binding and beta-lactamase induction and which map in the amino- and carboxyl-terminal ends of AmpR, respectively . The mutation in the amino terminus (S35F) was located in a helix-turn-helix region showing high homology to other members of the LysR regulator family . Therefore this mutation may directly abolish the contact between AmpR and its operator sequence . It is suggested that the C-terminal mutation (Y264N) affects subunit interactions in AmpR . One constitutive mutant was isolated which mapped in the centre of the ampR gene . This G102E mutant leads to constitutive beta-lactamase expression in the absence of both beta-lactam inducer and ampG, a gene essential for induction in wild-type enterobacteria . Another mutant protein, D135Y, showed wild-type properties in an ampG+ and an ampG::kan background, but could, unlike wild-type AmpR, activate the ampC gene in an ampG1 mutant background . It is thought that ampG1 is a missense mutant . These two types of ampR mutants suggest that activation of ampC transcription is dependent on the conversion of AmpR into a transcriptional activator and that this activation may normally involve interactions with AmpG.

Antimicrob Agents Chemother, 1991 Jul, 35(7), 1508 - 11
In vitro comparison of GR69153, a novel catechol-substituted cephalosporin, with ceftazidime and ceftriaxone against 5,203 recent clinical isolates; Washington JA et al.; The activity of GR69153, a novel catechol-substituted cephalosporin, was compared with those of ceftazidime and ceftriaxone in a multicenter study against 5,203 fresh clinical isolates of gram-negative and gram-positive bacteria . GR69153 was generally very active at concentrations equivalent to or two- to fourfold lower than those of ceftazidime and ceftriaxone against gram-negative bacilli other than Citrobacter freundii, Enterobacter cloacae, and Xanthomonas maltophilia . Against Pseudomonas aeruginosa, MICs of GR69153 and ceftazidime for 50% of isolates tested (MIC50s) were, respectively, 1 and 2 micrograms/ml; the corresponding MIC90s were 4 and 16 micrograms/ml . Although MIC50s of GR69153 for staphylococci were two- to eightfold lower than those of ceftazidime or ceftriaxone, MIC90s against staphylococci and enterococci were greater than or equal to 16 micrograms/ml for all three compounds . Quality control MIC ranges for reference strains are proposed for the broth microdilution method on the basis of the GR69153 data derived from this multicenter study.

Antimicrob Agents Chemother, 1991 Jul, 35(7), 1343 - 7
Influence of beta-lactamase inhibitors on the potency of their companion drug with organisms possessing class I enzymes; Cavalieri SJ et al.; The ability of beta-lactamase inhibitors to induce class I beta-lactamases in certain organisms in vitro suggests a potential for antagonism in vivo . Therefore, a study was designed to assess the ability of sulbactam and clavulanate to induce beta-lactamases in two strains each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa both in vitro and in vivo . Induction in vitro was observed only with S . marcescens and P . aeruginosa and generally only when inhibitor concentrations greater than 2 micrograms/ml were examined . A mouse model of lethal infection, designed to detect in vivo antagonism arising from beta-lactamase induction, was used to determine what effect sulbactam and clavulanate would have on the 50% protective doses (PD50s) of cefoperazone and ticarcillin . Antagonism (a significant increase in the PD50) was observed in only 4 of 32 tests . Three of these involved antagonism of cefoperazone by clavulanate, and one involved antagonism of cefoperazone by sulbactam . In 6 of 32 tests, enhancement of efficacy (a significant decrease in PD50) was observed . In four of these, sulbactam enhanced cefoperazone; in one, sulbactam enhanced ticarcillin; and in one, clavulanate enhanced ticarcillin . Four of the six cases of enhancement occurred when the beta-lactamase inhibitor was given at the time of challenge . None of these positive or negative in vivo effects were predicted by in vitro tests . These data suggest that beta-lactamase inhibitors can influence the in vivo potency of their companion drug in both a beneficial and detrimental fashion against organisms with class I beta-lactamases and that these effects cannot be predicted from in vitro assays.

Eur J Clin Microbiol Infect Dis, 1991 Jul, 10(7), 581 - 5
In vitro activity of cefpodoxime against bacterial isolates obtained from patients with cancer; Rolston KV et al.; The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX) . Cefpodoxime inhibited the majority of Streptococcus spp., Haemophilus influenzae and Proteus mirabilis at a concentration of less than or equal to 0.12 microgram/ml . It was also active against Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus vulgaris, Serratia marcescens and methicillin-susceptible Staphylococcus aureus isolates . Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients.

J Clin Microbiol, 1991 Jul, 29(7), 1480 - 5
Trabulsiella guamensis, a new genus and species of the family Enterobacteriaceae that resembles Salmonella subgroups 4 and 5; McWhorter AC et al.; In 1985 the vernacular name Enteric Group 90 was coined for a small group of strains that had been referred to our laboratory as probable strains of Salmonella but did not agglutinate in Salmonella typing antisera . By DNA-DNA hybridization (hydroxyapatite method, 32P), seven strains of Enteric Group 90 were found to be closely related (98 to 100% at 60 degrees C and 94 to 100% at 75 degrees C) to the first strain received (0370-85) . The relatedness of Enteric Group 90 to 62 strains of other species of the family Enterobacteriaceae was only 6 to 41%, with the highest values obtained with strains of Salmonella, Kluyvera, Shigella, Klebsiella, Enterobacter, and Citrobacter . We propose a new genus, Trabulsiella, with a single new species, Trabulsiella guamensis, for the highly related group of eight strains formerly known as Enteric Group 90 . The type strain is designated ATCC 49490 (CDC 0370-85) . T . guamensis strains grew well at 36 degrees C and had positive reactions in the following tests: methyl red, citrate utilization (Simmons) (38% positive at day 1, 88% positive at 2 days), H2S production, lysine decarboxylase, arginine dihydrolase (50% positive at 2 days, 100% positive at 7 days), ornithine decarboxylase, motility, growth in KCN medium, mucate fermentation, acetate utilization, nitrate reduction to nitrite, weak tyrosine hydrolysis (88% positive at 2 days, 100% positive at 7 days), and ONPG (o-nitrophenyl-beta-D-galactopyranoside) test . The strains fermented D-glucose with gas production and fermented L-arabinose, cellobiose, D-galactose, D-galacturonate, maltose, D-mannitol, D-mannose, L-rhamnose, D-sorbitol, trehalose, and D-xylose . T . guamensis strains had negative reactions in the following tests: indole production (13% positive), Voges-Proskauer, urea hydrolysis, phenylalanine deaminase, malonate utilization, lipase (corn oil), DNase, oxidase, pigment production, and acid production from adonitol, D-arabitol, dulcitol, erythritol, myo-inositol, melibiose, alpha-methyl-D-glucoside, raffinose, and sucrose . There were delayed positive reactions for gelatin liquefaction (22 degrees C), which was positive at 12 to 23 days, esculin hydrolysis (13% positive at day 1, 50% positive at 7 days), lactose fermentation (13% positive at 3 to 7 days, 100% positive at 8 to 10 days), glycerol fermentation (88% positive at 7 days), and salicin fermentation (13% positive at day 1, 88% positive at 7 days) . All strains were susceptible by the disk diffusion method to colistin, nalidixic acid, gentamicin, streptomycin, kanamycin, chloramphenicol, and trimethoprim-sulfamethoxazole, and most strains were susceptible to sulfadiazine (75% susceptible), tetracycline (88%), and carbenicillin (75%) . The strains were resistant to penicillin, cephalothin, and ampicillin . The strains were isolated from vacuum cleaner dust (five strains), soil (one strain), and human feces (two strains) . Although T . guamensis can occur in human diarrheal stools, there is no evidence that it actually causes diarrhea . Its main interest to clinical microbiologists may be its possible misidentification as a strain Salmonella.

J Biochem (Tokyo), 1991 Jul, 110(1), 22 - 8
Cloning and nucleotide sequence of the gene (citA) encoding a citrate carrier from Salmonella typhimurium; Shimamoto T et al.; A cryptic citrate transport gene (citA) from Salmonella typhimurium chromosome was cloned and its nucleotide sequence was determined . The cloned plasmid conferred citrate-utilizing ability on wild-type Escherichia coli, which cannot grow on citrate as the sole source of carbon . The resultant E . coli transformant was able to transport citrate . A 1,302-base-pair open reading frame with a preceding ribosomal binding site was found in the cloned DNA fragment . The 434-amino-acid protein that could be translated from this open reading frame is highly hydrophobic (69% nonpolar amino acid residues), consistent with the fact that the transport protein is an intrinsic membrane protein . The molecular weight of this protein was calculated to be 47,188 . The gene sequence determined is highly homologous to those of Cit+ plasmid-mediated citrate transport gene, citA, from E . coli, the chromosomal citA gene from Citrobacter amalonaticus and the chromosomal cit+ gene from Klebsiella pneumoniae . The hydropathy profile of the deduced amino acid sequence suggests that this carrier has 12 hydrophobic segments, which may span the membrane lipid bilayer.

J Bacteriol, 1991 Jun, 173(12), 3656 - 62
A weak adaptive response to alkylation damage in Salmonella typhimurium; Vaughan P et al.; An efficient adaptive response to alkylation damage was observed in several enterobacterial species, including Klebsiella aerogenes, Shigella sonnei, Shigella boydii, Escherichia alkalescens, Escherichia hermanii, and Escherichia fergusonii . Increased O6-methylguanine-DNA and methylphosphotriester-DNA methyltransferase activities correlated with the induction of a 39-kDa protein recognized by monoclonal antibodies raised against the Escherichia coli Ada protein . Induced methyltransferase activities were similarly observed in Aerobacter aerogenes and Citrobacter intermedius, although no antigenically cross-reacting material was present . Weak induction of a 39-kDa protein immunologically related to the E . coli Ada protein occurred in Salmonella typhimurium . This protein encoded by the cloned S . typhimurium ada gene was shown to be an active methyltransferase which repaired O6-methylguanine and methylphosphotriesters in DNA as efficiently as did the E . coli Ada protein . However, the mehtyltransferase activity of the weakly induced 39-kDa protein in S . typhimurium was not detected, apparently because it was self-methylated and thus inactivated during the adaptive N-methyl-N-nitro-N-nitrosoguanidine pretreatment . In contrast, the E . coli ada gene on a low-copy-number plasmid was efficiently induced in S . typhimurium, and high methyltransferase activities were observed . We concluded that the inefficient induction of the adaptive response in S . typhimurium results from weak transcriptional activation of its ada gene by the self-methylated protein.

Antimicrob Agents Chemother, 1991 Jun, 35(6), 1235 - 8
In vitro susceptibility testing procedures for fosfomycin tromethamine; Barry AL et al.; Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which may be used for single-dose therapy of uncomplicated urinary tract infections . Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited greater than 90% of 352 bacterial isolates representing 25 different species; trimethoprim and nalidixic acid had narrower spectrums of activity . Strains of Escherichia, Citrobacter, Enterobacter, and Klebsiella species were much more susceptible when glucose-6-phosphate was added to the test medium, but isolates belonging to other genera were not affected.

Eur J Clin Microbiol Infect Dis, 1991 Jun, 10(6), 479 - 85
Review of Citrobacter bacteremia in cancer patients over a sixteen-year period; Samonis G et al.; A review was conducted of 65 episodes of Citrobacter bacteremia in cancer patients during a 16-year period . Cases of polymicrobial bacteremia were excluded from this analysis . The infection occurred most commonly in patients with acute leukemia . Most patients acquired the infection in the hospital, and 57% had received antibiotic therapy during the preceding ten days . Fever occurred in 98% of cases and shock in 17% . Thirty-eight percent of patients had concomitant pneumonia . Patients with shock, pneumonia or hemorrhage had a substantially poorer prognosis . The response rate was 72% for patients who received appropriate antibiotics . Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor prognosis . Beta-lactam antibiotics were more effective than aminoglycosides.

Acta Paediatr Scand, 1991 Jun-Jul, 80(6-7), 602 - 10
Intestinal colonization with Enterobacteriaceae in Pakistani and Swedish hospital-delivered infants; Adlerberth I et al.; Rectal cultures from Swedish and Pakistani hospital-delivered newborn infants were analysed regarding the early acquisition of enterobacteria . Swedish infants were delivered vaginally, Pakistani infants were delivered either vaginally or by caesarean section . The Swedish infants were all breast-fed, whereas breastfeeding was incomplete and often started late among the Pakistani infants . Both groups of Pakistani infants were more rapidly colonized with enterobacteria than were the Swedish infants . Cultures from Swedish infants seldom yielded more than one kind of enterobacteria; E . coli and Klebsiella were most frequently isolated . E . coli dominated in both Pakistani groups, but especially caesarean section delivered infants were in addition often colonized with Proteus, Klebsiella, Enterobacter or Citrobacter species . Breastfeeding from the first day of life reduced colonization with Klebsiella/Enterobacter/Citrobacter . The results suggest that environmental exposure, delivery mode and early feeding habits all influence the early intestinal colonization with enterobacteria.

Appl Microbiol Biotechnol, 1991 Jun, 35(3), 339 - 47
DNA sequence of a Salmonella-specific DNA fragment and the use of oligonucleotide probes for Salmonella detection; Tsen HY et al.; Hybridization specificity of a 1.8-kb HindIII DNA fragment isolated from Salmonella typhimurium by a molecular cloning technique was confirmed by colony hybridization with 327 Salmonella isolates of various serotypes and 56 non-Salmonella isolates including Enterobacteriaceae closely related to Salmonella, such as Escherichia coli, Klebsiella, Citrobacter and Shigella . It was found that this 1.8-kb DNA fragment was highly specific for all the Salmonella isolates tested . The DNA sequence of this 1.8-kb fragment was then determined by the dideoxynucleotide chain termination method . According to this DNA sequence, six oligonucleotide fragments ranging from 17- to 26-mer were then chemically synthesized and tested for their hybridization specificities . Results show that three of the six oligonucleotide fragments are highly specific for all 327 Salmonella strains tested and can be used as probes for the specific detection of Salmonella in foods or other samples.

Biochem J, 1991 May 1, 275 ( Pt 3), 629 - 33
Proteolytic interconversion and N-terminal sequences of the Citrobacter diversus major beta-lactamases; Franceschini N et al.; The N-terminal sequences of the two major beta-lactamases produced by Citrobacter diversus differed only by the absence of the first residue in form II and the loss of five amino acid residues at the C-terminal end . Limited proteolysis of the homogeneous form I protein yielded a variety of enzymatically active products . In the major product obtained after the action of papain, the first three N-terminal residues of form I had been cleaved, whereas at the C-terminal end the treated enzyme lacked five residues . However, this cannot explain the different behaviours of form I, form II and papain digestion product upon chromatofocusing . Form I, which was sequenced up to position 56, exhibited a very high degree of similarity with a Klebsiella oxytoca beta-lactamase . The determined sequence, which contained the active serine residue, demonstrated that the chromosome-encoded beta-lactamase of Citrobacter diversus belong to class A.

Zentralbl Hyg Umweltmed, 1991 May, 191(5-6), 449 - 56
Formaldehyde-resistance in Enterobacteriaceae and Pseudomonas aeruginosa: identification of resistance genes by DNA-hybridization; Wollmann A et al.; A 4.1 . Kb large DNA fragment of a E . coli plasmid pVU 3695, on which the genes for formaldehyde-resistance are located, was used as a DNA probe to identify bacteria that carry this segment among formaldehyde-resistant bacteria . It was shown by Southern Blot-, Dot Blot-, and Colony Blot- Hybridization studies that the DNA of all formaldehyde-resistant E . coli, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii and Klebsiella pneumoniae strains tested hybridize with the DNA probe from E . coli . In contrast the E . coli DNA probe does not hybridize with the DNA from formaldehyde-resistant Pseudomonas aeruginosa strains.

Jpn J Antibiot, 1991 May, 44(5), 529 - 37
{Combined antibacterial activity of aztreonam and clindamycin against clinically isolated strains}; Deguchi K et al.; It has been reported in some studies that the combination of aztreonam (AZT) and clindamycin (CLDM) have high clinical effectiveness in the treatment of intractable infections . We, therefore, studied combined in vitro antibacterial activity of these 2 compounds using many freshly isolated strains . 1 . AZT and CLDM in combination had synergistic effects on Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae, which are sensitive or quasi-sensitive to CLDM, in the presence of CLDM at MIC or sub-MIC . 2 . For Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa, which are not sensitive to CLDM, the 2 drugs in combination showed synergistic effects on some species and additive or slightly additive effects on most species in the presence of CLDM at those concentrations which are usually maintained in blood . 3 . The 2 drugs showed no antagonism.

J Dairy Sci, 1991 May, 74(5), 1539 - 43
N-acetyl-beta-D-glucosaminidase, etiologic agent, and duration of clinical signs for sequential episodes of chronic clinical mastitis in dairy cows; Wilson DJ et al.; This study examined effects of repeated episodes of clinical mastitis in chronically infected quarters on milk N-acetyl-beta-D-glucosaminidase activity and duration of clinical signs . Milk samples were collected at each clinical onset from 49 chronic mastitis cases on a 1700-cow Michigan dairy farm . There were 49 first episodes of clinical mastitis, 49 second episodes, and 13 episodes of third or more . Agents isolated were Staphylococcus aureus (18.4%), Staphylococcus (7.3%), no growth (20.2%), environmental pathogens (streptococci other than agalactiae, Escherichia coli, Klebsiella spp., Enterobacter spp., and Citrobacter spp.) (22.0%), other pathogens (Serratia spp., Bacillus spp., diphtheroids {Corynebacterium spp . and Actinomyces pyogenes}, Pseudomonas spp., and Nocardia spp.) (11.9%), mixed pathogens (two agents isolated) (12.8%), and contaminated samples (7.3%) . Etiologic agents, duration of clinical signs, and NAGase did not differ by episode number . The correlation between log of NAGase and log of time until clinical recovery was .34 . The relationship between NAGase and duration of clinical signs was strongest for second episodes, and weakest for third and greater episodes of chronic mastitis.

Antimicrob Agents Chemother, 1991 May, 35(5), 976 - 82
Modulation of the intestinal flora of mice by parenteral treatment with broad-spectrum cephalosporins; van Ogtrop ML et al.; A study was performed to determine the effect of parenteral treatment with four broad-spectrum cephalosporins (cefoperazone, ceftriaxone, ceftazidime, and cefepime) on the number of aerobic gram-negative rods and on the outgrowth of Candida albicans and a multiresistant strain of Citrobacter freundii in the feces of mice . The estimated fractions of a parenteral dose that were excreted into the gastrointestinal tract were 0.37 for cefoperazone, 0.11 for ceftriaxone, 0.03 for ceftazidime, and 0.002 for cefepime . All four cephalosporins significantly decreased the number of aerobic gram-negative rods in the feces, and virtually all gram-negative rods were eliminated at high doses of cefoperazone, ceftazidime, and ceftriaxone . Furthermore, at high doses these three compounds led to a significant increase of the outgrowth of resistant Citrobacter freundii . The outgrowth of Candida albicans was increased at high doses of cefoperazone and ceftriaxone, whereas ceftazidime and cefepime did not have this effect . The most profound changes in the gastrointestinal ecology were observed during treatment with high doses of cefoperazone . The results suggest that the colonization resistance of the gastrointestinal tract can be substantially decreased by parenteral treatment with cefoperazone and, to a lesser extent, with ceftriaxone and ceftazidime.

Infect Immun, 1991 Apr, 59(4), 1352 - 8
Pathophysiology of Citrobacter diversus neonatal meningitis: comparative studies in an infant mouse model; Soriano AL et al.; Citrobacter diversus is a cause of devastating neonatal meningitis, with illness characterized by formation of multiple brain abscesses . We developed an infant mouse intracranial inoculation model to evaluate the pathophysiology of C . diversus neonatal infections . Eighteen of 26 strains inoculated intracranially at a dose of ca . 3.3 x 10(3) CFU caused greater than 50% mortality in 2-day-old mice . No correlation was seen between the epidemiologic characteristics of a strain and its rate of mortality . When seven C . diversus isolates (four isolates from patients with meningitis, three from non-central nervous system {CNS} sites) were further evaluated, mortality was significantly correlated with bacteremia . The initial lesion in the CNS was a suppurative ventriculitis beginning 1 to 2 days postinoculation . Subsequent ventriculomegaly was associated with ventriculitis and periventricular abscessation . Brain lesions were seen with all strains, although strains of low virulence (as measured by having no bacteremia and low mortality) caused less-severe damage . An age-related susceptibility to C . diversus brain lesions was demonstrated, with 5-day-old mice showing a significant reduction in, and 8-day-old mice being apparently resistant to, infection and CNS damage . Our data indicate that C . diversus has a propensity to cause abscess formation in the neonatal mouse brain, with characteristic pathologic findings; however, the factors that determine whether a strain will cause meningitis in a human infant remain to be identified.

J Chemother, 1991 Apr, 3(2), 83 - 5
Some molecular properties of Citrobacter diversus beta-lactamases; Amicosante G et al.; Citrobacter diversus ULA-27, a clinical isolate showing a broad resistance pattern towards both penicillins and cephalosporins, produces chromosome encoded beta-lactamases . However, the strain remains susceptible to some cephamycins, imipenem, ceftazidime and tetracyclines . Crude bacterial extracts analyzed by isoelectric focusing on polyacrylamide gels, revealed the presence of two main isoforms and some "satellite" bands focusing in the pH range 5.7-7.2 . The isoform showing the pIs 6.8 and 6.2 were characterized as class "A" beta-lactamases (according to Ambler's classification) based on the rate of interaction of beta-iodopenicillanate and the amino acid sequence around the active site serine . The substrate specificity of the Citrobacter diversus beta-lactamases explains the resistance phenomenon of this bacterium to penicillins and cephalosporins.

Indian J Exp Biol, 1991 Apr, 29(4), 338 - 41
Antigen sharing of Salmonella typhi non-flagellar proteins with other salmonellae and some shigellae and Escherichia coli; Jesudason M et al.; Cathodal moving protein components were identified in agarose gel electrophoresis of the Veronal buffer extract of a non-motile strain of S . typhi (8393, Colindale) . Rabbit antiserum was raised against these cationic proteins; it had both agglutinating and precipitating activity . A total of 80 salmonella strains belonging to serogroups A, B, C1, C2, D, E1 and E2 including 26 S . typhi and 10 S . paratyphi A were tested against this antiserum in a slide agglutination test; all strains were agglutinated . Among 94 other bacterial strains tested, the antiserum agglutinated all 16 strains of Shigella flexneri, 2 of 5 Shigella sonnei, 5 of 34 E . coli and 1 of 8 Citrobacter species . These results show that there is antigenic sharing of the non-flagellar proteins of S . typhi with many other salmonellae as well as with some shigellae and E . coli.

J Antimicrob Chemother, 1991 Apr, 27(4), 441 - 57
Concomitant dissemination of three extended-spectrum beta-lactamases among different Enterobacteriaceae isolated in a French hospital; de Champs C et al.; From January 1988 to August 1989, 267 non-repetitive strains of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBla) derived from TEM (CTX-1/TEM-3, CAZ-6) or SHV (CAZ-5) were isolated from 219 colonized or infected patients . ESBlas were characterized by analytical isoelectric focusing . Biotypes, resistance phenotypes and plasmid patterns were determined in order to differentiate the isolates in each species . Among the 116 CTX-1-producing Enterobacteriaceae, 48 strains were differentiated: 27 from 74 Klebsiella pneumoniae isolates, seven from 22 Enterobacter aerogenes isolates, and 14 from a combined total of seven K . oxytoca, five Serratia marcescens, six Escherichia coli, 1 Enterobacter cloacae and 1 Citrobacter freundii . CAZ-5 has been isolated since January 1988 in 16 different strains among 101 K . pneumoniae isolates . CAZ-6 was first identified in K . pneumoniae (January 1988) . Among the 48 Enterobacteriaceae producing CAZ-6, 12 strains were differentiated: four from 39 E . aerogenes isolates, three from four K . pneumoniae, and five from a combined total of two S . marcescens, two E . coli and one E . cloacae . During this outbreak, CTX-1 was found to be encoded by 85 kb (Inc 7/M) or greater than or equal to 150 kb (Inc 6/C) plasmids . CAZ-6 was always encoded by an 85 kb (Inc 7/M) plasmid and CAZ-5 by a greater than 150 kb plasmid . These results show that strain epidemics and plasmid dissemination occurred mainly in K . pneumoniae and E . aerogenes for CTX-1, in E . aerogenes for CAZ-6, and in K . pneumoniae for CAZ-5 . They also suggest that the bla(tem) gene (CTX-1) has spread between different plasmids present in the same ecosystem.

Rev Med Chil, 1991 Mar, 119(3), 303 - 7
{Bacteremic pneumonia caused by Citrobacter diversus: report of a case}; Zuniga J et al.; A 61 year old male with a localized gastric cancer developed a post-operative pneumonia by C . diversus which was isolated from blood and from bronchoalveolar lavage . A satisfactory response was observed after treatment with penicillin and amikacin . A brief review of the literature concerning the clinical relevance of infections by this unusual agent is offered.

Eur J Biochem, 1991 Feb 26, 196(1), 197 - 201
Core region of Citrobacter O23 lipopolysaccharide . Structure elucidation by chemical methods, gas chromatography/mass spectrometry and NMR spectroscopy at 500 MHz; Katzenellenbogen E et al.; A novel enterobacterial core region in Citrobacter O23 lipopolysaccharide is described . Its structure was determined by methylation analysis/mass spectrometry, chemical degradation and one- and two-dimensional 1H-NMR spectroscopy: {formula; see text} where PPEtN stands for diphosphorylethanolamine, and dOclA for 3-deoxy-D-manno-octulosonic acid.

Acta Paediatr Scand, 1991 Feb, 80(2), 205 - 12
Antibiotic susceptibility of 629 bacterial blood and CSF isolates from Swedish infants and the therapeutic implications; Tullus K et al.; Blood and CSF isolates (n = 629) from Swedish infants up to one year of age were tested in vitro against 13 antimicrobial agents in order to update the guidelines for empiric therapy of septicaemia and meningitis . Ampicillin plus gentamicin provided inadequate empiric therapy for meningitis, due to the poor CSF penetration of the aminoglycoside and the frequent occurrence of bacterial resistance to ampicillin . Ceftazidime and cefuroxime were moderately active, particularly against isolates from small infants . Cefotaxime today seemed to provide the best empiric therapy of septicaemia and meningitis in infants . Because of the occurrence of Listeria and enterococcal infections, ampicillin should initially be added and other combinations are also advisable for the occasional cases of Enterobacter, Citrobacter, Serratia, and Pseudomonas infections . For coagulase-negative staphylococci only vancomycin offered a broad activity (100% at achievable serum levels).

Antimicrob Agents Chemother, 1991 Feb, 35(2), 329 - 34
In vitro activity of a catechol-substituted cephalosporin, GR69153; Wise R et al.; The in vitro activity of GR69153, a new catechol-substituted cephalosporin, was compared with those of ceftazidime, imipenem, meropenem, and ceftriaxone against 604 recent clinical isolates and other strains with known mechanisms of resistance . The MICs of GR69153 for 90% of the members of the family Enterobacteriaceae tested were less than 0.5 micrograms/ml, with the exceptions of those for Serratia spp . (4 micrograms/ml), Citrobacter spp . (2 micrograms/ml), and Enterobacter spp . (8 micrograms/ml) . Ninety percent of Pseudomonas aeruginosa isolates were susceptible to less than or equal to 1 microgram of GR69153 per ml . With the exception of methicillin-resistant strains, 90% of Staphylococcus aureus isolates were susceptible to less than or equal to 2 micrograms/ml, and GR69153 was four- to eightfold more active than ceftazidime and ceftriaxone against these strains . Isolates of Haemophilus influenzae, Branhamella catarrhalis, Neisseria spp., and Streptococcus pneumoniae (penicillin susceptible) were highly susceptible (MIC for 90% of the strains, less than or equal to 0.12 micrograms/ml) . GR69153 was stable to hydrolysis by the TEM-1 and TEM-5, SHV-1 and SHV-2, and K1 beta-lactamases, but some susceptibility to hydrolysis by the TEM-3, TEM-9, and P99 enzymes was observed . The protein-binding activity of GR69153 was 74.5 to 66.8%, depending on the concentration, and serum had little effect upon activity.

Antimicrob Agents Chemother, 1991 Feb, 35(2), 259 - 66
In vitro activity and beta-lactamase stability of GR69153, a new long-acting cephalosporin; Chin NX et al.; GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90) . It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040 . Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species . Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant . GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml . For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040 . Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml . The activity of GR69153 was not affected by serum . GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae . GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations . It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are . GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties.

FEMS Microbiol Lett, 1991 Feb, 62(1), 7 - 10
Phosphatase production by a Citrobacter sp . growing in batch cultures retarded by anaerobic or osmotic stress, and the effect of the osmoprotectant glycine betaine; Hallett DS et al.; The effect of 500 mM NaCl on the growth, and phosphatase production of a Citrobacter sp . was investigated . Although growth was retarded, phosphatase production was enhanced by 50% . Relief from osmotic stress using the osmoprotectant glycine betaine gave normal growth, but phosphatase activity was reduced . The Citrobacter sp . ceased to grow following a shift to anaerobic conditions, but anaerobically-incubated cells continued to produce phosphatase after a transient lag.

FEMS Microbiol Immunol, 1991 Feb, 3(1), 1 - 5
Saccharide-protein covalent conjugates: immunochemical characterization of Citrobacter 036 core oligosaccharide-tetanus toxoid conjugates; Lugowski C et al.; Core oligosaccharides (complete and incomplete) isolated from Citrobacter 036 lipopolysaccharide were covalently conjugated with tetanus toxoid . Serological examination of the Citrobacter 036 core oligosaccharide-tetanus toxoid conjugates showed that they are strong immunogens . The monospecific anti-conjugate sera prepared by immunization of rabbits, were used to study the antigenic relations between lipopolysaccharide core regions of 8 strains of Citrobacter . Immunoelectrophoresis, immunoblotting and quantitative microprecipitation were performed in the experiments.

