Citrobacter

Biochemistry, 1988 May 31, 27(11), 4153 - 61
Structure elucidation of the core regions from Citrobacter O4 and O36 lipopolysaccharides by chemical and enzymatic methods, gas chromatography/mass spectrometry, and NMR spectroscopy at 500 MHz; Romanowska E et al.; Novel enterobacterial core oligosaccharides were isolated from Citrobacter O4 and O36 lipopolysaccharides, and their structures were determined by methylation analysis, Smith degradation and enzymatic degradations, gas chromatography/mass spectrometry, and two-dimensional phase-sensitive correlated, relayed coherence transfer, double-quantum, triple-quantum-filtered, and nuclear Overhauser effect (NOE) 1H NMR spectroscopy at 500 MHz . In the formulas, all hexose residues are D-hexopyranoses, and heptoses are L-glycero-D-manno-heptopyranoses; the alternative locations of the side-chain heptose and pyrophosphorylethanolamine (PPEtN) residues are marked by dashed lines; dOclA stands for 3-deoxy-D-manno-octulosonic acid . (formula; see text) Along with these complete cores, incomplete ones, lacking the hexosamine trisaccharides, occur in the lipopolysaccharides of both types . Qualitative NOE data were in good agreement with the minimum energy conformation of the above O36 oligosaccharide, calculated with the aid of the SUGAR program {Sundin, A., Carter, R . E., & Liljefors, T . (1988) J . Mol . Graphics (in press)}.

FEBS Lett, 1988 May 23, 232(2), 381 - 2
Crystallization and crystal data on tyrosine phenol-lyase; Demidkina TV et al.; Crystals of the apoenzyme of tyrosine phenol-lyase (EC 4.1.99.2), a pyridoxal 5'-phosphate-dependent enzyme from Citrobacter intermedius, have been grown by vapor diffusion of an ammonium sulfate solution to a protein solution . The crystals belong to space group P2(1)2(1)2, with dimensions of a = 75.5 A, b = 138.4 A and c = 94.1 A and diffract up to 2.7 A resolution . The asymmetric unit contains one half of the enzyme tetrameric molecule . Two heavy-atom derivatives of the crystals have been obtained.

Transfusion, 1988 May-Jun, 28(3), 229 - 32
Kell blood group activity of gram-negative bacteria; Savalonis JM et al.; To understand better the relationships between blood-group antigens and bacterial constituents, examples of 23 gram-negative bacteria (representing the 10 genera Citrobacter, Edwardsiella, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia, and Shigella) were tested for the presence of Kl-like antigens by hemagglutination-inhibition (HAI) assays against both IgG and IgM anti-Kl . Saline-suspended whole organisms, cell-free culture media, and disrupted organisms were used to test for such antigens in, on, and secreted by the microorganisms examined . Disrupted organisms of an isolate of Shigella sonnei nonspecifically inhibited IgG anti-Kl as well as IgG antibodies of the specificities Kpb, Fya, S, and c . However, only Escherichia coli 0125:B15, subtype 12808, had specific K1-like activity (no activity with other IgG {(k, Kpb, Jka, Fya, S, c} and IgM {A, B, M, P1} antibodies) . Disrupted organisms inhibited IgM but not IgG anti-K1 in the HAI assay . A second subtype, E . coli 0125:B15, subtype 12809, exhibited no K1-like activity . These findings support the report of K1 activity in cell-free broth cultures of E . coli 0125:B15 (subtype unspecified) . Thus, although not all E . coli 0125:B15 possesses K1-like activity, the finding of such activity in at least one E . coli subtype confirms the idea that bacterial components may play a role in the production of naturally occurring antibodies directed against non-ABO red cell antigens.

Antimicrob Agents Chemother, 1988 May, 32(5), 671 - 7
In vitro activity of an oral iminomethoxy aminothiazolyl cephalosporin, R-3746; Chin NX et al.; The in vitro activity of R-3746, an iminomethoxy aminothiazolyl cephalosporin with a CH2OCH3 moiety at position 3, was compared with those of other antibiotics . R-3746 inhibited the majority of hemolytic streptococci (groups A, B, C, F, and G) and Streptococcus pneumoniae at less than 0.06 micrograms/ml, which was comparable to the activity of amoxicillin, 2- to 8-fold more active than cefixime, and 16- to 64-fold more active than cefaclor and cephalexin . Ninety percent of beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited at a concentration 0.25 micrograms/ml, but it was less active against Branhamella spp . It did not inhibit (MIC, greater than 16 micrograms/ml) enterococci, viridans group streptococci, or methicillin-resistant staphylococci . The MICs of R-3746 for 90% of strains tested for Escherichia coli; Klebsiella pneumoniae; Citrobacter diversus; Proteus mirabilis; and Salmonella, Shigella, and Yersinia spp . were less than or equal to 1 micrograms/ml . It was two- to eightfold less active than cefixime but was markedly superior to cefaclor, cephalexin, amoxicillin-clavulanate, and trimethoprimsulfamethoxazole . R-3746 inhibited 50% of Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Morganella spp., Providencia spp., Proteus vulgaris, and Serratia marcescens at less than or equal to 8 micrograms/ml . Pseudomonas spp . were resistant . Fifty percent of Clostridium spp . were inhibited by 0.5 micrograms/ml, but MICs for Bacteroides spp . were greater than 128 micrograms/ml . R-3746 was not appreciably hydrolyzed by most chromosomal and plasmid-mediated beta-lactamases.

Jpn J Antibiot, 1988 May, 41(5), 594 - 601
{In vitro synergy between cefotaxime and its main metabolite, desacetylcefotaxime}; Kobayashi S et al.; In vitro synergistic interaction between cefotaxime (CTX) and its main metabolite, desacetyl-cefotaxime (DCTX), against 7 species of clinical isolates (23-27 strains per species) was examined . Complete or partial synergy was noted with a 1:1 combination of CTX and DCTX against 22-78% of the Bacteroides fragilis, Staphylococcus aureus, Citrobacter freundii, Pseudomonas cepacia and Enterobacter cloacae isolates examined . Antagonistic effects of the drugs appeared against 11% of Proteus vulgaris and 4% of Serratia marcescens . When combined at various ratios by the checkerboard method and tested against B . fragilis, CTX and DCTX were found to act synergistically, and no antagonism occurred . The combined use of CTX and DCTX exhibited strong bactericidal activity against B . fragilis and inhibited bacterial regrowth . An experiment with concentrations of CTX and DCTX simulating human serum levels after intravenous administration also showed that the coexistence of DCTX augmented bactericidal activity of CTX against B . fragilis and brought inhibitory effects on bacterial regrowth . It is presumed from the present results that clinically applied CTX would have more potent effects than expected from in vitro sensitivity test data.

Antimicrob Agents Chemother, 1988 May, 32(5), 656 - 62
In vitro activity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones; Chin NX et al.; Lomefloxacin (SC-47111; NY-198) is a new difluoroquinolone agent . It inhibited 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Morganella morganii, Proteus vulgaris, Serratia marcescens, Salmonella spp., Shigella spp., Aeromonas spp., Yersinia spp., Haemophilus influenzae, and Neisseria gonorrhoeae at less than or equal to 2 micrograms/ml . Lomefloxacin inhibited 90% of Pseudomonas aeruginosa at 4 micrograms/ml . Lomefloxacin was equal in activity to norfloxacin against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, and Neisseria gonorrhoeae but was twofold less active against Proteus spp., Providencia spp., Serratia marcescens, Salmonella spp., and Shigella spp . Ofloxacin was generally 2- to 4-fold more active, and ciprofloxacin was 4- to 16-fold more active . Lomefloxacin inhibited Staphylococcus aureus, including methicillin-resistant isolates, but MICs for 90% of streptococcal species tested were 8 micrograms/ml . In the presence of 9 mM Mg2+, MICs for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa were increased, as they were when they were tested in urine . A single-step increase in resistance to eightfold above the MIC occurred at a frequency of less than 10(-10), but serial transfer of bacteria in the presence of the agent produced MIC increases . Lomefloxacin had activity and properties comparable to those of many of the new quinolones.

Pathol Biol (Paris), 1988 May, 36(5), 425 - 9
{Activity of 9 beta-lactam antibiotics combined with clavulanic acid or sulbactam against the strains of broad-spectrum beta-lactamase (CTX-1) producing Enterobacteriaceae isolated at the Henri Mondor Hospital}; Legrand P et al.; Minimal inhibitory concentrations (MICs) of seven cephalosporins: cefotaxime (CTX), ceftriaxone (CRO), ceftazidime (CAZ), latamoxef (MOX), cefoxitin (FOX), cefotetan (CTT) and CM 40876 (CM), of aztreonam (ATM) and imipenem (IPM) were evaluated by agar dilution with and without 5 mg/l of clavulanic acid (AC) or sulbactam (SB) for 28 strains isolated in 1986 (15 K . pneumoniae, 3 . K . oxytoca, 4 E . coli, 4 E . cloacae, 1 E . aerogenes and 1 C . freundii) . Comparatively to MICs of sensitive strains and to those of cured variants, MICs of these strains were very increased for CTX, CRO, ATM (mode MIC: 1 mg/l), and CAZ (2); weakly increased for MOX and CTT (0.25), and identical for IMP (0.12-0.25), CM (0.06) and FOX (2-4), except for Enterobacter and Citrobacter (64) . Association with AC or SB did not modify MICs of FOX, CM and IMP . For the other antibiotics, MICs were reduced by addition of AC: Klebsiella: 5 log2 for CTX and CRO, 4 for CAZ and ATM, 2 for MOX and CTT; E . coli: 4 log2 for CTX and ATM, 3 for CRO and CAZ, 1 for MOX and CTT; Enterobacter and Citrobacter 2 log2 for CTX, CRO, CAZ and ATM, 1 for MOX and CTT . With SB, decrease of MICs was two to for fold lesser than with AC . AC, and less efficiently SB, restored activity of CTX, CRO, CAZ and ATM on CTX-1 producing Enterobacteriaceae, particularly Klebsiella and E . coli . It was the same for MOX and CTT, weakly affected by this resistance . AC and SB had not effect on FOX, CM and IPM which remained active on these strains.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 May, 268(3), 306 - 17
Further differentiation of Enterobacteriaceae by means of siderophore-pattern analysis; Reissbrodt R et al.; By means of a combination of 5 siderophore bioassays using several indicator strains, genera, species and subspecies of Enterobacteriaceae can be further differentiated . Enterobactin, aerobactin and other siderophores produced can be detected . Each strain shows specific pattern which we called siderophore-pattern . It is easy to separate Morganella, Proteus, Providencia, Yersinia strains from the genera Salmonella, Shigella, Escherichia coli, Enterobacter, Citrobacter, Klebsiella, Serratia . Enterobacter agglomerans strains differ from other Enterobacter species with respect to their siderophore pattern . In Salmonella strains there are differences between the subspecies I and IV . Additionally the most strains of Salmonella subspecies I from nosocomial infections produced aerobactin, in the most cases determined by plasmids . Among Shigella strains different siderophore pattern exist according to other epidemiological markers . S . flexneri strains of serovar 6 produced contrary to the strains of other serovars enterobactin . By means of the siderophore-pattern analysis E . coli strains of serovars 01; 02; 018 can be further differentiated . E . coli 01:K1 strains containing the fimbrial antigen F11 produced aerobactin whereas the F9 strains did not . All Hafnia alvei strains produced a uniform siderophore pattern, different from all other members of the enterobacteriaceae family . With this aim Hafnia alvei strains can be easily separated under practical conditions.

J Hosp Infect, 1988 May, 11(4), 321 - 7
Prior antimicrobial therapy and resistance of Enterobacter Citrobacter and Serratia to third generation cephalosporins; Nicolle LE; During a 6-month period all inpatients from whom Enterobacter, Citrobacter or Serratia . had been isolated were reviewed and information on selected variables recorded . Two groups, one including 19 patients with organisms resistant to third generation cephalosporins and the other 111 patients with susceptible organisms were compared . In the initial analysis, the mean number of antimicrobials received in the prior 2 months was the variable most strongly associated with isolation of resistant organisms (2.6 +/- 1.5 vs 1.5 +/- 1.6; P = 0.002) . When patients who had received no antimicrobials were omitted from the analysis, the mean number of antimicrobials was similar (2.6 +/- 1.5 vs 2.3 +/- 1.5; P = 0.19) . Comparisons of antimicrobials received in the prior 2 months showed only cefoxitin (9/70 vs 7/19; P = 0.016) and cefotaxime (4/70 vs 5/19; P = 0.008) to be associated with isolation of resistant organisms . These data suggest that, at our institution, antimicrobial therapy with an extended spectrum cephalosporin is an important risk factor for subsequent acquisition of an organism resistant to third generation cephalosporins.

Bioorg Khim, 1988 May, 14(5), 697 - 700
{The structure of O-specific polysaccharide chains of lipopolysaccharides from Citrobacter 032 and Salmonella arizonae 064 (Arizona 29)}; Kocharova NA et al.; On the basis of acid hydrolysis, methylation, Smith degradation, selective cleavage with anhydrous hydrogen fluoride, and 13C NMR analysis, the repeating unit of the O-specific polysaccharide of Citrobacter O32 was concluded to have the following structure: (Formula: see text) . The repeating unit of the Salmonella arizonae O64 O-specific polysaccharide has the same structure lacking the O-acetyl group.

J Biol Chem, 1988 Apr 15, 263(11), 5217 - 23
Lipid A precursor from Pseudomonas aeruginosa is completely acylated prior to addition of 3-deoxy-D-manno-octulosonate; Goldman RC et al.; Inhibition of lipopolysaccharide (LPS) synthesis in Pseudomonas aeruginosa at the stage of incorporation of 3-deoxy-D-manno-octulosonate (KDO) caused accumulation of a lipid A precursor which contained all of the fatty acids present on the lipid A of mature LPS . The enzyme CTP:CMP-3-deoxy-D-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase) from P . aeruginosa is inhibited by the KDO analog alpha-C-{1,5-anhydro-8-amino-2,7,8-trideoxy-D-manno-octopyranosyl} carboxylate (I), and I is effectively delivered to P . aeruginosa following attachment by amide linkage to the carboxyl terminus of alanylalanine . Intracellular hydrolysis releases the free inhibitor (I) which then inhibits activation of KDO by CMP-KDO synthetase causing accumulation of lipid A precursor and subsequent growth stasis . The major lipid A precursor species accumulated was purified and found to contain glucosamine, phosphate, C12:O, 2OH-C12:O and 3OH-C10:0 (in ester linkage), and 3OH-C12:0 (in amide linkage) in molar ratios of 1:1:0.5:0.5:1:1 . Analysis of precursor by fast atom bombardment mass spectroscopy yielded a major ion (M - H)- of mass 1616 and fragments which were consistent with the structure of lipid A from P . aeruginosa . In contrast, Salmonella typhimurium, Escherichia coli, Citrobacter sp., Serratia marcescens, Enterobacter aerogenes, and Enterobacter cloacae all accumulated underacylated lipid A precursors which only contained 3-OH-C14:0, glucosamine, and phosphate . This difference and species-specific patterns of major and minor precursor species show that early steps in the assembly of lipid A are similar, but not identical in enteric and nonenteric Gram-negative bacteria.

J Clin Microbiol, 1988 Apr, 26(4), 719 - 25
Application of optical properties of the Vi capsular polysaccharide for quantitation of the Vi antigen in vaccines for typhoid fever; Stone AL et al.; The capsular polysaccharide of Salmonella typhi and of Citrobacter freundii (Vi) is a linear homopolymer of alpha 1,4-linked N-acetylgalactosaminuronic acid, variably O-acetylated at the C-3 position . Vaccines composed of Vi confer protection against typhoid fever with an efficacy of about 70%; Vi has recently been conjugated to proteins to increase its immunogenicity and effectiveness (I.L . Acharya, R . Tapa, V.L . Gurubacharya, M.B . Shrestha, C.U . Lowe, D.D . Bryla, R . Schneerson, J.B . Robbins, T . Crampton, B . Trollfors, M . Cadoz, D . Schulz, and J . Armand, N . Engl . J . Med . 317:1101-1104, 1987; K.P . Klugman, I . Gilbertson, H.J . Kornhof, J.B . Robbins, R . Schneerson, D . Schulz, M . Cadoz, and J . Armand, Lancet ii:1165-1169, 1987; S.C . Szu, A.L . Stone, J.D . Robbins, R . Schneerson, and J.B . Robbins, J . Exp . Med . 166:1510-1524, 1987) . Vi, however, cannot be measured by conventional colorimetric methods . Two optical techniques were adapted to quantitate Vi in vaccines . The first, Fourier-transformed infrared spectroscopy, was performed on salt-free, freeze-dried samples . The intensities of the absorbance peaks of Vi were proportional to the amount of Vi within the range of 0.25 to 2.0 mg . The amount of Vi was determined from integrated absorptions at the 1,235- or 1,417-cm-1 band . The second technique, spectrophotometric titration, was more sensitive than the Fourier-transformed infrared spectroscopy and could be performed on dilute solutions . The metachromatic effect of the reaction between the aromatic cationic dye acridine orange and the carboxyl groups of Vi was quantitative within +/- 2% in the range of 20 to 700 micrograms of Vi per ml . The accuracy of the titration of Vi in the vaccines was within +/- 8% . These two methods may be applicable to measure other capsular polysaccharides in vaccines.

Mikrobiyol Bul, 1988 Apr, 22(2), 164 - 71
{Microbiological analysis of well water samples in the rural areas near Ankara}; Yulug N et al.; The water from wells and running water in different rural parts of Ankara were analyzed microbiologically with the thought in mind that the use of unhealthy well water could cause infections, as shown in other cities . We found that of the 50 running water samples all (100%) were drinkable from the microbiological point of view regard to coliform bacteria and total germ count, while only 20 of the 150 well water samples (13.3%) met these standards . It was pointed out by the users that chlorination was carried out in only 22 of the wells (14.6%) and only irregularly; no coliform bacteria were found in water samples from these wells . In 117 well water samples (78%) 120 coliform bacteria strains were isolated, of these 80 were E . coli, 27 Enterobacter and 13 Citrobacter . All samples were analyzed for Giardia intestinalis cysts but found to be negative.