Zentralbl Mikrobiol, 1991, 146(2), 149 - 56
{Microbiological quality of mechanically deboned beef}; Prasovska M et al.; Microbial quality of mechanically deboned beef (MDB), which was obtained by the discontinuous hydraulic horizontal separator, type Inject-Star (firm LASKA, Austria), was analyzed for the presence of indicatory microorganisms (coliforms and enterococci), pathogenic and conditionally pathogenic microorganisms . The basic microbial parameters have been determined separately for MDB of 1st, 2nd degrees as well as for average daily samples from one collecting vessel . Apart from it, also a raw material (beef from flesh bones intended for separation) and salt MDB after 24 hrs storing in chiller before working it into meat products were examined by the same way . From our results it follows that the number of all microorganisms observed in MDB of 1st degree was lower than that of 2nd degree . During the separation process the increase of microbial parameters compared with those in initial raw material occurred by 1-2 radices and following subsequent salting and storing in chiller there was a repeated decrease by 1 radix (with exception of the number of Staphylococci remaining unchanged) . The change in the amount of microflora present was also influenced by season--in summer there was an increase by about 1 radix . From the view point of food hygiene the finding of salmonellas and the presence of large number of Staphylococci including Staphylococcus aureus on average 10(5).g-1 as well as the presence of wide extent of conditionally pathogenic microorganisms from the family of Enterobacteriaceae, especially from genera Proteus, Providencia, Morganella and Citrobacter are of great importance.

Antimicrob Agents Chemother, 1991 Jan, 35(1), 14 - 9
Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin; Limbert M et al.; Cefquinome is a new injectable aminothiazolyl cephalosporin derivative . It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum . Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations . Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci . Its in vitro activity against gram-negative anaerobes is very limited . The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria . We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves . After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively . The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses . In dogs the urinary recovery was more than 70% within 24 h of dosing.

Diagn Microbiol Infect Dis, 1991 Jan-Feb, 14(1), 79 - 83
Antimicrobial effects of the combination of ceftibuten and an orally absorbed penem SCH 29482; Chin NX et al.; 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.

DICP, 1991 Jan, 25(1), 27 - 9
Successful treatment of neonatal Citrobacter freundii meningitis with ceftriaxone; Rae CE et al.; Citrobacter meningitis is an uncommon enteric gram-negative infection that afflicts neonates and young children . Approximately 30 percent of children treated or untreated die from the infection . We report a case of C . freundii meningitis that was resistant to ampicillin and was successfully treated with ceftriaxone, a third-generation cephalosporin . A 13-day-old, full-term baby was admitted to the hospital with a one-day history of fever up to 38.8 degrees C . On admission the infant had a temperature of 39.2 degrees C, pulse of 140 beats/min, and a respiratory rate of 32 breaths/min . Except for a slightly bulging fontanelle, the rest of the physical examination was within normal limits . Complete blood count revealed a white blood cell (WBC) count of 12.5 x 10(9)/L, with 0.66 polymorphonuclear cells, 0.10 bands, 0.18 lymphocytes, and 0.06 monocytes . A stat lumbar puncture showed 10 WBCs per high-power field with gram-negative rods . Empiric therapy with ampicillin 225 mg q12h and gentamicin 11 mg q8h was started . Both antibiotics were discontinued after culture and sensitivity results were positive for C . freundii in the blood and spinal fluid . The patient was successfully treated with nine days of ceftriaxone 250 mg q12h.

Scand J Infect Dis Suppl, 1991, 78, 7 - 16
Mechanisms of resistance to beta-lactam antibiotics; Livermore DM; The use of new beta-lactam antibiotics has led to selection of novel forms of resistance . Newer-generation cephalosporins, ureidopenicillins and monobactams, but not carbapenems (e.g . imipenem), are labile to Class I chromosomal beta-lactamases and tend to select mutants of E . cloacae and P . aeruginosa that constitutively synthesize high levels of these enzymes . Selection occurs more rarely with Serratia, Citrobacter and indole positive protease . Third-generation cephalosporins and monobactams, but not carbapenems and cephamycins, are inactivated by a range of new variants of the well-known TEM and SHV-1 plasmid-mediated beta-lactamases . These variants have arisen by spontaneous mutation and differ only marginally in amino-acid sequence from their parent enzymes . Already prevalent in France, their potential for spread is a major concern . Outer membrane impermeability is another source of resistance to beta-lactams in Gram-negative bacteria . Rare in enterobacteria, it is more important in P . aeruginosa, where broad and narrow spectrum forms can arise via mutation . The narrow spectrum form involves loss of the D2 outer membrane protein and gives resistance to carbapenems but not other beta-lactams . The broad spectrum form, of unknown mechanism, simultaneously affects many beta-lactam and unrelated (e.g . quinolone) drugs, but not imipenem . Target (penicillin-binding protein) insensitivity also can mediate resistance, most notably in MRSA . Unlike the mechanisms described above, this affects all beta-lactams, including carbapenems as well as penicillins and cephalosporins.

Scand J Infect Dis Suppl, 1991, 78, 54 - 63
Clinical implications of multi-drug resistance in the intensive care unit; Snydman DR; A prospective in vitro survey of Gram-negative isolates obtained from patients hospitalized in intensive care units in 10 Boston teaching hospitals was undertaken to document current susceptibility patterns and analyze patterns of cross-resistance . One thousand and five isolates were obtained, 18% were pseudomonas, 18% Escherichia coli, 13% klebsiella, and 22% were in the enterobacter, citrobacter, serratia group . Cross-resistance among beta-lactams and beta-lactamase inhibitors was common for species with a potential to produce the type I inducible beta-lactamase (p less than 0.01) . In contrast, resistance to imipenem was not associated with cross-resistance . Ciprofloxacin and netilmicin also remained active . Clinical observations of the development of cross-resistance to the beta-lactams in enterobacter and citrobacter infections in four patients (two bacteremias and two wound infections) seen in one institution confirm these in vitro findings . Unanswered questions remain regarding the frequency of beta-lactam cross-resistance, the most likely sites of occurrence and the overall clinical significance . Clinicians should be aware of the potential selection of type-I beta-lactamase hyperproducers by the use of second or third generation cephalosporins or related beta-lactam agents.

Chemotherapy, 1991, 37(3), 202 - 5
Bactericidal effect of 15-deoxyspergualin on Staphylococcus aureus; Hibasami H et al.; 15-Deoxyspergualin (DSG), an immunosuppressive agent used in organ transplantation, exerts metabolic and antiproliferative effects on methicillin- and gentamicin-resistant Staphylococcus aureus and other bacteria (e.g . Sarcina lutea, Bacillus subtilis, Shigella sonnei, Salmonella typhi and Citrobacter freundii) . DSG, at the concentration of 20 mg/l, depleted intracellular putrescine and spermidine in S . aureus to 43 and 40% of the controls, respectively . In these polyamine-depleted S . aureus cells, the synthesis of protein, DNA and RNA was decreased to 20, 85, 78% of the controls . The minimal inhibitory concentrations (MIC) of DSG for growth of S . aureus, S . lutea, B . subtilis, S . sonnei, S . typhi and C . freundii were 17, 13, 7, 15, 4, and 29 mg/l, respectively.

J Hyg Epidemiol Microbiol Immunol, 1991, 35(1), 57 - 64
Bacterial isolates and drug susceptibility tests at Kaffa Regional Public Health Laboratory, south west Ethiopia; W/Tenssay Z; A two year period bacteriological data was analysed and the frequent bacterial isolates from different clinical specimens included: S . aureus, 25% E . coli, 15%; Proteus spp 14%; Citrobacter-Enterobacter group, 10% coagulase negative Staphylococcus species, 9%; and other miscellaneous bacteria each less than 9% . The majority of the bacterial isolates were resistant to commonly available antimicrobial agents like tetracycline, ampicillin, and chloramphenicol.

Zhonghua Yi Xue Za Zhi (Taipei), 1991 Jan, 47(1), 39 - 44
{Pediatric bacteremia strains grow in blood culture media}; Chiang TM et al.; Bacteremia strains may influence the clinical therapy, the isolation of bacteremia strains is important for patients . In order to understand the distribution and the growth in the blood culture media of bacteremia strains, from January 1982 through December 1988 we studied the blood culture sent to us from the pediatric ward . These were three hundred and forty one bacterial strains (3.1%) isolated from patients . In the meantime we also studied the bacteremia strains growth in the blood culture media . In these positive cultures, there were 83 gram-positive, and 258 gram-negative strains . The 83 gram-positive included Staphylococcus aureus (38 strains), hemolytic streptococcus (22 strains), Enterococcus (13 strains), Streptococcus pneumoniae (8 strains) and others (2 strains) . The 258 gram-negative strains included Escherichia coli (97 strains), Salmonella spp . (43 strains), Enterobacter spp . (31 strains) . Klebsiella spp . (23 strains), Pseudomonas spp . (25 strains), Proteus spp . (17 strains), Citrobacter spp . (11 strains) and others (11 strains) . The Growth of bacteremia strains in the blood culture medium, showed that first day isolation strains were 33.7%, second day strains 24.9%, third day were 19.9%, fourth day were 13.5%, fifth day were 3.2%, sixth day were 4.1% and seventh day were 0.6% . In conclusion, the bacteremia strains showed that the gram-negative, which were 75.7%, were more prevalent than the gram-positive which were 24.3%, the isolation of the strains was more in the first to fourth day and grew by 92%, on the fifth day it grew by 3.2% and on the seventh day by only 0.6% . On the fifth day the baby had recovered and we were able to discontinue antibiotic therapy.

Bull Soc Pathol Exot, 1991, 84(5 Pt 5), 627 - 34
{Virological and bacteriological study of materno-fetal infections in Brazzaville}; Yala F et al.; Serological study of serum samples taken from pregnant women and umbilical cord and bacteriological study of vaginal secretions samples and cerebrospinal fluid (CSF) showed in mothers: T . pallidum antibody (Tp ab) 9%, Rubella virus antibody (Ru ab) 85%; HBs Ag 16%, HIV antibody (HIV ab) 4% . Microbe culture showed: S . aureus 18%, Streptococcus sp . 9%, E . coli 4.9%, Klebsiella 3.6%, Citrobacter 3.6%, Candida albicans 15%; direct immunofluorescence: Chlamydia 26% . In infants: IgG umbilical cord: Tp ab 4.8%, Rub ab: 80.6%, HIV ab 4/4, Hbs Ag 11.3% Microbe culture in CSF: global frequency: 5.1%; Streptococcus sp . 31.8%, Staphylococcus 20.5%, enterobacteriaceae 27.2%, other Gram negative bacilli 20.5%.

Pediatr Neurosurg, 1991-92, 17(1), 23 - 4
Neonatal meningitis and bilateral cerebellar abscesses due to Citrobacter freundii; Joaquin A et al.; We report bilateral cerebellar abscesses in a neonate with Citrobacter freundii meningitis . The mortality and morbidity of Citrobacter abscess is high . Rapidly developing drug resistance may play a role as illustrated by our case.

Acta Microbiol Hung, 1991, 38(2), 147 - 54
What is the diagnostic value of beta-D-glucuronidase (BDG) activity of bacteria using Fluorocult ECD agar for their cultivation?
Ralovich B, Ibrahim GA, Fabian A, Herpay M.
A total of 1510 strains from 15 genera of Gram-negative and Gram-positive bacteria were studied . More than 94% of 327 Escherichia coli strains showed beta-D-glucuronidase (BDG) activity . Seventeen serotypes from 170 E . coli O serogroup representatives were negative . Relationship between the existence of BDG positive and negative E . coli strains in the same serogroup or serotype has not been observed . The rate of BDG positivity was 42% among Salmonella arizonae strains and 42.2% among Shigella strains . Only one Citrobacter strain out of the 971 strains belonging to Citrobacter, Edwardsiella, Enterobacter, Hafnia, Klebsiella, Proteus, Serratia, Yersinia, Pseudomonas, Aeromonas, Vibrio and Listeria was BDG positive . A screening method based on only BDG activity is not sufficient for the primary diagnosis of E . coli.

Chemotherapy, 1991, 37(5), 310 - 7
In vitro and in vivo activity of carbamate-linked dual-action antibacterial Ro 24-4383; Beskid G et al.; Ro 24-4383 contains desacetylcefotaxime linked by a carbamate bond at the 3' position to ciprofloxacin . Ro 24-4383 was active against 99% of the 363 gram-positive and gram-negative aerobes tested in vitro, while the comparative agents cefotaxime and ciprofloxacin were active against 77 and 97%, respectively . The activities (ED50: mg/kg s.c.) of Ro 24-4383, cefotaxime and ciprofloxacin in systemic murine infections were: Escherichia coli 257, 1.4, less than 0.5, less than 0.2; Klebsiella pneumoniae A, 11, 30, 0.7; Enterobacter cloacae 5699, 3.2, 35, less than 0.2; Citrobacter freundii BS16, 3, 41, less than 0.5; Serratia marcescens SM, 35, greater than 100, 1.6; Pseudomonas aeruginosa 5712, 67, 100, 10; P . aeruginosa 8780, 33, 193, 3; Staphylococcus aureus Smith (oxacillin-susceptible), 12, 3.7, 1; S . aureus 753 (oxacillin-resistant), 28, greater than 100, 2; Streptococcus pneumoniae 6301, 10, 15, greater than 50, and S . pyogenes 4, 3.3, 1.6, 54 . Ro 24-4383, although inactive against the S.-pneumoniae-induced pneumonia following one administration of the agent, was highly active (ED50 = 1.5) when three treatments were given following infection . Ro 24-4383 was active against the K.-pneumoniae-induced pneumonia (ED50 = 37), as well as the meningitis induced by S . pneumoniae (ED50 = 158) or K . pneumoniae (ED50 = 100) . The protective effect of Ro 24-4383 was demonstrated when administered 8 h before infection with E . coli (ED50 = 37) and 4 h before infection with S . pyogenes (ED50 = 199).

Drugs, 1991, 42 Suppl 3, 6 - 12
Microbiological evaluation of cefpodoxime proxetil; Wiedemann B et al.; Cefpodoxime, the active de-esterified molecule of the orally absorbable cephalosporin cefpodoxime proxetil, inhibits streptococci, Neisseria spp., and most Enterobacteriaceae, with MIC50 and/or MIC90 values of less than or equal to 2 mg/L; with regard to the latter family of bacteria, the MIC50 and/or MIC90 values of cefpodoxime are consistently greater than or equal to 4 mg/L for only Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Morganella morganii . The MIC50 of cedpodoxime for coagulase-negative staphylococci is greater than 2 mg/L, while the MIC for Staphylococcus aureus strains is 4 mg/L . In comparison with other orally absorbable cephalosporins, cefpodoxime is slightly less active than cefixime, cefetamet, and cefotiam against Gram-negative bacteria, but more active than cefuroxime, cefaclor, and cefalexin . Against staphylococci, the activity of cefpodoxime is comparable to that of cefotiam and cefuroxime, and superior to that of cefaclor, while cefixime and cefetamet have insufficient activity against these species . In common with other cephalosporins, cefpodoxime has no activity against enterococci . In vitro models simulating human serum cefpodoxime concentrations demonstrate that a dosage regimen of 200mg is probably sufficient to treat most infections . However, further study is needed to clarify whether infections due to bacteria such as S . aureus, with higher cefpodoxime MICs, can be treated with this dose regimen.

Lab Delo, 1991, (7), 52 - 4
{The serologic diagnosis of group B salmonelloses}; Karal'nik BV et al.; Antibacterial sera activities towards Citrobacter O22 and Salmonella typhimurium were tested with O22, O1, O4, O5, O12 erythrocytic diagnostic agents . Cross activities of O22, O1, O4, O5, O12, and Hi antigens were tested with the same and Hi erythrocytic diagnostic agents in the antibody neutralization test . The findings have confirmed the identity or very close relationship between the tested O antigens . Screening for antigens of the excretions from patients with S . typhimurium and Citrobacter O22 infections has shown that indication of Hi antigen may be considered as the differentiating criterion between these infections.

Lab Delo, 1991, (4), 62 - 4
{The etiologic structure of acute intestinal infections caused by opportunistic microorganisms (Irkutsk, 1984-1988)}; Kuznetsov VI et al.; The authors analyze the results of bacteriologic studies carried out in patients with intestinal infections at the laboratory of the Sanitary Epidemiologic Center of the town of Irkutsk over 1984-1988 . The records of 24,490 case histories show infections induced by opportunistic microflora in 37 percent of cases . The most frequent etiologic agents were Staphylococcus aureus and Enterobacteriaceae, genera: Proteus, Enterobacter, Citrobacter, Klebsiella, Hafnia . Analysis of the incidence of acute intestinal infections induced by opportunistic bacteria in various age groups evidence that mostly infants aged under 1 suffer from them . In older children S . aureus is no longer etiologically significant and it is replaced by Enterobacter and Klebsiella . The authors find it interesting to compare the etiological patterns of enteritis induced by opportunistic microorganisms in various regions of our country.

Infection, 1991, 19 Suppl 5, S264 - 75
In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE2787 and piperacillin plus tazobactam) in comparison with established compounds (cefotaxime, latamoxef and piperacillin); Bauernfeind A et al.; The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of piperacillin plus tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species . Escherichia coli, Klebsiella spp . Enterobacter sakazakii, Proteus spp . and Shigella spp . were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for piperacillin plus tazobactam was between 2 and 16 mg/l . Enterobacter cloacae, Enterobacter aerogenes and Serratia spp . were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and piperacillin plus tazobactam . For Citrobacter spp., Providencia spp . and Yersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l . Flomoxef was between 2 to 4 log2 less active against these species but more active than piperacillin plus tazobactam (MIC90: 2 and 8 mg/l) . Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and piperacillin plus tazobactam (MIC90: 8 and greater than 64 mg/l) were the least active compounds . SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l) . The oxacephems were the least active compounds against NFB . Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC90: 16 mg/l) . Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l) . Latamoxef had the lowest activity of all compounds against gram-positive cocci . Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1991 Jan, 27(1), 29 - 40
In-vitro evaluation of ampicillin/brobactam and comparison with other beta-lactam antibiotics; Melchior NH et al.; The ability of brobactam to inhibit beta-lactamases and the in vitro activity of ampicillin combined with brobactam was compared with another beta-lactamase inhibitor, clavulanic acid, and other beta-lactam antibiotics . Both inhibitors showed good and similar activity against staphylococcal penicillinase and most broad-spectrum beta-lactamases found in the Enterobacteriaceae, whether plasmid or chromosomally mediated . Both inhibitors were less active against chromosomally mediated cephalosporinases in Enterobacteriaceae, but brobactam was 8-50 times more potent than clavulanic acid . The amount and type of beta-lactamase produced by a particular bacterial strain was reflected in its sensitivity to a combination of ampicillin and brobactam, and correlated well with the sensitivity of extracted beta-lactamase to inhibition by brobactam . The in-vitro activity of ampicillin/brobactam in a 3:1 ratio was compared to amoxycillin/clavulanic acid (4:1 ratio), amoxycillin, cefaclor and cefuroxime . The two inhibitor combinations were generally of similar activity, but the brobactam combination had superior activity against Proteus vulgaris, Morganella morganii, Citrobacter freundii and Yersinia enterocolitica . The cephalosporins were less effective against the Bacteroides fragilis group, Prot . vulgaris and M . morganii, but had advantages in the case of Escherichia coli, Klebsiella spp . and C . diversus . The MBC of ampicillin/brobactam was similar to the MIC . No resistant sub-populations were observed amongst the staphylococcal strains investigated . Exposure of bacteria to sub-inhibitory levels of ampicillin/brobactam did not lead generally to the development of resistance.

J Antimicrob Chemother, 1990 Dec, 26 Suppl E, 7 - 12
In-vitro activity of cefpodoxime against 1834 isolates from domiciliary infections at 20 UK centres; Holt HA et al.; A total of 1834 non-copy, general practice or outpatient isolates were collected by 20 hospital laboratories within the British Isles, and identified and tested for susceptibility to nine antimicrobial agents available by oral administration at one centre . Against Enterobacteriaceae cefpodoxime was the most active beta-lactam agent tested, the MIC90s being: for Escherichia coli 1.0 mg/l, for Proteus mirabilis 1.0 mg/l, for Citrobacter spp . 2.0 mg/l, and for Enterobacter spp., Serratia spp., Morganella spp . and Klebsiella spp . 16-64 mg/l . Cefpodoxime also showed a certain amount of activity against staphylococci and high activity against streptococci, the MIC90s being for Staphylococcus aureus 2 mg/l, for coagulase negative staphylococci 8 mg/l, for Streptococcus pyogenes 0.015 mg/l, for Str . pneumoniae 0.06 mg/l and for Str . agalactiae 0.5 mg/l.

Int J Food Microbiol, 1990 Dec, 11(3-4), 351 - 4
Antibiotic resistance among coliform bacteria isolated from carcasses of commercially slaughtered chickens; Turtura GC et al.; A total of 322 coliform bacteria Escherichia coli, Enterobacter spp., Citrobacter spp., Klebsiella spp . and Serratia spp., were isolated from 50 carcasses of commercially slaughtered chickens . Their resistance to ampicillin, tetracycline, gentamicin, chloramphenicol, cephalotine, cotrimoxazole, nalidixic acid and nitrofurantoin, were determined . The most commonly found resistance was to tetracycline followed by cephalotine, cotrimoxazole and nalidixic acid . A large percentage of E . coli (41%) and Klebsiella spp . (38%) showed multiple antibiotic resistance.

J Bacteriol, 1990 Dec, 172(12), 7138 - 44
Genetic analysis of Escherichia coli urease genes: evidence for two distinct loci; Collins CM et al.; Studies with two uropathogenic urease-producing Escherichia coli strains, 1021 and 1440, indicated that the urease genes of each are distinct . Recombinant plasmids encoding urease activity from E . coli 1021 and 1440 differed in their restriction endonuclease cleavage sites and showed minimal DNA hybridization under stringent conditions . The polypeptides encoded by the DNA fragments containing the 1021 and 1440 urease loci differed in electrophoretic mobility under reducing conditions . Regulation of urease gene expression differed in the two ureolytic E . coli . The E . coli 1021 locus is probably chromosomally encoded and has DNA homology to Klebsiella, Citrobacter, Enterobacter, and Serratia species and to about one-half of the urease-producing E . coli tested . The E . coli 1440 locus is plasmid encoded; plasmids with DNA homology to the 1440 locus probe were found in urease-producing Salmonella spp., Providencia stuartii, and two E . coli isolates . In addition, the 1440 urease probe was homologous to Proteus mirabilis DNA.

Antimicrob Agents Chemother, 1990 Dec, 34(12), 2429 - 30
Induction of the Citrobacter freundii group I beta-lactamase in Escherichia coli is not dependent on entry of beta-lactam into the cytoplasm; Everett MJ et al.; Induction of the cloned ampC Citrobacter freundii beta-lactamase in Escherichia coli by 6-aminopenicillanic acid was prevented by periplasmic TEM beta-lactamase in the same cell . In contrast, cytoplasmic TEM beta-lactamase did not prevent induction . This result implies that entry of the beta-lactam into the cytoplasm is not necessary for induction of ampC.

J Antimicrob Chemother, 1990 Dec, 26(6), 749 - 62
A comparison of the mechanisms of decreased susceptibility of aztreonam-resistant and ceftazidime-resistant Enterobacteriaceae; Piddock LJ et al.; Twenty five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii and Providencia stuartii) were exposed to aztreonam and ceftazidime at 1/2 and 1 x MIC in liquid medium for 22 h, and also to 3, 5 and 10 x MIC and 16 mg/l of each agent in agar . Any putative mutant with an increase in the MIC of greater than or equal to 4 fold was examined for beta-lactamase expression and outer membrane protein profile . Mutants were selected on agar at approximately 10(7); however in liquid medium not all strains yielded mutants . Mutants lacking an outer membrane protein (OMP) with a molecular weight of 40,000 (+/- 5000) were selected with both agents, as were mutants expressing constitutive Richmond and Sykes Class 1 beta-lactamase . For the Ent . cloacae mutants increased beta-lactamase gave rise to MICs above the breakpoint of both agents, whereas with the other species ceftazidime susceptibility was more affected . Strains that were OMP- rarely had MICs above the breakpoint, unless there was also increased beta-lactamase expression, as in species such as M . morganii . Hence the major mechanism of resistance in these strains would appear to be beta-lactamase mediated rather than due to altered expression of outer membrane proteins.

Diagn Microbiol Infect Dis, 1990 Nov-Dec, 13(6), 509 - 16
In vitro activity of HRE 664, a penem antibiotic; Chin XN et al.; HRE 664, a new penem antibiotic, inhibited 90% of Escherichia coli, Klebsiella, Citrobacter diversus, Proteus mirabilis, Proteus vulgaris, Salmonella, Shigella, Providencia, Aeromonas, and Morganella at less than or equal to 2 micrograms/ml but was considerably less active than cefotaxime, ceftazidime, and imipenem . It did not inhibit Pseudomonas aeruginosa (MIC greater than 128 micrograms/ml) . HRE 664 inhibited Enterobacter spp., Citrobacter freundii, and Serratia marcescens at 1-8 micrograms/ml, two- to fourfold higher MICs than imipenem . HRE 664 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 0.12 micrograms/ml, but methicillin-resistant S . aureus and S . epidermidis were resistant . Group A, C, and G streptococci and Streptococcus pneumoniae were inhibited by 0.06 micrograms/ml . Bacteroides and Clostridium species were inhibited by 0.25 micrograms/ml comparable to imipenem . HRE 664 was not hydrolyzed by beta-lactamases TEM-1, TEM-2, TEM-3, TEM-5, SHV-1, PSE-1, PSE-4, OXA-2, OXA-3, K-1, P99, Morganella, P . vulgaris, and S . aureus PC-1 but was hydrolyzed by the beta-lactamase of Xanthomonas maltophilia.

Indian J Pediatr, 1990 Nov-Dec, 57(6), 781 - 4
Neonatal citrobacter sepsis: clinical and epidemiological aspects; Christo GG et al.; Fourteen neonates were diagnosed to have Citrobacter sepsis during 1986-89, representing 4.6% of all cases with bacteriologically proven sepsis . Most of these infants were low birth weight (mean 2046 gm, +/- 750) and preterm (mean 34.8 weeks, +/- 3.8) . Mean age at onset of sepsis was five days . In 10 cases the hematological profile was suggestive of sepsis . Infants had clinical evidence of multisystem infection; 2 with septic arthritis and 3 meningitis . The case fatality rate was 61% . Resistance to antibiotics was frequent . Citrobacter species were also cultured from other sites: umbilical stumps, eye swabs, urine, skin pustules and umbilical catheter tips . The epidemiological features and virulence of this organism call for vigilance and strict control measures.

Res Microbiol, 1990 Nov-Dec, 141(9), 1103 - 16
Palindromic unit highly repetitive DNA sequences exhibit species specificity within Enterobacteriaceae; Gilson E et al.; Palindromic units (PU, or REP for repetitive extragenic palindrome) constitute a family of DNA sequences of 40 nucleotides which is highly repeated in the genome of Escherichia coli . We analysed the presence of PU sequences in 99 different bacterial genomes by cross-hybridization . When PU sequences were used as a probe, only DNA from Enterobacteriaceae closely related to E . coli exhibited an appreciable hybridization signal: Shigella sonnei, Shigella boydii, Salmonella enteritica serotype Typhimurium, Citrobacter freundii and Levinea malonatica . Furthermore, these bacteria could be divided into two groups which corresponded to a slight difference in their PU sequence: the E . coli group includes S . sonnei and S . boydii; the S . enteritica serotype Typhimurium group includes C . freundii and L . malonatica.

Eur J Clin Microbiol Infect Dis, 1990 Nov, 9(11), 841 - 6
Antimicrobial activity and beta-lactamase stability of BMY-28232, parent compound of an oral cephalosporin; Chin NX et al.; BMY-28232, an aminothiazolyl imino methoxy cephalosporin which is available as an orally absorbed acetoxyethyl ester, inhibited strains of methicillin-susceptible Staphylococcus aureus, hemolytic streptococci, Streptococcus pneumoniae, Escherichia coli, Klebsiella species, and many strains of Proteus and Providencia stuartii at concentrations less than 1 microgram/ml, including isolates resistant to cephalexin and cefaclor . It had activity similar to that of cefixime, but was more active against methicillin-susceptible staphylococci . BMY-28232 was a poor substrate for beta-lactamases but was destroyed by the new TEM-3 enzyme, and had less activity against Enterobacter species, Citrobacter freundii, and Proteus vulgaris isolates . Methicillin-resistant staphylococci, Pseudomonas species, enterococci, Listeria monocytogenes, Corynebacterium jeikeium, Bacteroides fragilus and some strains of Clostridium species were resistant to BMY-28232.

J Biol Chem, 1990 Oct 25, 265(30), 18278 - 83
An oligosaccharide-tetanus toxoid conjugate vaccine against type III group B Streptococcus; Paoletti LC et al.; We have developed an oligosaccharide-tetanus toxoid conjugate vaccine against type III group B Streptococcus . Purified group B streptococcal type III capsular polysaccharide was depolymerized by enzymatic digestion using endo-beta-galactosidase produced by Citrobacter freundii . Following enzymatic digestion, oligosaccharides were fractionated by gel filtration chromatography on Sephadex G-75 . An oligosaccharide pool of average Mr = 14,500 (corresponding to 13.6 repeating units of the type III polysaccharide) was used for conjugation to tetanus toxoid . Tetanus toxoid was covalently coupled via a synthetic spacer molecule to the reducing end of the oligosaccharide by reductive amination . The oligosaccharide-tetanus toxoid conjugate elicited type III-specific anticapsular antibodies (measured in enzyme-linked immunosorbent assay) in three out of three rabbits whereas the unconjugated native type III polysaccharide was nonimmunogenic . Antiserum from rabbits vaccinated with the oligosaccharide-protein conjugate protected mice against lethal challenge with live group B streptococci (16 out of 16 mice survived) and opsonized group B streptococci for phagocytosis in vitro . No protection was conferred by preimmune serum nor by serum from rabbits vaccinated with unconjugated native type III polysaccharide . An oligosaccharide-protein conjugate vaccine of this design may prove to be an effective immunogen for protection against group B streptococcal infection in humans . In addition, the approach to vaccine design utilized in these studies will facilitate further definition of the structural parameters that determine immune response to glycoconjugate vaccines.