J Bacteriol, 1988 Apr, 170(4), 1775 - 82
Distribution and diversity of hsd genes in Escherichia coli and other enteric bacteria; Daniel AS et al.; We screened Salmonella typhimurium, Citrobacter freundii, Klebsiella pneumoniae, Shigella boydii, and many isolates of Escherichia coli for DNA sequences homologous to those encoding each of two unrelated type I restriction and modification systems (EcoK and EcoA) . Both K- and A-related hsd genes were identified, but never both in the same strain . S . typhimurium encodes three restriction and modification systems, but its DNA hybridized only to the K-specific probe which we know to identify the StySB system . No homology to either probe was detected in the majority of E . coli strains, but in C . freundii, we identified homology to the A-specific probe . We cloned this region of the C . freundii genome and showed that it encoded a functional, A-related restriction system whose specificity differs from those of known type I enzymes . Sequences immediately flanking the hsd K genes of E . coli K-12 and the hsd A genes of E . coli 15T- were shown to be homologous, indicating similar or even identical positions in their respective chromosomes . E . coli C has no known restriction system, and the organization of its chromosome is consistent with deletion of the three hsd genes and their neighbor, mcrB.

Biochem J, 1988 Mar 15, 250(3), 753 - 60
Sequence and comparative analysis of three Enterobacter cloacae ampC beta-lactamase genes and their products; Galleni M et al.; The sequences of three Enterobacter cloacae ampC beta-lactamase genes have been determined . The deduced amino acid sequences are very similar: out of a total of 361 residues, only eight positions were found to be variable, and several mutations yielded residues with very similar properties . The kinetic properties of two of the enzymes were not significantly different . The three enzymes also exhibited a high degree of homology (greater than 70%) with the ampC beta-lactamases of Escherichia coli K12 and Citrobacter freundii, confirming the homogeneity of class-C beta-lactamases.

J Clin Pharmacol, 1988 Feb, 28(2), 179 - 89
A survey of clinical experience with ciprofloxacin, a new quinolone antimicrobial; Arcieri G et al.; Ciprofloxacin is a new quinolone antimicrobial agent with activity against a broad spectrum of gram-negative and gram-positive organisms, including Pseudomonas aeruginosa and methicillin-resistant strains of staphylococci . The efficacy and safety results of 80 clinical studies of the oral form of ciprofloxacin are reported . Drug safety was assessed in 2236 courses in 2203 adult patients treated primarily in the United States . Data from 1676 courses were suitable for analysis of drug efficacy . The unit dose for most patients ranged from 250 mg to 750 mg (median, 500 mg), usually given every 12 hours . The duration of treatment ranged from 3 to 231 days (median, 10 days) . Predominant among 1722 infections were those of the urinary tract (43%), skin structures (29%), and respiratory tract (19%); the remainder were bone and joint infections (5%), bacteremias (2%), and intra-abdominal (1%), gastrointestinal (1%), and pelvic infections (less than 1%) . Signs and symptoms of infection resolved in 79% of all cases; a further 15% improved, and 5% failed to improve . Pathogens were eradicated in 89% of urinary tract infections and persisted in 5%; 80% of patients still had sterile urine at the 3-to 6-week follow-up . In 81% of nonurinary tract infections, pathogens were eradicated; they persisted in 11%, and superinfection occurred in less than 5% . After treatment, 89% of the 2253 causative organisms were eradicated and 2% were reduced to clinically insignificant counts; 8% persisted . Of 411 isolates of P . aeruginosa, 77% were eradicated, as were 97% of 421 Escherichia coli and 80% of 248 Staphylococcus aureus isolates . Also eradicated were 95% of 166 Klebsiella, 96% of 139 Proteus mirabilis, 100% of 20 other Proteus, 94% of 123 Enterobacter, 100% of 68 Haemophilus influenzae, 96% of 49 Citrobacter, 89% of 45 Serratia, 95% of 41 Streptococcus pneumoniae, 91% of 43 Salmonella, 100% of 38 Morganella morganii, and 100% of 35 Providencia isolates . Adverse reactions were judged probably or possibly drug-related in 14.8% of courses; drug treatment had to be stopped prematurely in 3.5% . The most frequent reactions were gastrointestinal complaints (chiefly nausea, diarrhea, and vomiting), metabolic disorders (elevated SGOT, SGPT, serum creatinine, or blood urea nitrogen), and nervous system effects (dizziness, light-headedness, restlessness, tremor, and headache) . Crystalluria, judged to be related to ciprofloxacin, occurred in two patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemioterapia, 1988 Feb, 7(1), 3 - 9
Carumonam's in-vitro activity against gram-negative bacteria and its stability to their beta-lactamases; Raimondi A et al.; The in vitro activity of the novel monobactam carumonam (RO17-2301) was evaluated on 311 gram-negative clinical isolates in comparison to aztreonam, cefotaxime, ceftazidime, cefotetan and ceftriaxone . Carumonam showed an antibacterial potency equal to or higher than any other reference compound; in particular it was the most effective against Proteus indole positive and Klebsiella sp . Its antipseudomonal activity was comparable to that of ceftazidime and it showed, together with aztreonam, the highest activity against the Citrobacter, Enterobacter and Escherichia coli isolates . The minimal inhibitory concentrations performed on permeability altered organisms indicated that carumonam has a penetration rate comparable to aztreonam and higher than cefotetan and ceftriaxone . Carumonam demonstrated excellent stability to chromosomal and plasmid-mediated beta-lactamases and that correlated with its antibacterial activity against the producing strains and inoculum size effect.

Jpn J Antibiot, 1988 Feb, 41(2), 152 - 64
{Clinical evaluation of ceftriaxone in the treatment of neonatal infections}; Okura K et al.; Ceftriaxone (CTRX) was administered to the newborn and its clinical effectiveness as well as its blood and cerebrospinal fluid levels were studied . 1 . Average blood levels of CTRX 1 hour after single intravenous administration were 39 micrograms/ml in 2 cases receiving about 10 mg/kg, 70 micrograms/ml in 2 other cases receiving 20 mg/kg and 208 micrograms/ml in one receiving 52.6 mg/kg . As is apparent from these cases data, blood levels of CTRX were dose dependent . Blood levels of the drug were between 3.7 to 12.4 micrograms/ml 24 hours later . Half-lives of the drug in blood in the 5 newborns ranged from 7.13 to 10.6 hours . In a 53-day-old patient receiving 43.4 mg/kg of CTRX via intravenous injection, the one-hour blood level of the drug was 140 micrograms/ml and the half-life was 3.68 hours . The blood level of the drug 36 hours after single intravenous administration with 17.3 to 20.0 micrograms/ml to 5 other cases 0 to 5 days of age ranged from 4.6 to 13.7 micrograms/ml . 2 . The cerebrospinal fluid level of CTRX 4 hours after intravenous administration with 49.6 mg/kg to cases of Escherichia coli meningitis was 9.7 micrograms/ml on the first day following the start of the treatment . It increased to 23.6, 25.2 and 31.0 micrograms/ml on the third, fourth and fifth days, respectively, and then gradually decreased . Cerebrospinal level was still 5.8 micrograms/ml on the 22nd day during the recovery period . These levels were far more than 1,000 times as much as the MIC for the pathogen at the highest level, and more than 100 times even at the lowest level . 3 . CTRX was administered via intravenous injection once or twice a day (11.0-39.5 mg/kg in total) to 13 newborns and 3 infants . The efficacy of CTRX was good to excellent in 10 cases for treatment of 11 diseases (sepsis 1, pneumonia 4, urinary tract infection 4 and fetal infection 2) and all the pathogens (Streptococcus agalactiae 1, E . coli 3, Klebsiella pneumoniae 2, Citrobacter diversus 1) disappeared . In 6 cases where CTRX was used prophylactically, infection did not occur at all . The efficacy was excellent in another newborn with E . coli meningitis intravenously receiving 49.6 mg/kg of CTRX twice daily for 25 days . 4 . No adverse reactions were observed . Mild eosinophilia was observed in 4 cases . Follow-up examinations of 3 of the 4 cases showed that these abnormal levels were returned to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

J Hosp Infect, 1988 Feb, 11 Suppl A, 367 - 73
Infections with gram-negative bacilli in a cardiac surgery intensive care unit: the relative role of enterobacter; Flynn DM et al.; A 7-month prospective survey for cefazolin-resistant Gram-negative bacilli in cardiac surgery patients, receiving cefazolin prophylaxis, showed that 58 (67%) of 87 were colonized with enterobacter, 37 (64%) with citrobacter, 33 (57%) with Pseudomonas aeruginosa, and seven (2%) with Serratia marcescens . About 50% of colonization occurred before cefazolin prophylaxis and was present on admission to the intensive care unit . Typing of strains showed that horizontal transmission accounted for at most 14% of carriage . Cefazolin prophylaxis (and high gastric pH) were associated with increased levels of postoperative colonization, most notably for enterobacter . About 25% of colonization with enterobacter, pseudomonas, and serratia was followed by clinical infection . Enterobacter cloacae was the most common pathogen and pneumonia the most common infection . Infections contributed to eight of 11 deaths; four of the eight involved enterobacter . Potential control measures include eliminating endogenous Gram-negative flora by gut decontamination or at least stemming the increase in level of colonization that occurred after surgery.

J Hosp Infect, 1988 Feb, 11 Suppl A, 340 - 51
The bacterial flora of neonates in intensive care-monitoring and manipulation; Goldmann DA; Unlike healthy babies, newborns hospitalized in the neonatal intensive care unit (NICU) are colonized with bacterial flora that reflects their exposure to pathogens in the NICU, not bacterial acquired from mother in the perinatal period . For example, nosocomial Gram-negative bacilli, such as klebsiella, enterobacter, and citrobacter but not Escherichia coli tend to colonize the gastrointestinal tract . Colonization with Gram-negative bacilli generally is a prerequisite for nosocomial infection with these pathogens, but surveillance cultures may not be a cost effective approach to predicting which babies will ultimately become ill . However, screening cultures to detect the emergence of antibiotic-resistant Gram-negative bacilli facilitate containment and guide empiric antibiotic therapy, and surveillance cultures are necessary to detect colonized babies when nosocomial Gram-negative bacilli become epidemic in the NICU . Such cultures are inexpensive and easy to perform if appropriate selective media are used . Surveillance cultures to detect coagulase-negative staphylococci, which numerous investigators claim are increasingly important NICU pathogens, are of little value since colonization is virtually universal in the first week of life . Documentation of colonization with group B streptococci or Staphylococcus aureus also cannot be justified on a routine basis . Screening for methicillin-resistant S . aureus, however, may be indicated since early detection of these strains can limit dissemination in the NICU . Research aimed at restoring colonization resistance with elements of normal bacterial flora or preventing colonization by nosocomial pathogens is in its infancy.

Drugs, 1988, 35 Suppl 2, 1 - 5
Activity of cefotaxime and amikacin against 14,272 gram-negative bacteria from clinical samples in the period 1980 to 1985; Damaso D et al.; The sensitivity to cefotaxime and amikacin of 14,272 Gram-negative bacilli (Enterobacteriaceae and non-fermenting Gram-negative bacilli) isolated from clinical samples was studied during the period 1980 to 1985 . The minimum inhibitory concentration (MIC) was determined by means of diffusion in agar . Strains were considered resistant to cefotaxime and amikacin if the MIC values were greater than 16 mg/L and greater than 8 mg/L, respectively . The MIC90 reached the critical value for cefotaxime in the case of Citrobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp . and Shigella spp., and for amikacin in the case of Citrobacter spp., Enterobacter spp., E . coli, Klebsiella spp., P . mirabilis, Proteus vulgaris, Salmonella spp . and Serratia spp . Only Shigella spp . were sensitive to cefotaxime but not to amikacin, and only strains of Enterobacter spp . and Serratia spp . were sensitive to amikacin but not to cefotaxime.

Mol Biol (Mosk), 1988 Jan-Feb, 22(1), 249 - 56
{Interaction of tyrosine-phenol-lyase from Citrobacter intermedius with amino acids and their derivatives: factors determining the effectiveness of binding}; Faleev NG et al.; The inhibition by L-amino acids and their derivatives of tyrosine phenol-lyase is investigated . Tyramine, alpha-phenylethylamine and tryptamine have no detectable inhibition effect and hence are weakly bonded by an active site . The aromatic amino acid amides are competitive inhibitors but do not manifest an enzymatic isotope exchange of alpha-proton in D2O . Free amino acids however are competitive inhibitors and in the majority of cases exchange alpha-proton . The presence of COOH-group is therefore an important feature which determines the binding efficiency and causes the "active" conformation of the amino acid-PLP complex labelising alpha-proton . In the absence of functional and bulky groups in the amino acid side chain the hydrophobicity is found to be the main factor determining the binding efficiency . For these amino acids a correlation exists between-RTlnKi and side chain hydrophobicity . The amino acids bearing the bulky groups, i . e . valine, leucine and isoleucine have reduced binding efficiency . Lysine and arginine bearing positively charged functional groups possess no inhibition effect . Aspartic and glutamic acids are anomalously strong inhibitors taking into consideration low hydrophobicity of their side chains . One can assume that the electrophilic group able to interact with the terminal COO- -group of aspartic and glutamic acids is located in the active site of tyrosine phenollyase.

J Infect Dis, 1988 Jan, 157(1), 106 - 12
Pathogenesis of brain abscess formation in an infant rat model of Citrobacter diversus bacteremia and meningitis; Kline MW et al.; The pathogenesis of Citrobacter diversus meningitis and brain abscess was studied in infant rats . Two-day-old rats were inoculated intraperitoneally and intranasally with C . diversus . C . diversus strain 4277, lacking the 32,000-molecular-weight outer membrane protein that appears to be a marker for strains causing meningitis in human neonates, was more likely to produce bacteremia, meningitis, and death in rats than was strain 4036, which possesses this outer membrane protein . Strain 4036 was, however, more likely than strain 4277 to produce ventriculitis and brain abscess . In the infant rat, central nervous system involvement by C . diversus begins with bacteremia and leptomeningitis, followed by ventriculitis and direct extension of infection into periventricular brain parenchyma . Large numbers of bacteria persist inside inflammatory cells, an observation suggesting resistance to intraphagocytic killing . Bacterial strain differences, possibly related to the presence of a 32,000-molecular-weight outer membrane protein, may account for histopathologic differences in the brains of infant rats with C . diversus meningitis.

J Antibiot (Tokyo), 1988 Jan, 41(1), 86 - 93
Cephalosporinase interactions and antimicrobial activity of BMY-28142, ceftazidime and cefotaxime; Hiraoka M et al.; Cephalosporinases of Enterobacter cloacae and Citrobacter freundii were responsible for resistance to newer cephalosporins such as cefotaxime and ceftazidime but not BMY-28142 . Interaction of these cephalosporins including hydrolysis, binding, inhibition, and inactivation with cephalosporinases from E . cloacae GN7471 and C . freundii GN7391 were studied . BMY-28142 was much more stable against the both enzymes than cephalothin, but more hydrolyzable than cefotaxime and ceftazidime at higher concentration such as 100 microM . Because of low affinity for the enzymes, i.e . large Km and Ki, the calculated hydrolysis rate of BMY-28142 at 0.1 microM was smaller than those of cefotaxime and ceftazidime, that explained the difference in activity against cephalosporinase-producing strains between BMY-28142 and cefotaxime or ceftazidime . The effects of cephalosporinase production on susceptibility of Escherichia coli omp mutants were examined using a plasmid having cephalosporinase gene of C . freundii GN346 . Decrease in susceptibility of E . coli by cephalosporinase production was larger in the strain lacking outer membrane proteins (Omp) F and C, and smaller in the strain producing OmpF constitutively.

J Clin Microbiol, 1988 Jan, 26(1), 151 - 2
RAPIDEC UR, a 2-h miniaturized system for pinpointing uropathogens; von Graevenitz A et al.; A miniaturized 2-h system (RAPIDEC UR; API System, la Balme-les-Grottes, Montalieu-Vercieu, France) that uses nine enzymatic tests for the diagnosis of most uropathogens was challenged with 330 strains . With few exceptions (Citrobacter, Enterobacter, and Providencia spp., Morganella morganii, and staphylococci other than Staphylococcus saprophyticus), there were distinct patterns that allowed at least a preliminary species diagnosis.

Am J Perinatol, 1988 Jan, 5(1), 37 - 9
Sonography of brain abscesses complicating Citrobacter neonatal meningitis; Wilson DA et al.; The incidence of cerebral complications from citrobacter meningitis is high, and these problems are often difficult to diagnose clinically . Cranial sonography provides the ideal imaging modality to detect the early complications of meningitis and the problems that may occur during or after treatment . Early and serial use of cranial sonography should help to preserve brain tissue and minimize the long-term neurologic deficits that arise from this disease.

Drugs Exp Clin Res, 1988, 14(1), 25 - 30
On the kinetic interaction between ceftriaxone and some beta-lactamases; Amicosante G et al.; The activity of beta-lactamases from Citrobacter diversus ULA-27 on ceftriaxone, a widely recognized third-generation cephalosporin, has been examined and compared to the activity of various other beta-lactamases from different sources . Ceftriaxone (Roche S.p.A . Milan) was found to be resistant to hydrolysis by beta-lactamases from Enterobacter cloacae and Bacillus cereus, but susceptible to beta-lactamases from Mycobacterium fortuitum strain Cow 18 and, mostly, to beta-lactamases from various strains of Citrobacter diversus . Derivatives with substituents in the 3-position of ceftriaxone, namely cefotaxime (Roussel Maestretti S.p.A., Milan) and ceftizoxime (Farmitalia Carlo Erba, Milan), were much less susceptible to hydrolysis by C . diversus ULA-27 enzymes (22 and 6% of ceftriaxone hydrolysis, respectively), the hydrolysis rate being paralleled by differences in MIC values . Ceftriaxone inhibited the activity of E . cloacae beta-lactamases toward cefazolin as substrate, but the inhibition was totally abolished by preincubation of ceftriaxone with the enzyme before addition of the substrate . Overall, the data point to a relevance of C . diversus ULA-27 beta-lactamases in the mechanism of resistance of this strain to the various third-generation cephalosporins.

Diagn Microbiol Infect Dis, 1988 Jan, 9(1), 11 - 26
BMY-28100, a new oral cephalosporin: antimicrobial activity against nearly 7,000 recent clinical isolates, comparative potency with other oral agents, and activity against beta-lactamase producing isolates; Jones RN et al.; The antimicrobial activity of BMY-28100 was tested against approximately 7,000 bacterial pathogens in a multicenter, multiphased collaborative investigation . The BMY-28100 spectrum and antimicrobial potency was most similar to that of cefaclor and superior to that of cephalexin among currently available cephalosporins . Species that had greater than or equal to 90% of clinical strains inhibited by BMY-28100 (less than or equal to 8.0 micrograms/ml) were: Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, N . meningitidis, methicillin-susceptible Staphylococcus supp., Streptococcus pneumoniae, S . pyogenes, S . agalactiae, S . bovis, serogroup C and G streptococci, Listeria monocytogenes and gm-positive anaerobes . BMY-28100 inhibited 9% more of the 6286 fresh clinical isolates at less than or equal to 8.0 micrograms/ml than cefaclor at the same concentration . BMY-28100 was generally bactericidal, but MICs for some species were markedly increased when an inoculum concentration of 10(7) CFU/ml was used . Strains producing plasmid-mediated beta-lactamases (TEM, OXA, SHV, HMS) were susceptible to BMY-28100, cefaclor, and cefuroxime . BMY-28100 was less active against strains producing chromosomal-mediated beta-lactamases (Types I and IV) . BMY-28100 was not hydrolyzed significantly by the tested plasmid-mediated beta-lactamases, but was destroyed by Type I cephalosporinases and Klebsiella K1 enzymes.

Drugs Exp Clin Res, 1988, 14(10), 665 - 7
Clinical efficacy of carumonam; Drabu YJ et al.; Carumonam is a new N-sulfo-beta-lactam antibiotic active against aerobic Gram-negative bacteria . An open study was carried out to evaluate the efficacy, safety and tolerance of carumonam with either 1 g t.i.d . (group A) or 2 g t.i.d . (group B) in bacterial septicaemia or severe sepsis . A total of 24 patients (14 men and 10 women) were included in the study, their ages ranged from 48-87 years (mean age 59) . Eighteen patients were treated for bacteraemia, three for bronchopneumonia, two for urinary tract infection and one for a subphrenic abscess; seven were in group A and fourteen in group B; three were treated with a variable regimen . The pathogens isolated included E . coli {10}, Klebsiella aerogenes {9}, Enterobacter cloacae {3}, Citrobacter freundii {2}, Pseudomonas spp . {4}, Providence stuartii {2}, Serratia marcescens {1} and Haemophilus influenzae {1} . Clinical improvement occurred in all patients in both groups . One patient in group A and four patients in group B required further antibiotic therapy . The overall clinical cure rate was 84% and the bacteriological cure rate was 72% . Supra-infection occurred in three patients and adverse reactions attributable to carumonam were seen in two patients: diarrhoea (in one), and aggravation of renal failure in the other . Carumonam is well tolerated at both the dosage regimens; it is effective in the treatment of aerobic Gram-negative sepsis.

J Antimicrob Chemother, 1988 Jan, 21(1), 9 - 16
Induction of chromosomal beta-lactamases by different concentrations of clavulanic acid in combination with ticarcillin; Stobberingh EE; The effect of different concentrations of clavulanic acid (CA) in combination with ticarcillin on beta-lactamase production and ticarcillin MIC was studied in four clinical isolates of Pseudomonas aeruginosa, Enterobacter cloacae, Serratia marcescens, Citrobacter freundii and indole positive Proteus strains . Ticarcillin alone showed a low inducing effect for all species tested, Ser . marcescens excepted . The increase in beta-lactamase activity after addition of CA (2-10 mg/l) was strain and species dependent . No synergy or antagonism was observed on the ticarcillin MIC for the micro-organisms producing only a chromosomally mediated beta-lactamase, though the susceptibility to ticarcillin strongly increased if the strains also produced a plasmid-mediated beta-lactamase . Addition of 50 or 100 mg/l CA resulted in all strains . C . freundii excepted, in a strong increase in beta-lactamase activity and in a strong synergistic effect on the ticarcillin MIC . However, these concentrations are unlikely to be achieved at clinical doses . Thus, irrespective of the inducing effect of ticarcillin and CA (2-10 mg/l) combinations, induction of the chromosomal beta-lactamase did not result in a decrease in ticarcillin susceptibility.

J Infect Dis, 1988 Jan, 157(1), 101 - 5
Characterization of Citrobacter diversus strains causing neonatal meningitis; Kline MW et al.; We studied 17 strains of Citrobacter diversus isolated from the cerebrospinal fluid of infants with meningitis and compared these strains with 21 strains isolated from other body sites . The two groups of strains were similar with respect to biotype, piliation, hemolysin production, and resistance to the killing effects of serum . By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found that 14 (82%) of 17 strains from cerebrospinal fluid, but only two (10%) of 21 strains isolated from other body sites, possessed a minor outer membrane protein with a molecular weight of 32,000 (P less than .0001) . This protein may serve as a marker for strains of C . diversus that are likely to cause meningitis or brain abscess in human neonates.

Chemotherapy, 1988, 34(4), 318 - 25
Beta-lactamase inhibition by acetylmethylene penicillanic acid compared to that of clavulanate and sulbactam; Chin NX et al.; The beta-lactamase inhibitory properties of 6-acetylmethylene penicillanic acid (6-AMPA) were investigated and compared with those of other beta-lactamase inhibitors . 6-AMPA inhibited the TEM-1, TEM-2, SHV-1, PSE-1, PSE-2, PSE-3, PSE-4, OXA-2, OXA-3, and Staphylococcus aureus beta-lactamases . It also inhibited the chromosomally-mediated beta-lactamases of the Richmond-Sykes type Ia, Ic and Id type and the type IV Klebsiella enzymes . Beta-lactamases of Branhamella catarrhalis and Bacteroides fragilis were inhibited . The 6-AMPA I50 values for various enzymes were less than 0.01 microgram/ml TEM-1 and PSE-4, and 0.01 microgram/ml SHV-1, 0.02 microgram/ml S . aureus, 0.04 microgram/ml Proteus vulgaris, 0.04 microgram/ml K . oxytoca, 6.8 micrograms/ml P99, and 9.7 micrograms/ml Sabath-Abraham Pseudomonas enzyme . With isolated beta-lactamases 6-AMPA was a more potent inhibitor than clavulanate or sulbactam . 6-AMPA was an irreversible inhibitor of beta-lactamases . The penetration index for Escherichia coli JT4 was 23 compared to 3 for clavulanate . 6-AMPA at 10 micrograms/ml acted synergistically with ampicillin against beta-lactamase containing bacteria, but it was less active than clavulanate and did not act synergistically with ampicillin against Enterobacter, Citrobacter or Pseudomonas . Although 6-AMPA has excellent beta-lactamase inhibitory properties with isolated enzymes, it is less useful with intact organisms.

Antimicrob Agents Chemother, 1988 Jan, 32(1), 104 - 9
Purification of Citrobacter freundii DNA gyrase and inhibition by quinolones; Aoyama H et al.; DNA gyrase is a bacterial enzyme which catalyzes the ATP-dependent negative supercoiling of DNA . It is the accepted target of quinolones . The enzyme from Citrobacter freundii IID976 was purified by affinity chromatography on novobiocin-Sepharose and heparin-Sepharose . It had two subunits, designated A and B, which closely resembled those of the enzyme from Escherichia coli and Micrococcus luteus in enzymatic requirements . The inhibitory effects of the quinolones on the supercoiling activities of the enzyme correlated with their antibacterial activities . New quinolones were better inhibitors of DNA gyrase than nalidixic acid and pipemidic acid . We also purified DNA gyrase from a spontaneous nalidixic acid-resistant mutant (M2-5) . The gyrases from IID976 and M2-5 were defined as mixtures of subunits As+Bs (s, susceptible) and Ar+Br (r, resistant), respectively . The supercoiling activities of reconstituted Ar+Br and Ar+Bs were more resistant to quinolones than As+Bs and As+Br . These findings indicate that one mechanism of C . freundii resistance against quinolones is resistance modification of the A subunit protein.

J Bacteriol, 1988 Jan, 170(1), 471 - 3
Cloning and sequencing of a gene encoding an aminoglycoside 6'-N-acetyltransferase from an R factor of Citrobacter diversus; Tenover FC et al.; The aacA1 gene, which encodes a 6'-N-acetyltransferase {AAC(6')-I} mediating resistance to kanamycin, tobramycin, and amikacin, was cloned from the Citrobacter diversus R plasmid pBWH100 into the Escherichia coli vector pBR322 . The complete nucleotide sequence of the gene and flanking regions was determined . A protein of approximately 21 kilodaltons was identified when the chimeric plasmid encoding the aacA1 gene was introduced into E . coli maxicells . This value is consistent with the size predicted for a protein translated from the open reading frame of the gene.

Arch Immunol Ther Exp (Warsz), 1988, 36(2), 119 - 28
The heterogeneity of lipopolysaccharides from Citrobacter 023 serotype; Katzenellenbogen E; Chemical studies on carbohydrate part of lipopolysaccharides isolated from Citrobacter 87/57 and Citrobacter 1556 strains (serotype 023) were carried out . Lipopolysaccharides (LPS) were hydrolyzed with 1% acetic acid and the carbohydrate material was fractionated on Sephadex G-50 and Bio-Gel P-4 columns . All fractions obtained were subjected to chemical analysis by colorimetric methods and by gas-liquid chromatography . It was found that O-specific polysaccharide from LPS 87/57 is composed of mannose and N-acetylgalactosamine in the molar ratio of 3:1 . Both lipopolysaccharides contain unsubstituted core oligosaccharides (built of heptose, glucose and galactose in molar ratio of 3:3:1) as well as core oligosaccharides substituted with shorter (LPS 87/57 and LPS 1556) and longer (LPS 87/57) O-specific oligosaccharides . Strain 87/57 is of S (smooth) type and strain 1556 lacking O-specific polysaccharide is of SR (semi-rough) type . The data of Sephadex G-100 chromatography showed that O-antigen from Citrobacter 87/57 is heterogeneous; it contains polysaccharide chains of different length but the same composition . The heterogeneity of Citrobacter 023 lipopolysaccharides has been also detected by SDS-polyacrylamide gel electrophoresis.

J Infect Dis, 1988 Jan, 157(1), 54 - 64
Failure of antisera to J5 and R595 rough mutants to reduce endotoxemic lethality; Greisman SE et al.; Rabbit antisera to J5 (Rc) Escherichia coli and R595 (Re) Salmonella minnesota rough mutants were selected for the highest content of hemagglutinating antibodies to their respective core glycolipids . Despite titers of 1:2560 vs . J5 and 1:640 vs . R595 core glycolipids, the antisera failed to passively protect ICR or CF-1 mice against lethality induced by endotoxins from a variety of wild-type, smooth enterobacteria: E . coli O111:B4, E . coli O127:B8, Salmonella typhimurium, S . minnesota, and Citrobacter freundii . J5 antisera, however, reduced lethality from J5 core glycolipid . In contrast, O-specific rabbit antisera were consistently protective against the lethal activity of wild-type, smooth enterobacterial endotoxins, but such protection was limited to the homologous endotoxin . These findings are consistent with in vitro demonstrations of a highly restricted ability of antibodies to J5 and R595 core glycolipids to bind to endotoxins from wild-type, smooth enterobacteria.

Eur J Biochem, 1987 Dec 30, 170(1-2), 311 - 6
Transamination catalysed by tyrosine phenol-lyase from Citrobacter intermedius; Demidkina TV et al.; The interactions of tyrosine phenol-lyase with its substrates: L-tyrosine and L-serine, and the competitive inhibitors: L-alanine, L-phenylalanine, L-m-tyrosine, were studied . It was demonstrated that the enzyme catalyzed a half-transamination reaction between substrates or inhibitors and the protein-bound pyridoxal phosphate . The products of this side-reaction, pyridoxamine phosphate and the respective keto acids, were identified . The kinetic parameters were determined for beta-elimination of L-tyrosine and of L-serine, and for the transamination of L-serine and the inhibitors used . The transfer of the amino group to the coenzyme takes place in the direction from amino acid to pyridoxal phosphate, but not in the opposite direction, i.e . the transamination is irreversible.

Jpn J Antibiot, 1987 Dec, 40(12), 2026 - 142
{Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985) . III . Secular changes in susceptibility}; Kosakai N et al.; Sensitivities to antimicrobial agents of Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Proteus spp., Pseudomonas aeruginosa and Serratia marcescens isolated from infected patients were evaluated and compared according to the types of their infections, i.e., simple and complicated urinary tract infections with or without indwelling catheter . There were no apparent decreases in the sensitivity of E . coli isolated from patients with simple urinary tract infections . When data obtained in 1982-1985 were summarized, it was found that a new quinoline derivative, ofloxacin (OFLX), showed the strongest activity among oral antimicrobial and antibiotic agents . This agent inhibited 100% of bacterial growth at MIC of 1.56 micrograms/ml . The next strongest activity was found with mecillinam (MPC) which showed 89.3% growth inhibition at the same concentration . Cefaclor (CCL) also showed 84.9% growth inhibition at the same concentration . When sensitivities of E . coli isolated from patients with complicated urinary tract infections with or without indwelling catheter to first and second generation cephems were determined, cefotiam (CTM), which inhibited 88.9%: 91.4% bacterial growth at MIC of 0.39 micrograms/ml, had the strongest activity among CTM, cefazolin (CEZ), cefoxitin (CFX) and cefmetazole (CMZ) . Among third generation cephems, including cefmenoxime (CMX), latamoxef (LMOX), ceftizoxime (CZX), cefotaxime (CTX) and cefoperazone (CPZ), the strongest activity was observed with CZX, and the agent having the next strongest activity was CMX . LMOX and CPZ showed relatively low activities . Carumonam (CRMN) and aztreonam (AZT), monobactams, showed strong activities against E . coli . As for Klebsiella spp., activities of pencillins against these strains were low . When activities of oral cephems (cephalexin (CEX) and CCL) and of a quinoline derivative OFLX against these strains were determined, OFLX showed strong activity; i.e., the growth of Klebsiella spp . isolated from complicated urinary tract infections was inhibited at 87.2%: 82.1% at MIC of 0.20 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1987 Dec, 40(12), 1975 - 2011
{Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985) . I . Susceptibility distribution}; Kosakai N et al.; The results of determinations of sensitivities of bacterial strains to various antibiotics are summarized as follows: 1 . Against Escherichia coli, ofloxacin (OFLX) showed the strongest activity among oral antibacterial and antibiotic agents . Its MIC90 was below 0.10 micrograms/ml . The next strongest activity was found in mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA); MIC90's of these agents 3.13 micrograms/ml . Cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) had MIC90 below 0.39 micrograms/ml . MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were 1.56 micrograms/ml . Aztreonam (AZT) and carumonam (CRMN) in the monobactam group showed strong activities with MIC90's at 0.20 micrograms/ml . 2 . Although Klebsiella pneumoniae had a strong resistance to ampicillin (ABPC) and showed relatively low sensitivities to other oral antibacterial and antibiotic agents, OFLX maintained high activity against this species and showed MIC90 of 0.39 micrograms/ml . Among injectable antibiotics, third generation cephems showed the strongest activity to this species with MIC90 of CZX below 0.10 micrograms/ml, of CTX and CMX 0.20 micrograms/ml, and of LMOX 0.78 micrograms/ml . MIC90 of CPZ was 6.25 micrograms/ml, which was the same as those of cefazolin (CEZ) and cefoxitin (CFX) . CTM had similar MIC90 to LMOX, namely, 1.56 micrograms/ml . MIC90 of CMZ was 3.13 micrograms/ml . Monobactams AZT and CRMN showed strong activities to this species; their MIC90's were below 0.10 micrograms/ml and 0.20 micrograms/ml . 3 . Although Citrobacter freundii generally exhibited low sensitivities to antibacterial and antibiotic agents examined, it showed high sensitivity to OFLX, at MIC80 of 0.78 micrograms/ml . This species showed low sensitivities to MPC, nalidixic acid (NA), PPA, and sulfamethoxazole-trimethoprim (ST) . Among injectable antibiotics, LMOX and CMX had activities against this species; namely, MIC80's were 6.25 and 3.13 micrograms/ml, respectively . Among monobactams, AZT showed MIC80 of 12.5 micrograms/ml, and CRMN had that of 6.25 micrograms/ml . 4 . Against Enterobacter cloacae, the strongest antibacterial activity was found with OFLX which had MIC90 of 0.39 micrograms/ml . A relatively strong activity was seen with MPC . MIC80 of MPC was 1.56 micrograms/ml . Except to CTM, this species had poor sensitivities to injectable first and second generation cephems, and their MIC80's were over 200 micrograms/ml . MIC80 of CTM was 25 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurosurgery, 1987 Dec, 21(6), 923 - 7
Brain abscesses and ischemic necrotic lesions during early childhood; Tavora L et al.; The cases of seven children, all under 6 months of age, with cerebral abscesses are presented . In four cases, there was previous meningitis; the others presented with expanding mass lesions . The infectious agent was Proteus in four cases and Escherichia coli and Citrobacter in one each; in another patient, no agent was isolated . In six children, there were multiple areas of ischemic necrosis . In one instance, these areas were in the hemisphere contralateral to the purulent collection . The peculiar clinical, diagnostic, and therapeutic aspects of brain abscesses in this age group are discussed.