Can J Microbiol, 1990 Oct, 36(10), 728 - 31
Homology among bacterial catalase genes; Switala J et al.; Catalase activities in crude extracts of exponential and stationary phase cultures of various bacteria were visualized following gel electrophoresis for comparison with the enzymes from Escherichia coli . Citrobacter freundii, Edwardsiella tarda, Enterobacter aerogenes, Klebsiella pneumoniae, and Salmonella typhimurium exhibited patterns of catalase activity similar to E . coli, including bifunctional HPI-like bands and a monofunctional HPII-like band . Proteus mirabilis, Erwinia carotovora, and Serratia marcescens contained a single band of monofunctional catalase with a mobility intermediate between the HPI-like and HPII-like bands . The cloned genes for catalases HPI (katG) and HPII (katE) from E . coli were used as probes in Southern hybridization analyses for homologous sequences in genomic DNA of the same bacteria . katG was found to hybridize with fragments from C . freudii, Ent . aerogenes, Sal . typhimurium, and K . pneumoniae but not at all with Ed . tarda, P . mirabilis, S . marcesens, or Er . carotovora . katE hybridized with C . freundii and K . pneumoniae DNAs and not with the other bacterial DNAs.

J Clin Microbiol, 1990 Oct, 28(10), 2360 - 1
Aerobic bacteria cultured from the mouth of the American opossum (Didelphis virginiana) with reference to bacteria associated with bite infections; Howell JM et al.; The American opossum inflicts bite injuries both when hunted for food and when accidentally provoked when handled in captivity . This study involved aerobically culturing organisms from the mouths of seven wild opossums (Didelphis virginiana) . Isolates included streptococci, coagulase-positive and -negative staphylococci, Aeromonas spp., Citrobacter freundii, Eikenella corrodens, and Escherichia coli.

FEBS Lett, 1990 Oct 1, 271(1-2), 243 - 6
Function of the conserved triad residues in the class C beta-lactamase from Citrobacter freundii GN346; Tsukamoto K et al.; The conserved KTG triad in the class C beta-lactamase from Citrobacter freundii GN346 was examined as to its function by means of site-directed mutagenesis . The following conversions were performed; Lys-315 to arginine, alanine or glutamic acid, Thr-316 to valine, and Gly-317 to alanine, proline or isoleucine . The resultant mutant enzymes revealed that a basic amino acid at position 315 and a small uncharged residue at position 317 are essential for the enzyme activity, but a hydroxyl group at residue 316 is not required for the enzymatic catalysis . The kinetic properties of the purified Arg-315 and Val-316 enzymes provided information on the function of these residues.

Jpn J Antibiot, 1990 Sep, 43(9), 1545 - 58
{Clinical laboratory approach to estimate effective administrative dose of minocyclin . Reevaluation of in vitro MIC break points in disc susceptibility test}; Uete G et al.; Antimicrobial activities of minocycline (MINO) against various clinical isolates, 270 strains obtained in 1988, were determined and the reliability of the MINO disc susceptibility test in estimating approximate values of MICs was studied . Clinical significance of a 4 category system for the interpretation of the disc tests, which is widely used in Japan, and that of a 3 category system used in the USA and Europe, were also evaluated to determine which system would be more suitable for the evaluation of proper dose levels of administration . In this study, MICs were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml . MIC80 values of MINO against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pneumoniae were all less than or equal to 0.78 micrograms/ml . Those against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris were 0.39, 6.25, 3.13, 25, 50 micrograms/ml, respectively . MIC80 values against Pseudomonas aeruginosa, Serratia marcescens, Enterobacter spp., and Citrobacter spp . were 50, 100, 50 and 12.5 micrograms/ml, respectively . The inhibition zones obtained with the disc method were compared with MICs . The results of MINO disc susceptibility test either with 200 micrograms disc (Showa) or 30 micrograms disc (prepared in this laboratory) were well correlated with MICs, showing the reliability of the disc method in estimating approximate values of MICs . In the 4 category classification system currently used, break points in MIC values proposed are ( ) MIC less than or equal to 2 micrograms/ml, (++) MIC greater than 2-10 micrograms/ml, (+) greater than 10-50 micrograms/ml, (-) MIC greater than 50 micrograms/ml . The results obtained with 200 micrograms and 30 micrograms discs showed false positive in 26.6% and 20.5% of the samples, and false negative in 5.8% and 23.6% of the samples, respectively . The disc results of S . aureus, S . epidermidis, S . pneumoniae, etc . were relatively well classified, but those of E . coli, K . pneumoniae, Proteus spp . were not, showing more false positive results . Changing the lower 2 MIC break points in the 4 category system to: ( ) MIC less than or equal to 3 micrograms/ml and (++) MIC greater than 3-15 micrograms/ml, the false positive results with both 200 micrograms and 30 micrograms discs were reduced to 12% and 6.2%, respectively . The false negative results were 5.8% and 23.6%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Eur J Epidemiol, 1990 Sep, 6(3), 287 - 92
Circulation in Italy of beta-lactamase-producing strains within the major groups of bacterial pathogens; Varaldo PE et al.; A multicenter study was undertaken in Italy to assess the circulation of beta-lactamase-producing organisms and their current incidence within the major groups of bacterial pathogens . Almost four thousand strains, all freshly isolated from clinical material, were examined at four centers serving different areas of Italy . Despite some significant center-to-center differences, this survey documented the occurrence of a large overall circulation of beta-lactamase-producing organisms among clinical bacterial isolates . In particular, ampicillin resistance was recorded in one third to one half of the isolates of some Enterobacteriaceae, including Escherichia coli, Proteus, and Citrobacter species, and 80-90% of these resistant strains proved to be beta-lactamase producers . Both ampicillin resistance and beta-lactamase production were almost the rule in other Enterobacteriaceae, including Klebsiella, Enterobacter, and Serratia species . beta-lactamase was also produced by about 80% of glucose-non-fermenting gram-negative bacteria and Aeromonas hydrophila strains, by all of the isolates of Branhamella catarrhalis manifesting ampicillin resistance (i.e . more than half the total number of isolates), and by about two thirds of the ampicillin-resistant Haemophilus strains (which accounted for 20-25% of all Haemophilus isolates examined) . In contrast, no beta-lactamase producers were observed among Neisseria gonorrhoeae isolates.

J Antimicrob Chemother, 1990 Sep, 26(3), 329 - 41
In-vitro antibacterial activity of DQ-2556 and its stability to various beta-lactamases; Fujimoto T et al.; DQ-2556, a new cephalosporin, showed a broad antibacterial spectrum over Gram-positive and -negative organisms . The activity of DQ-2556 against recent clinical isolates of Gram-positive cocci and Enterobacteriaceae was comparable with that of cefpirome, and superior to that of ceftazidime . DQ-2556 was almost as active as cefpirome against Pseudomonas aeruginosa, but was less active than ceftazidime . With the exception of Ps . aeruginosa, DQ-2556 was bactericidal against various organisms at either the MIC or twice the MIC . DQ-2556 bound preferentially to penicillin-binding proteins (PBPs) 2, 1 and 3 of Staphylococcus aureus, PBPs 3, 1A and 1B of Escherichia coli and PBPs 1A, 3 and 4 of Ps . aeruginosa . DQ-2556 was stable to various penicillinases and cephalosporinases, but was unstable to oxyiminocephalosporinases . The Km values of DQ-2556 for the cephalosporinases of Citrobacter freundii and Enterobacter cloacae were only two- or three-fold higher than those of ceftazidime, indicating that DQ-2556 had a relatively high affinity for these enzymes compared with other recently developed cephalosporins . The MIC of DQ-2556 for Esch . coli increased four-fold in an OmpF-deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch . coli cells.

Eur J Clin Microbiol Infect Dis, 1990 Sep, 9(9), 685 - 91
In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522; Chin NX et al.; The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents . Bay v 3522 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 2 micrograms/ml, compared to MICs of greater than or equal to 8 micrograms/ml for the other cephalosporins tested . It was more active against Streptococcus pyogenes (MIC less than or equal to 0.06 microgram/ml) than cefuroxime, cefixime, cephalexin and cefaclor . Groups B, C and G streptococci were inhibited at less than or equal to 0.12 microgram/ml, while the MI"90 for Streptococcus bovis and viridans streptococci was 0.5 and 2 micrograms/ml, respectively . The MIC90 for enterococci and Listeria monocytogenes was 8 micrograms/ml . Clostridium perfringens was inhibited by 0.12 microgram/ml, but most Bacteroides spp . were resistant . The MIC90 for beta-lactamase positive Escherichia coli (producing primarily TEM-1) was greater than 64 micrograms/ml and for beta-lactamase negative strains 16 micrograms/ml . The MIC90 for high-level beta-lactamase producing Klebsiella pneumoniae was greater than 64 micrograms/ml versus 4 micrograms/ml for other isolates . The MIC90 for Moraxella catarrhalis was 2 micrograms/ml, for Haemophilus influenzae 1 micrograms/ml, and for Neisseria gonorrhoeae 4 micrograms/ml . Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp . and Pseudomonas aeruginosa were resistant . Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1990 Sep, 6(3), 174 - 6, 236-7
{Susceptibility and R plasmids conjugation tests for 44 strains of gram negative bacilli in a burn unit}; Xu FM; 44 strains of 9 species Gram negative bacilli were isolated and identified in a burn unit, among them 25 strains were from patients and 19 from ward environment . All strains were tested for susceptibility to antibiotics and R plasmids . Using both agar dilution and disc diffusion methods to test susceptibility to 12 kinds of antibiotics, namely, Streptomycin Chloramphenicol, Tetracycline, Ampicillin, Kanamycin, Gentamycin, Nalidixic acid, Amikacin Rifampin, Carbenicillin, Cefazolin and Polymyxin, we found that all 44 strains were susceptible to Rifampin and Polymyxin . To the other 10 kinds of antibiotics, the susceptibilities varied . 40 strains of bacteria (91%) were resistant to 3 kinds or more of antibiotics, i.e, multiple resistant bacteria, 2 strains resistant to 2 kinds of antibiotics (4.6%), and 2 strains susceptible to all 12 kinds of antibiotics (4.6%) . The multiple resistant strains consisted of 9 strains (22.5%) of R plasmid-harboured bacteria, Pseudomonas aeruginosa 2 strains, Citrobacter 4 strains, Proteins 1 strain, Enterobacter aerogenes 1 strain and Escherichia coli 1 strain . All the R plasmids carried the marks of resistance to chloramphenicol, tetracycline, ampicillin, kanamycin, gentamycin, streptomycin, and carbenicillin, but no one carried marks of resistance to Cefazolin and Amikacin indicating that drug-resistance of the last two antibiotics might not be mediated by R plasmids . Two strains of Citrobacter freundii isolated from 2 patients and showing susceptibility to all antibiotics were induced to be Rifampin-resistance (Rif) strains without changing their original biological characters . They both could receive the R plasmids of the multiple resistance strains one from patient and the other from ward environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Zentralbl Bakteriol, 1990 Sep, 273(4), 455 - 8
{Obtaining, by means of a strain of Citrobacter freundii, a serum specific agglutinant for Salmonella of the subspecies I of group B, without the necessity for absorption}; Sechter I et al.; A strain of Citrobacter freundii possessing the factors O:4,27 of Salmonella, without factor O:12, may be used for preparation of a diagnostic serum for identification of strains of Salmonella sub-species I belonging to O-group B, without absorption.

J Clin Microbiol, 1990 Aug, 28(8), 1760 - 5
Genotypic heterogeneity of strains of Citrobacter diversus expressing a 32-kilodalton outer membrane protein associated with neonatal meningitis; Li J et al.; Genetic diversity and relationships among 42 strains of Citrobacter diversus recovered from the cerebrospinal fluid of human infants with meningitis and from other clinical sources in the United States were estimated on the basis of electrophoretically detectable allelic variation in 20 genes encoding metabolic enzymes . Sixteen distinctive multilocus enzyme genotypes were identified, among which the mean genetic diversity per locus was 0.244 . The recovery of isolates of the same genotype in several regions of the United States and over periods as long as 20 years indicates that the population structure of C . diversus is clonal . There was little association between multilocus enzyme genotype and biotype, piliation, or presence of a 32-kilodalton outer membrane protein . The observation that the 32-kilodalton outer membrane protein, which is expressed predominantly by strains recovered from infants with meningitis, occurs in a variety of genotypically diverse clones belonging to several phylogenetic lineages supports the hypothesis that this protein confers virulence.

FEMS Microbiol Lett, 1990 Aug, 58(3), 295 - 9
Nucleotide sequence of the Serratia marcescens SR50 chromosomal ampC beta-lactamase gene; Nomura K et al.; The Serratia marcescens SR50 chromosomal beta-lactamase gene (ampC) was cloned and sequenced . It contains 1128 nucleotides encoding a protein of 355 amino acids preceded by 21 amino acids which probably constitutes the signal peptide . The mature protein has a predicted molecular mass of 38,901 Da . About 40% of the amino acid sequence was identical among AmpC beta-lactamases resided in S . marcescens, Citrobacter freundii OS60, Escherichia coli K12 and Enterobacter cloacae P99 . All of these enzymes are highly similar around the active site serine at the position 59 of the mature enzyme.

Eur J Clin Microbiol Infect Dis, 1990 Aug, 9(8), 625 - 9
In vitro antibacterial activity and beta-lactamase stability of the new carbapenem LJC10,627; Yoshida M et al.; In in vitro susceptibility tests the new carbapenem LJC10,627 showed potent antibacterial activity against gram-positive and gram-negative bacteria, except that most methicillin-resistant Staphylococcus aureus strains tested were found to be resistant to LJC10,627 . LJC10,627 showed high activity against Pseudomonas aeruginosa and was active against Enterobacter cloacae and Citrobacter freundii strains which were resistant to ceftazidime and cefpirome . The Ki values of LJC10,627 for penicillinase Type I, cephalosporinase and oxyiminocephalosporinase were low, whereas the Ki value for L-1 enzyme from Xanthomonas maltophilia was high.

J Bacteriol, 1990 Aug, 172(8), 4348 - 51
Extension of the substrate spectrum by an amino acid substitution at residue 219 in the Citrobacter freundii cephalosporinase; Tsukamoto K et al.; The cephalosporinase of Citrobacter freundii GN346 is a class C beta-lactamase, consisting of 361 amino acids and exhibiting the substrate profile of a typical cephalosporinase . On the conversion of a conserved glutamic acid at residue 219 to lysine, the substrate spectrum of the cephalosporinase was extended to oxyimino cephalosporins, aztreonam and carbenicillin, which are essentially undesirable substrates for the enzyme . Escherichia coli cells carrying the mutant gene showed higher resistance levels to cefuroxime, aztreonam, and carbenicillin, but a lower resistance level to cefoxitin, than cells carrying the wild gene . The kcat values of the purified mutant enzyme for ceftazidime, cefuroxime, and cefmenoxime were 77,100, and 300 times those of the wild enzyme, respectively . The relative Vmax values of the mutant enzyme for aztreonam and carbenicillin were determined to be 11 and 23 times those of the wild enzyme, respectively, but the value of the mutant enzyme for cefoxitin was only one-third that of the wild enzyme.

J Antibiot (Tokyo), 1990 Jul, 43(7), 820 - 9
Direct introduction of a formamido group into the 7 alpha (6 alpha)-position of cephalosporins (penicillins); Kamachi H et al.; A novel direct introduction of a formamido group into the 7 alpha (6 alpha)-position of cephalosporins (penicillins) was achieved by treatment of 7 beta (6 beta)-{(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1- ylidene)methylimino}cephem (penam) esters with N,N-bis(trimethylsilyl)formamide, followed by deblocking with Girard reagent T to give the corresponding 7 alpha (6 alpha)-formamido-7 beta (6 beta)-amino derivatives . Three 7 alpha-formamidocephalosporins were prepared by the conventional N-acylation of 7 alpha-formamidocephem . All of them were resistant to beta-lactamases, showing similar MIC values against both of a pair of a beta-lactamase-producing strain and the corresponding non or low-producing strain of the same species of bacteria, when tested on Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Enterobacter cloacae and Citrobacter freundii.

J Gen Microbiol, 1990 Jun, 136 ( Pt 6), 1037 - 42
Isolation of a Citrobacter species able to grow on malonate under strictly anaerobic conditions; Janssen PH et al.; An anaerobic enrichment from lake mud yielded a pure culture of a facultatively anaerobic bacterium able to grow on malonate under strictly anaerobic conditions . Strain 16mal1 was identified as a member of the family Enterobacteriaceae, and assigned to the genus Citrobacter on the basis of morphological, metabolic and biochemical characteristics . Malonate was fermented under strictly anaerobic (sulphide-reduced) conditions to acetate and CO2 concomitant with growth . A maximum growth rate of 1.88 generations h-1 (mu = 1.30 h-1) was measured . The dry weight yield of cells from malonate was estimated at 2.5 g mol-1 . Yeast extract was required for growth on malonate: other additives, or a vitamin solution, could not replace this requirement . Other dicarboxylic acids were not degraded in the absence or presence of malonate . Malonate was degraded under anaerobic, but not aerobic conditions . Malonate-decarboxylating activity was inducible by malonate under both anaerobic and aerobic conditions, and was not expressed in glucose- or citrate-grown anaerobic cultures . Monensin had no effect on malonate degradation, while 2,4-dinitrophenol decreased the rate of malonate degradation . This, with the lack of a sodium requirement for anaerobic growth on malonate, suggested that ATP generation may not be mediated by a sodium-pumping mechanism.

J Clin Microbiol, 1990 Jun, 28(6), 1460 - 2
Production of Shiga-like toxin among Escherichia coli strains and other bacteria isolated from diarrhea in São Paulo, Brazil; Giraldi R et al.; An elevated level of Shiga-like toxin I (SLT-I) production was found in 1 of 466 Escherichia coli strains studied . Among the 34 sonic lysates obtained from classical enteropathogenic E . coli, 5 produced SLT-I . The Aeromonas, Citrobacter, Edwardsiella, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, Salmonella, Serratia, Shigella, Yersinia, and Vibrio strains also studied were not SLT producers, except for a Shigella dysenteriae type 1 strain . Although SLT-I-producing E . coli strains were isolated from diarrhea, they seem to be an uncommon cause of disease in children less than 1 year old in our community.

Jpn J Antibiot, 1990 Jun, 43(6), 968 - 1136
{Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987) . III . Secular changes in susceptibility}; Kosakai N et al.; Sensitivity spectra of major species of bacteria (namely Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa) which were among the clinical isolates mentioned in the first and second reports to various antibacterial and antibiotic agents and time courses of the spectra are reported below . 1 . E . coli was sensitive to cefmenoxime (CMX), latamoxef (LMOX), ceftazidime (CAZ), cefzonam (CZON) and flomoxef (FMOX) which are third generation cephems, carumonam (CRMN) which is a monobactam, imipenem (IPM) which is a carbapenem, ofloxacin (OFLX) and ciprofloxacin (CPFX) which are new quinolones . Compared to the preceding 5-year period, sensitivities to most drugs have increased . 2 . Klebsiella spp . were sensitive to CMX, CZON and FMOX which are third generation cephem antibiotics, CRMN which is a monobactam and gentamicin (GM) and arbekacin (HBK) which are aminoglycosides . Compared to the preceding 5-year period, the sensitivity on the whole has increased slightly . 3 . Proteus spp . were sensitive to CMX, LMOX, CAZ and CZON which are third generation cephems, CRMN, a monobactam and OFLX and CPFX which are new quinolones . Compared to the preceding 5-year period, increased sensitivities, particularly to parenteral cephems, were found . 4 . Citrobacter spp . were sensitive to CPFX which is a new quinolone antibiotic and CRMN, a monobactam . Compared to the preceding 5-year period, the sensitivity as a whole increased but there were still strains against which cefotiam, cefmetazole and, cefoperazone (CPZ) showed high MIC values . 5 . Enterobacter spp . were sensitive to OFLX and CPFX, which are new quinolones, IPM, a carbapenem, and GM and HBK which are aminoglycosides . Compared to other bacteria, bacteria of this group were less sensitive to CPZ, CAZ, CZON, and FMOX which are third generation cephems . Compared to the preceding 5-year period, slight increases in sensitivity were found in cases of simple urinary tract infections . 6 . S . marcescens as a whole was not very sensitive to antibiotics tested . Compared to the preceding 5-year period, sensitivities to CRMN and minocycline improved slightly . 7 . P . aeruginosa was not very sensitive to any drug, as other bacteria were . Compared to the preceding 5-year period, sensitivities to new quinolones OFLX and CPFX and carbapenem IPM decreased slightly.

FEBS Lett, 1990 May 21, 264(2), 211 - 4
Substitution of aspartic acid-217 of Citrobacter freundii cephalosporinase and properties of the mutant enzymes; Tsukamoto K et al.; On the assumption that Asp-217 of a Citrobacter freundii cephalosporinase forms a salt-bridge with the conserved Lys-67, Asp-217 was changed to glutamic acid, threonine or lysine . The mutant enzymes retained about the same level of activity as that of the wild-type enzyme, and the participation of Asp-217 in the salt-bridge was ruled out . However, the mutations resulted in an increase in hydrolytic activity toward oxyimino-cephalosporins such as cefuroxime, cefmenoxime and ceftazidime, suggesting a possible mechanism of the bacterial resistance to the novel beta-lactams by a single mutation in cephalosporinases.

Chem Pharm Bull (Tokyo), 1990 May, 38(5), 1326 - 8
Urethane-hydrolyzing enzyme from Citrobacter sp; Kobashi K et al.; Urethane, a cancer-causing chemical, was reported to contaminate alcoholic beverages such as whisky, liquor, wine and sake . Enzymatic removal of urethane would be a possible approach to remove this potentially hazardous chemical from alcoholic beverages . We found that Citrobacter sp . isolated from mouse feces stoichiometrically decomposed urethane to ethanol and ammonia . We named this enzyme "urethanase." Partially purified urethanase could hydrolyze several carbamates and some amides . However, urea, N-alkyl ureas and ethyl esters of organic acids were not hydrolyzed at all . These results suggest that urethanase belongs to the category of amidase . The enzyme was inactive in high concentrations of alcohol and at acidic pH and was practically ineffective for the elimination of urethane from alcoholic beverages.

Mol Gen Mikrobiol Virusol, 1990 May, (5), 12 - 7
{Microcin R51 and a plasmid determining its synthesis}; Kurepina NE et al.; A new microcin produced by an Citrobacter R51 strain has been detected . This antibiotic has been shown to inhibit the growth of a number of Gram-negative as well as Gram-positive strains of bacteria on the minimal medium plates . The properties of partially purified microcin were characterized . Constitutive synthesis of microcin is determined by a conjugative plasmid . The genes of microcin synthesis and immunity were cloned on a plasmid and plasmid vehicles . A physical map of the 12 kb fragment coding for the production of microcin R51 and immunity to this antibiotic is presented.

J Infect, 1990 May, 20(3), 237 - 40
Dysgonic fermenter 3-associated abscess in a diabetic patient; Bangsborg JM et al.; We report a case in which a strain of the U.S.A . Centers for Disease Control (CDC) dysgonic fermenter (DF) 3, together with Citrobacter freundii, was isolated from an abscess in a diabetic patient . DF 3 may be easily overlooked due to its fastidious nature, a characteristic shared with two former DF groups now placed in the genus Capnocytophaga . To our knowledge, this is the first European case report of DF 3-associated infection.

Am J Med Sci, 1990 May, 299(5), 331 - 3
Citrobacter freundii: a newly reported cause of pyomyositis; Fincher RM et al.; Pyomyositis has been uncommonly reported in temperature climates, but is being recognized with increasing frequency . The most common etiologic agent is Staphylococcus aureus, although other pathogens have been rarely implicated . The authors describe the first case of pyomyositis caused by Citrobacter freundii . Because of the rarity of this disease in North America, it is often initially misdiagnosed . Neuromuscular sonography, a non-invasive imaging technique, identified the muscle abscess in this patient.

Appl Environ Microbiol, 1990 May, 56(5), 1397 - 9
Production of Escherichia coli-specific hybridomas by using gnotobiotic mice; Tartera C et al.; Monoclonal antibodies provide a rapid and specific means of direct detection of microorganisms in water and food samples . However, monoclonal antibodies specific for some bacteria are difficult to obtain; a good example of such a bacterium is Escherichia coli . Gnotobiotic BALB/c mice immunized with whole-cell preparations of heat-treated strains of E . coli and subjected to high-frequency antigen injection showed a significant increase in the number of specific hybridomas produced . Fusions obtained by using regular BALB/c mice immunized by using standard immunization protocols produced nonspecific hybridomas . Twenty-one stable hybridomas that did not cross-react with Klebsiella pneumoniae ATCC 13883 or Citrobacter freundii 1604770 were obtained from gnotobiotic mice . The bacterial strains were selected for the specificity tests because of their high cross-reactivity, which has been detected in previous fusion experiments . The method of immunization described here offers the potential of improving the production of highly specific hybridomas for bacteria which have been difficult to obtain.

Am J Med, 1990 Apr 9, 88(4A), 18S - 24S
Serious pediatric infections; Kaplan SL; Third-generation cephalosporins are important additions to the range of antibiotics available for treating children with serious bacterial infections . They are highly active against the common pathogens, which cause bacterial meningitis in children . Strains of Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol, and Streptococcus pneumoniae relatively resistant to penicillin remain susceptible to cefotaxime and ceftriaxone . Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, as well as the other more common gram-negative bacilli isolated from neonates and children are susceptible to these agents . However, Listeria monocytogenes is not cephalosporin-sensitive . Ceftazidime is the only third-generation cephalosporin useful for treating serious infections due to Pseudomonas aeruginosa in children . As with other beta-lactam antibiotics, the clearance of cephalosporins is prolonged in neonates, particularly premature babies . Cefotaxime and ceftriaxone are equivalent to ampicillin and chloramphenicol for the treatment of bacterial meningitis in children over two to three months of age with respect to neurologic outcome and safety, despite the in vitro activity of cefotaxime and ceftriaxone being much greater than the standard antibiotics for the meningeal pathogens . Cefotaxime and ceftriaxone are effective in the treatment of serious gram-negative infections in children . In many instances, ceftriaxone can be administered once daily, which allows for more convenient therapy, particularly on an outpatient basis . Although controversial, ceftazidime has been used as single-agent therapy for empiric treatment of neutropenic immunocompromised children with fever.

Antimicrob Agents Chemother, 1990 Apr, 34(4), 568 - 75
In vitro and in vivo activities of a new quinolone, WIN 57273, possessing potent activity against gram-positive bacteria; Sedlock DM et al.; The antibacterial activity of a new 7-dimethylpyridinyl quinolone, WIN 57273, was assessed by using in vitro and in vivo models . Agar inclusion and broth dilution in vitro tests revealed broad-spectrum activity against gram-positive and selected gram-negative organisms, with the greatest potency observed against the staphylococci . The MIC for 90% of coagulase-positive strains tested (MIC90) was less than or equal to 0.002 micrograms/ml; for the coagulase-negative strains the MIC90 was 0.008 micrograms/ml . Against enterococci the MIC90 was 0.06 micrograms/ml, with comparable activity observed against group A and group B streptococci as well as against the pneumococci . In general, the MIC90s for the gram-negative bacteria were less than or equal to 1 micrograms/ml . Exceptions were Serratia marcescens (MIC90, 16 micrograms/ml), Citrobacter freundii (MIC90, 4 micrograms/ml), and Pseudomonas aeruginosa (MIC90, 8 micrograms/ml) . The greatest potency was observed against Haemophilus spp . and Neisseria spp., with MIC90s of 0.06 and 0.016 micrograms/ml, respectively . Broad-spectrum activity was also observed against anaerobes, with MIC90s ranging from 0.125 to 0.5 micrograms/ml among the species tested . The in vivo efficacy was determined by using a murine model by calculating the 50% protective doses against a lethal bacterial infection caused by strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa . The staphylocci were most susceptible, with 50% protective doses for all strains ranging from 0.1 to 0.7 mg/kg . With the exception of the Pseudomonas infection, which was refractory to treatment, animals that were part of the other infection models responded to less than 10 mg/kg . Equivalent activity was seen with the subcutaneous or the oral route of drug administration . WIN 57273 was significantly more potent than ciprofloxacin in treating gram-positive bacterial infections (2- to 20-fold) but was significantly less effective at treating gram-negative bacterial infections (30- to 300-fold).

Wei Sheng Wu Xue Bao, 1990 Apr, 30(2), 112 - 6
{Transpon Tn5 mutagenesis in Citrobacter}; Wang AQ et al.; When E . coli 1830/PJB4JI mating with four Citrobacter strains all were Kanamycin resistant, but a majority of KanrGens transconjugants were obtained from C-3-1 . Among 3000 KanrGens 21 were auxotrophs, these are Lys-(1), Ura-(1), Arg-(2), Iso-(2), His-(2), Met-(1), Phe-(1), Tyr-(1), Ser-(1), Thr-(1), Leu-(3), Pro-(1), Ade-(3), Lac-(1), PJB4JI plasmid DNA were detected in parent strain E . coli 1830, but not in auxotrophs strains which carrying Tn5 induced mutations . Twenty auxotrophs chromosome DNA were hybridized with Tn5 DNA labeled with 32P respectively, all auxotrophs has positive reaction . Therefore, we concluded from genetic and physical data that auxotrophs resulted from Tn5 transposition from PJB4JI into C-3-1 chromosome.

J Antibiot (Tokyo), 1990 Apr, 43(4), 403 - 10
Characteristics of aztreonam as a substrate, inhibitor and inducer for beta-lactamases; Sakurai Y et al.; Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined beta-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of beta-lactamases was also evaluated . Aztreonam was hydrolyzed at measurable rates by class A beta-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range . However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A beta-lactamases . Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the beta-lactamase . While the MICs of aztreonam in the cases of the constitutive producers of class C beta-lactamases were evidently affected by enzyme production . An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable beta-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam . Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of beta-lactamases.