South Med J, 1987 Nov, 80(11), 1439 - 41
Citrobacter freundii endocarditis in an intravenous drug abuser; Plantholt SJ et al.; We have reported the third case of Citrobacter endocarditis . Echocardiograms were invaluable in establishing the diagnosis . Ours is the first reported case of Citrobacter endocarditis to be cured by antimicrobial therapy alone.

Jpn J Antibiot, 1987 Nov, 40(11), 1895 - 905
{The antimicrobial activity of sisomicin against fresh clinical isolates}; Deguchi K et al.; Antimicrobial activities of sisomicin (SISO) against clinical isolates obtained in the second half of 1986 were investigated together with other 4 aminoglycosides (AGs) (gentamicin (GM), tobramycin (TOB), dibekacin (DKB), amikacin (AMK} and 2 cephems (cefotiam, cefotaxime), and were compared to the results reported in the period of late 1970's through early 1980's in Japan . 1 . The incidence of SISO-resistant Staphylococcus aureus in the present study was 18% and is comparable to that of the other studies suggesting that the incidence of SISO resistant strains remains on the stable level . The incidence of SISO-resistant Pseudomonas aeruginosa showed the tendency of slight increase . 2 . SISO-resistant strains of Enterobacter spp., Serratia marcescens and Citrobacter freundii did not show increase from the 1970/1980 levels . 3 . Isolation rates of SISO-resistant indole(+) Proteus varied depending on strains . Isolation rates of SISO-resistant P . vulgaris and Morganella morganii were both as low as 4%, but that of Providencia rettgeri was as high as 60% . Refering to an American study reporting that the Genus Providencia including P . rettgeri showed high incidence of resistance to SISO as well as to GM or TOB, we pointed out that the antimicrobial activity of AGs against Genus Providencia should be evaluated separately from those of other indole(+) Proteus strains . 4 . No SISO-resistant strains of Escherichia coli, Klebsiella pneumoniae or P . mirabilis were found . 5 . SISO had good antimicrobial activity against most of the investigated species and SISO may still be regarded as one of the clinically useful AGs.

Ann Inst Pasteur Microbiol, 1987 Nov-Dec, 138(6), 693 - 707
{Demonstration of glycocalyx formation in vitro in Citrobacter freundii, Proteus mirabilis and Planococcus sp.: the effect of polyosidases}; Richelle-Maurer E et al.; Three bacterial species of different origin, Citrobacter freundii, Proteus mirabilis and Planococcus sp., formed glycocalyx in vitro and thereby showed that the phenomena does not only occur in vivo contrary to the opinion of many authors . The glycocalyx was produced in the attachment processes used or both extra- and intercellular attachment . The aggregates formed caused large errors in bacterial counts and led to questioning of the very principle of the counting procedures . The glycocalyx was not destroyed by the polyosidases utilized nor by ultrasound treatment . The glycocalyx structure differed only according to the bacterial species of origin and was unchanged by culture media or nutrient deprivation.

J Appl Bacteriol, 1987 Nov, 63(5), 459 - 64
A modified conductance medium for the detection of Salmonella spp; Ogden ID et al.; Selenite-cystine/trimethylamine oxide/dulcitol medium has been used in conjunction with conductance instruments to detect the presence of Salmonella spp . in foods and faeces . However, a small but significant number of salmonella strains were missed by this method . The majority of these strains were detected when dulcitol was substituted by mannitol and tested on two separate Malthus conductance instruments . Some strains of Citrobacter freundii and Escherichia coli continued to give false positive results . Attempts are made to explain why the substitution of mannitol for dulcitol gives an improved medium.

Jpn J Antibiot, 1987 Oct, 40(10), 1752 - 61
{Antimicrobial activity of sulbactam/cefoperazone . Comparison with other new cephems}; Deguchi K et al.; Antimicrobial activities of sulbactam/cefoperazone (SBT/CPZ) against 50 fresh clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were compared to those of CPZ, Cefotiam (CTM), Cefotaxime (CTX) and Latamoxef (LMOX) . Minimal inhibitory concentrations (MIC's) of SBT and CPZ mixed in a ratio of 1:1 were determined by the dilution method using Mueller-Hinton agar and expressed by absolute concentrations of CPZ . Antimicrobial activities of SBT/CPZ against principally penicillinase (PCase) producing bacteria, i.e., S . aureus, E . coli, K . pneumoniae, P . mirabilis, were superior to those of CPZ alone . The presence of SBT in concentrations around 0.39 approximately 1.56 micrograms/ml clearly enhanced CPZ's antimicrobial activities against these PCase producing strains . The synergistic antimicrobial effects of SBT in combination with CPZ were less pronounced against principally cephalosporinase (CEPase) producing bacteria, i.e., C . freundii, Enterobacter spp., S . marcescens, P . vulgaris, and P . aeruginosa, and exerted with SBT at concentrations around 3.13 approximately 12.5 micrograms/ml . Comparative antimicrobial activities indicated by MIC80's of tested agents showed that SBT/CPZ had more stable activities against bacteria ranging from Gram-positive to Gram-negative bacteria than CTM, CTX and LMOX . MIC's of SBT/CPZ were higher than 25 micrograms/ml against 8% of S . aureus, 18% of C . freundii, 10% of Enterobacter spp., 26% of S . marcescens, 2% of P . vulgaris, and 18% of P . aeruginosa . These resistant strains against which the addition of SBT showed no synergism, may possess other mechanism of resistance than beta-lactamase production . It is concluded that the presence of CPZ resistant strains is an actual current problem and not an imaginary future problem, and that the number of resistant strains against other new cephems which have different chemical structure from CPZ is increasing . When these present bacteriological environments are considered, the appearance of SBT/CPZ in the clinical practice is timely and meaningful.

Chemioterapia, 1987 Oct, 6(5), 315 - 8
In vitro susceptibility of nosocomial Pseudomonas aeruginosa, enterobacteriaceae, and staphylococci to ciprofloxacin and ten other broad-spectrum antibiotics; Weinstein RA et al.; We determined microdilution minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for ciprofloxacin and 10 beta-lactam and aminoglycoside antibiotics against 329 unique nosocomial isolates of Pseudomonas aeruginosa, citrobacter, enterobacter, serratia, and staphylococci . All were susceptible to ciprofloxacin, including 109 aminoglycoside-resistant gram-negative bacilli and 59 oxacillin-resistant staphylococci . Ciprofloxacin was generally 2-4 fold less active against aminoglycoside-resistant isolates than against their aminoglycoside-susceptible counterparts.

Infect Immun, 1987 Sep, 55(9), 2183 - 90
Identification of two different hemolysin determinants in uropathogenic Proteus isolates; Welch RA; DNA sequences similar to those of the Escherichia coli hemolysin genes were detected among uropathogenic isolates of Proteus vulgaris and Morganella morganii by using the Southern blotting technique and hly gene-specific DNA probe . Immunoblotting revealed that among the hemolytic P . vulgaris and M . morganii isolates there was expressed a polypeptide species similar in molecular size (110 kilodaltons) and antigenicity to Escherichia coli HlyA . A plasmid-mediated P . vulgaris hemolysin determinant identified by Southern blotting analysis was molecularly cloned, and the recombinant plasmid (pWPV100) was characterized by restriction endonuclease fragment mapping . A second recombinant library of genomic DNA prepared from a hemolytic, urinary tract isolate of Proteus mirabilis was constructed in E . coli . A 5.5-kilobase XhoI fragment encoding an extracellular hemolytic activity was molecularly cloned (pWPM100), and this plasmid was subjected to transposon-mediated mutagenesis with TnphoA . The P . mirabilis hemolytic phenotype was determined to be encoded by a polypeptide species (HpmA) with an estimated molecular size of 140 kilodaltons based on minicell polypeptide analysis of pWPM100 and its mutant derivatives . Southern blotting analysis with a HpmA-specific DNA probe revealed that this novel determinant is commonly found in both Proteus species but is not present in hemolytic isolates of M . morganii, E . coli, Citrobacter freundii, and Serratia marcescens.

Jpn J Antibiot, 1987 Sep, 40(9), 1698 - 706
{Susceptibility of clinical bacterial isolates to aztreonam}; Murase M et al.; In vitro activities of 7 antimicrobial agents against organisms (474 strains) isolated from patients with various infections in Ehime University Hospital from May to July 1986 were investigated . Summarized results are as follows: 1 . Aztreonam (AZT) showed potent activities against Escherichia coli, Citrobacter sp., Klebsiella pneumoniae, Serratia marcescens, Proteus sp., Pseudomonas aeruginosa and Haemophilus influenzae . 2 . Antimicrobial activities of AZT were especially superior against Proteus sp . to the third generation cephem antibiotics . 3 . Enterobacter sp . seemed more susceptible to AZT than to cephem antibiotics, but minimum inhibitory concentrations of AZT against may isolates of Enterobacter sp . were in wide ranges.

J Clin Microbiol, 1987 Sep, 25(9), 1668 - 74
Epidemiologic factors affecting antimicrobial resistance of common bacterial isolates; Ellner PD et al.; The pattern of antimicrobial resistance of common bacterial isolates obtained from various groups of patients at a large tertiary-care center was compared with the pattern of resistance seen at a primary-care community hospital . At the tertiary-care center, significant differences in susceptibility were seen between pediatric and adult groups . In the tertiary-care center, the inpatients were more likely than the outpatients to have resistant staphylococcal and enterobacterial strains . Comparison of the overall resistance at the tertiary-care center and the primary-care hospital showed that resistance to cephalosporins, piperacillin, and aminoglycosides was significantly higher at the tertiary-care hospital than at the community hospital . Striking differences were noted in the resistance of nosocomial Enterobacter and Citrobacter isolates . Hospitals should be cautious in extrapolating nationwide data to their particular institutions.

Eur J Clin Microbiol, 1987 Aug, 6(4), 439 - 45
Clinical significance of beta-lactamase induction and stable derepression in gram-negative rods; Livermore DM; Most strains of enterobacteria and Pseudomonas aeruginosa produce chromosomally-determined Class I beta-lactamases . When synthesized copiously these enzymes cause resistance to almost all beta-lactams, except imipenem and, sometimes, carbenicillin and tenocillin . Elevated beta-lactamase production arises transiently, via induction, in Pseudomonas aeruginosa and Enterobacter, Citrobacter, Morganella, indole-positive Proteus and Serratia spp . when these organisms are exposed to beta-lactams . Permanent high-level enzyme production arises via mutation, in the stably-derepressed mutants of these species . These mutants arise spontaneously at high frequency (10(-5) -10(-8) . Most early penicillins and first-generation cephalosporins are strong inducers of Class I enzymes at sub-inhibitory concentrations, as are cefoxitin and imipenem . Consequently their MICs reflect what lability these antibiotics have to inducibly-expressed beta-lactamase . Except with imipenem this lability usually is so great that the inducible enzyme causes clinical resistance . Although most other newer cephalosporins and ureidopenicillins are labile to the Class I enzymes they induce poorly below the MIC, and their lability is not reflected in resistance unless secondary inducers (e.g . cefoxitin or imipenem) are present . Although the weak inducer activity of these agents helps to maintain their activity against the inducible cells it renders the drugs highly selective for the pre-existing stably-derepressed mutants . Many cases have been reported where stably-derepressed mutants have overrun inducible populations of bacteria in patients undergoing therapy with beta-lactamase-labile weak inducers such as ureidopenicillin and third-generation cephalosporins.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1987 Aug, 184(6), 459 - 69
{Bacteriologic quality of water from the Rhine and its tributaries in the Rhine-Neckar region . I . Bacterial count and Enterobacteriaceae of the current status of pollution}; Mersch-Sundermann V et al.; During the period of May 1982 to January 1983 and March 1986 to May 1986, 164 water-specimens had been collected along the river Rhine and its affluxes in the overcrowded Rhine-Neckar-Region from 34 collecting-sites on 8 different days . The specimens were tested for the total-germ-count and the titers of different Enterobacteriaceae-species . The total-germ-count examined concentrations of several hundreds up to 1.8 million germ in 1 ml river-water . Extremely high concentrations were found along the waste-water-influxes (purification-plants) and the overloaded Rhine-affluences (Leimbach, Kraichbach, Speyerbach, Rehbach, Neckar) . The waste-water-samples from the central flow of the Rhine-river showed germ-concentrations of less than 10.000/ml, due to the mix-up of the waste water with the Rhine-water . Enterobacteriaceae--549 isolates together--could be found mainly in specimens from all collected sites in low titers . E . coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia liquefaciens and Citrobacter freundii had been the highest recovery rate . The isolation of Salmonellae was examined because of specific methods in a separate study (2 . Communication) . Based on these data, it has to be concluded, that the water of the Rhine-river and its affluxes in the Rhine-Neckar-Region is an uncontrolled germ-reservoir . The use of this water for bathing, unprocessed drinking-water or for agriculture purpose has to be refused from the hygienic point of view.

Eur J Clin Microbiol, 1987 Aug, 6(4), 460 - 6
Incidence of inducible beta-lactamases in gram-negative septicemia isolates from twenty-nine European laboratories . European Study Group on Antibiotic Resistance; Clinical consequences of development of resistance to third generation cephalosporins; Department of Medicine, University Hospital (Kantonspital), Basel, SwitzerlandEighteen patients are described in whom initially sensitive microorganisms were replaced by resistant isolates during administration of ceftriaxone (n = 8), cefoperazone (n = 5), moxalactam (n = 4), cefotaxime (n = 2) or ceftazidime (n = 1), despite combination with aminoglycosides . All patients had documented gram-negative infections; in 12 patients underlying haematological diseases were present . Resistant strains of Enterobacter cloacae (14), Serratia marcescens (4), Klebsiella oxytoca (3), Pseudomonas aeruginosa (2) and Citrobacter freundii (2) emerged within 2 to 19 (mean 9) days after the beginning of treatment . In 12 patients relapse or secondary infections occurred . Seven of the patients with haematological disorders died . Resistance development was seen in 8 of 29 patients on ceftriaxone and 4 of 10 patients on moxalactam during prospective evaluations; the other drugs were used sporadically . Thus, selection of resistant bacteria is relatively frequent and may have serious clinical consequences in patients with impaired host-defense mechanisms.

Appl Biochem Biotechnol, 1987 Aug, 15(2), 97 - 106
Basic studies of hydrogen evolution by Escherichia coli containing a cloned Citrobacter freundii hydrogenase gene; Kanayama H et al.; Citrobacter freundii genes that complemented Escherichia coli hyd-(hydrogenase activity) mutation were cloned in plasmids pCBH4 (6.2 kb) and pCBH6(5.7 kb) . Hydrogen evolution by the transformant E . coli HK-8(pCBH4 or pCBH6) was investigated . The optimum culture temperature of recombinant E . coli cells for hydrogen evolution from glucose was in the neighborhood of 18 degrees C . The recombinant E . coli cells cultured at this condition showed a several-fold increase of hydrogen evolution, as compared with that of the wild-type cells . The plasmid-retention stability of this recombinant E . coli was extremely high, especially plasmid pCBH4, which was completely retained during 2 wk without any restriction . Hydrogen production by immobilized recombinant E . coli was then investigated using cells cultured at 18 degrees C . The hydrogen evolution rate from glucose and Lennox-broth were about twofold higher than that of E . coli C600, and this high hydrogen evolution rate was maintained for more than 1 mo.

J Antimicrob Chemother, 1987 Jul, 20(1), 23 - 35
Citrobacter diversus ULA27 produces two forms of a chromosomal beta-lactamase; Oliva B et al.; A multi-resistant clinical isolate of Citrobacter diversus, particularly resistant to penicillins and cephalosporins, has been studied . The strain produced constitutively high levels of beta-lactamase which efficiently hydrolysed cephaloridine but not ampicillin . The apparent Km value for cephaloridine (125 +/- 25 microM) was within the range usually observed for beta-lactamases in similar bacteria . The strain possessed two forms of the enzyme as indicated by isoelectric focusing patterns, HPLC analysis and two pH optima . SDS-PAGE analysis indicated a single protein responsible for both forms . The strain possessed a single plasmid, as revealed by agarose gel electrophoresis, but beta-lactamase production was not plasmid encoded . The available data indicate the beta-lactamase(s) of C . diversus ULA27 to be chromosomally encoded.

Antimicrob Agents Chemother, 1987 Jul, 31(7), 1085 - 92
In vitro and in vivo antibacterial activities of CS-807, a new oral cephalosporin; Utsui Y et al.; CS-807 is a new oral prodrug of R-3746, a cephalosporin derivative, with potent in vitro and in vivo antibacterial activity against both gram-positive and gram-negative bacteria . The susceptibility of about 1,200 clinical isolates to R-3746 was determined by the agar dilution method . Ninety percent or more of pathogens such as Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, indole-positive and indole-negative Proteus spp., Providencia rettgeri, and Haemophilus influenzae were inhibited at concentrations ranging less than or equal to 0.01 to 1.56 micrograms/ml . Furthermore, at a concentration of 3.13 micrograms/ml, 50% or more of Staphylococcus epidermidis, Morganella morganii, Citrobacter freundii, and Serratia marcescens strains were also inhibited . Pseudomonas aeruginosa and Xanthomonas maltophilia were resistant to R-3746 . The activity of R-3746 was scarcely influenced by several growth conditions . R-3746 was highly resistant to hydrolysis by beta-lactamases derived from various species of bacteria . Killing-curve studies demonstrated bactericidal activity of R-3746 at concentrations above the MIC . R-3746 showed high affinity for penicillin-binding proteins 1, 3, and 4 of Staphylococcus aureus and 1A, 1Bs, and 3 of Escherichia coli . Systemic infections in mice caused by various pathogens, including beta-lactamase-producing strains, responded well to therapy with oral doses of CS-807.

Prev Med, 1987 Jul, 16(4), 580 - 5
Cell turnover and colon tumor development; Deschner EE; The proliferative characteristics of the large bowel are determined genetically and can vary over a wide range, the lower range being resistant to chemically induced tumors and the upper range expressing susceptibility . Basically, the colon has a relatively high level of cell renewal . It can be further elevated or depressed by a number of dietary and environmental conditions . A hyperproliferative state has been induced by the presence of carrageenan, Citrobacter freundii, nonspecific injury, or dietary factors such as high levels of bile acids . The effect of high proliferation levels is to produce more S-phase cells, which are sensitive to DNA damage, to increase the risk of neoplastic transformation and to shorten the tumor latency period . In animal models, hyperactivity has meant enhanced tumor incidence . A hypoproliferative state has been induced in the colon of man and mouse . Experimentally, the net effect of lower proliferative levels has been to reduce colon tumor incidence . It remains to be determined whether clinical trials involving hypoproliferation can be maintained chronically and are an effective means of reducing colon tumor incidence in high-risk groups.

FEBS Lett, 1987 Jun 22, 218(1), 126 - 30
Identification of the active site of Citrobacter freundii beta-lactamase using dansyl-penicillin; Yamaguchi A et al.; The active site sequence of a beta-lactamase encoded by chromosomal gene(s) in Citrobacter freundii GN346 was determined using dansyl-penicillin as a fluorescent probe . The tryptic digest of the labelled enzyme gave a fluorescent peptide containing 22 amino acids . The sequence of this peptide was identical to the consensus sequence of class C beta-lactamases, Gly-Ser-X-Ser-Lys . The residue labelled was the serine adjacent to the glycine . The active site sequence corresponded to positions 46-67 of the entire sequence of the Citrobacter freundii beta-lactamase determined on the basis of the DNA sequence of the structural gene {(1986) Eur . J . Biochem . 156, 441-445} . The labelled serine corresponded to Ser-64.

Infect Control, 1987 Jun, 8(6), 241 - 4
In vitro activity of cefixime and six other agents against nosocomial pathogens of the Enterobacteriaceae family; Mulligan ME; Cefixime, a broad-spectrum, orally active cephalosporin, was more active in vitro than ampicillin, cefaclor, cephalothin, and trimethoprim/sulfamethoxazole against 194 nosocomial pathogens of the family Enterobacteriaceae . Activity was especially good against Klebsiella spp, Proteus spp, Serratia spp, and Providencia stuartii . Although gentamicin had equivalent or better activity against Citrobacter spp, Enterobacter spp, Escherichia coli, and Morganella morganii, all 23 of the gentamicin-resistant strains studied were susceptible to cefixime . Isolates tested were from urinary tract infections, abdominal infections, wounds, vascular infections, and respiratory infections; they were sequentially collected nosocomial pathogens from a single institution . This orally active cephalosporin should be considered for therapy of a variety of nosocomial infections involving gram-negative bacillary pathogens.

Epidemiol Infect, 1987 Jun, 98(3), 311 - 22
Inhibition of colonization of the chicken alimentary tract with Salmonella typhimurium gram-negative facultatively anaerobic bacteria; Barrow PA et al.; Oral administration of strains of food poisoning salmonellas to day-old chickens produced a profound inhibition in the subsequent colonization of the caeca by a strain of Salmonella typhimurium given one day later . Closely related genera were unable to produce a similar inhibition . The inhibition was not the result of bacteriophages produced by the first strain . Neither was it the result of an immunological response by the host induced by the first strain . In additional experiments in day-old chickens, inhibition of an Escherichia coli Nalr strain and of a Citrobacter sp . Nalr strain was produced by the antibiotic-sensitive forms of the homologous strains while strains from other genera did not produce any inhibition . When an avirulent mutant of S . typhimurium was used for pre-treatment a statistically significant reduction in the excretion of the super-infecting S . typhimurium Nalr strain over several weeks was produced . A genus specific inhibition was reproduced in vitro by mixed culture experiments . Live cultures were necessary for in vitro inhibition . Killed cells or a culture supernatant produced no inhibition.

Minerva Med, 1987 May 15, 78(9), 617 - 22
{In vitro chemo-antibiotic sensitivity of gram-negative bacteria from various biological materials . Comparison between aztreonam and other agents}; Monaci E et al.; 527 Gram negative bacterial strains isolated from different biological substances were studied by chemo-antibiotic sensitivity . The examination was carried out by the agar diffusion test (Kirby-Bauer) . A very good sensitivity to aztreonam (E . coli, Serratia spp., Klebsiella spp., Proteus spp.), to amikacin (Pseudomonas spp., Enterobacter spp., Citrobacter spp.) and to norfloxacin (Citrobacter spp.) was found . Even when it was not the best, aztreonam was the second (Citrobacter spp.) or the third choice (Pseudomonas spp.), always near to the drug of first choice.

J Antimicrob Chemother, 1987 May, 19(5), 685 - 93
Enteric colonization with antibiotic resistant bacteria in nurses working in intensive care units; Chambers ST et al.; To determine whether nurses who worked in an intensive care unit (ICU) might acquire enteric colonization with Gram-negative aerobic bacteria from their patients, rectal swabs were obtained from the patients and nurses in the ICU, from nurses working in a coronary care unit (CCU) and from young women with urinary tract infection who had not been exposed to the hospital environment . The healthy women differed from the patients in that their enteric flora contained greater numbers of lactose fermenting bacteria, they were less often colonized by resistant organisms and when resistant bacteria were present they were less abundant than in the patients . Nurses who had been treated with antimicrobial agents during the preceding six months were colonized more often with antibiotic resistant enteric bacteria . There was no evidence of transmission of antibiotic resistant Escherichia coli from patients to nurses largely because this species had been virtually eliminated from the patients by intensive use of antimicrobial agents . Instead, several multiresistant species of Klebsiella, Citrobacter and Pseudomonas were isolated from the patients and ICU nurses . It was difficult, however, to define clearly patient-nurse controls who had no exposure to the ICU patients . These observations and those of other investigators emphasize the need for examination of control populations and of therapeutic use of antibiotics when examining the issue of environmental acquisition of antibiotic resistant bacteria.

Antimicrob Agents Chemother, 1987 May, 31(5), 829 - 30
In vitro susceptibility of Citrobacter species to various antimicrobial agents; Samonis G et al.; The in vitro activities of 16 antimicrobial agents against 14 clinical isolates of Citrobacter diversus and 27 isolates of Citrobacter freundii were studied . C . freundii isolates were more resistant, being susceptible only to amikacin, netilmicin, gentamicin, imipenem, ciprofloxacin, and enoxacin . C . diversus isolates were susceptible to many more of the agents tested.

Pediatr Neurol, 1987 May-Jun, 3(3), 178 - 80
Citrobacter diversus and neonatal brain abscess; Kline MW et al.; A 23-day-old infant presented with apnea and was found to have Citrobacter diversus meningitis and brain abscess . The organism persisted in brain abscess fluid for over 4 weeks despite adequate antibiotic therapy . Cranial computed tomography demonstrated persistent radiolucencies in both frontal lobes, and midline shift, long after completion of antibiotic therapy . Effective therapy of C . diversus meningitis and brain abscess may require use of an antibiotic active within phagocytes, and judicious surgical drainage . A high prevalence of brain abscess mandates cranial computed tomography for any infant with C . diversus meningitis.

Appl Environ Microbiol, 1987 May, 53(5), 1073 - 7
Coagglutination and enzyme capture tests for detection of Escherichia coli beta-galactosidase, beta-glucuronidase, and glutamate decarboxylase; Kaspar CW et al.; Polyclonal antibodies to Escherichia coli beta-galactosidase, beta-glucuronidase, and glutamate decarboxylase were used in coagglutination tests for identification of these three enzymes in cell lysates . Enzyme capture assays were also developed for the detection of E . coli beta-galactosidase and beta-glucuronidase . The enzymes were released by using a gentle lysis procedure that did not interfere with antibody-enzyme interactions . All three enzymes were detected in 93% (51 of 55) of the E . coli strains tested by coagglutination; two of the three enzymes were identified in the remaining 7% . Of 42 non-E . coli tested by coagglutination, only four nonspecifically agglutinated either two or three of the anti-enzyme conjugates . Thirty-two (76%) non-E . coli isolates were negative by coagglutination for all three enzymes . The enzyme capture assay detected the presence of beta-galactosidase in seven of eight and beta-glucuronidase in all eight strains of E . coli tested . Some strains of beta-galactosidase-positive Citrobacter freundii and Enterobacter cloacae were also positive by the enzyme capture assay, indicating that the antibodies were not entirely specific for E . coli beta-galactosidase; however, five other gas-positive non-E . coli isolates were negative by the enzyme capture assay . The coagglutination tests and enzyme capture assays were rapid and sensitive methods for the detection of E . coli beta-galactosidase, beta-glucuronidase, and glutamate decarboxylase.

Ann Clin Lab Sci, 1987 May-Jun, 17(3), 171 - 7
In vitro antimicrobial activity of diethyldithiocarbamate and dimethyldithiocarbamate against methicillin-resistant Staphylococcus; Taylor EH et al.; Staphylococcus aureus has appeared which is highly resistant to both methicillin and aminoglycosides . Current therapy involves long-term intravenous therapy of vancomycin . Since vancomycin is currently the only drug used to treat these patients, there is a need to develop additional antimicrobial therapy . The in vitro antimicrobial effect of the metal chelator, diethyldithiocarbamate (DDTC) and its structural analog dimethyldithiocarbamate (DMTC) were investigated . Both DDTC and DMTC were effective against S . aureus including methicillin-resistant S . aureus (MRSA) . By agar diffusion, DDTC at 10 micrograms per disk produced zone sizes of 12 to 21 mm and at 100 micrograms per disk produced zone sizes of 26 to 34 mm against MRSA . The DMTC produced slightly greater zone sizes against MRSA of 16 to 24 mm and 24 to 37 mm for 10 micrograms per disk and 100 micrograms per disk, respectively . The minimum inhibitory concentration (MIC) for DMTC against MRSA was 6 micrograms per ml . Both DDTC and DMTC were also effective against enterococci, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Salmonella species, Serratia marcescens and Citrobacter freundii at 100 micrograms per disk . The MICs of DMTC for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Salmonella and Citrobacter freundii were approximately 128 micrograms per ml while the MICs for Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens was greater than or equal to 256 micrograms per ml . In addition, DMTC was synergistic with gentamicin against MRSA and coagulase-negative staphylococcus species, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa . Additive and synergistic effects of DMTC were displayed with gentamicin against S . aureus including methicillin-resistant S . aureus.(ABSTRACT TRUNCATED AT 250 WORDS)

J Bacteriol, 1987 May, 169(5), 1923 - 8
Inactivation of the ampD gene causes semiconstitutive overproduction of the inducible Citrobacter freundii beta-lactamase; Lindberg F et al.; In Citrobacter freundii and Enterobacter cloacae, synthesis of AmpC beta-lactamase is inducible by the addition of beta-lactams to the growth medium . Spontaneous mutants that constitutively overproduce the enzyme occur at a high frequency . When the C . freundii ampC beta-lactamase gene is cloned into Escherichia coli together with the regulatory gene ampR, beta-lactamase expression from the clone is inducible . Spontaneous cefotaxime-resistant mutants were selected from an E . coli strain carrying the cloned C . freundii ampC and ampR genes on a plasmid . Virtually all isolates had chromosomal mutations leading to semiconstitutive overproduction of beta-lactamase . The mutation ampD2 in one such mutant was caused by an IS1 insertion into the hitherto unknown ampD gene, located between nadC and aroP at minute 2.4 on the E . coli chromosome . The wild-type ampD allele cloned on a plasmid could fully trans-complement beta-lactamase-overproducing mutants of both E . coli and C . freundii, restoring the wild-type phenotype of highly inducible enzyme synthesis . This indicates that these E . coli and C . freundii mutants have their lesions in ampD . We hypothesize that induction of beta-lactamase synthesis is caused by blocking of the AmpD function by the beta-lactam inducer and that this leads directly or indirectly to an AmpR-mediated stimulation of ampC expression.

Am J Med, 1987 Apr 27, 82(4A), 295 - 300
Oral ciprofloxacin in the treatment of elderly patients with complicated urinary tract infections due to trimethoprim/sulfamethoxazole-resistant bacteria; Preheim LC et al.; The effectiveness and safety of ciprofloxacin, a new quinolone antibiotic, were prospectively evaluated in the treatment of patients with complicated urinary tract infections caused by gram-negative organisms resistant to trimethoprim/sulfamethoxazole . Twenty-five elderly (mean age, 70.4 years) patients (24 men and one woman) were enrolled . Initial pathogens included Pseudomonas aeruginosa (15 isolates), Escherichia coli (five isolates), Enterobacter aerogenes (one isolate), Citrobacter freundii (one isolate), Serratia species (two isolates), Proteus vulgaris (one isolate), and enterococcus (one isolate) . Patients received 500 mg of ciprofloxacin orally twice daily for one week (mean, 6.98 days) . Results of urine cultures obtained during therapy were negative in all cases, and at one week post-therapy, 21 of 25 (84 percent) infections were cured . Four patients experienced a relapse with P . aeruginosa . Repeat urine culture specimens were obtained at four to six weeks from 14 patients who had cures at one week post-therapy, and seven continued to have cures . Three patients had late relapses with P . aeruginosa, E . coli, or Serratia marcescens, and four were reinfected with new strains . Five patients who received concomitant oral antacids had lower mean peak and trough serum ciprofloxacin levels than did patients not receiving antacids (p less than 0.05, Wilcoxon rank sum test) . Mild adverse effects were seen in seven patients: eosinophilia (one patient), eosinophilia and reduced white blood cell count (one patient), crystalluria (one patient), granular casts (one patient), elevation of serum creatinine and blood urea nitrogen levels (one patient), and nausea (two patients), but none warranted discontinuation of ciprofloxacin therapy . P . aeruginosa isolates from two patients who experienced a relapse showed increases in minimal inhibitory concentrations from 0.13 to 0.5 and 2.0 micrograms/ml, respectively, to ciprofloxacin and other antibiotics . Orally administered ciprofloxacin was a safe and effective therapy for complicated urinary tract infections in elderly patients.

Chemioterapia, 1987 Apr, 6(2), 79 - 81
A comparative study of the sensitivity of bacteria of various origin to ofloxacin; Gubina M; The sensitivity of 6 antimicrobials (chloramphenicol, tetracycline, ampicillin, cephalothin, trimethoprim/sulfamethoxazole and ofloxacin) was tested on 174 bacteria isolated from three sources: 60 from wounds, 84 from urine and 30 from bronchial excretions . Hospital-borne bacteria were compared to those of non-hospital origin for their susceptibility . Consecutively, Pseudomonas aeruginosa (24 strains), Escherichia coli (58), Klebsiella sp . (13), Enterobacter sp . (3), Citrobacter sp . (3), Enterococcus sp . (25) and Staphylococcus sp . (48) were tested . With the exception of 7.1% of bacteria (Enterococcus) isolated from urine, 96.6% of all strains tested were sensitive to ofloxacin.

J Clin Microbiol, 1987 Mar, 25(3), 531 - 5
Production of Vi monoclonal antibodies and their application as diagnostic reagents; Tsang RS et al.; Serum antibodies to Vi antigen were detected in mice immunized with the purified antigen but not with Vi-bearing Salmonella typhi whole cells . Fusion of the spleen cells from one of the Vi antibody-producing mice with NSI myeloma cells produced four stable hybridomas that secreted antibodies to Vi . Monoclonal antibodies from these four clones were all of the immunoglobulin G class and, as determined by competition, appeared to have the same epitope specificity . Despite their immunoglobulin G nature, mouse ascitic fluids induced by one of the hybridomas strongly agglutinated the Vi-positive strains of S . typhi, S . dublin, and Citrobacter strain 5396/38 . Thus, 10 clinical isolates of S . typhi but not 98 strains of other bacteria were reactive in slide agglutination tests with the monoclonal antibodies.

Am J Dis Child, 1987 Mar, 141(3), 335 - 42
Imipenem and cilastatin in acute osteomyelitis and suppurative arthritis . Therapy in infants and children; Freij BJ et al.; Twenty-five infants and children with acute osteomyelitis (n = 7), suppurative arthritis (n = 11), or both (n = 7) were treated with imipenem and cilastatin sodium . Patients ranged in age from 5 months to 11.3 years . Needle aspiration of infected sites was performed in all patients, and 11 (44%) required further surgical drainage . Imipenem and cilastatin sodium in a dosage of 100 mg/kg/d was used for children 3 years of age or younger, while older ones received 60 mg/kg/d intravenously, divided in four equal doses . Bacterial pathogens were identified in 15 patients (60%): Staphylococcus aureus in five, Haemophilus influenzae b in four, Pseudomonas aeruginosa in two, Streptococcus pneumoniae in one, group A Streptococcus in one, Kingella kingae in one, and Citrobacter amalonaticus in one . All isolates were susceptible to imipenem in vitro . Imipenem and cilastatin therapy was continued for a median of six days followed by treatment with appropriate orally administered antibiotics . Median peak serum bactericidal titers after imipenem and cilastatin infusions were 1:512 for S aureus, 1:32 for H influenzae b, 1:512 for streptococci, and 1:16 for gram-negative rods . All but one patient with P aeruginosa osteomyelitis responded favorably to imipenem and cilastatin . The median duration until resolution of symptoms was six days . Imipenem and cilastatin infusions were well tolerated, and side effects included maculopapular rash in one patient, watery diarrhea in one, and mild transient elevation of alanine aminotransferase levels in three . Because of imipenem and cilastatin's unusually broad spectrum of activity and its relative safety, this drug combination can be used for the initial, empiric therapy of acute bone and joint infections in pediatric patients.