Yakugaku Zasshi, 1990 Mar, 110(3), 191 - 201
{Solid-state stability and preformulation study of a new parenteral cephalosporin antibiotics (E1040)}; Ashizawa K et al.; In designing the dosage form, one major factor controlling their physicochemical properties is solid forms of the drug powder . The method for improving the physicochemical stability of unstable beta-lactam antibiotics is very important . E1040 is a novel parenteral 3-betaine type cephalosporin which has a broad antibacterial spectrum and potent activities against Citrobacter, freundii, Enterobacter cloacase, and glucose-non-fermentative bacteria, including P . aeruginosa . The present study was intended to provide the solid-state chemical stability of perenteral steril dry dosage form of E1040 . The chemical stability differences among the various solid forms, dry amorphous, additive freeze dried amorphous solid and crystalline powder, were evaluated as a function of temperature by thermo stress tests . Freeze dried anhydrous amorphous form was the first steril dry dosage form investigated during the preformulation study . However, this compound is chemically unstable, in the titer of them, reduction are observed in the freeze dried amorphous solid . In order to select the most suitable solid form of E1040, two methods were used . One was crystalline solid and the other was NaCl additive freeze-dried formulation . Through our experiments, the solid-state chemical stabilization can be achieved by these two methods (effect of crystal structure and effect of NaCl additive).

J Antimicrob Chemother, 1990 Mar, 25(3), 335 - 41
Broad spectrum beta-lactamases of Citrobacter diversus; Oliva B et al.; Citrobacter diversus NF85 produced a chromosomal beta-lactamase that was induced by a variety of beta-lactam antibiotics . Two major forms of the enzyme, with isoelectric points (pI's) of 5.7 and 6.2, were found in crude cell extracts . Derepressed mutants of NF85, generated by nitrosoguanidine treatment, displayed different levels of beta-lactamase expression to the parent strain and had different patterns of resistance to a range of beta-lactam antibiotics . Those mutants of NF85 that were totally derepressed, expressing high, constitutive levels of enzyme, were found to have an additional beta-lactamase activity with a pI of 6.8.

J Gen Microbiol, 1990 Mar, 136 ( Pt 3), 431 - 40
Characterization of enterobacteria by esterase specific-activity profiles; Goullet P et al.; The spectrum of specific activities and the electrophoretic mobilities of esterases produced by 550 strains of Enterobacteriaceae belonging to 36 species and subclassified into six groups (group 1, Escherichia coli, Shigella and Escherichia hermanii; group 2, genus Salmonella and genus Citrobacter; group 3, genus Klebsiella and genus Enterobacter; group 4, genus Serratia and Serratia fonticola; group 5, genus Proteus, genus Providencia and genus Morganella; and group 6, genus Yersinia) were analysed by acrylamide/agarose gel electrophoresis using standardized methods for staining and mobility comparisons . Nineteen types of esterase were defined by their respective esterase specific-activity profile (ESAP) . A multiple correspondence analysis (MCA) of the ESAP data enabled 82% of the strains in the 36 species to be correctly classified . In each group, the species were clearly delineated after MCA on both ESAP and electrophoretic mobility data . In addition, the smallest number of characters providing species identification of Yersinia strains by esterase polymorphism was identified by means of a binary segmentation tree technique.

FEMS Microbiol Lett, 1990 Mar 1, 56(1-2), 7 - 11
Conjugational cotransfer of IncFI and IncI conjugative plasmids forming aggregate in a pathogenic Citrobacter freundii strain; Morzejko E et al.; Two plasmids, pEM4 (IncFI) determining virulence and pEM6 (IncI) determining colicine I production and resistance to tetracycline, have been found in a pathogenic strain of Citrobacter freundii . Even though pEM4 and pEM6 plasmids are conjugative and transfer themselves very efficiently during conjugation, a high cotransfer of both plasmids is observed--an unusually high fraction of transconjugants acquiring pEM6 acquires pEM4 and vice versa . The observed cotransfer of these plasmids is connected with their ability to complement their conjugational functions . An insertion mutant of pEM4 with decreased frequency of conjugational transfer has been isolated . This mutant (pEM44) lost its ability to mobilize nonconjugative plasmids . Its transfer is stimulated by pEM6 and it is transferred from (pEM44, pEM6) donors almost exclusively with pEM6 plasmid . The role of cotransfer and stimulation phenomena in spreading of plasmid aggregates in bacterial population is discussed.

Eur J Biochem, 1990 Feb 22, 188(1), 15 - 22
Role of lysine-67 in the active site of class C beta-lactamase from Citrobacter freundii GN346; Tsukamoto K et al.; Citrobacter freundii GN346 produces a class C beta-lactamase exhibiting the substrate profile of a typical cephalosporinase . The structural and promoter regions of the cephalosporinase gene, comprising 1408 nucleotides, were completely sequenced . The amino acid sequence of the mature enzyme, comprising 361 amino acids, and its molecular mass, 39,878 Da, were determined . The active site was confirmed to be Ser-64 . The amino acid sequence of the enzyme differs from that of the cephalosporinase of C . freundii OS60 by nine residues . The nucleotide sequence of the promoter region suggests a possible attenuator structure . Lys-67, one of the most conserved residues found in class A and C beta-lactamases and penicillin-binding proteins, was converted into arginine, threonine or glutamic acid through site-directed mutagenesis . The Glu-67 enzyme had lost the catalytic activity and the Thr-67 enzyme only showed a trace of activity . The Arg-67 enzyme, which retained a significant amount of the activity, was purified . The Km values of the Arg-67 enzyme for cephalothin, cephaloridine and benzylpenicillin are 13-19 times those of the wild-type enzyme; the kcat values for the three substrates are 37%, 3%, and 36% those of the wild-type enzyme, respectively.

Antimicrob Agents Chemother, 1990 Feb, 34(2), 219 - 24
Molecular epidemiology of TEM-3 (CTX-1) beta-lactamase; Petit A et al.; A total of 33 clinical isolates encoding TEM-3 (CTX-1) from four French hospitals were studied . The strains belonged to seven species, Klebsiella pneumoniae (n = 24), Escherichia coli (n = 3), Serratia marcescens (n = 2), Citrobacter freundii (n = 1), Enterobacter aerogenes (n = 1), Enterobacter cloacae (n = 1), and Klebsiella oxytoca (n = 1) . All the strains harbored an Inc7 or M self-transferable plasmid with a size of approximately 85 kilobases . The plasmids had closely related EcoRI, HincII, HindIII, and PvuII restriction endonuclease-generated patterns and conferred resistance to all beta-lactams, except cephamycins and imipenem; to tetracycline, because of the presence of the genes blatem-3 and tetC, respectively, as determined by hybridization with specific probes; and to sulfonamide . Depending on the presence or absence and level of expression of the genes aacA4, aadA, and dfrI and of insertion element IS15, four types of plasmids could be distinguished . Plasmid pCFF04, the prototype plasmid encoding TEM-3, was widespread and appeared, by Southern hybridization, as the progenitor of the other types of replicons . The plasmid epidemic responsible for dissemination of TEM-3 in clinical isolates of members of the family Enterobacteriaceae may have originated in S . marcescens since pCFF04 was first detected in this species.

J Bacteriol, 1990 Feb, 172(2), 1051 - 61
Evolution of aromatic amino acid biosynthesis and application to the fine-tuned phylogenetic positioning of enteric bacteria; Ahmad S et al.; A comprehensive phylogenetic tree for virtually the entire assemblage of enteric bacteria is presented . Character states of aromatic amino acid biosynthesis are used as criteria, and the results are compared with partial trees based upon sequencing of 16S rRNA, 5S rRNA, and tryptophan leader peptide . Three major clusters are apparent . Enterocluster 1 possesses a gene fusion (trpG-trpD) encoding anthranilate synthase: anthranilate 5-phosphoribosylpyrophosphate phosphoribosyltransferase of tryptophan biosynthesis . This cluster includes the genera Escherichia, Shigella, Citrobacter, Salmonella, Klebsiella, and Enterobacter . The remaining two clusters lack the trpG-trpD gene fusion, but differ in the presence (enterocluster 2) or absence (enterocluster 3) of the three-step overflow pathway to L-phenylalanine . Enterocluster 2 consists of the genera Serratia and Erwinia . Enterocluster 3 includes the genera Cedecea, Kluyvera, Edwardsiella, Hafnia, Yersinia, Proteus, Providencia, and Morganella . Within these three major clusters, a tentative hierarchy of subcluster ordering is formulated on the basis of all data available . This hierarchical framework is proposed as a general working basis for continued refinement of the phylogenetic relationships of enteric bacteria.

Antimicrob Agents Chemother, 1990 Feb, 34(2), 269 - 72
Double-blind study of endotracheal tobramycin in the treatment of gram-negative bacterial pneumonia . The Endotracheal Tobramycin Study Group; Brown RB et al.; A prospective, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of endotracheal tobramycin (ETT) for treatment of gram-negative bacterial pneumonia . Patients were randomized to either 40 mg of tobramycin or a placebo instilled endotracheally every 8 h . Patients also received intravenous tobramycin plus either cefazolin or piperacillin . Of 85 patients enrolled, 41 were assessable . Most microbiologic diagnoses were made by endotracheal aspiration with strict grading criteria . The clinical-radiographic responses of patients and standard demographic data were recorded . Pseudomonas aeruginosa, "multiple pathogens," and Klebsiella-Enterobacter-Serratia-Citrobacter species were isolated in 41, 32, and 15% of the instances, respectively . Causative pathogens were eradicated from sputum significantly more frequently by patients who received ETT (P less than 0.05) . However, no significant differences were noted in the clinical outcomes of the two study groups . No local adverse reactions attributable to the administration of this agent were observed, but four patients had supraventricular tachycardia, compared with none who received the placebo (P = 0.053) . ETT may be considered as adjunctive therapy for seriously ill individuals.

J Antimicrob Chemother, 1990 Feb, 25(2), 199 - 208
Interactions of tazobactam and clavulanate with inducibly- and constitutively-expressed Class I beta-lactamases; Akova M et al.; Clavulanate and tazobactam (YTR 830) were tested as inhibitors and inducers of the AmpC-type Class I beta-lactamases of Pseudomonas aeruginosa, Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii and the Ic beta-lactamase of Proteus vulgaris . Both clavulanate and tazobactam inhibited the Pr . vulgaris Class Ic beta-lactamase and potentiated ticarcillin and piperacillin against beta-lactamase derepressed variants of this species . Tazobactam, but not clavulanate, also had some ability to inhibit the AmpC Class I enzymes of M . morganii, C . freundii, Ps . aeruginosa, E . cloacae and S . marcescens . The piperacillin + tazobactam combination, unlike ticarcillin + clavulanate, showed some degree of synergy against most derepressed strains of these species . This behaviour partly depended upon the greater inhibitory activity of tazobactam for the enzymes, but also on piperacillin being easier to potentiate than ticarcillin . The synergy between piperacillin and tazobactam was greatest for M . morganii and C . freundii, least for Ps . aeruginosa and E . cloacae . Unfortunately, it is in the last two species that these enzymes pose the greatest resistance threat . Tazobactam caused little or no antagonism of piperacillin against beta-lactamase inducible species, whereas clavulanate antagonized ticarcillin against beta-lactamase inducible strains of E . cloacae and M . morganii (not other species) . The antagonism of ticarcillin was attributable to beta-lactamase induction . The lack of antagonism with the tazobactam+piperacillin combination was related to tazobactam being a weaker inducer than clavulanate, not to piperacillin being less susceptible to antagonism than ticarcillin.

Nature, 1990 Jan 18, 343(6255), 284 - 8
Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis; Oefner C et al.; Beta-Lactamases (EC 3.5.2.6, 'penicillinases') are a family of enzymes that protect bacteria against the lethal effects of cell-wall synthesis of penicillins, cephalosporins and related antibiotic agents, by hydrolysing the beta-lactam antibiotics to biologically inactive compounds . Their production can, therefore, greatly contribute to the clinical problem of antibiotic resistance . Three classes of beta-lactamases--A, B and C--have been identified on the basis of their amino-acid sequence; class B beta-lactamases are metalloenzymes, and are clearly distinct from members of class A and C beta-lactamases, which both contain an active-site serine residue involved in the formation of an acyl enzyme with beta-lactam substrates during catalysis . It has been predicted that class C beta-lactamases share common structural features with D,D-carboxypeptidases and class A beta-lactamases, and further, suggested that class A and class C beta-lactamases have the same evolutionary origin as other beta-lactam target enzymes . We report here the refined three-dimensional structure of the class C beta-lactamase from Citrobacter freundii at 2.0-A resolution and confirm the predicted structural similarity . The refined structure of the acyl-enzyme formed with the monobactam inhibitor aztreonam at 2.5-A resolution defines the enzyme's active site and, along with molecular modelling, indicates a mechanism for beta-lactam hydrolysis . This leads to the hypothesis that Tyr 150 functions as a general base during catalysis.

Antimicrob Agents Chemother, 1990 Jan, 34(1), 156 - 8
Diverse potential of beta-lactamase inhibitors to induce class I enzymes; Weber DA et al.; The ability of various beta-lactamase inhibitors to induce class I beta-lactamases was assessed . Clavulanate was the most active compound, inducing Morganella morganii, Aeromonas caviae, and Enterobacter aerogenes over a broad concentration range and Citrobacter freundii, Pseudomonas aeruginosa, and Serratia marcescens at high concentrations . Disk approximation tests paralleled these results, with clavulanate, but not sulbactam or tazobactam, antagonizing the activity of several beta-lactams against these organisms.

Arch Microbiol, 1990, 154(3), 221 - 5
Hemolysin as a marker for Serratia; Ruan Y et al.; All Serratia marcescens strains (total of 33) of different sources were hemolytic including clinical strains previously classified as being nonhemolytic . DNA fragments of the two hemolysin genes hybridized with the chromosomal DNA of S . marcescens, S . liquefaciens, S . kiliensis, S . grimesii, S . proteamaculans, S . plymutica, S . rubridaea which were also hemolytic . The restriction pattern of the hemolysin locus differed in each strain . S . ficaria and S . marinorubra expressed a different hemolysin which was much smaller than the S . marcescens hemolysin since it diffused through dialysis membranes . The DNA of the latter strains did not hybridize with the S . marcescens hemolysin DNA probes . Some S . marcescens strains, S . kiliensis and S . liquefaciens also expressed in addition the small hemolysin . No hybridization was found with DNA of Escherichia coli, Salmonella typhimurium, Proteus mirabilis, Proteus vulgaris, Citrobacter freundii, Enterobacter cloacae, Klebsiella arerogenes, Klebsiella pneumoniae, Shigella dysenteriae, Yersinia enterocolitica, Yersinia pseudotuberculosus, Listeria sp., Aeromonas sp., Legionella sp . and a Meninococcus sp., indicating that the hemolysin DNA probes are specific for Serratia, or that the hemolysin genes occur rarely in genera other than Serratia.

Chemotherapy, 1990, 36(5), 356 - 64
Antibacterial activity of piperacillin and tazobactam against beta-lactamase-producing clinical isolates; Cullmann W et al.; The effectiveness of a combination of the recently developed penam sulphone tazobactam with piperacillin was studied in clinical isolates with defined beta-lactamase production . The combination was highly effective against piperacillin-resistant beta-lactamase-producing Staphylococcus aureus, TEM-1-producing Escherichia coli and Proteus vulgaris isolates . It was less effective against E . coli isolates producing the OXA-1 enzyme and marginally active against TEM-1-producing Klebsiella spp . isolates . The presence of tazobactam at a concentration of 10 mg/l markedly reduced the minimal inhibitory concentrations for piperacillin in most of the beta-lactamase-derepressed Enterobacter cloacae, Serratia marcescens and Citrobacter freundii isolates; however, this synergism was much less pronounced in beta-lactamase-derepressed Klebsiella spp . isolates . The selection frequency of resistant clones from clinical E . cloacae and C . freundii isolates could be markedly reduced by the addition of 10 mg/l tazobactam to the piperacillin-containing selective medium . Resistant clones could be obtained only from part of the wild-type strains at 2 or 4 times the MIC of piperacillin in the presence of tazobactam, whereas resistant clones could be selected up to 64 times the MIC of piperacillin without the addition of tazobactam . This aspect deserves attention with respect to the rapid selection of beta-lactamase-derepressed clones from nosocomial pathogens.

Acta Clin Belg, 1990, 45(2), 113 - 9
In vitro activity of cefonicid compared to other antibiotics against clinical bacterial isolates; Verbist L et al.; The in vitro activity of cefonicid compared to that of other antibiotics has been evaluated against 401 Enterobacteriaceae, 20 H . influenzae, 17 Branhamella catarrhalis and 71 staphylococci . Cefonicid was always more active than cefazolin, and usually more active than cefamandole and cefuroxime against susceptible gram-negative organisms (E . coli, P . mirabilis, Klebsiella, Shigella, Salmonella, H . influenzae) . Cefonicid was ineffective against most strains of Enterobacter, Citrobacter, S . marcescens and M . morganii . Staphylococci were 6 to 8 times less susceptible to cefonicid than to the other cephalosporins.

Chemotherapy, 1990, 36(1), 13 - 23
Role of the outer membrane for quinolone resistance in enterobacteria; Dechene M et al.; Quinolone-resistant clones were selected from clinical Escherichia coli, Citrobacter freundii and Serratia marcescens isolates in a frequency ranging from 10(-8) to 10(-6) . The outer membrane proteins of quinolone-resistant E . coli clones remained unaltered, as was the case for 10 of 11 C . freundii and 4 of 11 S . marcescens clones ('nal B' type) . There was no strong relation between alterations of outer membrane proteins and cross-resistance with chemically unrelated compounds such as tetracycline or chloramphenicol; however, tetracycline resistance was observed in some C . freundii clones with unaltered outer membrane proteins ('mar A') . Most of the quinolone-resistant S . marcescens clones can be considered 'nor B' or 'nor C' mutants due to their cross-resistance with other compounds, their altered outer membrane proteins and changes of lipopolysaccharide . In a few cases, subinhibitory quinolone concentrations caused alterations of outer membrane proteins in S . marcescens during mid log phase without development of resistance.

Lab Delo, 1990, (2), 46 - 9
{Standardization of the determination of the fimbriae (adhesins) of Citrobacter}; Karal'nik BV et al.; Trials of guinea pig formalin-treated red cells have shown their stability for at least 3 years and fitness, equal to that of native cells, for the detection of Citrobacter mannose-sensitive and resistant adhesins in hemagglutination and adhesion tests (red cell binding of bacteria) . Comparison of the results of bacterial binding and bacterial agglutination of red cells in tests on slides and in wells has shown that the use of fixed red cells accelerates agglutination and makes it more sensitive, probably at the expense of altering the red cell physicochemical characteristics by fixation . Use of formalin-treated red cells essentially simplifies Citrobacter adhesion determination and makes it possible in any conditions.

Lab Delo, 1990, (2), 40 - 4
{The etiological structure of acute intestinal infections}; Khubka EI et al.; The share of various etiologic forms of acute intestinal infections, diagnosed by bacteriologic methods, is presented . The share of gastroenterocolitis induced by opportunistic microflora makes up 35.6%, that of dysentery 25.6%, salmonellosis 18.5%; mixed infection (dysentery + salmonellosis) is diagnosed in 7% of cases with acute intestinal infections . The principal representative of opportunistic microflora isolated from patients with acute intestinal infections is the Klebsiella genus (40.6%), whereas in the reference group Citrobacter, Morganella, and Klebsiella detection rates are approximately the same (27.0-18.3%) . Opportunistic microorganisms in titers under 10(6) are isolated from normal subjects 5 times more frequently than from the patients, this indicating the diagnostic value of this level of feces contamination with opportunistic microflora.

Nucleic Acids Res, 1989 Dec 11, 17(23), 9823 - 32
Sequence motifs characteristic of DNA{cytosine-N4}methyltransferases: similarity to adenine and cytosine-C5 DNA-methylases; Klimasauskas S et al.; The sequences coding for DNA{cytosine-N4}methyltransferases MvaI (from Micrococcus varians RFL19) and Cfr9I (from Citrobacter freundii RFL9) have been determined . The predicted methylases are proteins of 454 and 300 amino acids, respectively . Primary structure comparison of M.Cfr9I and another m4C-forming methylase, M.Pvu II, revealed extended regions of homology . The sequence comparison of the three DNA{cytosine-N4}-methylases using originally developed software revealed two conserved patterns, DPF-GSGT and TSPPY, which were found similar also to those of adenine and DNA{cytosine-C5}-methylases . These data provided a basis for global alignment and classification of DNA-methylase sequences . Structural considerations led us to suggest that the first region could be the binding site of AdoMet, while the second is thought to be directly involved in the modification of the exocyclic amino group.

Onderstepoort J Vet Res, 1989 Dec, 56(4), 263 - 9
The biochemical differentiation between Salmonella and Citrobacter; van der Walt ML et al.; A number of bacterial isolates which could not be identified as either Salmonella or Citrobacter by conventional biochemical tests and could not be typed as Salmonella with available antisera, were further examined biochemically and by lysis with phage Felix 0.1 . Glycerol-positive salmonellae and lysine-positive citrobacters were encountered, which could be confused with the other genus, but when the reactions of such strains were examined in the other tests, accurate identifications could be done . Of the tests examined, glycerol fermentation, the beta-galactosidase test, lysine decarboxylation, sorbose fermentation, galacturonate fermentation and lysis by the phage could be used in the differentiation . These tests in combination, rather than 1 or 2 single tests gave reliable and conclusive differentiation.

Antimicrob Agents Chemother, 1989 Dec, 33(12), 2157 - 9
Interaction of E1040 with cephalosporinase from Citrobacter freundii GN7391; Inoue E et al.; The interactions of E1040 with cephalosporinase from Citrobacter freundii, including affinity and hydrolysis, were studied in comparison with those of cefotaxime and ceftazidime . E1040 showed a higher stability at low drug concentrations and a much lower affinity for the enzyme than did cefotaxime or ceftazidime . These enzymological properties explain the high activity of E1040 against cephalosporinase-producing C . freundii.

Zh Mikrobiol Epidemiol Immunobiol, 1989 Dec, (12), 11 - 3
{The characteristics of amino acid catabolism in bacteria of the genus Citrobacter}; Artiukhina AI et al.; The comparison of the occurrence of enzymes effecting the deamination of dicarbon, aromatic and oxyamino acids, as well as transamination enzymes, in Citrobacter bacteria and the activity levels of these enzymes was made . The constant sign of such bacteria was the presence of serine and threonine dehydratase activity . 92% of the strains showed the presence of phenylalanine deaminase . No tryptophan activity was established . 96-98% of Citrobacter strains possessed phenylalanine, tyrosine and tryptophan aminotransferases with alpha-ketoglutaric acid functioning as the acceptor of the amino group.

J Chemother, 1989 Dec, 1(6), 399 - 402
The beta-lactamases of Citrobacter diversus and their hydrolysis kinetics for some structurally-related cephalosporins; Amicosante G et al.; We measured the kinetics of hydrolysis of various cephalosporins by the chromosomally-encoded beta-lactamases of Citrobacter diversus ULA-27 . Cefonicid, cefamandole, cefatrizine and cefoperazone were all hydrolyzed but these antibiotics showed a different feature in their kinetic parameters . Moreover, cefoperazone was a non-competitive inhibitor of this type of enzyme . Cefotetan was stable to hydrolysis and behaved like a progressive inactivator . The ability of these enzymes to inactivate the reported antibiotics contributes largely to the resistance of the studied strain . We conclude that hydrolysis is the main mechanism of resistance of this strain to the new cephalosporins.

J Chemother, 1989 Dec, 1(6), 394 - 8
Do inert beta-lactamase inhibitors act as synergizers of beta-lactam antibiotics? Utility of boric and boronic acids; Amicosante G et al.; Boric and boronic acids were used as inhibitors of beta-lactamases produced by two Citrobacter diversus strains and by one strain of Pseudomonas aeruginosa; all strains were clinical isolates . The beta-lactamases produced by the two Citrobacter diversus strains were inhibited by both borates and boronates, using cephazolin as substrate . The enzyme from Pseudomonas aeruginosa was inhibited only by boronates, using benzylpenicillin as substrate . These inhibitors were also used in combination with selected beta-lactams so as to determine if a synergism of antimicrobial activity occurred . All data reported in the present paper indicate that the minimum inhibitory concentration (MIC) values were lowered in the presence of these inhibitors for the two Citrobacter diversus strains . In the Pseudomonas aeruginosa strains the MIC values were not significantly altered, thus indicating the presence of a permeability barrier for 3-aminophenylboronic acid.

J Antimicrob Chemother, 1989 Nov, 24 Suppl B, 141 - 6
Ticarcillin/clavulanate in the treatment of severe peritonitis; Inthorn D et al.; A prospective study was performed on 50 consecutive patients with secondary peritonitis . All patients received ticarcillin/clavulanate 5.2 g three times daily as initial antibiotic therapy . In 30 patients a primary perforation was found in the gastro-intestinal tract and 20 had post-operative peritonitis . In two thirds of the patients a diffuse peritonitis was found which affected the whole abdomen . Thirty-six patients underwent one or two laparotomies and 11 patients had more than three laparotomies . Subsequently, 17 patients died . The cause of death was a therapeutic failure as a result of the surgical procedure in ten patients (nine patients with persisting intestinal fistulae, one patient with bleeding), whereas in seven cases antibiotic therapy failed . Micro-organisms found in the latter patients were producers of type 1 beta-lactamase (Pseudomonas aeruginosa, Enterobacter sp., Citrobacter sp., Serratia marcescens) and enterococci . Ticarcillin/clavulanate is characterized by its broad antimicrobial spectrum against anaerobic and aerobic bacteria and seems, therefore, to be well suited for initial chemotherapy in patients with diffuse peritonitis.

Mikrobiologiia, 1989 Nov-Dec, 58(6), 1043 - 4
{Genetic determination of degradation of ampholytic surfactants}; Ovcharov LF et al.; Plasmid DNA was detected in Pseudomonas putida 141 and P . stutzeri AT strains which caused destruction of the ampholytic surfactants alkylamino-bis-propionate (AABP) and amidobetaine, respectively . As was demonstrated using genetic analytic procedures, the plasmids controlled AABP and amidobetaine destruction . No plasmid DNA was found in P . desmolytica C37 which caused cyclimide destruction or in Pseudomonas sp . 1 and Citrobacter freundii TO strains responsible for AABP destruction . Apparently, destruction of these xenobiotics was controlled by chromosomal genes.

Jpn J Antibiot, 1989 Nov, 42(11), 2363 - 76
{Determination of the MIC of cefotetan against freshly isolated gram-negative bacilli}; Deguchi K et al.; Antimicrobial activities (MICs) of cefotetan (CTT) against 575 strains of 16 spp . of Gram-negative bacilli isolated in 1988 were determined to investigate distribution of MICs in comparison with those of cefmetazole (CMZ), cefoxitin (CFX), latamoxef (LMOX) and cefazolin (CEZ) . The change in frequencies of incidence of cephem-resistant strains in the latter half of the 1980 was also investigated . Distribution of MIC of CTT varied with test strains . No or very few MICs were at or higher than 12.5 micrograms/ml at an inoculation of 10(6) cfu/ml, thus rates of CTT-resistant strains were low among Escherichia coli, Citrobacter diversus, Klebsiella spp., Proteus spp., Providencia spp., and Haemophilus influenzae . High rates of resistance to CTT were observed, however, among Citrobacter freundii, Enterobacter spp., Serratia marcescens, Morganella morganii, and Bacteroides fragilis . 2 . Most CTT-resistant strains of C . freundii, Enterobacter spp . and S . marcescens were also resistant to LMOX . These resistant strains were considered to be multi-resistant strains to antibiotics including oxime type cephalosporins and monobactams . 3 . Cephem-resistant E . coli was confirmed to be resistant to 22% of CEZ, 14% of CFX, 10% of CMZ and 2% of CTT tested . The incidence of cephem-resistant E . coli unconditionally showed an increasing tendency . 4 . The incidence of resistant strains against cephamycins including CTT is discussed with regard to the mechanism of resistance against all beta-lactam antibiotics, and the problem of the appearance of resistant strains is close and inseparable from social background.

J Antimicrob Chemother, 1989 Nov, 24 Suppl B, 23 - 33
Clavulanate and beta-lactamase induction; Livermore DM et al.; Concern has been expressed that clavulanate can antagonize ticarcillin against enterobacteria and pseudomonads that have inducible expression of chromosomal 'Class I' beta-lactamases . It is suggested that clavulanate-induced enzyme inactivates ticarcillin, which itself is a feeble inducer . We confirmed that this mechanism applied, showing that antagonism was abolished in beta-lactamase-basal mutants of inducible strains . Antagonism has been reported in double disc tests with strains of Pseudomonas aeruginosa, Enterobacter cloacae, Citrobacter freundii, Serratia spp . and indole-positive Proteeae . Only with some strains of Ent . cloacae and Morganella morganii, however, did the presence of 1-32 mg/l clavulanate elevate the MIC of ticarcillin by more than one or two dilutions in chequerboard studies . Clavulanate was synergistic with ticarcillin against Proteus vulgaris strains, being a potent inhibitor of the unusual Class I enzyme of this species . Induction-determined antagonism was not reduced in Ent . cloacae transconjugants that produced the plasmid-mediated TEM-1 beta-lactamase, despite the ability of this enzyme to bind clavulanate . Our results suggest that Ent . cloacae and M . morganii strains should be confirmed not to be more sensitive to ticarcillin alone than to ticarcillin/clavulanate, before the latter combination is used clinically . Otherwise, it appears that beta-lactamase induction is unlikely to cause significant antagonism . It is emphasized that induction is reversible, causing, at worst, a transient resistance . It should not be confused with the selection of stably-derepressed mutants that can occur, for example, in the clinical use of newer cephalosporins.

Antimicrob Agents Chemother, 1989 Nov, 33(11), 1998 - 2003
In vitro activity of dactimicin, a novel pseudodisaccharide aminoglycoside, compared with activities of other aminoglycosides; Gu JW et al.; The in vitro activity of dactimicin, a new pseudodisaccharide aminoglycoside which possesses a formimidoyl group, was compared with those of gentamicin, tobramycin, and amikacin against 500 isolates . Dactimicin inhibited 90% of isolates from the family Enterobacteriaceae at a concentration of less than or equal to 4 micrograms/ml . It was more active than amikacin against Klebsiella pneumoniae, Serratia marcescens, Citrobacter diversus, Enterobacter agglomerans, Yersinia species, and Salmonella species, with an MIC for 90% of the strains (MIC90) of less than or equal to 4 micrograms/ml . The MIC90s for the Pseudomonas aeruginosa isolates were greater than 128 micrograms/ml . Dactimicin did not inhibit most methicillin-resistant Staphylococcus aureus isolates and coagulase-negative staphylococci but had an MIC50 (MIC for 50% of strains tested) of 2 micrograms/ml against methicillin-susceptible S . aureus isolates and coagulase-negative staphylococci . Dactimicin in combination with piperacillin acted synergistically against 75% of Escherichia coli, K . pneumoniae, S . marcescens, and S . aureus isolates . It exhibited an excellent postantibiotic suppressive effect on E . coli . Dactimicin was active against organisms possessing aminoglycoside-modifying enzymes including AAC(2')-b, AAC(3)-III, -IV, and -V, and AAC(6')-Ia, -Ib, Ic, -II, and -IV but was not active against isolates which contained AAC(3)-I and the bifunctional APH(2")-AAC(6')-I . Its lack of activity against P . aeruginosa appeared to be permeability related since in the presence of EDTA P . aeruginosa was susceptible, as were mutant isolates resistant because of permeability barriers.

J Mol Biol, 1989 Oct 5, 209(3), 335 - 44
Conservation of organization in the specificity polypeptides of two families of type I restriction enzymes; Kannan P et al.; We have identified the recognition sequence for the Citrobacter freundii restriction endonuclease CfrA, a member of the A-family of type I R-M enzymes . This bipartite target sequence differs in both its components from those of other type I enzymes . We determined the nucleotide sequence of its specificity gene (hsdS) and a comparison of this with its relative EcoA identifies two extensive variable regions, an organization analogous to that found in the K-family of type I R-M enzymes . The specificity polypeptides of the A-family, unlike those of K, have an N-terminal conserved region, and this includes a sequence repeated within the central conserved region . A second repeat sequence, identified at the amino acid level, coincides with the only sequence similarity common to all type I S polypeptides . Sequences immediately downstream from the hsdS genes of EcoA, CfrA, EcoK, B and D are almost identical, consistent with an allelic chromosomal location.

J Clin Microbiol, 1989 Oct, 27(10), 2366 - 8
Evaluation of Spectrum-10 system for identification of members of the family Enterobacteriaceae; Vuye A; A total of 378 isolates of the family Enterobacteriaceae were tested with conventional biochemical tests and with the Spectrum-10 identification system . Of these, 97.4% were correctly identified to the species level by using the seven-digit profile of Spectrum-10 . The preliminary four-digit profile provided the correct species for 61.1% and the correct genus for 79.4% of the strains . Most misidentifications were observed with aberrant biotypes of Citrobacter freundii.

Antibiot Khimioter, 1989 Oct, 34(10), 751 - 5
{Normal microflora of the pharyngeal mucosa}; Kolotilova LV et al.; Aerobic microflora of the throat mucosa was studied in 518 healthy persons aged 1 to 50 years . On the basis of the study results, criteria for estimating microbiocenoses of the upper respiratory tracts were defined . It was shown that the throat symbiotic flora included three groups of microorganisms playing different roles in the development of microbiocenosis . The indigenous group consisted of representatives of Streptococcus and Neisseria and was characterized by permanent (90-100 per cent) and intensive (3-8 lg CFU/ml) colonization, broad species spectrum, associations of 2-3 and more species and no significant influence of sociological, age and season factors . The representatives of the facultative group i.e . bacteria belonging to Staphylococcus, Corynebacterium and Haemophilus were less frequent (25-50 per cent) . The intensity of their isolation was lower (1-4 lg CFU/ml) and their species spectrum was narrow . The microorganisms of the transitory group were characterized by low frequency (5-20 per cent) and insignificant contamination of the throat mucosa (1-2 lg CFU/ml) . The nature of the colonization was monospecific . The group was more numerous by generic composition (Candida, Escherichia, Klebsiella, Citrobacter, Enterobacter, Pseudomonas, Branhamella, Moraxella and Micrococcus) . However, it was generally limited by one colonization type . The facultative and transitory groups were subject to age and season variation . They were also different in urban and rural populations.

Jpn J Antibiot, 1989 Oct, 42(10), 2189 - 312
{Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986) . III . Secular changes in susceptibility}; Kosaki N et al.; Changes in the susceptibility of various infectious microorganisms to antimicrobial agents from 1982 to 1986 were evaluated . The microorganisms investigated were Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Proteus spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections . We compared susceptibilities of microorganisms obtained from simple urinary tract infections with those from complicated infections with or without indwelling catheter . Among penicillins, mecillinam (MPC) showed the strongest activity against E . coli obtained from the patients: 3.13 to 6.25 micrograms/ml of MPC inhibited the growth of over 90% of the isolates . Among the second and the third generation cephalosporins, cefotiam and cefmenoxime (CMX) showed the strongest activity and the growth of isolates was inhibited at concentrations of 0.39 to 0.78 microgram/ml and below 0.10 to 0.20 microgram/ml, respectively . The activities of penicillins against Klebsiella spp . were weak . CMX showed strong activity against Klebsiella spp; 91.7% of the isolates from patients with simple infections were inhibited at 0.39 microgram/ml of the agent; 90.7% and 91.6% of isolates from patients with complicated infections with or without indwelling catheter were inhibited at 0.78 microgram/ml and 1.56 microgram/ml of the agent, respectively . Gentamicin (GM) also showed strong activity against isolates from patients with simple infections and weaker activity against isolates from patients with complicated infections with the catheter; 0.78 microgram/ml of ofloxacin (OFLX) inhibited the growths of 90% of the isolates from these patients . Penicillins showed weak activity against Citrobacter spp . obtained from the patients . Among the second and the third generation cephalosporins, CMX and latamoxef (LMOX) showed strong activities against the Citrobacter isolates; about 50% of the isolates were inhibited at 0.20 microgram/ml of either agent . 1.56 microgram/ml of minocycline inhibited the growth of 75 to 90% of the isolates and 1.56 microgram/ml of OFLX inhibited the growth of 93 to 100% of the isolates . Against isolates of Proteus spp . penicillins also showed weak activities . Among them, however, piperacillin (PIPC) inhibited the growth of over 90% of the isolates at concentrations ranging from 0.78 to 1.56 micrograms/ml . Among the second and third generation cephalosporins, CMX and LMOX showed strong activities; 0.20 microgram/ml of CMX inhibited the growth of 94.4%, 90.4%, and 83.1% of isolates from the 3 types of the patients, respectively . 0.20 microgram/ml of LMOX inhibited the growth of 94.4%, 91.8%, and 88.3% of the isolates, respectively . Enterobacter spp . showed resistance to the beta-lactam antibiotics.(ABSTRACT TRUNCATED AT 400 WORDS)

Pathol Biol (Paris), 1989 Oct, 37(8), 881 - 7
{Activity of 5 fluoroquinolones on hospital Gram-negative bacilli with different sensitivities to pefloxacin}; Aubert G et al.; The minimum inhibitory concentrations (MIC) of 5 fluoroquinolones, fleroxacin (FLE), ciprofloxacin (CIP), ofloxacin (OFL), enoxacin (ENO) and norfloxacin (NOR) have been determined by the agar dilution method towards 140 strains of Pseudomonas aeruginosa (Pa) and 146 Enterobacteriaceae showing different sensitivities to pefloxacin (PEF) . The strains were isolated in 1988 at the Bellevue Hospital . The modal MIC is 0.12 for CIP, 0.25 for NOR, 0.5 for OFL, and 1 for FLE and ENO when used on Pa strains which are sensitive to PEF (n = 35) (MIC less than or equal to 1mg/1) . The modal MIC is 0.25 - 0.5 for CIP, 0.5 for NOR, 1 for OFL and ENO, and 2 for FLE when used on Pa strains which are of intermediate sensitivity to PEF (n = 70) (1 less than MIC less than or equal to 4) . The modal MIC is 2 for CIP, 8 for NOR and OFL, 8 - 16 for ENO, and 32 for FLE when used on Pa strains which are resistant to PEF (n = 35) (MIC greater than 4) . The modal MIC is 0.015 for CIP, 0.06 for OFL, 0.12 for FLE, NOR and ENO when used on Escherichia coli strains which are sensitive to PEF (n = 47) . The modal MIC is 0.5 for CIP, 1 for OFL and NOR, and 2 FLE and ENO, when used on Escherichia coli strains which are of intermediate sensitivity to PEF (n = 38) . The modal MIC is 1 for CIP, 4 for OFL and NOR, 16 for FLE, and 32 for ENO when used on E coli strains which are resistant to PEF (n = 15) . The 26 Serratia marcescens and 20 Citrobacter with MIC greater than or equal to 8 for PEF all have MICs greater than 1 and modal MICs greater than or equal to 4 for all the fluoroquinolones studied . CIP always showed greater activity than the other quinolones whatever the sensitivity shown towards PEF.

Eur J Clin Microbiol Infect Dis, 1989 Oct, 8(10), 908 - 16
In vitro antibacterial activity and beta-lactamase stability of the new carbapenem SM-7338; Sumita Y et al.; The in vitro activity of the new carbapenem SM-7338 was tested in comparison with imipenem, ceftazidime, cefotaxime, flomoxef, cefuzonam and cefmetazole against 2850 clinical bacterial isolates . SM-7338 showed good activity against a broad spectrum of gram-positive and gram-negative bacteria . SM-7338 was very active against gram-negative bacteria, inhibiting all Enterobacteriaceae, except 25% of Serratia marcescens isolates, at a concentration of 0.78 mg/l . SM-7338 inhibited the majority of Pseudomonas spp . at concentrations of less than or equal to 3.13 mg/l, its activity being twofold higher than that of imipenem . However, the activity of SM-7338 against gram-positive cocci was about one-fourth that of imipenem . Against anaerobes, SM-7338 also had the best activity of the beta-lactams tested . The compound was inactive against methicillin-resistant staphylococci, Enterococcus faecium, Xanthomonas maltophilia and Flavobacterium spp., as were the other beta-lactams . SM-7338 was quite stable in the presence of various types of beta-lactamase, but was hydrolyzed by Xanthomonas maltophilia beta-lactamase, as was imipenem . This high degree of stability was responsible for the potent activity of SM-7388 against beta-lactamase-producing species such as Enterobacter cloacae, Citrobacter freundii and Proteus vulgaris . SM-7338 also showed bactericidal activity against clinical isolates at the MIC or at concentrations slightly above the MIC.

Infect Immun, 1989 Oct, 57(10), 3159 - 64
Characterization of the Salmonella paratyphi C Vi polysaccharide; Daniels EM et al.; The Vi capsular polysaccharide (Vi) is both a virulence factor and a protective antigen of Salmonella typhi; its pathogenic role for Salmonella paratyphi C is less well understood . We found no differences between the antigenic and immunogenic properties and the structure of the Vi from representative strains of S . paratyphi C, S . typhi, and Citrobacter freundii . There were, however, differences in both the amount produced per cell and the degree of association with the cell among the Vi from the three species of Enterobacteriaceae . S . paratyphi C produced less Vi than both the wild-type S . typhi and C . freundii did, and it showed the fastest release of Vi into the media . These findings may provide an explanation for the inability of the Vi to inhibit completely the agglutination of S . paratyphi C by anti-O sera . In an outbreak of enteric fever caused by S . paratyphi C, 66 of 78 isolates (85%) were Vi positive.

Antimicrob Agents Chemother, 1989 Sep, 33(9), 1580 - 7
In vitro evaluation of BRL 42715, a novel beta-lactamase inhibitor; Coleman K et al.; The penem BRL 42715, C6-(N1-methyl-1,2,3-triazolylmethylene)penem, is a potent inhibitor of a broad range of bacterial beta-lactamases, including the plasmid-mediated TEM, SHV, OXA, and staphylococcal enzymes, as well as the chromosomally mediated enzymes of Bacteroides, Enterobacter, Citrobacter, Serratia, Morganella, Escherichia, Klebsiella, and Proteus species . The concentration of BRL 42715 needed to reduce the initial rate of hydrolysis of most beta-lactamase enzymes by 50% was less than 0.01 micrograms/ml, which was 10- to 100-fold lower than for other beta-lactamase inhibitors . These potent inhibitory activities were reflected in the low concentrations of BRL 42715 needed to potentiate the antibacterial activity of beta-lactamase-susceptible beta-lactams . Concentrations of 0.25 micrograms/ml or less considerably enhanced the activity of amoxicillin against many beta-lactamase-producing strains . The MIC50 (MIC for 50% of strains tested) of amoxicillin for 412 beta-lactamase-producing members of the family Enterobacteriaceae fell from greater than 128 to 2 micrograms/ml in the presence of 1 microgram of BRL 42715 per ml, whereas 5 micrograms of clavulanic acid per ml brought the MIC50 down to 8 micrograms/ml . Among these 412 strains were 73 Citrobacter and Enterobacter strains, and 1 microgram of BRL 42715 per ml reduced the MIC50 of amoxicillin from greater than 128 to 2 micrograms/ml for the 48 cefotaxime-susceptible strains and from greater than 128 to 8 micrograms/ml for the 25 cefotaxime-resistant strains.

J Antimicrob Chemother, 1989 Sep, 24 Suppl A, 207 - 17
Interactions of meropenem with class I chromosomal beta-lactamases; Yang YJ et al.; Most newer penicillins and cephalosporins are labile to the Class I beta-lactamases that are inducible in Pseudomonas aeruginosa . Enterobacter spp., Citrobacter spp., Serratia spp . and indole-positive Proteeae, but fail to induce enzyme synthesis below the MIC . They remain active against the inducible strains but not against mutants (termed 'stably depressed') that manufacture beta-lactamase copiously without induction . Such mutants are segregated at high frequency and may be selected during therapy, sometimes causing clinical failure . Meropenem induced Class I enzymes weakly below the MIC in Ps . aeruginosa, Ent . cloacae, C . freundii, Ser . marcescens, Morganella morganii and Pr . vulgaris . Nonetheless it remained equally active against inducible strains and their derepressed mutants, and was no more active against laboratory-derived beta-lactamase basal mutants . It did not select derepressed mutants from beta-lactamase-inducible populations . These data suggested great stability to Class I beta-lactamases, and this deduction was confirmed by direct assays with purified beta-lactamases . Initial hydrolysis rates ranged from 0.9-10.0 drug molecules hydrolysed/enzyme molecule/minute but these values declined by 80-90% before 5% of the antibiotic had been hydrolysed, indicating that the carbapenem could deactivate the enzymes . Deactivation was reversible, full activity being restored once the meropenem was removed . These results suggest that meropenem, like imipenem and various experimental penems, may overcome the resistance problems presented by Class I beta-lactamases.

Food Chem Toxicol, 1989 Sep, 27(9), 613 - 8
Potentiation of ferrous sulphate and ascorbate on the microbial transformation of endogenous trimethylamine N-oxide to trimethylamine and dimethylamine in squid extracts; Lin JK et al.; 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.

Indian J Exp Biol, 1989 Sep, 27(9), 824 - 5
Hydrogen production from glucose by Citrobacter freundii; Kumar GR et al.; C . freundii, a member of Enterobacteriaceae was isolated from nearby sewage and characterised . With optimum conditions, its hydrogen production capacity and efficiency was tested in synthetic medium containing glucose as carbon and energy source . C . freundii was grown in a 51 fermentor under batch anaerobic conditions . The total production of gas was 8.91 in the volumetric ratio of 63% H2 and 37% CO2 in 11 hr from 30.8 g glucose . From 1 mole of glucose 1.286 mole of hydrogen was produced (YH2/s) . The rate of gas production (rQ) and hydrogen production (rH2) was 0.71 and 0.45 1/hr respectively . The strain appears to be a better one for hydrogen production compared to the earlier Citrobacter spp reported.

Kansenshogaku Zasshi, 1989 Sep, 63(9), 1013 - 21
{Study on bacterial infection by the investigation of antimicrobial susceptibility of various clinical isolates . III . Comparison of drug susceptibility between the isolates from the materials of out- and in-patients, and among the isolates from the materials of different hospital units}; Yamazaki E et al.; Antimicrobial agents susceptibility of 42, 940 strains of clinical isolates (from 1979 to 1986) were investigated and the data were analyzed on the basis of the sources of isolates; materials from in- and out-patients or from the different hospital units . Bacteria studied were limited to the species of which isolates were 100 or more during 1979 to 1986 . The following results were obtained . i) When the antibiotic susceptibility of the isolates from the out-patient-materials were compared with that from the in-patient-materials, the following 13 bacterial species isolated from the former source were found to be more susceptible to antibiotics than that of the latter . These were S . aureus, S . epidermidis, E . coli, Citrobacter sp., Klebsiella sp., Serratia sp., P . vulgaris, P . rettgeri, M . morganii, P . aeruginosa, P . putida, S . sonnei and Salmonella sp. . ii) The frequency of isolation and their antibiotic susceptibility of S . aureus, Enterobacter sp . and P . aeruginosa from both the in- and out-patients were comparable through 1979 . However, S . aureus isolated from the in-patient-materials tended to show increased antibiotic resistance since 1983 . This is probably due to the frequent use of the 3rd generation cephalosporins . iii) Comparison of the antibiotic susceptibility of the isolates from the different hospital units showed that the resistant strains were more frequently isolated in the materials from the urology unit and the susceptible strains were more frequently isolated in the materials from the infectious diseases unit . iv) Antibiotic resistant S . aureus and P . aeruginosa increased abruptly since 1983 in the materials from the surgery and urology unit, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Ig, 1989 Sep-Oct, 1(5), 1279 - 89
{Gram-negative flora of horticultural produce destined for consumption mainly in the raw state}; Cavazzini G et al.; A survey has been carried out to evaluate the recovery of Enterobacteriaceae in freshly consumed horticultural products . 64 samples of these vegetables random chosen in different stores in the General Vegetable Market of Ferrara have been examined among the families of Compositae (lettuce, prickly lettuce, cabbage lettuce, common chicory, artichoke), Umbrelliferae (curly parsley, carrot, celery, fennel), Cruciferae (garden cabbage, red radish), Liliaceae (onion), and Solanaceae (tomato) . 654 bacterial lines were isolated, of which 92.5% were Enterobacteriaceae, found in all kinds of horticultural products, the more contaminated being celery, followed by fennel, onion, common chicory, curley parsley, tomato; less contaminated were the other vegetables . Serratia was found in 29.6% of the samples, Escherichia in 28%, Enterobacter in 21.6%, Hafnia in 8.3%, citrobacter in 4.9%, Klebsiella in 2.3% and Yersinia enterocolitica in 1.5% . The importance of horticultural products as source of contamination and colonization by Enterobacteriaceae, especially in hospital, is emphasized . On the basis of reported data, the Authors suggest an accurate observance on hygienic regulations in order to contain the microbic charge under borderline values, even if it is not demonstrated that environmental Enterobacteriacee have the same pathogenicity than clinical ones.

Singapore Med J, 1989 Aug, 30(4), 356 - 8
Septic arthritis in the newborn--a 17 years' clinical experience; Ho NK et al.; Septic arthritis is an uncommon, yet serious disorder in the newborn . Most patients survive with permanent handicaps . We encountered 11 cases of neonatal septic arthritis in the Hospital over the past 17 years (1971-87), an incidence of 0.12 per 1000 livebirths or 0.67 per 1000 admissions to the neonatal nursery . The clinical experience is presented . The diagnosis of septic arthritis in the newborn is more difficult than in the older children . Joint swelling (10/11), tenderness (9/11) and limitations of joint movement (8/11) were the common presenting clinical signs . Constitutional symptoms (fever, leucocytosis, gastrointestinal disturbances) were unremarkable . More than half of the babies (6/11) were prematurely born . The knees and the hips were frequently infected, many had multiple joint involvement (6/11) . Septic arthritis commonly manifested between 20-40 days of life . The causative agents viz . Staphylococcus aureus (4/11), Candida (2/11), Citrobacter (1/11) and Methicillin Resistant Staphylococcus aureus MRSA (4/11) showed that septic arthritis was a nosocomial infection . Many babies (9/11) had insertion of intravascular catheter for 1-3 weeks and 9/11 babies had concomitant positive blood culture, 2/11 coexisting osteomyelitis and 1, meningitis . Though there was no death, majority of the babies had joint destruction and severe handicap . Early diagnosis including frequent examinations of joints, prompt treatment and control of nosocomial infection are important in management.

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1260 - 7
In vitro activity of ME1228, a new parenteral cephalosporin; Neu HC et al.; ME1228 is a new cephalosporin with an iminocarboxymethyl moiety on the acyl side chain and a novel pyridiniumthiomethyl group at position 3 of the bicyclic ring . Its activity was compared with those of ceftazidime, imipenem, piperacillin, and gentamicin . ME1228 inhibited most members of the family Enterobacteriaceae, except for some Enterobacter spp . and Citrobacter freundii, at less than or equal to 0.25 micrograms/ml, and it inhibited gentamicin- and piperacillin-resistant isolates . It had MICs for Pseudomonas aeruginosa between 1 and 32 micrograms/ml, comparable to those of ceftazidime, and it inhibited piperacillin- and gentamicin-resistant isolates . Most group A, B, C, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.25 micrograms/ml . Enterococci and listeriae were resistant (MICs, 64 to 128 micrograms/ml) . The MICs for staphylococci were 4 to 8 micrograms/ml, and methicillin-resistant Staphylococcus aureus was resistant . There was a minimal inoculum effect and no effect of the medium . ME1228 was not hydrolyzed by TEM-1, TEM-2, SHV-1, and S . aureus plasmid beta-lactamases and was stable against hydrolysis by Richmond-Sykes type 1a, 1c, 1d, and IV chromosomal beta-lactamases . It was hydrolyzed by TEM-3 and Xanthomonas maltophilia beta-lactamases . Overall, ME1228 had activity comparable or superior to that of ceftazidime.

Mol Gen Genet, 1989 Aug, 218(2), 353 - 4
High efficiency transduction of single strand plasmid DNA into enteric bacteria; Benedik MJ; This report demonstrates high efficiency transduction of enteric bacteria using single strand plasmids packaged in M13 phage capsids . Transformation by plasmid DNA is usually a very inefficient process in many enteric bacteria other than Escherichia coli K12 . Plasmids carrying an M13 origin of replication can be replicated and packaged when cells carrying such plasmids are infected with M13 or a derivative helper phage . By introducing an F' plasmid into E . coli, Serratia marcescens, Citrobacter freundii, and Enterobacter aerogenes, these species can now be infected at high efficiency with M13 phage and with packaged single strand plasmids, yielding an efficient method to introduce cloned DNA fragments into these bacteria . The titer of colony forming units in a lysate was essentially equivalent in all the bacteria, demonstrating an equal efficiency of transduction of these other enteric bacteria compared to E . coli.

Mol Microbiol, 1989 Aug, 3(8), 1091 - 102
Signalling proteins in enterobacterial AmpC beta-lactamase regulation; Lindquist S et al.; The cloned Citrobacter freundii ampC beta-lactamase is inducible in the presence of its regulatory gene ampR in Escherichia coli (Lindberg et al., 1985) . The basal level of expression and inducibility are affected by two E . coli proteins encoded by the closely linked ampD and ampE genes . Deletion of both genes led to constitutive ampR-dependent overproduction of beta-lactamase, whereas an out-of-frame deletion in AmpD caused the basal expression to increase two-fold . This ampD1 mutant was inducible at lower beta-lactam concentrations than the wild type . An IS1 insertion in ampD was polar on ampE expression and increased basal beta-lactamase expression 30-fold while mediating a semi-constitutive phenotype . AmpE expressed from a recombinant plasmid in an ampD-ampE deletion mutant reduced basal beta-lactamase expression to wild-type levels but did not markedly reduce beta-lactam resistance since the cells became hyperinducible . In the absence of AmpD, increasing levels of AmpE therefore decrease the basal expression of AmpC beta-lactamase in an AmpR-dependent manner . AmpD modulated the response exerted on beta-lactamase expression by AmpE . The ampD gene encodes a 20.5kD cytoplasmic protein while the 32.1kD ampE gene product is an integral membrane protein with a likely ATP-binding site between the second and third putative transmembrane region . Since neither AmpD nor AmpE are needed for beta-lactam induction and since these proteins could not be covalently labelled by benzylpenicillin, they are not thought to act as beta-lactam-binding sensory transducers . Instead it is suggested that AmpD and AmpE sense the effect of beta-lactam action on peptidoglycan biosynthesis and relay this signal to AmpR.

Mol Microbiol, 1989 Aug, 3(8), 1011 - 23
A novel, non-invasive promoter probe vector: cloning of the osmoregulated proU promoter of Escherichia coli K12; Park SF et al.; We have constructed a novel promoter probe plasmid pSB40, containing a unique lac-alpha-tetracycline marker gene tandem, which allows for both positive and negative selection of active promoters . Promoters cloned in pSB40 can be readily mobilized as EcoRI cassettes . Using this vector we have performed a non-invasive analysis of the E . coli chromosome for promoters regulated by osmotic upshift . Only one such promoter, subsequently identified as part of the proU operon, was isolated . A sequence of 253 bp, sufficient to mediate osmotic regulation of the proU promoter, was defined . This E . coli promoter was normally regulated in Salmonella typhimurium, Klebsiella and Citrobacter but not in Shigella . A proU-luxAB fusion plasmid was constructed and used to monitor in vivo real-time kinetics of proU induction following osmotic upshock.

Bol Med Hosp Infant Mex, 1989 Aug, 46(8), 564 - 6
{Acute necrotizing cholecystitis in infancy: report of a case}; Ugalde-Fernandez JH et al.; We present a case-report of a six weeks old premature baby who developed acute acalculous gangrenous cholecystitis related to septicemia due to Citrobacter freundii . We analyze other etiological factors and remark the importance of physical examination and ultrasonographic exploration of the biliary tract . Early cholecystectomy is suggested.

J Antimicrob Chemother, 1989 Aug, 24(2), 165 - 72
In-vitro activity of FCE 22101 and other beta-lactam antibiotics against Enterobacteriaceae resistant to third generation cephalosporins; Jarlier V et al.; The in-vitro activity of FCE 22101 was compared with those of imipenem, aztreonam, cefotaxime, ceftriaxone and latamoxef against 225 Enterobacteriaceae (209 clinical isolates and 16 derivatives of Escherichia coli K12) chosen for their resistance (MIC greater than or equal to 8 mg/l) to third-generation cephalosporins . The beta-lactamases produced by the strains of Enterobacter cloacae, Klebsiella pneumoniae and Esch . coli were identified . The mean MICs of FCE 22101 were 2-8 mg/l for Ent . cloacae, Citrobacter freundii and Morganella morganii . For Ent . cloacae, the MICs were slightly higher for the cephalosporinase non overproducing (5.5-8 mg/l) than for the cephalosporinase overproducing (4.5 mg/l) strains . The mean MIC was 9 mg/l for Serratia spp . but for half of the strains the MICs were greater than or equal to 16 mg/l . The MICs of FCE 22101 were 0.5-1 mg/l for the resistant clinical isolates or isogenic derivatives of K . pneumoniae and Esch . coli producing extended broad-spectrum beta-lactamases (SHV-2, SHV-3 or CTX-1), whether measured in the presence of clavulanate or not, and against the sensitive controls . This showed that the compound was not affected by these new beta-lactamases . The MICs of imipenem, on the average four to five times lower than those of FCE 22101, were found to be very similar for resistant and sensitive strains . The MICs of aztreonam were high (32-128 mg/l) for C . freundii, K . oxytoca and cephalosporinase overproducing strains of Ent . cloacae . There was cross-resistance between the third-generation cephalosporins, but the MICs of latamoxef remained low (1 mg/l) against M . morganii, Klebsiella spp . and Esch . coli.

Mol Gen Genet, 1989 Aug, 218(2), 323 - 9
Mutagenic DNA repair genes on plasmids from the 'pre-antibiotic era'; Sedgwick SG et al.; Resistance transfer factors are natural conjugative plasmids encoding antibiotic resistance . Some also encode mutagenic DNA repair genes giving resistance to DNA damage and induced mutagenesis . It has been shown that antibiotic resistance has been acquired by recent transposition events; however, we show here that mutagenic repair genes existed much earlier on these types of plasmids . Conjugative plasmids from eight incompatibility groups from the Murray collection of 'pre-antibiotic era' enterobacteria were tested for complementation of mutagenic repair-deficient Escherichia coli umuC36 . Although none of these plasmids carry transposon-encoded drug resistance genes, IncI1 and IncB plasmids were identified which restored ultraviolet resistance and induced mutability to umuC36 mutants . Furthermore they increased the UV resistance and induced mutability of wild-type E . coli, Klebsiella aerogenes and Citrobacter intermedius, thus showing that they could confer a general selective advantage to a variety of hosts . Like known mutagenic repair genes, complementation by these plasmid genes required the SOS response of the host cell . Nucleotide hybridisation showed that these plasmids harboured sequences similar to the impCAB locus, the mutagenic repair operon of modern-day IncI1 plasmids . The evolution of mutagenic repair genes is discussed.

Zentralbl Hyg Umweltmed, 1989 Aug, 188(5), 475 - 80
{Microbial contamination of water by pipe and tube materials . 3 . Behavior of E . coli, Citrobacter freundii and Klebsiella pneumoniae}; Schoenen D et al.; Materials water comes into contact with can promote the microbial growth as it could be shown before . The reaction of an unspecific microorganism flora and of Legionella pneumophila in pipes and hoses has been described in the two previous communications . The investigation with L . pneumophila has shown that even a pathogen organism can grow upon the materials . Therefore it was of special interest to prove whether indicator organisms for the testing of drinking water can grow in pipes and hoses as well . Escherichia coli, Citrobacter freundii and Klebsiella pneumoniae grew after the experimental contamination for many weeks on the rubber hose until the test was finally stopped, in the other pipes and hoses (glass, high-grade steel, PVC, PE, PA, PTFE and silicone) E . coli could be found for maximal 7 weeks, Citrobacter freundii for 1 week and Klebsiella pneumoniae for maximal 3 weeks . In the copper pipe the organisms could be found only for a few days.