Klin Monatsbl Augenheilkd, 1987 Mar, 190(3), 161 - 6
{Etiology of corneal ulcers with special reference to bacterial genesis}; Bialasiewicz AA et al.; The authors report on 134 patients (141 eyes) seen between May 1982 and December 1985 with corneal ulcers with or without hypopyon . Eight patients (11 eyes) had a facial palsy, 7 (7 eyes) a varicella zoster infection, 1 (2 eyes) a marginal ulcer ("furrow keratitis") associated with collagenosis, 29 (29 eyes) an ulcerative keratitis with endophthalmitis, 1 (2 eyes) a pemphigoid-associated ulcer and 90 (92 eyes) a herpetic infection . Pathogenic bacterial strains were isolated from 20 patients: 10 coagulase-positive Staphylococcus aureus (4 coinfections), 3 Pseudomonas aeruginosa (1 coinfection), 2 Proteus mirabilis (1 coinfection), 2 Escherichia coli and Enterobacter cloacae, Citrobacter freundii and beta-hemolyzing streptococci as well as enterococci in one case each, and non-hemolyzing streptococci and alpha-hemolyzing streptococci in two cases each as coinfections . A comparison of the range of bacterial strains of postoperative endophthalmitis and kerato-/conjunctivitis with bacterial corneal ulcers revealed a high percentage of gram-negative organisms in the latter . Laboratory work-up should include microscopy, agar plating and differentiation as well as antibiotic sensitivity testing and modern immunofluorescent direct techniques . Management includes bactericidal topical and systemic antibiotic regimens as well as surgical procedures if necessary, e.g., perforating tectonic and mini-keratoplasty, and conjunctival flapping followed by lamellar keratoplasty.

Prikl Biokhim Mikrobiol, 1987 Mar-Apr, 23(2), 192 - 8
{Kinetic study of 3,4-dihydroxyphenyl-L-alanine synthesis in Citrobacter freundii cells immobilized in carrageenan}; Voivodov KI et al.; A kinetic study was carried out of the enzymatic synthesis of 3,4-dihydroxyphenyl-L-alanine (DOPA) by the Citrobacter freundii 62 cells, possessing tyrosine-phenol-lyase (TPL) activity, immobilized in carrageenan, and optimum conditions of the reaction were found . The dependence of the TPL activity and its stability on the conditions of the DOPA synthesis was investigated . The TPL activity was higher and more stable in the immobilized cells as compared to free ones.

J Clin Microbiol, 1987 Feb, 25(2), 439 - 41
Rapid catalase supplemental test for identification of members of the family Enterobacteriaceae; Chester B et al.; A simple, rapid, semiquantitative slide catalase test useful for differentiating members of the family Enterobacteriaceae is described . Judging by the time required for appearance of oxygen bubbles in 3% hydrogen peroxide, the immediate catalase reactors were Yersinia, Serratia, Proteus, Morganella, Providencia, Cedecea, and Hafnia spp . The delayed catalase reactors were Escherichia, Shigella, Klebsiella, Enterobacter, Salmonella, Citrobacter, Edwardsiella, Kluyvera, and Tatumella spp . This information is especially useful for differentiating Serratia from Enterobacter spp . and Yersinia from Escherichia and Shigella spp.

J Antimicrob Chemother, 1987 Feb, 19(2), 175 - 85
In-vitro activity of two new quinolone antimicrobial agents, S-25930 and S-25932 compared with that of other agents; Neu HC et al.; S-25930 and S-25932, two new 4-quinolones, were compared to ciprofloxacin, enoxacin, ofloxacin, norfloxacin, cefotaxime, gentamicin, trimethoprim, and ampicillin . S-25930 and S-25932 inhibited 90% of Enterobacteriaceae at less than or equal to 1 mg/l, usually differing only two-fold . The MIC90 for Pseudomonas aeruginosa was 8 mg/l for S-25930 and 16 mg/l for S-25932, compared to MICs of 1 to 8 for the other four quinolones . Both drugs inhibited Enterobacter cloacae, Serratia marcescens and Citrobacter freundii resistant to cefotaxime and Klebsiella species resistant to gentamicin and trimethoprim . The MICs90 were 0.125 and 0.25 mg/l against staphylococci, including methicillin-resistant Staphylococcus aureus and were superior to the MICs of other quinolones; activity against haemolytic streptococci at 1-2 mg/l was also superior . S-25930 and S-25932 showed rapid bactericidal activity at the MBC concentration and both agents showed post-antibiotic suppression of growth of bacteria . The agents were active in acid medium, but activity was reduced by magnesium at 9 mM . A stepwise increase in resistance was produced by serial passage in increasing concentrations of drug.

Am Ind Hyg Assoc J, 1987 Feb, 48(2), 106 - 10
Seasonal variation in aerobic bacterial populations and endotoxin concentrations in grain dusts; DeLucca AJ 2nd et al.; Settled and respirable grain dust samples were collected at intervals over a 16-month period at two grain terminals on the lower Mississippi River . Total and gram-negative aerobic bacterial (GNB) populations, as well as endotoxin concentrations, were studied . Plate counts indicated that no viable bacteria were found to be present in the respirable samples . Endotoxin concentrations ranged from 0.0 to 6.4 ng (0.0 to 7.9 ng/m3 air) per respirable sample, indicating that bacteria were once viable in dust of respirable size or contamination occurred from larger, non-respirable particles . Numbers of bacteria from settled dusts, both total and GNB, remained relatively stable; however, the genera of the GNB populations varied . Enterobacter agglomerans was the predominant species in warm months, but not in winter . Pseudomonas and Klebsiella species increased in winter and decreased in summer . Other genera found were Citrobacter and Serratia . Endotoxin concentrations in settled dust samples ranged from 1.7 to 5.6 ng/mg dust.

Acta Pathol Microbiol Immunol Scand {B}, 1987 Feb, 95(1), 85 - 7
Failure to detect hydrogen-sulphide production in lactose/sucrose-fermenting Enterobacteriaceae, using triple sugar iron agar; Kolmos HJ et al.; Triple Sugar Iron agar failed to detect hydrogen sulphide in 44 out of 69 hydrogen-sulphide producing strains of Enterobacteriaceae, which at the same time fermented lactose and/or sucrose . The species involved were Salmonella typhi, Salmonella enteritidis, Citrobacter freundii, Escherichia coli, and Proteus vulgaris . By contrast, no false-negative reactions were observed in 74 strains, which fermented neither lactose nor sucrose . Failure to detect hydrogen sulphide was probably due to acidification of the medium following the fermentation of carbohydrates . A medium without carbohydrates is preferable in diagnostic situations where hydrogen-sulphide detection is of great importance.

J Bacteriol, 1987 Feb, 169(2), 687 - 93
Cloning of genes from members of the family Enterobacteriaceae with mini-Mu bacteriophage containing plasmid replicons; Groisman EA et al.; An in vivo cloning system that uses derivatives of the Escherichia coli bacteriophage Mu with plasmid replicons has been extended to five different species of the family Enterobacteriaceae . Mu and these mini-Mu replicon elements were introduced into strains of E . coli, Shigella flexneri, Salmonella typhimurium, Citrobacter freundii, and Proteus mirabilis by infection, by transformation, or by conjugation with newly constructed broad-host-range plasmids containing insertions of these elements . Lysates from these cells, lysogenic for Mu and mini-Mu elements, were used to infect sensitive recipient strains of E . coli, S . typhimurium, and C . freundii . Drug-resistant transductants had mini-Mu replicon elements with inserts of different DNA sequences . All of the lysogens made could be induced to yield high phage titers, including those coming from strains that were resistant to Mu and Mu derivatives . Clones of 10 particular genes were isolated by their ability to complement specific mutations in the recipient strains, even in the presence of the E . coli K-12 restriction system . Some of the mini-Mu replicon elements used contained lac gene fusing segments and resulted in fusions of the lac operon to control regions in the cloned sequences.

J Bacteriol, 1987 Feb, 169(2), 758 - 63
Common mechanism of ampC beta-lactamase induction in enterobacteria: regulation of the cloned Enterobacter cloacae P99 beta-lactamase gene; Lindberg F et al.; Expression of the chromosomal beta-lactamase from the ampC gene in inducible in both Enterobacter cloacae and Citrobacter freundii . Cloning of ampC as well as its regulatory gene, ampR, from E . cloacae P99 revealed a gene organization indentical to that of C . freundii in the corresponding region . Although almost no similarities could be found between the restriction maps of ampC and ampR in the two species, the genes cross-hybridize . Also, both ampR gene products have a size of about 31,000 . The regulatory features of E . cloacae beta-lactamase induction are very similar to those in C . freundii, i.e., beta-lactamase synthesis is repressed by AmpR in the absence, and stimulated in the presence, of inducer . The AmpR function can be transcomplemented between the two species, but there are quantitative regulatory aberrations in such hybrids, in contrast to the total complementation obtained within each system . These results suggest that the mechanism of beta-lactamase induction is the same in E . cloacae, C . freundii, and other gram-negative bacteria with inducible chromosomal beta-lactamase expression.

FEBS Lett, 1987 Jan 26, 211(2), 175 - 8
Structure determination of the O-specific polysaccharides from Citrobacter O4- and O27-lipopolysaccharides by methylation analysis and one- and two-dimensional 1H-NMR spectroscopy; Romanowska E et al.; Using sugar and methylation analyses, and one- and two-dimensional 1H-NMR spectroscopy at 500 MHz it was established that poly-beta-1,2-4-deoxy-D-arabinohexopyranose occurs as O-specific chains of lipopolysaccharides in Citrobacter serotypes O4, O27 and O36 . Strong serological cross-reactivity between these serotypes is in full agreement with the chemical identity of their O-specific polysaccharides.

Pediatr Infect Dis J, 1987 Jan, 6(1), 50 - 5
Outbreak of neonatal Citrobacter diversus meningitis in a suburban hospital; Lin FC et al.; Between February and June, 1983, four cases of Citrobacter diversus neonatal meningitis were identified at a suburban Baltimore hospital . One of the 4 infants died at age 13 months, 2 (both of whom had brain abscesses) have evidence of developmental delay and 1 appears to be normal after 33 months of follow-up . A review of microbiology records revealed that C . diversus had been present in the hospital nursery prior to identification of the first infant with meningitis, with isolation from infants born 7 months, 4 months and 4 days, respectively, before the first meningitis case . C . diversus was isolated from 21 infants born during the outbreak period and from hand or rectal cultures of 5 nursing personnel . All isolates were biotype E, with two distinct clusters of cases identified on the basis of plasmid profile and serotype . In a case-control study isolation of C . diversus was significantly associated with male sex, low birth weight and care by house pediatricians . The outbreak was controlled by stringent infection control measures and exclusion of personnel carriers . During the 24 months following the outbreak 3431 babies discharged from the nursery were cultured for C . diversus; 3 were colonized with the organism.

Arkh Patol, 1987, 49(7), 80 - 2
{Practical recommendations for examining the pulmonary pleura of fetuses and newborn infants using contact microscopy}; Andreeva TV; It has been found that the pleura visceralis of fetuses and neonates is consistently involved in inflammatory processes occurring in pneumonias caused by Gram-negative organisms (Citrobacter sp., Escherichia coli, Klebsiella sp., Serratia marcescens) and may display signs of infection when the pneumonia is not yet apparent . This property of the pleura as a filtration membrane may help the pathologist in the early diagnosis of infectious disorders in neonates . Recommendations are given on the excision of pulmonary pleura and the staining of its preparations for contact microscopy whereby these can be examined during or shortly after the autopsy . Morphologic features of the infections caused by the indicated organisms are detailed . Citrobacter infections, for example, show a preponderance of macrophage responses, Klebsiella-caused lesions are characterized by involvement of the lymphatic bed, while those due to S . marcescens have hemolysis in the lung tissue and pleura as their main feature.

Chemotherapy, 1987, 33(3), 165 - 71
Comparative in vitro activity of carumonam (Ro 17-2301/AMA-1080), a new monobactam, and ceftriaxone against aerobic or facultative gram-negative isolates; Barclay CA et al.; Carumonam (Ro 17-2301/AMA-1080) is a new monobactam antibiotic . A comparative in vitro evaluation with ceftriaxone was undertaken against 153 gram-negative clinical aerobic or facultative bacteria, both producers and nonproducers of beta-lactamase . Results indicated that carumonam had an enhancement of activity for Pseudomonas aeruginosa, Klebsiella oxytoca, Citrobacter freundii and Enterobacter cloacae and parallelled that of ceftriaxone against Escherichia coli, Klebsiella pneumoniae, Proteus spp . and Serratia marcescens . It can be concluded that carumonam could be an alternative of interest for the treatment of patients with infections due to gram-negative strains presumably or proven to be multiresistant.

Chemotherapy, 1987, 33(2), 103 - 9
Comparative in vitro antimicrobial activity of carumonam (Ro 17-2301) and its influence on the activity of other antibiotics; Hoepelman IM et al.; The antimicrobial activity of carumonam (Ro 17-2301) was compared with that of 20 antibiotics against 338 clinical isolates . Carumonam did not possess activity against gram-positive cocci, MIC90 of carumonam were less than or equal to 0.5 mg/l for Enterobacteriaceae, except for Citrobacter (less than or equal to 8 mg/l) and less than or equal to 32 mg/l for nonfermenters . It was slightly more active than aztreonam against gentamicin-resistant bacilli (MIC90 less than or equal to 64 vs greater than or equal to 256) . Combinations of carumonam with antibiotics with activity against gram-positive microorganisms were indifferent.

Chemotherapy, 1987, 33(1), 28 - 39
In vitro activity of two new aryl-fluoroquinolone antimicrobial agents, difloxacin (A-56619) and A-56620 compared to that of other antimicrobial agents; Hirschhorn L et al.; The in vitro activity of difloxacin (A-56619) and A-56620, two new aryl-difluoroquinolones, was compared to that of other new quinolones and several parenteral and oral antimicrobial agents . A-56620 inhibited 90% of Enterobacteriaceae at less than or equal to 1 microgram/ml, Staphylococcus aureus 0.25 micrograms/ml, hemolytic streptococci 2 micrograms/ml, Pseudomonas aeruginosa 2 micrograms/ml, Bacteroides sp . and Clostridium at 8 micrograms/ml . A-56620 was equal or 2-fold more active than norfloxacin and ofloxacin, and 2-8-fold less active than ciprofloxacin . Difloxacin had similar in vitro activity with many isolates but usually was 2-8-fold less active than A-56620 . Both agents inhibited beta-lactamase positive Haemophilus influenzae (MIC 0.015 micrograms/ml) and Neisseria gonorrhoeae (MK less than or equal to 0.008 micrograms/ml) . Both agents were more active against streptococci and Streptococcus pneumoniae than norfloxacin, ofloxacin and enoxacin, but not more active than ciprofloxacin . They inhibited Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cephalosporins and methicillin-resistant S . aureus and Staphylococcus epidermidis . Spontaneously resistant mutants were seen with Enterobacteriaceae, P . aeruginosa and S . aureus at a frequency similar to that found for other new quinolones . These agents show overall in vitro activity comparable to other quinolones in clinical trial or recently approved for clinical use.

J Clin Microbiol, 1987 Jan, 25(1), 42 - 4
Premarket evaluation of IDS RapID SS/u system for identification of urine isolates; Halstead DC et al.; A total of 170 fresh clinical urine isolates were tested with a premarket configuration of the RapID SS/u system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.), a qualitative micromethod for the identification of selected organisms commonly isolated from urine specimens . Results were compared with those obtained with conventional methods of identifying gram-positive isolates and with the AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.), utilizing Gram-Negative Identification cards for the identification of gram-negative rods . Organisms representing 12 taxa were included in the study . Of the 170 isolates, 163 (95.9%) were correctly identified . A total of 144 strains (84.7%) were correctly identified without additional testing, whereas 19 isolates (11.2%) required further testing . Seven isolates (4.1%) were incorrectly identified . The SS/u system required minimal hands-on time inoculate and interpret reactions . Discrepancies most often occurred with regard to misinterpretation of Escherichia coli and Enterobacter sp . as Citrobacter sp . The IDS RapID SS/u system may indeed prove valuable for the rapid manual identification of urine isolates.

J Clin Microbiol, 1987 Jan, 25(1), 110 - 4
Production of Escherichia coli STa-like heat-stable enterotoxin by Citrobacter freundii isolated from humans; Guarino A et al.; Citrobacter species are often present in the stools of children and are generally considered a normal component of the intestinal microflora . Previous reports suggested that they might act as enteric pathogens . Aiming at defining the role of Citrobacter species in inducing diarrhea, we looked for their presence in the stools of 328 children with diarrhea and in 108 controls . Citrobacter strains were isolated from 46 patients (14%) and 7 controls (6.5%) (P less than 0.05) . All isolates were tested for heat-stable (ST) and heat-labile (LT) enterotoxin . No LT-producing organisms were found . Three C . freundii strains, all isolated from children with diarrhea, elaborated an enterotoxin detected by the suckling mouse assay . A crude extract was prepared by acetone precipitation and a sequential ultrafiltration technique . The enterotoxin was heat stable, and its estimated molecular weight was between 2,000 and 10,000 . Citrobacter enterotoxin was soluble in methanol and stable at acid and neutral pHs but not above pH 8, and its activity was destroyed by treatment with 2-mercaptoethanol . Citrobacter enterotoxin was inactive in the 18-h rabbit ileal loop test . All these characteristics closely resemble STa produced by Escherichia coli . The time course of Citrobacter enterotoxin-induced intestinal secretion in suckling mice was similar to that of E . coli STa . The enterotoxin produced by C . freundii cross-reacted with monoclonal antibodies raised against E . coli STa . These results suggest that C . freundii is capable of inducing diarrhea through the production of an E . coli-like STa, and its presence in the stools of patients with diarrhea should be considered as that of a possible etiologic agent.

J Hyg Epidemiol Microbiol Immunol, 1987, 31(4), 441 - 4
The morphology and nucleotide composition of DNA of Citrobacter phages; Gabrilovich IM et al.; Citrobacter phages 38/37, 31/37, 40/1 and 8/5, isolated from lysogenic cultures, were concentrated and purified by 2 cycles of differential centrifugation . Electron microscopy of the phages has shown that their particles have similar morphology and that they relate to the morphological group A1 . The heads of the phages are hexagonal, 50 +/- 2 nm in diameter . The tail of the phage is straight, 112-152 nm in length, with a contracting sheath 11.5-12.5 nm wide . The tails of the phages 38/37 and 40/1 were found to be slightly longer in comparison with the phages 31/37 and 8/5 . Chromatographic investigation of DNA preparations of the phages revealed the presence of 4 nitrous bases . Identification of the latter permitted us to relate them to common nitrous bases . DNA of the phages is double-stranded and belongs to a weakly expressed guanine-cytosine type . The content of guanine and cytosine in DNA of the phage 38/37 amounts to 56.68%, that of the phage 31/37 to 56.75, of the phage 40/1 to 57.36% and of the phage 8/5 to 55.58% . No substantial variations were observed in the DNA composition of the phages.

Rev Fac Cien Med Univ Nac Cordoba, 1987, 45(2), 33 - 5
{Pyogenic hepatic abscess}; Jakob E et al.; Ten patients, 6 men and 4 women, with a mean age of 53 years, having pyogenic liver abscess, were studied to review the principal features of the clinical and bacteriological diagnosis . In 9 cases the abscess was located in the right hepatic lobe . Bacteriological diagnosis was made in 6 cases: the etiology was nonmicrobian in 3 and two microorganisms were found in the other 3 cases . The isolated pathogens were: Escherichia coli (3 cases), Staphylococcus sp (3 cases), Enterobacter agglomerans (1 case), Citrobacter sp (1 case), Streptococcus sp (1 case) . The basic clinical pattern included fever in 9 patients, pain in upper right side of the abdomen in 8, jaundice in 5 and respiratory symptoms in 5 . In 2 cases the diagnosis was confirmed by ultrasonography, in 2 by scintigraphy and in 3 both methods were used . Surgical drainage was practiced in 7 patients, with favorable course in 6 . Three patients were not operated; 2 died and the third was cured with medical treatment . The importance of the clinical suspicion even with few data is pointed out, specially prolonged fever with painful syndrome in upper right side of the abdomen . The aid of the diagnosis imaging is valuable for verification . The precise bacteriological diagnosis by culture of the material obtained in surgery or by percutaneous drainage of the abscess allows the selection of the most suitable antibiotic therapy.

Diagn Microbiol Infect Dis, 1987 Jan, 6(1), 59 - 67
Ceftazidime and amikacin alone and in combination against Pseudomonas aeruginosa and Enterobacteriaceae; Moody JA et al.; The efficacy of ceftazidime alone and combined with amikacin was studied in a rabbit model simulating closed-space infections at locally neutropenic sites . Six strains of Pseudomonas aeruginosa, and six Enterobacteriaceae (two strains each of Klebsiella pneumoniae and Serratia marcescens and one strain each of Escherichia coli and Citrobacter freundii) in pooled rabbit serum were each inoculated into separate subcutaneous semipermeable chambers . Intramuscular antibiotic therapy was begun 4 hr later with ceftazidime (50 mg/kg) alone and combined with amikacin (15 mg/kg) for Enterobacteriaceae or ceftazidime (100 mg/kg) alone and combined with amikacin (15 mg/kg) for pseudomonads every 6 hr for 16 doses . Amikacin alone was ineffective for all 12 strains . Ceftazidime alone was successful (greater than or equal to 5.5 log10 colony forming units (CFU)/ml decrease from drug-free control) in eliminating five of six Enterobacteriaceae but was not successful against any of the pseudomonads . Ceftazidime plus amikacin was successful against the same five of six Enterobacteriaceae and five of six pseudomonads . The best in vitro tests for the prediction of in vivo outcome were high inoculum (greater than or equal to 7 log10 CFU/ml) susceptibility, checkerboard synergism testing, and conventional inoculum time-kill rates at concentrations of antimicrobials simulating extravascular levels obtained in vivo.

Gene, 1987, 61(3), 243 - 52
The araC gene of Citrobacter freundii; Burke KA et al.; The araC gene of Citrobacter freundii was cloned into plasmid pBR322 and expressed in Escherichia coli and Salmonella typhimurium . The nucleotide sequence and the predicted translational product were determined and compared to those of E . coli, S . typhimurium and Erwinia carotovora . The predicted translational product is 281 amino acids (aa) long, identical in size to that of S . typhimurium, and is 11 and 29 aa shorter than that of E . coli and E . carotovora, respectively . The nucleotide sequence of the araC gene of C . freundii is 83% homologous to the araC genes of both E . coli and S . typhimurium, but only 60% homologous to that of E . carotovora with respect to the regions they share . The predicted amino acid sequence is highly conserved and shows 96% and 94% homology to S . typhimurium and E . coli, respectively . E . carotovora shows only a 58% aa homology . The activator and autoregulatory activities of each plasmid encoded AraC protein in a S . typhimurium araC::lacZ protein fusion strain were examined.

Eur J Biochem, 1986 Dec 15, 161(3), 557 - 64
Core region of Citrobacter lipopolysaccharide from strain PCM 1487 . Structure elucidation by two-dimensional 1H-NMR spectroscopy at 500 MHz and methylation analysis/mass spectrometry; Romanowska E et al.; The core structure of Citrobacter PCM 1487 lipopolysaccharide has been established using methylation analysis/mass spectrometry, chemical degradations and one- and two-dimensional 1H-NMR spectroscopy at 500 MHz . 1H-NMR assignments are given for all sugar components of the core oligosaccharide . In the formula shown below, the alternative locations of branch terminal heptose (LDHep) and diphosphorylethanolamine (PPEtN) residues are marked by dashed lines; dOclA stands for 3-deoxy-D-manno-octulosonic acid . (Formula: see text) . The sample of the core oligosaccharide showed some microheterogeneity due to a slightly incomplete substitution by terminal N-acetylgalactosamine and a partial splitting of diphosphorylethanolamine residues.

Zh Mikrobiol Epidemiol Immunobiol, 1986 Dec, (12), 12 - 5
{Ability of Citrobacter freundii strains isolated in acute intestinal infections to produce LT-enterotoxin}; Bondarenko VM et al.; C . freundii enteropathogenic strains were found to be capable of producing choleroform thermolabile enterotoxin . Thus, in the study of 96 C . freundii strains 38 enterotoxin-producing cultures (39.5%) were revealed by means of the molecular-biological techniques and 29 such cultures (30.0%), by means of the radioimmunoassay (RIA) . 100% coincidence was noted in the results of tests for enterotoxigenicity, made by means of RIA or hybridization techniques with the use of the LT-probe containing a cloned fragment with the gene coding the synthesis of LT-enterotoxin in enterotoxigenic Escherichia coli . At the same time only 29 out of 38 Citrobacter strains found to be positive in the hybridization tests, yielded the positive result when tested in RIA for the presence of LT-enterotoxin . This fact should be taken into consideration in the determination of enterotoxin-producing cultures isolated in acute enteric infections, as the method of genetic probing is capable of bringing out the genetic information in bacteria even in the absence of its phenotypical expression.

J Appl Bacteriol, 1986 Dec, 61(6), 541 - 5
Evaluation of a commercial beta-glucuronidase test for the rapid and economical identification of Escherichia coli; Perez JL et al.; A commercial beta-glucuronidase (beta-GUR) test for the rapid and economical identification of Escherichia coli was evaluated . A total of 762 clinical strains and 228 environmental isolates were studied . More than 95% of the E . coli strains were found to be beta-GUR positive . Thirty-one clinical isolates of Shigella sonnei, 10 of Enterobacter cloacae, eight of Enterobacter aerogenes, nine of Citrobacter freundii and one of Salmonella enteritidis also gave positive results . The enzyme beta-GUR was also detected in two environmental strains of E . cloacae and one C . freundii . A comparative study between the beta-GUR test and the conventional identification system was carried out in 233 consecutive isolates of lactose positive enterobacteria . Agreement was observed in 223 cases and 190 E . coli strains were correctly identified using this test . Discrepancies were found in 10 cases: nine E . coli were beta-GUR negative and one C . freundii was beta-GUR positive . Escherichia coli was the only species positive for both beta-GUR and indole tests . This procedure permits a rapid, easy, precise and inexpensive identification of E . coli . beta-GUR positive Enterobacter strains have not previously been described.

Antimicrob Agents Chemother, 1986 Dec, 30(6), 828 - 34
In vitro activity against aerobic and anaerobic gram-positive and gram-negative bacteria and beta-lactamase stability of RS-533, a novel carbapenem; Neu HC et al.; RS-533 is a novel carbapenem antibiotic . Its activity was compared with that of imipenem and the new cephalosporins, aztreonam, piperacillin, and tobramycin . RS-533 had activity comparable to that of imipenem, inhibiting the majority of the Enterobacteriaceae, streptococci, staphylococci, and Bacteroides species at concentrations of less than or equal to 2 micrograms/ml . RS-533 inhibited Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens resistant to ceftazidime, aztreonam, and cefoperazone, but RS-533 did not inhibit all methicillin-resistant Staphylococcus aureus or Pseudomonas maltophilia . It inhibited tobramycin-resistant members of the Enterobacteriaceae and Pseudomonas aeruginosa . RS-533 was stable against attack by common chromosomal and plasmid-mediated beta-lactamases and was an effective inhibitor of many beta-lactamases.

J Antibiot (Tokyo), 1986 Dec, 39(12), 1744 - 53
Delayed inactivation of Citrobacter freundii cephalosporinase by 6 beta-{3-(2-chlorophenyl)-5-methyl-4-isoxazolyl}penicillin sulfone; Yamaguchi A et al.; When Citrobacter freundii cephalosporinase was incubated with 6 beta-{3-(2-chlorophenyl)-5-methyl-4-isoxazolyl}penicillin sulfone (cloxacillin sulfone) in phosphate buffer, the enzyme was suddenly inactivated just after the completion of enzymatic degradation of the cloxacillin sulfone . Such delayed inactivation was due to a secondary inhibitor formed from cloxacillin sulfone during the incubation period . The inactivation was delayed due to the protection of the enzyme by cloxacillin sulfone from the attack of the secondary inhibitor . Phosphate anions were essential for the formation of the secondary inhibitor . However, once the secondary inhibitor was formed, the inactivation occurred in the absence of phosphate anions although the degree of the inactivation depended on the length of the preincubation period with phosphate anions . The main species (more than 80%) of the inactivated enzyme was detected as a single protein band with a slightly lower pI value than that of the native enzyme on isoelectric focusing on a plate.

J Antimicrob Chemother, 1986 Dec, 18 Suppl E, 15 - 22
The effects on beta-lactam susceptibility of phenotypic induction and genotypic derepression of beta-lactamase synthesis; Shannon K et al.; We have compared the ability of beta-lactam antibiotics to induce beta-lactamase synthesis and antagonize the in-vitro activity of other beta-lactams and also to select mutants with derepressed beta-lactamase synthesis amongst representative Gram-negative bacilli that produce inducible beta-lactamases . Both imipenem and cefoxitin were potent inducers of beta-lactamase and were able to antagonize the activity of other beta-lactams against isolates of Enterobacter cloacae, Citrobacter freundii and Pseudomonas aeruginosa when the two beta-lactams were present simultaneously . However, there was no antagonism for any compound against any of the organisms when the imipenem or cefoxitin was removed immediately before susceptibility to the other compounds was measured . Cefotaxime was a less potent inducer of beta-lactamase and failed to antagonize the activity of other compounds, even when present concurrently with them . Neither imipenem nor cefoxitin induced beta-lactamase synthesis in a strain of Escherichia coli, nor did they antagonize the activity of other beta-lactams against this strain . Imipenem was compared with cefotaxime and cefoxitin as an agent for the selection of beta-lactam-resistant variants . Resistant variants were obtained from isolates of Ent . cloacae, C . freundii and P . aeruginosa when cefotaxime or cefoxitin was used as the selective agent . Most of them synthesized beta-lactamase constitutively and showed reduced susceptibility to a wide range of beta-lactams, but not to imipenem . Variants with reduced susceptibility to imipenem were obtained only from the two isolates of P . aeruginosa . They did not show cross resistance to other beta-lactams and were not distinguishable from the parent strains in beta-lactamase production.

Farmakol Toksikol, 1986 Nov-Dec, 49(6), 79 - 83
{Clinico-pathogenetic basis for using crystalline lysozyme in the combined therapy of food toxinfections}; Andreichin MA et al.; In food toxinfections caused by various microorganisms (Staphylococcus, Escherichia, Klebsiella, Proteus, Citrobacter, etc.) a decrease of lysozyme debit and an increase of pH of gastric juice were found . One third of patients exhibited lactose deficiency of the small intestine . Treatment with furazolidone contributed to the development of lactase deficit and delayed stools normalization . Crystalline lysozyme shortened duration of febrile reaction and diarrhea, its intake facilitated lactose hydrolysis.

Infect Control, 1986 Nov, 7(11), 538 - 45
Prevalence of colonization with antibiotic resistant gram-negative bacilli in a nursing home care unit: the importance of cross-colonization as documented by plasmid analysis; Shlaes DM et al.; A prevalence study was carried out on a 100-bed Veterans Administration nursing home care unit to determine the extent of colonization with gentamicin-resistant gram-negative bacilli (GRGNB) . Hand cultures of 12 employees and 17 environmental cultures were negative . Twenty-six of 86 (30%) patients were colonized with 49 GRGNB . Sixteen patients (19%) had urinary colonization . Multivariate analysis revealed significant associations between rectal or perineal colonization (P less than 0.01), and the presence of a urinary device (82% condom catheters) (P less than 0.05), with urinary colonization . The most common isolates were Providencia stuartii (20), Escherichia coli (nine) and Klebsiella pneumoniae (nine) . Twenty-six of 49 isolates carried plasmids . Restriction endonuclease digestion of plasmid DNA was performed for 21 . Cross-colonization, as defined by the presence of the identical species with the identical restriction endonuclease digestion profile of purified plasmid DNA found in different patients, was observed for eight of 21 (38%) strains . All were geographically clustered . No strains could transfer gentamicin-resistance by conjugation and only two plasmids could transform our E coli recipient to gentamicin resistance . One E coli plasmid was identical to two Citrobacter freundii plasmids and a P stuartii plasmid isolated from three different patients . This 105 kb plasmid is conjugative and encodes resistance to ampicillin, carbenicillin, tetracycline, and sulfonamides . Thus, 57% of strains were cross-colonizing or contained identical R-plasmids . Southern hybridization using a 1 kb TEM-1 gene probe demonstrated sequences homologous to this probe in five of five nursing home plasmids examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Virology, 1986 Nov, 155(1), 284 - 8
Magnesium-dependent plaque formation by bacteriophage P1cinC(-) on Escherichia coli C and Shigella sonnei; Tominaga A et al.; Phage P1C(-), in a state of the phage not infective to Escherichia coli K12, was able to form plaques on a wild-type strain of E . coli C and on Shigella sonnei in the presence of Mg2+ . Citrobacter freundii, Enterobacter aerogenes, and a Salmonella typhimurium galE mutant were not lysed by, but were lysogenized with P1cinC(-), whereas Klebsiella pneumoniae, Proteus rettgeri, and S . typhimurium LT2 were not susceptible to either P1cinC(-) or P1cinC(+) . The lipopolysaccharide structure of E . coli C and Sh . sonnei is discussed with reference to receptors for P1cinC(-) and P1cinC(+).

Antimicrob Agents Chemother, 1986 Nov, 30(5), 713 - 8
Beta-lactamase stability of cefpirome (HR 810), a new cephalosporin with a broad antimicrobial spectrum; Kobayashi S et al.; Cefpirome was highly stable to hydrolysis by various beta-lactamases, although it was hydrolyzed to some extent by R plasmid-mediated penicillinase of Richmond-Sykes type Va/b and by chromosomal cephalosporinases from Bacteroides species . The compound had a very low affinity for cephalosporinases from Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Proteus vulgaris . Cefpirome showed strong antimicrobial activity against eight beta-lactamase (cephalosporinase)-producing strains which have become resistant to broad-spectrum cephalosporins; especially against E . cloacae and C . freundii, it had the highest activity among the cephalosporins used . Its activity against ampicillin-resistant R plasmid-containing transconjugant isolates of Escherichia coli was as high as that against the recipient strain E . coli chi 1037 . The inducer activity of cefpirome in S . marcescens and P . vulgaris increased dose dependently, whereas cephamycin derivatives showed high inducer activity at low concentrations . A relatively low affinity of cefpirome for beta-lactamases is considered to be one of the reasons for its high antimicrobial activity against such enzyme-producing strains . In addition, other factors such as good penetration through the outer membrane and affinity for the target sites may also be involved in the high activity of cefpirome.