J Clin Microbiol, 1989 Aug, 27(8), 1793 - 6
Epidemiologic marker system for Citrobacter diversus using outer membrane protein profiles; Kline MW et al.; Investigations of nursery outbreaks of Citrobacter diversus sepsis and meningitis have been hampered by lack of adequate epidemiologic markers for the organism . We studied outer membrane protein profiles from clinical isolates of C . diversus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine whether this method might be useful in the epidemiologic differentiation of strains . Paired cerebrospinal fluid isolates from each of three separate nursery outbreaks of C . diversus meningitis, paired isolates from the vagina of a postpartum woman and the cerebrospinal fluid of her newborn infant, one isolate from an infant with pneumonia and two from colonized nursery cohorts, and 30 epidemiologically unrelated clinical isolates were included . Eleven distinct profiles were differentiated by the presence or absence of five outer membrane proteins . Complete concordance of profiles was observed for epidemiologically related isolates . Unrelated epidemic strains had outer membrane protein profiles distinct from one another . Biotyping complemented determination of outer membrane protein profiles; the two markers differentiated each of the five epidemic strains from all but one of 30 unrelated nonepidemic isolates . Determination of outer membrane protein profiles is potentially useful in epidemiologic investigations of disease caused by C . diversus.

Antimicrob Agents Chemother, 1989 Jul, 33(7), 1009 - 18
In vitro activity and beta-lactamase stability of a new carbapenem, SM-7338; Neu HC et al.; SM-7338, a new carbapenem, inhibited most members of the family Enterobacteriaceae at MICs of 0.015 to 0.25 microgram/ml, including Klebsiella oxytoca, Citrobacter freundii, Enterobacter cloacae, and Proteus vulgaris isolates resistant to cefotaxime, ceftazidime, piperacillin, and gentamicin . It was two- to eightfold more active than imipenem, but it inhibited Pseudomonas aeruginosa at 1 to 8 micrograms/ml, which was comparable to the activity of imipenem . Haemophilus, Neisseria, and Branhamella species were inhibited by less than or equal to 0.25 microgram/ml, which was superior to the activity of imipenem . SM-7338 inhibited Staphylococcus aureus and coagulase-negative staphylococci at 0.25 microgram/ml, but for methicillin-resistant isolates MICs were 4 to 16 micrograms/ml . Group A, B, and C streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.03 microgram/ml . Bacteroides species, including clindamycin-resistant isolates, were inhibited by 0.25 microgram/ml . There was no major inoculum size effect, and the MBCs were within a dilution of the MICs . SM-7338 was more active than imipenem at an acid pH under anaerobic conditions . Plasmid beta-lactamases of TEM-1, TEM-2, TEM-3, TEM-5, SHV-1, SHV-2, PSE-1, PSE-2, PSE-3, OXA-2, OXA-3, OXA-4, OXA-5, and OXA-7; Staphylococcus aureus enzymes; and the chromosomal beta-lactamases P-99 and K-1; Morganella species; and Proteus vulgaris did not hydrolyze SM-7338 . The repeated transfer of organisms increased the MICs of SM-7338, as it did the MICs of imipenem.

J Bacteriol, 1989 Jul, 171(7), 3746 - 53
Binding of the Citrobacter freundii AmpR regulator to a single DNA site provides both autoregulation and activation of the inducible ampC beta-lactamase gene; Lindquist S et al.; Citrobacter freundii encodes an inducible chromosomal beta-lactamase . Induction requires the product of the ampR gene, which is transcribed in the opposite orientation from the ampC beta-lactamase gene . We show here that the AmpR protein acts as a transcriptional activator by binding to a DNA region immediately upstream of the ampC promoter . The DNase I footprint pattern was not affected by growth in the presence of beta-lactam inducer or by the use of extracts prepared from cells carrying the ampD2 allele leading to semiconstitutive production of beta-lactamase . It is suggested that activation of AmpR facilitates binding or open complex formation for RNA polymerase at the ampC promoter . The AmpR-binding site overlaps the ampR promoter, and beta-galactosidase activity was decreased from an ampR-lacZ transcriptional fusion when AmpR was expressed from a coresident plasmid, suggesting that ampR is autogenously controlled . The AmpR protein belongs to a family of highly homologous transcriptional activators that includes LysR, which regulates the E . coli lysine synthetase gene, and the NodD protein, which regulates expression of a number of genes involved in nodulation in Rhizobium . The lack of sequence homology to any known beta-lactam-binding protein suggests that AmpR does not bind directly to the beta-lactam inducer but interacts with a second messenger of unknown nature.

Am J Perinatol, 1989 Jul, 6(3), 281 - 3
Sudden unexpected death in a neonate; Imaizumi SO et al.; A sudden and unexpected death, at 26 hours of age, of a term infant with no identifiable risk factors either in the prenatal or in the immediate neonatal period is described . The most remarkable postmortem findings were confined to the lungs, which had many areas of aspirated amniotic fluid, as well as extensive areas of bronchopneumonia . Postmortem cultures of the lung revealed Citrobacter freundii . This case is an atypical presentation of this devastating neonatal infection, both because of the absence of central nervous system involvement and because of the total absence of clinical signs before death.

Antimicrob Agents Chemother, 1989 Jul, 33(7), 1116 - 7
Penicillin-binding protein 2 is required for induction of the Citrobacter freundii class I chromosomal beta-lactamase in Escherichia coli; Oliva B et al.; Involvement of Escherichia coli penicillin-binding proteins (PBPs) in induction of the cloned ampC Citrobacter freundii beta-lactamase by 6-aminopenicillanic acid was investigated . The enzyme was not inducible at 42 degrees C in a mutant thermosensitive for expression of PBP 2 . The results imply that PBP 2 is involved in the process leading to induction of ampC.

Diagn Microbiol Infect Dis, 1989 Jul-Aug, 12(4 Suppl), 121S - 129S
Mechanism of beta-lactamase inhibition: differences between sulbactam and other inhibitors; Sawai T et al.; 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.

Eur J Clin Microbiol Infect Dis, 1989 Jul, 8(7), 644 - 50
In vitro activity of PD 117596-2, a broad-spectrum difluoroquinolone; Neu HC et al.; The activity of PD 117596-2, a novel quinolone, was compared to that of other quinolones, ceftazidime, imipenem and gentamicin . PD 117596-2 inhibited most Enterobacteriaceae at concentrations less than 0.25 micrograms/ml, being equal or superior in activity to ciprofloxacin and 2- to 4-fold more active than ofloxacin . It inhibited ceftazidime-resistant Enterobacter spp., Citrobacter spp . and Serratia marcescens . The MIC90 for Pseudomonas aeruginosa, including strains with imipenem MICs of 8 micrograms/ml and gentamicin MICs greater than 16 micrograms/ml, was 0.25 micrograms/ml . PD 117596-2 was more active than ciprofloxacin against Pseudomonas cepacia and Pseudomonas maltophilia, and it inhibited Neisseria gonorrhoeae and Haemophilus influenzae at less than 0.03 micrograms/ml . PD 117596-2 inhibited staphylococci at 0.5 micrograms/ml, being 2-fold superior to other quinolones, and with an MIC of 0.25 micrograms/ml was more active against group A, B, C and G streptococci and Streptococcus pneumoniae . MICs for Bacteroides spp . were 2 micrograms/ml compared to 8-32 micrograms/ml for other agents . The frequency of spontaneous resistance was low (less than 10(-10} . Differences in MICs and MBCs were within one dilution, and there was a minimal effect of inoculum size . Although PD 117596-2 was less active at pH 5.5, MICs were less than 0.5 micrograms/ml.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S1025 - 35
Synergy of fluoroquinolones with other antimicrobial agents; Neu HC; Synergy resulting from the combination of ciprofloxacin and an antipseudomonal penicillin has been reported for 20%-50% of isolates of Pseudomonas aeruginosa . A similar effect has also been reported for the combination of ciprofloxacin and fosfomycin . In contrast, the combination of quinolones and aminoglycosides rarely showed synergy when tested against P . aeruginosa . Most studies have shown that the combination of beta-lactams or aminoglycosides with quinolones is indifferent against Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, and Serratia species . The combination of ciprofloxacin and chloramphenicol can be antagonistic against E . coli . In general, the combination of quinolone antibiotics with other drugs tested against staphylococci, enterococci, and anaerobic species has shown indifference . The neutropenic mouse model of infection has demonstrated the synergistic effect of ciprofloxacin plus antipseudomonal penicillins; the combination of ciprofloxacin and rifampin has been superior to single agents in experimental Staphylococcus aureus osteomyelitis . Ciprofloxacin has been the quinolone studied most thoroughly, and few data are available about the combination of other quinolones with other antimicrobial agents . Overall, the occurrence of synergy when quinolones are combined with other antimicrobial agents is infrequent, and clinical studies that demonstrate the clinical relevance of data from in vitro and animal models of infection are not available . However, data from in vitro and animal model studies indicate that the combination of a quinolone with other antimicrobial agents rarely results in antagonism.

Jpn J Antibiot, 1989 Jun, 42(6), 1293 - 305
{Clinical and pharmacokinetic study on cefodizime, a new cephalosporin antibiotic, in the pediatric infections}; Arimasu O et al.; Cefodizime (THR-221, CDZM), a new cephalosporin antibiotic, was evaluated for its safety and efficacy in 27 children with various bacterial infections . The episodes of infections included pneumonia (6 cases), bronchopneumonia (11 cases), lung abscess (1 case), acute pharyngitis (2 cases), cervical lymphadenitis (1 case), infected cephalohematoma (1 case), urinary tract infection (1 case), sepsis (2 cases) and purulent meningitis (2 cases) . CDZM was effective in all but one, and its efficacy rate was 96.3% . The main etiologic pathogens were Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Escherichia coli, Citrobacter freundii and Branhamella catarrhalis . The elimination rate was 92.3% . As adverse reactions or abnormalities, diarrhea was encountered in 4 cases . A slight elevation of serum transaminases or eosinophils was observed in 4 cases . The serum half-life was approximately 1.8-1.9 hours in children after intravenous bolus injections . Concentrations of CDZM in cerebrospinal fluids were well above MIC values of CDZM against those organisms responsible for the infections . The data suggest that CDZM is a safe and effective antibiotic when used in children with bacterial infections including purulent meningitis.

J Clin Pharm Ther, 1989 Jun, 14(3), 207 - 12
Microbial contamination of cosmetics and personal care items in Egypt--body lotions and talcum powders; Ashour MS et al.; We examined a total of 54 samples, including 18 body lotions and 36 talcum powders, for their total aerobic bacterial, coliform and fungal counts . We also carried out anaerobic bacterial counts for talcum powder as well as tests to detect some potentially hazardous bacteria in all tested samples . Talcum powders were more heavily contaminated with bacteria and fungi than body lotions . More than 40% of the tested body lotions contained no viable bacteria or less than 100 c.f.u./g . while all the talcum powders tested contained more than 100 c.f.u./g . Thirty per cent of the talcum powders were contaminated with 10(4) c.f.u./g . and none of the body lotions were contaminated to that extent . No coliforms were recovered from any of the body lotions, while 17% of the talcum powder examined contained coliforms in the range of 230-500 c.f.u./g . Staphylococcus spp . were detected in 18 samples of both talcum powders and body lotions, three of these Staphylococci were of the aureus type . Three samples of talcum powder contained E . coli, two samples contained Enterobacter agglomerans and one sample contained Citrobacter freundii . Seventy per cent of the body lotions showed no fungal counts, while 83% of the talcum powders examined were contaminated with fungi and most of the contaminated talcum powders contained more than 100 fungal cells/g . With regard to the anaerobic bacterial counts for talcum powders, 50% of the samples showed no counts while the other 50% contained less than 100 c.f.u./g . Four samples were contaminated with Clostridium perfringens, although C . tetani was not recovered from any of the samples.

Epidemiol Infect, 1989 Jun, 102(3), 447 - 58
Enhancement of the infectivity of Fusobacterium necrophorum by other bacteria; Smith GR et al.; Necrobacillosis is caused by Fusobacterium necrophorum (FN), but other organisms are often present in the lesions . Their possible role was studied in experiments made with a virulent FN strain which, by itself, produced fatal necrobacillosis in mice provided that large doses (greater than 10(6) organisms, subcutaneously) were given . Mice were inoculated subcutaneously with FN suspended in sub-lethal doses (0.1 ml) of undiluted or diluted broth cultures of other bacteria . Undiluted culture of a strain of Escherichia coli reduced the infective dose of FN to less than 10 organisms; in the necrobacillosis lesions that developed, fusobacteria greatly outnumbered E . coli . A heat-killed preparation or sterile filtrate of E . coli culture had little if any effect on FN . Citrobacter freundii and comparatively small numbers of Corynebacterium (Actinomyces) pyogenes produced effects similar to that of E . coli . An alpha-haemolytic streptococcus, Pseudomonas aeruginosa, Bacteroides fragilis and Fusobacterium nucleatum also enhanced the infectivity of FN, though less strikingly than E . coli . FN increased the persistence in vivo of the alpha-haemolytic streptococcus and B . fragilis, and enabled the latter to multiply profusely.

J Chemother, 1989 Jun, 1(3), 155 - 61
In vitro and in vivo efficacy of YTR-830H and piperacillin combinations versus beta-lactamase-producing bacteria; Kuck NA et al.; YTR-830H, a beta-lactamase inhibitor, is a non-amino penicillanic sulfone . In vitro synergistic activity with piperacillin was determined for 226 beta-lactamase producing clinical cultures . Combination of piperacillin: YTR in ratios of 2:1, 4:1, and 8:1 were highly effective vs Escherichia coli, Proteus, Providencia, Morganella, Staphylococcus, and Bacteroides . Minimum inhibitory concentrations (MICs) of piperacillin were reduced from the resistant to susceptible range . The higher ratios were less effective vs Enterobacter, Serratia, and Citrobacter . YTR-830H was not antagonistic with piperacillin . Combinations of 2:1, 4:1, and 8:1 increased the therapeutic effectiveness of piperacillin 8 - to 36 - fold against acute lethal infections produced in mice with piperacillin-resistant Escherichia coli, Klebsiella pneumoniae, Morganella morganii, and Staphylococcus aureus.

J Chemother, 1989 Jun, 1(3), 151 - 4
In vitro activity of YTR 830; Jacobs MR et al.; YTR 830, now known as tazobactam, is a new penicillanic acid sulfone beta-lactamase inhibitor . The in vitro activity of YTR 830 combined with various penicillins was determined and compared to that of clavulanate and sulbactam combined with the same agents . Combined with ampicillin or amoxicillin, all three inhibitors were active against beta-lactamase producing strains of Staphylococcus aureus, Haemophilus influenzae, Klebsiella, Citrobacter diversus, and all anaerobes except for Bacteroides fragilis homology group II . YTR 830 was also effective against Escherichia coli and indole-positive Proteus . The inhibitors had no effect against Enterobacter or Serratia . Overall, the activity of YTR 830 was comparable to that of clavulanate, and superior to that of sulbactam.

J Chemother, 1989 May, 1 Suppl 2, 36 - 40
In vitro studies of tigemonam: a comparison of the minimum inhibitory and minimum bactericidal concentrations (MIC vs MBC); Gobernado M et al.; The in vitro activity of tigemonam, a new oral monobactam, was studied with special attention to minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) . Against 250 clinical isolates, it inhibited 100% of Escherichia sp., Klebsiella sp., Serratia sp., Citrobacter sp., Providencia sp., Proteus sp., Morganella sp., Aeromonas sp., Yersinia sp., Shigella sp., and Haemophilus sp . at 0.5 mg/L or less . With 1 mg/L, 75% of Enterobacter sp . were inhibited; however, three of the 20 strains tested needed more than 16 mg/L . Proteus sp., Morganella sp . and Providencia sp . were more susceptible, with MIC90s of 0.06 mg/L or less . The MBC was equal to or two times higher than the MIC . Increasing the inoculum size from 10(3) to 10(5) colony-forming units had little effect on MIC and MBC; with an inoculum of 10(7) or more, MIC and MBC increase three to eight times . MIC and MBC were a little lower in Mueller-Hinton base, and the presence of serum did not significantly change the MIC or the MBC . Tigemonam exhibits a rapid killing rate, but an increased antibiotic concentration was not accompanied by greater lethal effect, and the lethal rate at MBC was lower in trypticase soy broth (TSB) + 40% serum than in TSB alone.

J Chemother, 1989 May, 1 Suppl 2, 32 - 5
In vitro activity of tigemonam against multiresistant nosocomial Enterobacteriaceae; Giamarellou H et al.; Tigemonam, an oral monobactam that exhibits beta-lactamase stability similar to that of aztreonam, was tested in vitro against 240 species of Enterobacteriaceae (50 Escherichia coli, 48 Klebsiella pneumoniae, 52 Enterobacter cloacae, 32 Proteus mirabilis, 22 Proteus indole-positive {Providencia sp.}, 24 Serratia sp., and 12 Citrobacter sp . All strains were resistant to ampicillin and first-generation cephalosporins . In addition, 77.4% were resistant to amoxicillin plus clavulanic acid, 46.8% to cefuroxime, 23.3% to ceftriaxone, 22.2% to aztreonam, 46.9% to cotrimoxazole, and 0.9% to norfloxacin . Tigemonam at a concentration of 4 micrograms/mL or less inhibited 72.7% of the strains with minimum inhibitory concentrations ranging from 0.03 or less to more than 512 micrograms/mL . The highest intrinsic activity was observed against Proteus sp . Tigemonam proved to be a bactericidal antibiotic . Cross-resistance was chiefly observed with aztreonam and ceftriaxone . It is concluded that tigemonam should play an important role in the treatment of nosocomial infections that do not require parenteral therapy and in the treatment of multiresistant community-acquired infections.

J Chemother, 1989 May, 1 Suppl 2, 28 - 31
In vitro activity of tigemonam against urinary tract pathogens; Garcia-Rodriguez JA et al.; Tigemonam's in vitro activity was compared with that of aztreonam, cefotaxime, gentamicin, and norfloxacin . Thirty-two strains of Pseudomonas and 960 strains of Enterobacteriaceae were studied using the agar dilution method (including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter sp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris, Morganella morganii, and Salmonella enterica) . Tigemonam displayed good activity against Enterobacteriaceae . Minimum inhibitory concentrations (MICs), were as follows: MIC50S were 0.01 mg/L for P . mirabilis and 0.5 mg/L for S . marcescens, MIC90S were 0.03 mg/L for P . mirabilis and P . vulgaris and 4 mg/L for Citrobacter freundii . Tigemonam inhibited E . coli and P . mirabilis, the most common strains of urinary pathogens . Despite MIC90S of 9.5 and 4 mg/L for Enterobacter and C . freundii, respectively, resistance to tigemonam was observed . Tigemonam was found to be inactive against Pseudomonas aeruginosa, with MIC50S and MIC90S higher than 128 mg/L (range, 64 to greater than 128 mg/L) . Tigemonam's activity was found to be similar to that of cefotaxime, slightly less than that of norfloxacin and aztreonam, and substantially greater than that of gentamicin . Of all the drugs tested, only norfloxacin and aztreonam possessed activity profiles against P . aeruginosa that were compatible with their clinical usefulness (MIC90, 8 mg/L for norfloxacin; MIC50, 8 mg/L and MIC90, 32 mg/L for aztreonam) . Cefotaxime and gentamicin showed no activity on more than 90% of the P . aeruginosa strains tested.

J Chemother, 1989 May, 1 Suppl 2, 13 - 21
Antibacterial activity of tigemonam dicholate (SQ 30836) and interaction with beta-lactamases of gram-negative bacteria; Raimondi A et al.; SQ 30836 is an orally absorbed salt of tigemonam, a new monobactam similar to aztreonam in structure and microbiologic properties . When assayed against 400 clinical isolates, tigemonam's activity was similar to that of aztreonam and carumonam . It was highly effective against Enterobacteriaceae but showed poor activity against gram-positive organisms . It inhibited 90% of Escherichia coli, Klebsiella, Shigella, Yersinia, Proteus, Providencia, and Morganella strains at 0.5 micrograms/mL or less, and all Salmonella and Hafnia strains at 1 micrograms/mL or less . Citrobacter, Enterobacter, and Serratia strains were less susceptible (minimum inhibitory concentrations {MIC30} of 2, 32, and 8 micrograms/mL respectively) . The activity of the new compound against Enterobacteriaceae is comparable with and often higher than that of third-generation cephalosporins and oral comparison compounds . In contrast to aztreonam, tigemonam had minimal activity against Pseudomonas sp and glucose nonfermenting gram-negative bacteria . Data suggest that poor penetration through the outer membranes of Pseudomonas sp may be responsible for this failure . Tigemonam was stable to hydrolysis by plasmid-mediated and chromosomal beta-lactamases . It was more stable than aztreonam to hydrolysis by the Kl enzyme of Klebsiella and by the Proteus vulgaris beta-lactamase . Also, measurement of the IC50 (concentration of inhibitor able to reduce the activity of the enzyme by 59%) showed that tigemonam has less affinity than aztreonam for class I cephalosporinases . However, only levels of beta-lactamase, not hydrolysis rates or affinity, correlated to MICs of the two monobactams for the resistant Enterobacter and Citrobacter strains.

Diagn Microbiol Infect Dis, 1989 May-Jun, 12(3 Suppl), 51S - 52S
In vitro evaluation of lomefloxacin activity in Colombia; Trujillo H et al.; 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.

J Appl Bacteriol, 1989 May, 66(5), 385 - 91
Rapid impedance detection of salmonellas in confectionery using modified LICNR broth; Bullock RD et al.; A commercially available broth, with the addition of inhibitors, was used for the rapid impediometric detection of salmonellas in confectionery . Pre-enrichment in skimmed milk was followed by lysine-iron-cystine-neutral red broth in a Bactometer 123 system . Results were obtained 3 d earlier than is possible with conventional microbiological tests . Some false positives were obtained predominantly with Citrobacter freundii, but this problem is also frequently encountered with traditional methods . Organisms responsible for false positives may be isolated and identified more rapidly than is possible by conventional methods.

Wei Sheng Wu Xue Bao, 1989 Apr, 29(2), 117 - 23
{TNT-degrading enzyme of Citrobacter freundii and its regulation by carbon and nitrogen source}; Li WZ et al.; It was detected that both NAD(P)H-linked reductase (TNT-Red) and NAD(P)+-linked TNT dehydrogenase (TNT-Deh) were present in TNT-degrading enzymes of Citrobacter freundii simultaneously . The time course of formation for the enzymes and the actions of coenzymes in enzymatic reaction of TNT have been studied . The effects of varied carbon and nitrogen sources on the regulation of the enzymes were different clearly . When the concentration of NH4Cl or urea in culture medium was more than 0.1 mol/L, the formation of both TNT reductase and TNT dehydrogenase was promoted . However, the formation of these enzymes was inhibited by KNO3 in culture . The production of both reductase and dehydrogenase was promoted by glucose . The sodium citrate was able to help the formation of the TNT dehydrogenase . The activity of the TNT reductase was increased when the concentration of sodium citrate was less than 0.5%, but when it was more than 0.5%, the activity of this enzyme was decreased rapidly.

J Antimicrob Chemother, 1989 Apr, 23 Suppl D, 1 - 12
Review of the in-vitro spectrum and characteristics of cefmetazole (CS-1170); Jones RN; The in-vitro antimicrobial qualities of cefmetazole are summarized from a review of over 30 publications . Cefmetazole, a 7 alpha-methoxy cephalosporin, is shown to have an antimicrobial spectrum closely resembling cefoxitin's . However, cefmetazole is approximately two- to eight-fold more active than cefoxitin against commonly isolated species such as Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, pyogenic streptococci, pneumococci, and Haemophilus influenzae . Cefmetazole is also active against anaerobic pathogens, Neisseria spp., Citrobacter diversus, indole-positive Proteus spp . and Branhamella catarrhalis . Cefmetazole is bactericidal against aerobic and anaerobic pathogens . Its MICs and MBCs are minimally influenced by high inoculum concentrations . beta-Lactamases failed to hydrolyze cefmetazole significantly and cefmetazole is considered the most stable of the cephamycin drugs . Some Bacteroides strains produce beta-lactamases that are uniquely inhibited by cefmetazole . In-vitro tests with cefmetazole have been evaluated and interpretive criteria established for NCCLS methods: susceptible greater than or equal to 18 mm (less than or equal to 8.0 mg/l) and resistant less than or equal to 14 mm (greater than or equal to 32 mg/l) . The consistent cross-resistance and -susceptibility observed between cefmetazole and cefoxitin requires the testing of only one of these agents routinely . Quality control guidelines for cefmetazole disc diffusion (30 micrograms disc) and dilution tests are summarized in this review.

Biochimie, 1989 Apr, 71(4), 565 - 71
The activity and reaction specificity of tyrosine phenol-lyase regulated by monovalent cations; Demidkina TV et al.; 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.

Antimicrob Agents Chemother, 1989 Apr, 33(4), 498 - 502
Activity of cefepime against ceftazidime- and cefotaxime-resistant gram-negative bacteria and its relationship to beta-lactamase levels; Fung-Tomc J et al.; One hundred clinical isolates resistant to ceftazidime and/or cefotaxime were examined for susceptibility to cefepime . The most frequently encountered ceftazidime-cefotaxime-resistant strains belonged to the genera Enterobacter, Pseudomonas, and Citrobacter . Among these strains, 92% were resistant to cefoperazone, 91% were resistant to cefotaxime, 84% were resistant to ceftazidime, and 6% were resistant to cefepime . Of the members of the family Enterobacteriaceae, 57% were resistant to ceftriaxone . The six strains resistant to cefepime were all Pseudomonas aeruginosa and were resistant to both cefotaxime and ceftazidime . Cefepime-resistant P . aeruginosa strains had exceptionally high levels of beta-lactamase activity, higher than the levels found in strains resistant to ceftazidime but susceptible to cefepime . The beta-lactamases from the cefepime-resistant strains were type I (Richmond-Sykes), were constitutively produced, and did not have increased affinity or hydrolytic activity for cefepime . Thus, cefepime was active against most gram-negative bacteria which have developed resistance to the broad-spectrum cephalosporins, and resistance to cefepime in P . aeruginosa appears to be associated with higher beta-lactamase levels than in cefepime-susceptible strains.

APMIS, 1989 Apr, 97(4), 317 - 24
Evaluation of a disk approximation test of inducible beta-lactamases in Enterobacteriacae and Pseudomonas aeruginosa; Thore M et al.; A modified disk approximation test of inducible beta-lactamases in Enterobacteriacae and Pseudomonas aeruginosa was evaluated . The amount of inducer was adapted to produce the smallest possible zone of inhibition and the distance between the centre of the disks was standardized . Among several beta-lactam antibiotic disks tested, imipenem (0.06 microgram per disk) or cefoxitin (10 micrograms per disk) placed at a distance of 14-16 mm from a cefotaxime disk (30 micrograms) most efficiently revealed inducible beta-lactamases . A positive induction test (primarily expected with Enterobacter spp, Citrobacter freundii, Serratia spp, Pseudomonas aeruginosa and indole positive Proteus spp) may serve as a warning of the risk of selecting mutants with beta-lactamase mediated cross-resistance during systemic treatment with ureidopenicillins, later generations of cephalosporins or monobactams . Such resistance was exemplified by characterization of some laboratory mutants with hyperproduction of beta-lactamases . However, evaluation of the specificity and sensitivity of the disk approximation test (and other indirect induction tests) still remains to be done.

Med Clin (Barc), 1989 Mar 18, 92(10), 371 - 4
{Efficiency of tazobactam as inhibitor of beta-lactamases, combined with piperacillin, against resistant strains to this penicillin}; Roy C et al.; We studied the efficacy of tazobactam (YTR 830), a new beta-lactamase inhibitor in combination with piperacillin (P) against 198 Enterobacteriaceae strains . A comparative study of susceptibility (MIC determined on Mueller Hinton agar; inoculum 10(4) cfu) was made with the combination amoxicillin (A) + clavulanic acid (CA) . Of 181 strains resistant to P, 79.56% were susceptible to it in the presence of tazobactam (TZ) . The characteristics of the beta-lactamases of 37 strains resistant to P + TZ (MIC greater than 40 micrograms/ml) were studied; 11 were hyperproducers of chromosomic beta-lactamase and 7 produced two types of plasmidic beta-lactamase . The MICs of TZ alone were uniform and high (64-128 micrograms/ml), independently of the characteristics of the strains beta-lactamase . Of 17 strains susceptible to P, the efficacy of P + TZ was significant among carriers of plasmidic beta-lactamase; there was practically no change in the P susceptibility among the non carriers . The efficacy of P + TZ was similar to that of A + AC against E . coli strains; it was higher against strains of Enterobacter, Citrobacter and Serratia.

J Antimicrob Chemother, 1989 Mar, 23 Suppl C, 85 - 94
Interactions of FCE 22101 with class I beta-lactamases; Yang Y et al.; Hyperproduction of chromosomal Class I beta-lactamase causes resistance to newer cephalosporins in Enterobacter cloacae, Citrobacter freundii, Serratia spp . and indole-positive Proteeae . We examined the interactions of FCE 22101 with these enzymes, measuring (i) antibiotic lability to pure enzyme, (ii) inducing power and (iii) activity against beta-lactamase-inducible strains and their -depressed and -basal mutants . Turnover numbers of FCE 22101 were between 0.7 and 1.5 molecules hydrolysed/min/enzyme molecule, compared with ranges of 0.5-40 for cefotaxime (950 for the Proteus vulgaris cephalosporinase) and 4400-22,000 for cephaloridine . FCE 22101 induced enzyme synthesis strongly below the MIC and antagonized labile weak inducers such as cefotaxime and mezlocillin . Like imipenem, but unlike newer cephalosporins, FCE 22101 had equal activity against inducible strains and derepressed mutants, and did not significantly select derepressed mutants from inducible populations . beta-Lactamase basal mutants of E . cloacae and C . freundii were four- to eight-fold more sensitive than inducible and derepressed organisms whereas beta-lactamase-basal, -inducible and -derepressed Proteeae and Serratia spp . were equally sensitive . This difference reflected the larger amounts of enzyme produced by the E . cloacae and C . freundii strains, rather than kinetic differences in enzyme activity.

Cleve Clin J Med, 1989 Mar-Apr, 56(2), 161 - 6
Comparative activity of newer antibiotics against gram-negative bacilli; Knapp CC et al.; The in vitro activities of cefoperazone, cefotaxime, ceftriaxone, ceftazidime, azlocillin, mezlocillin, piperacillin, ticarcillin/clavulanate, aztreonam, imipenem, and ciprofloxacin were concurrently determined against over 1,000 isolates of gram-negative bacilli from clinical specimens of patients at the Cleveland Clinic . Cephalosporins, penicillins, and aztreonam were active against species of Enterobacteriaceae other than Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae . Ceftazidime was the most active cephalosporin against Pseudomonas aeruginosa . Against the Enterobacteriaceae, the rank order of activity of penicillins was ticarcillin/clavulanate greater than piperacillin greater than mezlocillin greater than azlocillin . Against P . aeruginosa, the rank order of activity of penicillins was piperacillin greater than ticarcillin/clavulanate greater than azlocillin greater than mezlocillin . Aztreonam was less active v P . aeruginosa than ceftazidime, cefoperazone, or piperacillin . The most active antimicrobials against all isolates tested were imipenem and ciprofloxacin.

FEMS Microbiol Lett, 1989 Mar, 49(1), 107 - 10
The structure of the lipopolysaccharide core region of Citrobacter 027; Romanowska E et al.; The structure of Citrobacter 027 lipopolysaccharide core has been established using sugar and methylation analyses and 1H-NMR spectroscopy, and was shown to be identical to the core described recently in PCM 1487 strain which represents a separate serotype in Citrobacter genus.

J Infect, 1989 Mar, 18(2), 171 - 3
Citrobacter freundii bacteraemia presenting as typhoid fever; Flegg PJ et al.; Citrobacter infections usually arise opportunistically in immunocompromised persons . We report the case of a young man in whom Citrobacter freundii caused a primary invasive illness similar to typhoid fever.

Antimicrob Agents Chemother, 1989 Mar, 33(3), 398 - 9
Interaction of cefpirome and a cephalosporinase from Citrobacter freundii GN7391; Satake S et al.; The interaction of cefpirome and a cephalosporinase from Citrobacter freundii, including hydrolysis and inhibition, was studied in comparison with those of cefotiam, cefotaxime, and ceftazidime . Cefpirome was hydrolyzed by the enzyme more rapidly at Vmax than were cefotaxime and ceftazidime . However, the low affinity of the enzyme for cefpirome caused a reduction in the hydrolytic rate of cefpirome at a low drug concentration (0.1 microM) . The high stability of cefpirome at a low concentration explains the high antimicrobial activity of the agent against cephalosporinase-producing bacteria.

Antimicrob Agents Chemother, 1989 Mar, 33(3), 382 - 6
Effects of beta-lactamases and omp mutation on susceptibility to beta-lactam antibiotics in Escherichia coli; Hiraoka M et al.; Four types of beta-lactamases consisting of a penicillinase type I (TEM-1), a penicillinase type II (OXA-1), a cephalosporinase of Citrobacter freundii, and a cephalosporinase of Proteus vulgaris were introduced into Escherichia coli MC4100 and its omp mutants, MH1160 (MC4100 ompR1) and MH760 (MC4100 ompR2), by transformation . Effects of the combination of the omp mutations and these beta-lactamases on the susceptibility of E . coli strains were studied with 15 beta-lactam antibiotics including cephalosporins, cephamycins, penicillins, imipenem, and aztreonam . The ompR1 mutant, MH1160, lacks OmpF and OmpC, and it showed reduced susceptibility to 11 of the 15 beta-lactam agents . The reduction in susceptibility to cefoxitin, moxalactam, and flomoxef was much greater than reduction in susceptibility to the other agents . When the ompR1 mutant produced the cephalosporinase of C . freundii, the susceptibility of the mutant to 12 of the 15 beta-lactam antibiotics decreased . The reduction in susceptibility of MH1160 to 10 of the 12 agents affected by the enzyme was two- to fourfold greater than that observed in MC4100 . Such a synergistic effect was also observed with the cephalosporinase of P . vulgaris and ompR1 mutation against six cephalosporins, moxalactam, and aztreonam.

Prikl Biokhim Mikrobiol, 1989 Mar-Apr, 25(2), 278 - 85
{Determination of 3,4-dioxyphenyl-L-alanine by spectrophotometric and chromatographic methods in enzymatic synthesis using microbial cells}; Voyvodov KI et al.; A possibility of using the ninhydrin reaction for 3,4-dihydroxyphenyl-L-alanine (DOPA) determining during the synthesis from pyrocatechol and ammonium pyruvate was verified by using free and immobilized cells of Citrobacter freundii, st . 62 . Spectrophotometric assay was performed at the adsorption maximum for the DOPA-ninhydrin complex at 390 nm . DOPA can be reliably quantified in the presence of all components at 20-fold and greater dilution of the reaction mixture . A high-sensitive quantitative assay of the reaction mixture was developed based on phase-reversed HPLC . A quantitative correlation was observed between spectrophotometric and chromatographic assays . The assays were employed to study in detail the initial period and equilibrium of DOPA synthesis and its characteristic features, which made it possible to construct a kinetic model of the process.

Berl Munch Tierarztl Wochenschr, 1989 Mar 1, 102(3), 93 - 5
{The rapid identification of E . coli by the detection of 3 enzymes}; Weber A et al.; 232 isolates of gram-negative, oxidase-negative bacteria, isolated from various samples of different animal species, were tested with help of RAPIDEC coli for the production of beta-glucuronidase, beta-galactosidase and indole . The test correctly identified 164 of 175 E . coli strains (sensitivity 93.7%) and correctly indicated that 57 of 57 isolates of the family Enterobacteriaceae (7 Citrobacter sp., 18 Enterobacter sp., 16 Klebsiella sp., 10 Proteus sp., 2 Providencia sp . and 4 Salmonella sp.) were not E . coli (specificity 100%).

J Clin Pharm Ther, 1989 Feb, 14(1), 21 - 8
Microbial contamination of cosmetics and personal care items in Egypt--eye shadows, mascaras and face creams; Abdelaziz AA et al.; We examined a total of 150 samples, including 27 eye shadows, 27 mascaras and 96 face creams, for their microbial contents . Mascaras were generally more contaminated than eye shadows . More than 75% of the examined eye shadows contained fewer than 100 c.f.u./g aerobic bacterial count compared to 63% of the mascaras examined . Viable bacteria were not recovered from 61% and 48% of the eye shadows and mascaras respectively . While 4% of the eye shadows were heavily contaminated (contained more than 10(4) c.f.u./g), 15% of the mascaras were as heavily contaminated (with more than 10(4) c.f.u./ml of bacteria) . Face creams were generally more heavily contaminated than eye shadows and mascaras . More than 70% of the examined creams contained more than 100 c.f.u./g of bacteria compared to 23% and 37% of eye shadows and mascaras respectively . Only 5% of the face creams were heavily contaminated . However, 27% of the creams were contaminated with more than 10(3)-10(4) c.f.u./g of bacteria compared to none in this range for both eye shadows and mascaras . Qualitative tests for detection of hazardous bacteria showed that none of the eye shadows were contaminated with any of those micro-organisms . Out of nine items of a specific brand of mascara, three isolates of Pseudomonas aeruginosa, one isolate of Citrobacter freundii and one isolate of Klebsiella pneumonia were detected . Among the creams, two brands showed the highest contamination levels with more than 85% of the tested samples containing more than 10(3) c.f.u./g fungi and at least 10(4) c.f.u./g bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Immun, 1989 Feb, 57(2), 649 - 52
Citrobacter freundii produces an 18-amino-acid heat-stable enterotoxin identical to the 18-amino-acid Escherichia coli heat-stable enterotoxin (ST Ia); Guarino A et al.; We purified and sequenced the heat-stable enterotoxin produced by Citrobacter freundii . The toxin was detected during purification by reaction with monoclonal antibody to Escherichia coli heat-stable enterotoxin . The C . freundii toxin amino acid sequence was identical to that of the 18-amino-acid heat-stable enterotoxin (STa) produced by toxigenic E . coli.

South Med J, 1989 Feb, 82(2), 262 - 6
Initial antibiotic therapy for alligator bites: characterization of the oral flora of Alligator mississippiensis; Flandry F et al.; An open thumb fracture resulting from an alligator bite became infected with Aeromonas hydrophila, Enterobacter agglomerans, and Citrobacter diversus . The patient was treated by surgical debridement and antibiotic therapy . We obtained cultures from the mouth of ten alligators to characterize their oral flora . Initial empiric therapy after alligator bites should be directed at gram-negative species, in particular, Aeromonas hydrophila and anaerobic species including Clostridium . Of the numerous fungi that were isolated, none has been reported to result in wound infection after alligator bites.

Int J Food Microbiol, 1989 Feb, 8(1), 35 - 46
The microbial ecology of soybean soaking for tempe production; Mulyowidarso RK et al.; Soybeans soaked in tap water for 24 to 36 h at 20, 30 or 37 degrees C underwent a natural fermentation that was characterized by the growth of microorganisms to 10(8)-10(10) cfu/ml (depending on temperature) and a reduction of pH from 6.5 to 4.5 . Lactobacillus casei, Streptococcus faecium, Staphylococcus epidermidis and Streptococcus dysgalactiae dominated the fermentation but, significant contributions were also made by Klebsiella pneumoniae, Klebsiella ozaenae, Enterobacter cloacae, Enterobacter agglomerans, Citrobacter diversus and Bacillus brevis, and the yeasts Pichia burtonii, Candida didensiae and Rhodotorula rubra . Fermentation of surface-decontaminated beans in sterile water with pure cultures of these isolates showed L . casei, Strep . faecium and Staph . epidermidis to be the main species responsible for the pH reduction . Soybeans were the main source of microorganisms for the fermentation . Boiled beans did not undergo an acid fermentation.

J Wildl Dis, 1989 Jan, 25(1), 124 - 5
Concurrent infection of a Patas monkey (Erythrocebus patas) by Citrobacter freundii and Trichuris trichiura; Ocholi RA et al.; Concurrent infection of Citrobacter freundii and Trichuris trichiura in a Patas monkey (Erythrocebus patas) is reported . A synergistic effect of both organisms contributing to host mortality in this case is suggested.

Am J Perinatol, 1989 Jan, 6(1), 49 - 54
Sepsis with Citrobacter diversus in sick newborns; Giacoia GP et al.; Citrobacter diversus has been increasingly recognized as a cause of life-threatening neonatal meningitis with frequent abscess formation . This condition is associated with high mortality and extremely poor prognosis . We report our experience with C . diversus septicemia without meningitis in critically ill newborns . Thirteen patients with mean birthweight 1530 +/- 925 gm and mean gestational age 31.3 +/- 3.5 weeks were affected . They were compared with a group of infants affected by Escherichia coli sepsis, matched for weight, gestational age, and age at diagnosis . The groups did not differ in the incidence of perinatal complications, peripheral white blood cells, platelet count, and death rate . Hypotension was more frequently found in E . coli sepsis (p less than 0.05) . All C . diversus isolates were resistant to gentamicin but sensitive to cephalosporins . C . diversus has become the most common nosocomial pathogen in our unit . Plasma profile analysis suggests that two different strains of C . diversus were involved in the outbreak reported here . Therapy for suspected C . diversus septicemia should include cephalosporins whenever resistance to aminoglycosides is demonstrated.

Respiration, 1989, 55(3), 189 - 92
Septic pulmonary embolization caused by Citrobacter diversus; Wyzan D et al.; Citrobacter diversus is an unusual human pathogen . This organism has never been reported as a cause of septic pulmonary embolization . We report a case of septic pulmonary embolization caused by C . diversus in a relatively healthy young woman following an otherwise uncomplicated cesarean section.

Arzneimittelforschung, 1989 Jan, 39(1), 26 - 30
In vitro and in vivo antibacterial activity of the new semisynthetic cephalosporin cefpirome; Mitsukude M et al.; Cefpirome (HR 810), a new semisynthetic cephalosporin derivative, was found to have a broad antibacterial spectrum against gram-positive and gram-negative bacteria . Against Staphylococcus aureus, cefpirome was more active than not only cefotaxime and ceftazidime but also cefotiam . Against gram-negative bacteria, especially, Enterobacter cloacae and Citrobacter freundii, it was also more active than the other antibiotics tested, but against Pseudomonas aeruginosa, it was less active than ceftazidime . Cefpirome was stable to hydrolysis by the common plasmid mediated beta-lactamases and was stable to the action of chromosomal cephalosporinases . But it was slightly hydrolyzed by both Rms 213 mediated penicillinase and oxyiminocephalosporinases produced by Proteus vulgaris and Pseudomonas cepacia . When cefpirome was administered subcutaneously to mice experimentally infected with Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa, its efficacy well reflected its in vitro potency.

Drugs Exp Clin Res, 1989, 15(3), 119 - 23
Microbiological characterization of dactimicin: antibacterial activity towards gram-positive and gram-negative bacteria; Stefani S et al.; Dactimicin is the first aminoglycoside antibiotic of Dactylosporangium origin, consisting of a pseudo-disaccharide and an amino acid . It has also a formimidoyl moiety instead of the deoxystreptamine found in other aminoglycosides . The authors considered the antibacterial activity of dactimicin compared with amikacin, gentamicin and the fortimicins against Gram-positive and Gram-negative bacteria . Dactimicin showed remarkable antibacterial activity against all strains tested: in particular the MIC90 values ranged from 2 mg/l for Citrobacter sp . to 32 mg/l for Proteus sp . Methicillin-resistant staphylococci were poorly susceptible to all aminoglycosides tested, while dactimicin showed good activity against the methicillin-susceptible strains . MBCs and killing curves indicated that this drug is rapidly bactericidal against all strains tested.

Drugs Exp Clin Res, 1989, 15(1), 1 - 10
Comparison of the in vitro and in vivo antibacterial activities of cefepime (BMY-28142) with ceftazidime, cefuzonam, cefotaxime and cefmenoxime; Masuyoshi S et al.; Cefepime (BMY-28142), a new semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefuzonam, cefotaxime and cefmenoxime . Cefepime showed a well-balanced, broad spectrum of activity against a number of clinical isolates collected in Japan . The activity of cefepime against Gram-positive bacteria was several times greater than that of ceftazidime, nearly comparable to cefotaxime and cefmenoxime, and slightly weaker than cefuzonam . Against Enterobacteriaceae, cefepime showed superior activity to the reference cephalosporins against Proteus inconstans, Providencia rettgeri, Morganella morganii, Citrobacter freundii and Enterobacter cloacae . The activity of cefepime against Pseudomonas aeruginosa was nearly comparable to that of ceftazidime . Cefotaxime, cefuzonam and cefmenoxime were substantially less active against P . aeruginosa . Cefepime was more stable than cefuzonam, cefotaxime and cefmenoxime to various types of beta-lactamases from Gram-negative bacteria . The high in vitro activity of cefepime was reflected in its in vivo efficacy against experimental infections in normal and immuno-suppressed mice . Cefepime was the most effective among the cephalosporins tested against four Gram-negative bacterial infections.

Antimicrob Agents Chemother, 1989 Jan, 33(1), 63 - 70
Chromosomal beta-lactamase of Klebsiella oxytoca, a new class A enzyme that hydrolyzes broad-spectrum beta-lactam antibiotics; Arakawa Y et al.; The chromosomally encoded beta-lactamase gene of Klebsiella oxytoca E23004, a strain resistant to cefoperazone and aztreonam, was cloned and expressed in Escherichia coli HB101 . The molecular mass and pI of this enzyme were 28 kilodaltons and 7.4, respectively . Although the beta-lactamase of K . oxytoca hydrolyzed many cephalosporins, including broad-spectrum drugs, the nucleotide sequence and deduced amino acid sequence lacked homology with chromosomal class C beta-lactamase genes (ampC) of E . coli or Citrobacter freundii . Rather, about 45% nucleotide sequence homology and 40% deduced amino acid sequence homology were observed between the K . oxytoca beta-lactamase and TEM-1, a class A beta-lactamase which does not efficiently hydrolyze cephalosporins . Values of Km, relative Vmax, and relative Vmax/Km for the K . oxytoca beta-lactamase indicated that the enzyme is a penicillinase but that it can hydrolyze cefoperazone effectively and other broad-spectrum cephems weakly . Hence, the chromosomal beta-lactamase of K . oxytoca E23004 belongs to class A but differences in its amino acid sequence provide a broader spectrum of activity.

Appl Environ Microbiol, 1989 Jan, 55(1), 33 - 5
Comparison of methods for enumeration of selected coliforms exposed to ozone; Adams JC et al.; mT7 medium performed no better than m-Endo medium in enumerating cells of Escherichia coli and Citrobacter freundii exposed to ozone . Also, there was no difference in the plate count of heterotrophic bacteria in ozonated raw water determined on modified Henrici agar or R2A agar . Statistically significant differences were seen between bacteria and the type of water in which they were suspended during ozonation.

Berl Munch Tierarztl Wochenschr, 1989 Jan 1, 102(1), 4 - 5
{The rapid identification of Escherichia coli using Bactident E . coli}; Weber A et al.; 165 (93.7%) of 175 E . coli strains isolated from various materials of different animal species were correctly identified as E . coli with help of commercially available Bactident E . coli (E . Merck, D-6100 Darmstadt) . Further 52 strains of the family of Enterobacteriaceae (2x Providencia sp., 2x Salmonella sp., 7 Citrobacter sp., 9 Proteus sp., 15 Klebsiella sp., 17 Enterobacter sp.) were correctly not identified as E . coli by this test . Bactident E . coli is a suitable test for rapid identification of E . coli in veterinary bacteriology.

J Bacteriol, 1989 Jan, 171(1), 620 - 3
Nucleotide sequence of a citrate utilization gene from Citrobacter amalonaticus; Daimon H et al.; The chromosomal DNA fragment (BamHI-BglII fragment of 2,972 base pairs) conferring citrate utilization in Citrobacter amalonaticus ATCC 25405 was cloned and sequenced . Two genes (citA and citB) identified in the Cit+ determinant were found in a BamHI-BglII fragment from C . amalonaticus . Southern DNA-DNA hybridization experiments and the construction of Cit- mutants of C . amalonaticus showed that C . amalonaticus has a single copy of the cit gene on the chromosome.

Indian J Med Res, 1989 Jan, 89, 28 - 35
Characterization of a wide host range plasmid pANV-6 from Citrobacter diversus; Misra AK et al.; pANV-6 is a 5.85 kb, streptomycin resistant, high copy number plasmid isolated from a multi drug resistant clinical isolate of C . diversus by transformation in Escherichia coli C-600 . The plasmid was very stable, noncurable and could not be amplified with chloramphenicol . It was non-conjugative among Enterobacteriaceae hosts . Plasmid was transferred by transformation to several Gram negative and Gram positive hosts . These included Esch . coli, Serratia marcescens, Salmonella typhimurium, Klebsiella pneumoniae, Staphylococcus aureus, Corynebacterium glutamicum . From Staph . aureus it was transferred by conjugation to other Staph . aureus, Staph . epidermidis and Bacillus subtilis . Plasmid was incompatible with standard plasmids belonging to incompatibility groups H1, H2 = S,J,P and T of coliform bacteria . Plasmid has one site for restriction enzyme EcoRI and Pst I, three for Bgl 1 and non for Bgl 1, Bam HI, Hind III and X ba I.

J Med Microbiol, 1989 Jan, 28(1), 59 - 67
Invasion of Vero cells by Salmonella species; Barrow PA et al.; The invasiveness of Salmonella strains for Vero cells was studied by quantitative bacteriology; the technique was more sensitive than phase contrast microscopy . All of 59 Salmonella strains, of 19 different serotypes, were more invasive than Escherichia coli K12 . Three strains of Shigella were as invasive as most of the Salmonella strains whereas 29 strains of E . coli, two of Proteus, three of Klebsiella and one of Serratia were much less invasive . Two Citrobacter strains exhibited intermediate invasiveness . Eleven Salmonella strains were also shown to be invasive in HeLa, int 407, bovine kidney, chick kidney and chick embryonic fibroblast cells . The difference between invasive and non-invasive organisms was apparent irrespective of the numbers of bacteria in contact with Vero cells or the duration of bacteria-cell contact . There was little intracellular multiplication of S . typhimurium in Vero cells . Unlike the situation with Shigella, incubation of Salmonella or Salmonella-cell mixtures at 41 degrees C, 22 degrees C or 0 degree C had little effect on invasiveness . Non-viable Salmonella organisms were non-invasive . Incubation of Vero cells with cholera toxin, dinitrophenol, iodoacetic acid, cytochalasin B or D-mannose did not substantially reduce invasiveness . Virulence-associated plasmids were not essential to invasion by S . typhimurium, S . gallinarum or S . pullorum . Neither somatic antigens nor mannose-sensitive haemagglutinins were essential to the invasiveness of an S . infantis strain, but an additional factor, eliminated by N-methyl, N-nitro, N-nitrosoguanidine mutagenesis did contribute to invasiveness.

Z Versuchstierkd, 1989, 32(1), 49 - 56
Can the association of athymic mice (Han:NMRI-nu) with Staphylococcus sciuri prevent infection with Staphylococcus aureus? Experiences from a field study; Wullenweber-Schmidt M et al.; An attempt was made to prevent the introduction of Staphylococcus aureus into a newly established colony of Han:NMRI-nu mice by means of preassociation with the rodent-specific Staphylococcus sciuri . Despite the successful colonization of the mice with S . sciuri the establishment of S . aureus into the colony was not impeded, and abscesses were observed with an increasing frequency until the end of the study . Random samples revealed the phage pattern 3A/3C/55/71 or very similar ones . A caretaker was identified as a possible vector of transmission, since he was found to be colonized with this S . aureus phage type previous to the outbreak . Finally, the later occurrence of Citrobacter freundii and Pseudomonas aeruginosa serovar P10 in the colony led to the decision to give it up after 21 months of existence.

Acta Microbiol Pol, 1989, 38(2), 159 - 70
Genetic properties of plasmids isolated from pathogenic strain of Citrobacter freundii; Morzejko E et al.; It was found that Citrobacter freundii SLJ10 strain was an etiological factor of swine diarrhoea in North Poland . This strain harboured a plasmid aggregate consisting of two plasmids-pEM4 responsible for virulence and pEM6 for selective advantage of the strain, determining resistance to tetracycline and production of bacteriocin . These two plasmids cooperated in conjugal transfer and formed an infective block of genetic information, which could be transferred to other strains of Enterobacteriaceae and cause their virulence.

Int J Food Microbiol, 1988 Dec 31, 7(4), 287 - 97
A conductance medium to distinguish between Salmonella and Citrobacter spp; Ogden ID; Published methods for detecting Salmonella by conductance methods yield some Citrobacter spp . as false positives . A medium is described which, when used in conjunction with selenite-cystine/trimethylamine oxide/mannitol (SC/T/M) resolves this difficulty . It is based on the ability of Salmonella to decarboxylate lysine in the presence of selenite (4 g/l), after pre-enrichment in buffered peptone water supplemented with glucose and lysine for 7-17 h . Salmonella produced a conductance change of 250-400 microS in 24 h with a maximum rate of conductance change of 10-15 microS/10 min . 299 samples were tested and the only false positives were due to Hafnia alvei which gave no conductance response in the SC/T/M medium . Using both media in a two tube system would lead to a rapid clearance of Salmonella negative samples.

Antimicrob Agents Chemother, 1988 Dec, 32(12), 1896 - 8
Antibacterial activities of cefpodoxime, cefixime, and ceftriaxone; Knapp CC et al.; Cefpodoxime, cefixime, and ceftriaxone inhibited Branhamella catarrhalis at less than or equal to 1 microgram/ml, beta-hemolytic streptococci at less than or equal to 0.25 microgram/ml, Neisseria meningitidis at less than or equal to 0.06 microgram/ml, and Haemophilus influenzae (other than beta-lactamase-negative, ampicillin-resistant isolates) at less than or equal to 0.12 microgram/ml . The MICs for 50% of isolates of the family Enterobacteriaceae other than Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae were less than or equal to 1 microgram/ml for all three cephalosporins . The MICs of each cephalosporin for 90% of staphylococci, enterococci, and Pseudomonas aeruginosa isolates were greater than 16 micrograms/ml . Inoculum effects were noted with cefpodoxime and cefixime with beta-lactamase-positive H . influenzae.

Mol Gen Genet, 1988 Dec, 215(1), 176 - 80
A selection cartridge for rapid detection and analysis of spontaneous mutations including insertions of transposable elements in Enterobacteriaceae; Raabe T et al.; We present a method that allows positive selection and rapid analysis of mutations in Enterobacteriaceae . Mutations are detected in a 2630 bp selection cartridge inserted in two different bacterial multicopy plasmid vectors . Spontaneous mutations in Escherichia coli, Enterobacter cloacae and Citrobacter freundii include insertions, deletions and point mutations . The small size of the target sequence facilitates rapid analysis of DNA rearrangements by cleavage with restriction enzymes and of any type of mutation by DNA sequence analysis . While in E . coli insertions of the mobile elements IS1, IS2 and IS5 were readily found, insertions of putative new transposable elements were detected in Enterobacter cloacae . The selection cartridge can thus serve as a tool for studying the spectrum of insertion mutations in Enterobacteriaceae and probably other Gram-negative bacteria, and the dependency of this spectrum on physiological and environmental factors and the host's genetic background can be investigated.

Zh Mikrobiol Epidemiol Immunobiol, 1988 Dec, (12), 21 - 6
{Protective properties of Vi-antigen preparations as dependent on their adhesin content}; Alliluev AP et al.; Adhesins contained in the preparation of Vi-antigen have been found to enhance its immunogenic and protective properties . In the preparations of Vi-antigen obtained from Salmonella typhi and Citrobacter freundii the presence of two antigenic determinants has been revealed . One of them is associated with the Vi-receptor and the other determinant, with adhesin . Both determinants take part in the protection of mice from Salmonella infection.

Jpn J Antibiot, 1988 Nov, 41(11), 1600 - 22
{Antibacterial activities of monobactams against fresh clinical isolates}; Deguchi K et al.; Antibacterial activities of monobactam antibiotics (carumonam (CRMN) and aztreonam (AZT} against Gram-negative bacilli isolated from inpatients in the latter half of 1987 were investigated using penicillin (PC: piperacillin (PIPC}, cephems (CEPs: ceftazidime (CAZ), cefotaxime (CTX), latamoxef (LMOX), cefsulodin (CFS}, carbapenem (imipenem (IPM} and pyridonecarboxylic acids (norfloxacin (NFLX) and ofloxacin (OFLX} as reference antibiotics . A total of 400 strains of 13 species, i.e . Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Pseudomonas aeruginosa and Haemophilus influenzae, were used as test strains . 1 . CRMN and AZT, both monobactam antibiotics, were roughly comparable in their activities and no resistant strain to these antibiotics were found among isolates of E . coli, Klebsiella spp., Proteus spp., M . morganii, P . rettgeri or H . influenzae and few resistant strains were observed among isolates of S . marcescens . On the other hand, isolates of C . freundii, Enterobacter spp . and P . aeruginosa included rather numerous strains resistant to the monobactam antibiotics . Among these cases, whereas R strains, i.e . resistant strains showing MICs greater than or equal to 50 micrograms/ml, accounted for a large proportion of strains resistant to PC and CEPs, I strains, i.e . intermediately resistant strains showing MICs between 12.5 and 25 micrograms/ml, accounted for a large proportion of strains resistant to the monobactam antibiotics . 2 . Strains resistant to PIPC, a PC, were detected with high and more or less uniform frequencies over the entire spectrum of the isolates examined . 3 . Antibacterial activities of CEPs varied against different bacterial species . While strains resistant to CTX, CAZ and LMOX were commonly detected with high frequencies among isolates of C . freundii, Enterobacter spp . and S . marcescens, large percentages of LMOX-resistant strains of C . freundii and Enterobacter spp . were of the I type . CTX-resistant strains were also found among isolates of P . vulgaris and M . morganii . Proportions of CEP-resistant strains of P . aeruginosa were 28% for CFS and 12% for CAZ . 4 . No or few strains among the isolates of 13 species investigated were resistant to IPM, a carbapenem antibiotic, which showed the most stable antibacterial activity, but it was less active than monobactam antibiotics and CEPs against Klebsiella spp., P . mirabilis and H . influenzae.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimicrob Agents Chemother, 1988 Nov, 32(11), 1666 - 75
In vitro activity of E-1040, a novel cephalosporin with potent activity against Pseudomonas aeruginosa; Neu HC et al.; The in vitro activity of E-1040 {(6R,7R)-3-{(4-carbamoyl-1-quinuclidinio)methyl}-7-{2-(5-amino-1,2 ,4- thiadiazol-3-yl)-(Z)-2-methoxyiminoacetoamido}-8-oxo-5-thia- 1- azabicyclo(4,2,0)oct-2-ene-2-carboxylate}, a novel cephalosporin, was compared with that of ceftazidime, cefpirome, cefepime, imipenem, and gentamicin . E-1040 inhibited 50% of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus and Neisseria species at less than or equal to 0.25 microgram/ml, and the MIC for 90% of strains tested ranged from 0.06 to 2 micrograms/ml . It was two- to fourfold more active than ceftazidime and similar in activity to cefepime and cefpirome . It inhibited Enterobacter, Citrobacter, Serratia, and Morganella species that were resistant to ceftazidime . E-1040 inhibited imipenem-, piperacillin-, aztreonam-, and tobramycin-resistant P . aeruginosa . It was less active against Xanthomonas maltophilia and P . cepacia but inhibited other Pseudomonas species . The activity of E-1040 against staphylococci and hemolytic streptococci was similar to that of ceftazidime, but E-1040 was less active than cefepime and cefpirome . It did not inhibit Bacteroides spp . There was no inoculum effect or medium effect, and MBCs were within a dilution of MICs . Plasmid beta-lactamases TEM-1, TEM-2, TEM-3 (CTX-1), SHV-1, Staphylococcus aureus, PSE, and CARB did not hydrolyze E-1040 . Chromosomal beta-lactamases P99 and K-1 did not hydrolyze E-1040; E-1040 had poor affinity for these enzymes, with a Ki of greater than 100 microM.

Jpn J Antibiot, 1988 Nov, 41(11), 1623 - 34
{Susceptibility of clinically isolated strains to aztreonam}; Daimon Y; In vitro antibacterial activities of aztreonam (AZT) and cephems against clinically isolated 334 strains were investigated . The results obtained in the study are summarized as follows: 1 . AZT showed excellent antibacterial activities against clinically isolated 334 strains . 2 . AZT showed potent activities against Escherichia coli, Klebsiella pneumoniae, Proteus spp., Enterobacter aerogenes and Citrobacter freundii . 3 . Antibacterial activities of AZT were superior against Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa to those of cephems.

Eur J Biochem, 1988 Nov 1, 177(2), 395 - 401
Tyrosine phenol-lyase from Citrobacter intermedius . Factors controlling substrate specificity; Faleev NG et al.; L-Amino acids are competitive inhibitors of tyrosine phenol-lyase from Citrobacter intermedius . For non-branched amino acids the correlation exists between -RTlnKi and side-chain hydrophobicity . Aspartic and glutamic acids are anomalously potent inhibitors taking into account low hydrophobicity of their side chains . This suggests the presence of an electrophilic group in the active site which interacts with the terminal carboxylic group of aspartic or glutamic acids . Tyramine, beta-phenylethylamine and tryptamine do not display detectable inhibition . The esters and amides of aromatic L-amino acids, D-phenylalanine and D-tryptophan are competitive inhibitors . The enzymatic isotope exchange of the alpha-proton in 2H2O was observed only in the case of L-amino acids . For L-phenylalanine and L-tryptophan it was shown to proceed with complete retention of configuration . The substrate specificity of tyrosine phenol-lyase is controlled during the stage of phenol elimination . The OH group in the para position of the ring is necessary for this stage to proceed . The same stage is also sensitive to the steric parameters of the substituent in the ring which ensures the second factor of control . When all the requirements of substrate specificity are fulfilled (L-tyrosine, 3-fluoro-L-tyrosine), the 'key' phenol-elimination step is not the rate-limiting one, the reaction velocity being determined by the preceding alpha-proton abstraction.

Lab Anim, 1988 Oct, 22(4), 335 - 6
An epizootic infection of Citrobacter freundii in a guineapig colony: short communication; Ocholi RA et al.; An epizootic infection of Citrobacter freundii in a guineapig colony is reported . From 1300 guineapigs maintained in a colony, a total of 115 guineapigs died . Lesions found postmortem were suggestive of acute pneumonia and enteritis . Citrobacter freundii was consistently isolated from necropsy specimens of lung, liver, spleen and intestines of the animals . The source of infection was not ascertained.

Jpn J Antibiot, 1988 Oct, 41(10), 1407 - 17
{Clinical laboratory approach for estimating effective administrative dose of cefuzonam . Evaluation of disc susceptibility test and its interpretation system}; Uete T et al.; In vitro activities of cefuzonam (CZON) against 273 clinical isolates were studied through the evaluation of MIC's and the results of disc susceptibility test . The MIC's were determined using the agar dilution method at an inoculum level of 10(6)CFU/ml . The MIC80's of CZON against Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae and Citrobacter spp . were less than 0.20 microgram/ml . The MIC80's against Serratia marcescens and Enterobacter aerogenes were both 6.25 micrograms/ml, and that against Pseudomonas aeruginosa was 100 micrograms/ml . The MIC80's against Staphy-lococcus epidermidis were 25 and 6.25 micrograms/ml, respectively . Approximately 70% of strains of S . aureus were inhibited at concentrations less than 1.56 microgram/ml . For the interpretation of the CZON Showa 30 micrograms disc susceptibility test a 4 category system was used . In the 4 category system for Showa disc containing CZON, the following classification 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 less than 60 micrograms/ml . Reliability of the CZON disc tests in estimating approximate MIC values was studied using Showa 30 micrograms discs and discs prepared in this laboratory containing 1-10 micrograms CZON . A good negative correlation was observed between inhibitory zone diameters and MIC's, showing the reliability of the disc method . The results of the test using Showa 30 micrograms disc against various clinical isolates were accurately classified into the 4 groups except those against P . aeruginosa . Some strains of P . aeuruginosa showed false positive results, exhibiting relatively larger inhibitory zone diameters compared with MIC's against these organisms . As CZON is not effective against P . aeruginosa a much better overall correlation between MIC's and the disc test would result when P . aeruginosa was excluded . With Showa 30 micrograms discs of various cephalosporins, sub-classification of strains with MIC less than 3 micrograms/ml cannot be achieved . In this study, however, it was demonstrated that differentiation of strains with MIC's less than 0.5-1.56 micrograms/ml was possible when discs containing 1-10 micrograms of CZON were used . According to recent concepts on pharmacokinetics for antibiotics including 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagn Microbiol Infect Dis, 1988 Oct, 11(2), 109 - 15
Bacteriological studies with ampicillin/sulbactam on selected strains of gram-negative bacteria; Bello H et al.; Antibacterial activity of sulbactam or ampicillin alone and in combination on ampicillin-resistant, beta-lactamase-producing Gram-negative bacteria (Citrobacter freundii and Escherichia coli) was studied . Inhibition of beta-lactamase activity by sulbactam was investigated using intact and disrupted cells . Minimal inhibitory concentrations of ampicillin were high but decreased significantly in the presence of sulbactam . Similar enzyme inhibition was observed with intact and disrupted bacterial cells, thus indicating efficient penetration by sulbactam into the periplasmic space . Bacterial killing was achieved in approximately 4 hrs with ampicillin/sulbactam at concentrations that neither killed nor inhibited the same strains when the drugs were used alone . Sulbactam was more effective against plasmid-cured strain of E . coli than the same plasmid-containing organism.

Biochemistry, 1988 Sep 20, 27(19), 7333 - 8
Mechanistic deductions from kinetic isotope effects and pH studies of pyridoxal phosphate dependent carbon-carbon lyases: Erwinia herbicola and Citrobacter freundii tyrosine phenol-lyase; Kiick DM et al.; The pH dependence of the kinetic parameters and primary deuterium isotope effects have been determined for tyrosine phenol-lyase from both Erwinia herbicola and Citrobacter freundii . The primary deuterium isotope effects indicate that proton abstraction from the 2-position of the substrate is partially rate-limiting for both enzymes . The C . freundii enzyme primary deuterium isotope effects {DV = 3.5 and D(V/Ktyr) = 2.5} are pH independent, indicating that tyrosine is not sticky (i.e., does not dissociate slower than it reacts to give products) . Since Vmax for both tyrosine and the alternate substrate S-methyl-L-cysteine is also pH independent, substrate binds only to the correctly protonated form of the enzyme . For the E . herbicola enzyme, both Vmax and V/K for tyrosine or S-methyl-L-cysteine are pH dependent, as well as both DV and D(V/Ktyr) . Thus, while both the protonated and unprotonated enzyme can bind substrate, and may be interconverted directly, only the unprotonated Michaelis complex is catalytically competent . At pH 9.5, DV = 2.5 and D(V/Ktyr) = 1.5 . However, at pH 6.4 the isotope effect on both parameters is equal to 4.1 . From these data, the forward commitment factor (cf = 5.2) and catalytic ratio (cvf = 1.1) for tyrosine and S-methyl-L-cysteine (cf = 2.2, cvf = 24) are calculated . Also, the Michaelis complex partition ratio (cf/cvf) for substrate and products is calculated to be 4.7 for tyrosine and 0.1 for S-methyl-L-cysteine.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochem J, 1988 Sep 15, 254(3), 885 - 90
Citrobacter diversus ULA-27 beta-lactamases . Improved purification and general properties; Amicosante G et al.; Two chromosome-encoded beta-lactamases have been purified from Citrobacter diversus ULA-27 . They exhibited slightly different isoelectric points (6.8 and 6.2) and very similar Mr values (congruent to 29,000) . Their specificity spectrum was rather wide, since they hydrolysed some cephalosporins with kcat: values similar to those observed with the best penicillin substrates . Cloxacillin, methicillin and imipenem were hydrolysed very slowly . Hydrolysis of azthreonam could not be detected.

Biochem J, 1988 Sep 15, 254(3), 891 - 3
Chromosome-encoded beta-lactamases of Citrobacter diversus . Interaction with beta-iodopenicillanate and labelling of the active site; Amicosante G et al.; Both forms of the chromosome-encoded beta-lactamase of Citrobacter diversus react with beta-iodopenicillanate at a rate characteristic of class A beta-lactamases . The active site of form I was labelled with the same reagent . The sequence of the peptide obtained after trypsin hydrolysis is identical with that of a peptide obtained in a similar manner from the chromosome-encoded beta-lactamase of Klebsiella pneumoniae.

J Antimicrob Chemother, 1988 Sep, 22(3), 299 - 306
Activity of temocillin and other penicillins against beta-lactamase-inducible and -stably derepressed enterobacteria; Yang Y et al.; MICs of temocillin, carbenicillin, ticarcillin, mezlocillin, piperacillin and ampicillin were determined for mutant series of Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, Morganella morganii and Serratia marcescens with inducible, stably derepressed or basal expression of chromosomal Class I beta-lactamases . Ampicillin was inactive (MIC greater than 256 mg/l) both against beta-lactamase-inducible organisms (except C . freundii) and their stably derepressed mutants, whereas basal mutants were sensitive (MIC 2-8 mg/l) . Carbenicillin, ticarcillin, mezlocillin, piperacillin (and ampicillin for C . freundii) were active against both inducible and basal organisms (MIC less than 16 mg/l), but inactive against the derepressed mutants (MICs usually greater than 64 mg/l) . Temocillin inhibited all the organisms, including the stably derepressed mutants, at 16 mg/l . Derepressed S . marcescens, M . morganii and Pr . vulgaris were as susceptible as the inducible strains and basal mutants . MICs of temocillin for derepressed mutants of E . cloacae and C . freundii were 4-16 fold above those for their inducible parent strains, but remained within the clinical range.

J Antimicrob Chemother, 1988 Sep, 22(3), 315 - 20
Antimicrobial activity of LY163892, an orally administered 1-carbacephem; Jones RN et al.; LY163892 was found to be similar to cefaclor and slightly superior to cephalexin in antimicrobial activity and spectrum . Bacteria with MIC50 less than or equal to 8.0 mg/l included Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Haemophilus influenzae, Branhamella catarrhalis, pathogenic Neisseria spp., oxacillin-susceptible staphylococci, and Streptococcus spp . Strains that produced plasmid-mediated beta-lactamases generally remained susceptible to LY163892 . LY163892 was found to be bactericidal in general, but its MICs for some bacterial strains were adversely affected by increased inocula.

Plasmid, 1988 Sep, 20(2), 127 - 36
The distribution and divergence of DNA sequences related to the Tn21 and Tn501 mer operons; Gilbert MP et al.; The mercury resistance (mer) operons of the Gram-negative bacterial transposons, Tn21 and Tn501, are phenotypically indistinguishable and have extensive DNA identity . However, Tn21 mer has an additional coding region (merC) in the middle of the operon which is lacking in Tn501 and there is also a discrete region of the mercuric ion reductase gene (merA) which differs markedly between the two operons . DNA fragment probes were used to determine the distribution of specific mer coding regions in two distinct collections of mercury-resistant (Hgr) Gram-negative bacteria . Colony blot hybridization analysis showed that merC-positive operons occur almost exclusively in Escherichia, although merC-negative operons can also be found in this genus . The merC-negative operons were found in Citrobacter, Klebsiella, and Enterobacter and in some Pseudomonas . Most of the Pseudomonas did not hybridize detectably with either of the two operons studied, indicating that they harbor an unrelated or more distantly related class of mercury resistance locus . Southern hybridization patterns demonstrated that the merC-positive mer operon is well conserved at the DNA level, whereas the merC-negative operons are much less conserved . The presence of merC also correlated with conservation of a specific variant region of the merA gene and with an antibiotic resistance pattern similar to that of Tn21 . Tn501 appears to be an atypical example of the merC-negative subgroup of Hgr loci.

Carbohydr Res, 1988 Aug 15, 179, 349 - 57
The structure of the O-specific polysaccharide chain from Citrobacter O23-lipopolysaccharide; Katzenellenbogen E et al.; The structure of Citrobacter O23-specific polysaccharide has been shown by sugar and methylation analyses of the native and chemically degraded polysaccharide and by 1H- and 13C-n.m.r . spectroscopy to consist of the tetrasaccharide repeating-units: ----4)-alpha-D-Man-(1----2)-alpha-D-Man-(1----2)-beta-D-Man- (1----3)-alpha-D-GalNAc-(1----, 80% of which are substituted by O-acetyl groups.

Arzneimittelforschung, 1988 Aug, 38(8), 1085 - 8
In vitro activity of the combination trimethoprim plus sulfamethoxazole compared with that of other chemotherapeutic agents; Focht J et al.; For many years now, the combination trimethoprim plus sulfamethoxazole (active ingredients of Bactrim) has proved to be an effective chemotherapeutic agent with a broad spectrum of antibacterial activity against both gram-positive and gram-negative organisms, including beta-hemolytic streptococci, staphylococci, pneumococci, Haemophilus influenza, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella, Enterobacter and Citrobacter . In this comparative study, the antibacterial activity of the combination against 2,229 gram-negative and 1,338 gram-positive strains encountered in domiciliary practice was tested and compared with that of other commonly used antimicrobials . Minimum inhibitory concentrations (MICs) were determined in microtitre plates using serial dilutions . With regard to the gram-negative strains, trimethoprim + sulfamethoxazole, with an MIC90 of less than 2 mg/l for most isolates, was the most active substance apart from norfloxacin . The combination also had a powerful inhibitory effect on gram-positive strains, the MIC90 being between 2 and 4 mg/l for all strains except Staphylococcus epidermidis.

Zh Mikrobiol Epidemiol Immunobiol, 1988 Aug, (8), 87 - 90
{The microbial factor in the chemiluminescence of the peripheral blood neutrophils of patients with suppurative surgical infection}; Belotskii SM et al.; The luminol-dependent chemiluminescence of neutrophils in the peripheral blood of 30 healthy adults and 39 patients with the local and generalized forms of purulent infection was studied . Nonstimulated chemiluminescence and the index of chemiluminescence stimulation in the presence of opsonized Staphylococcus aureus added in vitro were determined . The former characteristic was found to be directly and the latter one, inversely related to the concentration of S . aureus, Escherichia coli and Candida albicans, but not E . epidermidis, Pseudomonas aeruginosa or Citrobacter, in the primary focus . At the microbial concentration exceeding 10(4) cells/g of tissue, the former characteristic was essentially higher than the level of chemiluminescence in healthy persons . With the improvement of the general state of the patients and in the absence of microorganisms in the wound as the result of complex treatment this characteristic decreased to values comparable with the reaction of neutrophils in healthy persons.

Gene, 1988 Jul 30, 67(2), 203 - 11
Transcriptional regulation and gene arrangement of Escherichia coli, Citrobacter freundii and Salmonella typhimurium biotin operons; Shiuan D et al.; The bio operons of Citrobacter freundii and Escherichia coli K-12 (strain C600) were isolated by screening lambda banks for complementation of E . coli bio mutants . These were compared with the previously isolated bio operon of Salmonella typhimurium and previous data on E . coli K-12 . The restriction maps of the operon are very different in the three species, but no difference in gene order was found . Operator-promoter DNA, identified by repressible titration and by biotin-repressible transcription in E . coli, was sequenced and compared to the published E . coli K-12 sequence . In the segment previously identified as operator/bioB promoter, C . freundii and S . typhimurium DNA are identical and differ from E . coli only by 2 bp . The DNA to the right of this segment (indicated by previous data to be the bioA promoter of E . coli) has diverged in all three species, and only E . coli has a sequence resembling a consensus promoter.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 721 - 5
Amino acid sequence, active-site residue, and effect of suicide inhibitors on cephalosporinase of Citrobacter freundii GN346; Sawai T et al.; The structural gene for a cephalosporinase of Citrobacter freundii GN346 was sequenced . From the nucleotide sequence, the entire amino acid sequence of the mature enzyme with 361 amino acids and a molecular weight of 39,867 was determined . The active-site serine was directly confirmed to be serine 64 by studies in which the enzyme was labeled with dansylpenicillin . In investigations comparing the inhibitory effect of sulbactam (penicillanic acid sulfone) and cloxacillin sulfone on the cephalosporinase and on TEM-2-type penicillinase, sulbactam was found to be an effective progressive inhibitor but a poor competitive inhibitor for the cephalosporinase . The cephalosporinase and the inhibitor formed a long-lived complex with a half-life of 550 minutes . Cloxacillin sulfone could not inactivate the cephalosporinase progressively but irreversibly inactivated the penicillinase.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 752 - 60
Mechanism of inhibition of chromosomal beta-lactamases by third-generation cephalosporins; Charnas RL et al.; The kinetic interactions of the beta-lactamase from Enterobacter cloacae 908 R with ceftriaxone, cefotaxime, and ceftazidime have been examined in detail . With all of these cephalosporins, there is an initial rapid reaction involving opening of the beta-lactam that then decreases to a slower steady-state rate (kss) of beta-lactam hydrolysis (at 37 degrees C: ceftriaxone, kss = 0.044 s-1; cefotaxime, kss = 0.033 s-1; ceftazidime, kss = 0.011 s-1) . More than stoichiometric quantities of beta-lactam are cleaved during the rapid phase, during which there is accumulation of a transiently stable cephalosporin-enzyme complex whose rate of breakdown is slower than the overall rate of hydrolysis . Qualitatively similar behavior is observed with the E . cloacae M6300 beta-lactamase . These observations eliminate the possibility that the reaction follows a simple linear kinetic scheme . A branched kinetic scheme in which an initially formed acyl intermediate partitions between deacylation and elimination of the 3' substituent is proposed to explain the data . Investigations of the interaction of ceftriaxone with the chromosomally encoded beta-lactamases from Citrobacter freundii, Providencia rettgeri, Morganella morganii, Pseudomonas aeruginosa, and Escherichia coli show that the partitioning behavior of E . cloacae beta-lactamases is atypical . All of the data, however, clearly demonstrate that it is a physical impossibility for cephalosporin trapping to contribute to bacterial resistance phenotypes.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 879 - 84
Plasmid-mediated resistance to third-generation cephalosporins caused by point mutations in TEM-type penicillinase genes; Sougakoff W et al.; Infections due to strains of Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii resistant to third-generation cephalosporins have been observed recently in France and the Federal Republic of Germany . This resistance phenotype is due to the production of new plasmid-mediated, broad-substrate-range beta-lactamases designated TEM-3 to TEM-7 . DNA-DNA hybridization analysis with a probe specific for TEM-1 indicated that the corresponding genes blaT-3 to blaT-7 were variants of the structural genes for TEM-type beta-lactamases . In the present studies, a 2.5-kilobase BamHI plasmid DNA fragment encoding TEM-3 was cloned in E . coli, and the entire nucleotide sequence of blaT-3 was determined . The deduced amino acid sequence of TEM-3 differed in two positions from that of the TEM-2 enzyme: lysine (TEM-3) was substituted for glutamic acid (TEM-2) at residue 104 and serine (TEM-3) for glycine (TEM-2) at residue 238 in the numbering system of Ambler . Spontaneous mutants of TEM penicillinases with increased activity against third-generation cephalosporins were obtained in vitro by selection on cefotaxime or ceftazidime . It therefore appears that mutations in TEM-type beta-lactamases contribute to resistance to new-generation cephalosporins.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 860 - 6
Plasmid-mediated beta-lactamase (TEM-7) involved in resistance to ceftazidime and aztreonam; Gutmann L et al.; TEM-7, a novel TEM-type beta-lactamase (pI 5.41) encoded on a plasmid of approximately 85 kilobases, was found in a clinical isolate of Citrobacter freundii . Strains containing this enzyme exhibited decreased susceptibility to ceftazidime (64-fold) and aztreonam (16-fold) but not to other third-generation cephalosporins . Addition of a beta-lactamase inhibitor--clavulanic acid, sulbactam, or YTR 830--restored normal susceptibility to associated compounds such as ampicillin, piperacillin, ceftazidime, and aztreonam . DNA-DNA hybridization of an intragenic probe of TEM-1 occurred with a 19-kilobase EcoRI fragment of the plasmid encoding TEM-7 . A TEM-2 derivative, TEM-201, with characteristics similar to those of TEM-7 was selected spontaneously in the presence of ceftazidime in vitro.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 830 - 8
Inducible beta-lactamases: clinical and epidemiologic implications for use of newer cephalosporins; Sanders WE Jr et al.; The emergence of resistance to multiple beta-lactam antibiotics is a major problem in patients infected with organisms that characteristically produce inducible beta-lactamases--e.g., species of Pseudomonas, Enterobacter, Serratia, Citrobacter, indole-positive Proteus, and Providencia . Resistance has emerged in 14%-56% of patients infected with these organisms and treated with one of the newer cephalosporins . The emergence of resistance has been associated with clinical failure or relapse in 25%-75% of these patients . Combination therapy appears to have little impact on rates of resistance or its clinical consequences . Multiply resistant organisms have spread widely in some hospitals, and this trend has been correlated closely with the extent of use of the newer cephalosporins . The magnitude of the problem is frequently underestimated because many properly performed susceptibility tests fail to detect resistance when it is actually present and because some methods used to calculate rates minimize the impact of the emergence of resistance among organisms with inducible beta-lactamases.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 746 - 51
Hydrolytic rate at low drug concentration as a limiting factor in resistance to newer cephalosporins; Hiraoka M et al.; Hydrolysis kinetics of two cephalosporinases from Citrobacter freundii and Proteus vulgaris having different affinities for cefotaxime and ceftazidime was assessed in studies with cefotaxime, ceftazidime, BMY-28142, and imipenem . The two cephalosporinase genes were cloned into strains of Escherichia coli . The production of these cephalosporinases in strains of E . coli, as well as in the derepressed mutants of C . freundii and P . vulgaris, caused a decrease in susceptibility to the newer cephalosporins . The difference in the rate of hydrolysis at a 0.1 microM concentration of substrate adequately explains the difference in antibacterial activity between cefotaxime and BMY-28142 against E . coli strains with the two cephalosporinases . The results indicate that hydrolysis rate at low substrate concentration, rather than binding with beta-lactams, would be a limiting factor in resistance . The low affinity of cephalosporinases for BMY-28142 means high stability of the agent to the enzymes at low concentration . Furthermore, outer membrane permeability affects the susceptibility of E . coli to cephalosporins synergistically with hydrolysis by cephalosporinases.

J Med Microbiol, 1988 Jul, 26(3), 223 - 8
Ribosomal-RNA patterns of Escherichia coli, Salmonella typhimurium and related Enterobacteriaceae; Smith NH et al.; rRNA sequences are usually highly conserved among species . In Enterobacteriaceae we have shown that Salmonella typhimurium does not have an equivalent to the 23S rRNA of Escherichia coli but its 23S rRNA is cleaved in vivo into two smaller species . This cleavage appears to be a result of a difference between the S . typhimurium and E . coli rRNA sequences rather than to differences in ribonuclease activity . We have surveyed a wide range of Enterobacteriaceae for the presence or absence of 23S rRNA and found this rRNA species to be present in all strains of E . coli, Shigella and Citrobacter and all salmonellae examined except S . typhimurium . All S . typhimurium cultures, isolated at different times and from several different countries, lack an intact 23S rRNA . Thus, the presence or absence of this rRNA species is an excellent diagnostic characteristic for S . typhimurium.

J Biol Chem, 1988 Jun 5, 263(16), 7776 - 84
Sequence analysis, expression, and conservation of Escherichia coli uracil DNA glycosylase and its gene (ung); Varshney U et al.; The complete nucleotide sequence of the Escherichia coli ung gene is described . Transcription initiation and termination sites were determined by S1 nuclease and RNase mapping . The common prokaryotic -35, -10, and the ribosome binding site sequences are represented by TGTTCTGTA, TAAGCTA, and AGGAGAG at their respective locations . A putative hairpin transcription terminator structure is present at the major transcription terminator sites . The open reading frame of the ung gene codes for a protein of 229 amino acids (25,664 daltons) . The molecular weight, amino acid composition, and the N-terminal amino acid sequence of the uracil DNA glycosylase purified from E . coli cells match with the open reading frame of the ung gene . The protein sequence analysis shows that the N-terminal methionine is cleaved off in the mature protein . The in vitro transcription coupled translation of the ung gene directs the synthesis of a protein which comigrates with uracil DNA glycosylase . Also, the CNBr cleavage of the protein synthesized in vitro confirms the positions of the methionines deduced from the DNA sequence . The levels of ung gene expression remain constant up to the early stationary phase, but decline in the late stationary phase of the E . coli culture . The E . coli gene showed a strong sequence homology to Shigella, a weak sequence homology to Salmonella and Citrobacter, and a very weak sequence homology to Proteus genes . No sequence homologies were seen for Pseudomonas, Clostridium, Micrococcus, and several eukaryotic genomes.

Am J Clin Pathol, 1988 Jun, 89(6), 791 - 3
Evaluation of the IDS RapID SS/u system for rapid identification of urinary microorganisms; DeGirolami PC et al.; The accuracy of a new rapid identification system for common urinary pathogens was compared with that of conventional methods and of miniaturized 18-24-hour identification panels . The rapid system, RapID SS/u (Innovative Diagnostic System Inc., Atlanta, GA) is a non-growth-dependent micro-method that identifies selected gram-negative bacilli, gram-positive cocci, and yeasts in two hours by detection of constitutive enzymes acting on chromogenic substrates . A total of 185 representative clinical urinary isolates were tested, including 24 gram-positive cocci, 140 gram-negative bacilli, and 21 yeasts . Identifications by the rapid system were compared with the ones obtained by reference conventional methods for gram-positive cocci and yeasts . For gram-negative bacilli, identifications were compared with the ones obtained by MicroScan Combo Panel (American MicroScan, Mahwah, NJ), and all discrepancies were resolved by testing with API 20E (Analytab Products, Plainview, NY) . Overall, the RapID SS/u system correctly identified to genus 160 of 185 isolates (86.5%) . For 14 additional isolates (7.6%) the system provided probability overlap identifications that required further testing . Two (1%) isolates failed to be identified, and nine isolates (4.9%) were misidentified by the system . Discrepancies involved five strains of Citrobacter, one Enterobacter, one Morganella, and one Providencia species . The authors conclude that the RapID SS/u system provided rapid and accurate genus identification of most microorganisms commonly isolated from urine.

Appl Environ Microbiol, 1988 Jun, 54(6), 1564 - 9
Monoclonal antibodies which identify a genus-specific Listeria antigen; Butman BT et al.; Fifteen murine monoclonal antibodies (MAbs) which react specifically with a protein antigen found in all species of Listeria were developed and characterized . These MAbs were tested extensively by both enzyme-linked immunosorbent assay and Western blot (immunoblot) analyses for cross-reaction with non-Listeria organisms, such as Staphylococcus, Streptococcus, Citrobacter, Pseudomonas, and Salmonella species, and were found to be nonreactive . The genus-specific antigen was identified as a heat-stable protein with a molecular weight in the range of 30,000 to 38,000 (under both reducing and nonreducing conditions), depending on the species of Listeria tested . In Listeria monocytogenes, L . innocua, L . ivanovii, and L . seeligeri the antigen has a molecular weight of approximately 30,000 to 34,000 . In L . grayi and L . murrayi it has a molecular weight of approximately 35,000 to 38,000 . In addition, several of the MAbs recognize lower-molecular-weight protein bands . There appear to be at least two groups of Listeria-specific MAbs based upon isotype and results of enzyme-linked immunosorbent assay and Western blot analyses . These MAbs have proven to be useful in the development of a diagnostic assay for Listeria species in food products.

Antimicrob Agents Chemother, 1988 Jun, 32(6), 922 - 4
Clinical isolate of Citrobacter freundii highly resistant to new quinolones; Aoyama H et al.; About 30% of 150 recent clinical isolates of Citrobacter freundii were resistant to greater than or equal to 3.13 micrograms of norfloxacin and ofloxacin per ml . Study of one quinolone-resistant strain for which the norfloxacin MIC was 100 micrograms/ml suggested that resistance was associated with both an altered A subunit of DNA gyrase and reduction in drug uptake accompanied by a decrease in an outer membrane protein.

Proc Natl Acad Sci U S A, 1988 Jun, 85(12), 4402 - 5
Specific insertion and deletion of insertion sequence 1-like DNA element causes the reversible expression of the virulence capsular antigen Vi of Citrobacter freundii in Escherichia coli; Ou JT et al.; Citrobacter freundii strain WR7004 reversibly expresses the virulence capsular antigen Vi, whose production is controlled by two distinct chromosomal loci, viaA and viaB . The rate of oscillation between the Vi-producing (Vi+) state and the Vi-nonproducing (Vi-) state in strain WR7004 ranges from 2 X 10(-4) to 7 X 10(-3) transitions per bacterium per generation . A similarly high conversion rate from Vi+ to Vi- occurs in Escherichia coli HB101 harboring pWR127, a plasmid that contains the 18-kilobase-pair (kb) viaB region cloned from WR7004 . However, the Vi- state in HB101 harboring pWR127 was so stable that transition to the Vi+ state was not detected (less than 10(-10) per bacterium per generation) . When pWR127 DNA derived from Vi- strains of HB101 harboring pWR127 was transformed in HB101 recipient, a small number of Vi+ transformants were seen among the transformants, which were predominantly Vi- . The viaB region consists of two EcoRI digestion fragments, A (8.6 kb) and B (9.4 kb) . A discrete 700- to 800-base-pair DNA element was found to be inserted in the EcoRI B fragment of the viaB region of pWR127 when derived from Vi- strains . However, no such DNA element was found in the pWR127 DNA isolated from Vi+ strains . This discrete DNA element inserts into a recombinational hot spot 1.1 kb from the end of the EcoRI B fragment and behaves as an insertion sequence 1 (IS1)-like element . The insertion of this IS1-like element in the viaB region thus disrupts expression of the Vi antigen . Restoration of Vi expression results when this element is excised.

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