Jpn J Antibiot, 1986 Nov, 39(11), 3019 - 93
{Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1984) . III . Secular changes in susceptibility}; Kosakai N et al.; Cases with infections of urinary tracts were divided into 3 groups of the simple infections, and complicated infections without indwelling of catheter, and complicated infections with indwelling of catheter . Susceptibilities to antimicrobial agents of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Pseudomonas aeruginosa and Serratia marcescens which were isolated from patients with these infections were determined . There was no tendency of decline in the susceptibilities of E . coli isolated from the patients with simple urinary tract infections (UTI) . Susceptibilities of E . coli isolated from the patients with complicated UTI without and with indwelling of catheter to cephem antibiotics of the third generation were examined . The susceptibility of E . coli strains isolated from patients with complicated UTI without and with indwelling of catheter remained the same . More specifically, cefmenoxime (CMX) at a concentration of less than 0.10 microgram/ml inhibited the growth of E . coli isolated from cases without: with catheter at 74.1%: 78.3% in 1982, 75.4%: 73.3% in 1983, and 81.3%: 84.8% in 1984 . Also, ceftizoxime (CZX) at a concentration of less than 0.10 microgram/ml inhibited the growth at 83.3%: 95.7% in 1982, 89.2%: 86.7% in 1983, and 91.7%: 97.0% in 1984 . Latamoxef (LMOX) at less than 0.10 microgram/ml inhibited the growth at 59.3%: 43.5% in 1982, 47.7%: 40.0% in 1983, and 47.9%: 42.4% in 1984 . The antibacterial effect of penicillin against Klebsiella spp . was found to be poor, while those of oral cephem antibiotics, cephalexin (CEX), cefaclor (CCL), and cefazolin (CEZ) which is the cephem antibiotics of the so-called first generation and cefotiam (CTM) among other cephem antibiotics of the so-called second generation were relatively good . A study of susceptibilities of Klebsiella spp . isolated from patients with complicated UTI without and with indwelling of catheter revealed inhibition of growth by CTM at a concentration of 0.39 microgram/ml at 84.0%: 75.9% in 1982, 70.6%: 75.0% in 1983, and 95.8%: 77.8% in 1984 . Cefmetazole (CMZ) at a concentration of 0.39 microgram/ml showed a relatively lower rate of growth inhibition of Klebsiella spp., while at 0.78 microgram/ml it inhibited the growth at 88.0%: 72.4% in 1982, 52.9%: 50.0% in 1983, and 70.8%: 66.7% in 1984 . The antibacterial effects of both CTM and CMZ against Klebsiella spp . isolated from patients with indwelling of catheter were found to be poor, and some of the bacterial strains showed a MIC over than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Rev Infect Dis, 1986 Nov-Dec, 8 Suppl 5, S620 - 9
Sulbactam/ampicillin vs . chloramphenicol/ampicillin for the treatment of meningitis in infants and children; Rodriguez WJ et al.; Eighty-one patients ages one month to 14 years with meningitis were randomized to receive either sulbactam (50 mg/kg per day) and ampicillin (400 mg/kg per day; 41 patients) or chloramphenicol and ampicillin (40 patients) . The groups were comparable in terms of sex and degree of illness; however, more patients treated with chloramphenicol/ampicillin than patients treated with sulbactam/ampicillin were younger than 12 months of age (78% vs . 56%) . Pathogens were isolated from the cerebrospinal fluid (CSF) of 65 (80%) of the 81 patients . In the sulbactam/ampicillin group, there were 18 Haemophilus influenzae isolates (one resistant to ampicillin), five Streptococcus pneumoniae, five Neisseria meningitidis, one Klebsiella pneumoniae, one Pseudomonas aeruginosa, and one Listeria . In the chloramphenicol/ampicillin group, there were 19 H . influenzae isolates, 10 S . pneumoniae, three N . meningitidis, one Haemophilus parainfluenzae, and one Citrobacter . Of 63 patients with assessable CSF pathogens, one (3%) of 29 treated with sulbactam/ampicillin died (S . pneumoniae) and six (18%) of 34 treated with chloramphenicol/ampicillin died (two, H . influenzae; three, S . pneumoniae; and one, Citrobacter) . Twelve percent in the sulbactam/ampicillin group and 18% in the chloramphenicol/ampicillin group had neurologic sequelae . No clinically significant reactions or toxicities were noted . Sulbactam/ampicillin was as effective as chloramphenicol/ampicillin in the treatment of meningitis.

Rev Infect Dis, 1986 Nov-Dec, 8 Suppl 5, S562 - 8
Induction/inhibition of chromosomal beta-lactamases by beta-lactamase inhibitors; Moosdeen F et al.; Many species of gram-negative bacteria produce chromosomal beta-lactamases that can be induced to high-level expression by exposure to beta-lactam antibiotics . Fifty-four strains of Escherichia coli, Enterobacter, Proteus, Citrobacter, and Morganella were examined for beta-lactamase inducibility by clavulanic acid, sulbactam, YTR 830, ampicillin, and cefoxitin . Cefoxitin proved to be the most potent inducer, affecting most of the strains of Enterobacter and Morganella . Clavulanic acid induced 30% of all strains studied . Sulbactam and YTR 830 did not induce measurable levels of beta-lactamases . Inhibition of some chromosomal beta-lactamases by sulbactam and YTR 830 was demonstrated, whereas inhibitory activity by clavulanic acid was found only in Proteus and Citrobacter.

Chemioterapia, 1986 Oct, 5(5), 319 - 21
Use of aztreonam in patients suffering from urinary tract infections with contraindications for the use of aminoglycosides; Fraschini F et al.; The clinical efficacy and safety of aztreonam were studied in 30 patients suffering from urinary tract infections caused by gram-negative bacteria . Aztreonam was given in a dose of 1 g i.m . at intervals of 12 or 24 hours . Duration of therapy was 2-8 days . Bacteria isolated in urine cultures were: Escherichia coli (60%); Proteus mirabilis (10%); Pseudomonas aeruginosa and Citrobacter sp . (7%); Proteus vulgaris, Serratia marcescens; Klebsiella pneumoniae and Pseudomonas species (3%) . At completion of therapy and at follow-up all patients were bacteriologically and clinically cured . No significant side effects or toxicity were observed in all patients treated . It is concluded from these data that aztreonam is highly effective and well tolerated in patients affected either by upper or lower urinary tract infections.

J Clin Microbiol, 1986 Oct, 24(4), 650 - 1
o-Nitrophenyl-beta-D-galactopyranoside-urease-indole broth, a new composite tube medium for Salmonella screening; Berlutti F et al.; A new composite broth medium combining o-nitrophenyl-beta-D-galactopyranoside (ONPG) and urease and indole tests in a single tube is described . High-level agreement with individual conventional tests was recorded in comparative studies with 2,412 cultures of members of the family Enterobacteriaceae, i.e., 100% agreement with the exception of Hafnia spp . (96.3% agreement) for the ONPG test and Citrobacter, Enterobacter, and Hafnia spp . (75, 86.4, and 98.2% agreement, respectively) for the urease test . The new medium seems especially promising as a screen for Salmonella subgroup I which encompasses most pathogenic Salmonella species other than the Arizona subgroup.

Jpn J Antibiot, 1986 Oct, 39(10), 2547 - 56
{Antibacterial activity of cephem antibiotics against isolates from clinical specimens at the Yokohama City University Hospital}; Kaminaga Y et al.; Minimum inhibitory concentrations (MICs) of cephem antibiotics against 405 strains belonging to 17 species of clinical isolates were investigated using the standard method of the Japanese Congress of Chemotherapy . The results obtained are summarized below . Cephem antibiotics showed weak antibacterial activities against Enterococcus sp., B . fragilis and S . marcescens . S . pneumoniae, S . agalactiae, E . coli, K . pneumoniae and P . mirabilis were susceptible to cephem antibiotics . Cephem antibiotics of the 1st and the 2nd generations showed weak antibacterial activity against Citrobacter sp . and E . cloacae, while cephem antibiotics of 3rd generation had a good antibacterial activity against these species . Cephem antibiotics of the 2nd and the 3rd generations showed high antibacterial activity against H . influenzae and indole positive Proteus group . Cefoperazone showed high antibacterial activity against P . aeruginosa . Resistance to latamoxef, ceftizoxime and cefoxitin was observed among Staphylococcus sp., while the MICs of other antibiotics against Staphylococcus sp . were fairly low . Number of strains resistant to the 3rd cephem antibiotics seems to be increasing because the 3rd generation of cephem antibiotics have been used frequently . Further investigation will be required on resistant organism to these antibiotics including beta-lactamase producing strains.

J Wildl Dis, 1986 Oct, 22(4), 484 - 7
Gram-negative septicemia in American alligators (Alligator mississippiensis); Novak SS et al.; Six species of bacteria (family Enterobacteriaceae) not commonly reported as associated with disease in American alligators (Alligator mississippiensis) were documented, suggesting that Aeromonas is not the only bacterium responsible for septicemia in crocodilians . These included Citrobacter freundii, Enterobacter agglomerans, Proteus sp., Morganella morganii, Serratia marcescens, and Klebsiella oxytoca . Clinical signs of disease included intensive basking, anorexia, lethargy, flaccid limb paralysis, stomatitis, and dermatitis . Our data indicated that early treatment with broad-spectrum antibiotics was preferable to waiting for sensitivity results.

Carbohydr Res, 1986 Sep 1, 152, 7 - 20
Ultrasonic irradiation of bacterial polysaccharides . Characterization of the depolymerized products and some applications of the process; Szu SC et al.; Ultrasonic irradiation (u.i.) has been used to depolymerize biopolymers including DNA, dextran, and the Vi capsular polysaccharide from Citrobacter freundii . Representative bacterial polysaccharides were subjected to u.i . and the effect of this energy upon their molecular weight and chemical structure was characterized . U.i . depolymerized a neutral polysaccharide (dextran) and acidic polysaccharides containing either a phosphoric diester linkage {Haemophilus influenzae type b (Hib) and pneumococcus types 6A and 6B} or a uronic acid moiety (pneumococcus type 9N) . Prolonged u.i . depolymerized all the polysaccharides to a finite and similar molecular mass (approximately 50 000 daltons) . The rate of depolymerization induced by u.i . depended on the viscosity of the solvent and the concentration of the polysaccharide . 13C-N.m.r . data of the native Hib polysaccharide and its depolymerized products indicated that u.i . did not alter the chemical structure of the repeating units . Determination of the monophosphate terminal residues by 31P-n.m.r . spectroscopy and of the reducing end groups by the Park-Johnson reaction indicated that both the phosphoric diester and the glycosidic linkages were cleaved . The Vi polysaccharide, prepared as an investigational vaccine, could not be analyzed for its chemical structure by 13C-n.m.r . spectroscopy owing to its high viscosity but depolymerization by u.i . permitted this analysis . The finite molecular weight of the products observed after prolonged u.i . is best explained by the postulation that the mechanical torque necessary to rupture the linkages is dependent upon the length of the polysaccharide . The method of u.i . for depolymerization is useful for the preparation of homogeneous, low-molecular-weight polysaccharides without alteration of the chemical structure of the repeating units.

J Infect Dis, 1986 Sep, 154(3), 409 - 14
Molecular epidemiology of neonatal meningitis due to Citrobacter diversus: a study of isolates from hospitals in Maryland; Morris JG Jr et al.; Six cases of neonatal meningitis due to Citrobacter diversus were diagnosed in three Baltimore (Maryland) hospitals between 1983 and 1985 . Using plasmid profiles, biotypes, serotypes, and chromosomal restriction endonuclease digests as epidemiological markers, we studied 63 isolates of C . diversus (including four isolates from cerebrospinal fluid) from these and seven other hospitals in Maryland . Within two of the three hospitals with meningitis cases, the same strain of C . diversus was isolated from case infant(s), healthy neonates, and nursery personnel . In all three hospitals, C . diversus strains different from those implicated as a cause of meningitis were also isolated . Other than the meningitis-associated strains, 15 different strains of C . diversus were isolated from infants in the hospitals studied, with several distinct clusters of asymptomatic, colonized infants identified.

Antimicrob Agents Chemother, 1986 Sep, 30(3), 447 - 52
7 alpha-formylamino substituent confers beta-lactamase-inactivating potency on 1-oxacephalosporins; Murakami K et al.; 7 alpha-Formylamino-1-oxacephalosporins 7 alpha-formylamino-7 beta-{2- (methylaminocarbonyl)amino-2-(2-thienyl)acetamido}-3-{(1-methyl-1H -tetra zol-5-yl)thiomethyl}-1-oxa-3-cephem-4-carboxylic acid (F1) and 7 alpha-formylamino-7 beta-(2-{(4-ethyl-2,3-dioxopiperazine-1- yl)carbonylamino}-2-phenylacetamido)-3-{(1-methyl-1H-tetr azol-5-yl) thiomethyl}-1-oxa-3-cephem-4-carboxylic acid (F2) were stable against penicillinases and, moreover, inactivated cephalosporinases of Pseudomonas aeruginosa, Citrobacter freundii, and Enterobacter cloacae . Extensive studies of the inactivation of cephalosporinase of P . aeruginosa showed that it resulted from the formation of a transiently stable enzyme-compound complex . The 7 alpha-formylamino substituent was involved in the enzyme inactivation, because 7 alpha-methoxy congeners did not inactivate the enzyme . The number of compound molecules required for inhibition of an enzyme molecule was found to be 36 for F1 and 5.5 for F2, which suggests that the pathway to the complex formation branched off the hydrolysis pathway . Half-lives of the complexes were 400 min for F1 and 260 min for F2 . 7 alpha-Formylamino compounds F1 and F2 had antibacterial activities similar to those of 7 alpha-methoxy congeners against beta-lactamase-producing gram-negative bacteria, whereas they were less active against non-beta-lactamase-producing strains of Escherichia coli and Staphylococcus aureus . The conclusion was that the 7 alpha-formylamino substituent conferred the ability to inactivate cephalosporinase on the 1-oxacephalosporins tested, without much impairment of their antibacterial activity.

J Hosp Infect, 1986 Sep, 8(2), 149 - 58
A study of the skin flora of spinal cord injured patients; Fawcett C et al.; The skin flora of 11 spinally-injured patients was compared to that of 11 healthy control subjects . The perinea, groins, penile shafts and urethras of the patients were heavily colonized by a range of multi-drug resistant Gram-negative bacilli . Observations on patients from admission for up to 25 days suggest that the Gram-negative bacilli start to colonize the skin 2-3 days after admission . Some species, e.g., Citrobacter diversus and Escherichia coli appear as transient organisms while others such as Enterobacter aerogenes, Serratia marcescens, and Klebsiella pneumoniae seem to become stable skin residents . The relationship of the skin flora to the organisms causing urinary tract infections in these patients was studied.

J Antimicrob Chemother, 1986 Aug, 18(2), 271 - 6
Synergy of amoxycillin combined with clavulanate and YTR 830 in experimental infections in mice; Aronoff SC et al.; YTR 830, a new beta-lactamase inhibitor, is synergistic with amoxycillin in vitro against a number of beta-lactamase-producing organisms . The combination of amoxycillin-YTR 830 was compared to amoxycillin-clavulanate in the treatment of experimental Staphylococcus aureus, Citrobacter freundii and Proteus mirabilis infections in mice . Both combinations were synergistic with amoxycillin against all three test organisms . The amoxycillin-clavulanate combination was superior against S . aureus and C . freundii while amoxycillin-YTR 830 was more effective against P . mirabilis . The difference in efficacy between the two drug combinations appears to relate to the degree of protection afforded the animals by the beta-lactamase inhibitor alone . YTR 830 is a promising new agent and should undergo further investigation.

J Antimicrob Chemother, 1986 Aug, 18(2), 177 - 84
Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads; Jacobs MR et al.; The in-vitro synergistic activity of YTR 830, a new beta-lactamase inhibitor, combined with four extended-spectrum penicillins (ticarcillin, piperacillin, mezlocillin and apalcillin) against ticarcillin-resistant clinical isolates of Gram-negative enteric bacilli was compared with that of clavulanate and sulbactam . Synergy testing was performed with fixed concentrations of beta-lactamase inhibitors (8 mg/l) combined with doubling dilutions of beta-lactams in microdilution trays . Synergy was defined as a four-fold or greater decrease of beta-lactam MIC in the combination compared with the beta-lactam alone . For 79 ticarcillin-resistant Enterobacteriaceae, ticarcillin-YTR 830 and ticarcillin-clavulanate were synergistic against 90% of strains; for ticarcillin-sulbactam, 70% showed synergy . The synergistic activity of all three inhibitors was similar against strains resistant only to ticarcillin; for strains resistant to all four extended-spectrum penicillins, the activity of ticarcillin with YTR 830 and clavulanate was similar (synergy against 79% of strains) and superior to ticarcillin-sulbactam (synergy against 39% of strains) . YTR 830 was more active than clavulanate against Serratia, Citrobacter, Proteus and Providencia spp . Piperacillin, mezlocillin and apalcillin susceptible strains, with MICs of 8-16 mg/l, showed synergy with inhibitors against 37-87% of strains . Amongst pseudomonads, no synergy was demonstrated against Pseudomonas aeruginosa; ticarcillin produced synergy with the inhibitors against Ps . maltophilia, while piperacillin-YTR 830 and apalcillin-YTR 830 were synergistic against Ps . cepacia . YTR 830 appears to have comparable in-vitro activity to that of clavulanate, and further development of this compound is warranted.

J Antimicrob Chemother, 1986 Jul, 18(1), 35 - 44
The in-vitro activity and beta-lactamase stability of carumonam; Neu HC et al.; Carumonam is a monobactam with a beta-carbamyloxmethyl group at position 4 . It inhibited 90% of Enterobacteriaceae at less than or equal to 8 mg/l and had in-vitro activity similar to that of cefotaxime, ceftazidime and aztreonam . Fifty per cent of Enterobacter, Citrobacter and Serratia isolates were inhibited by 4 mg/l, but isolates resistant to aztreonam and ceftazidime were not inhibited . Carumonam, like aztreonam, did not inhibit Gram-positive or anaerobic species . Carumonam was not destroyed by the common plasmid- and chromosomally-mediated beta-lactamases and was more stable than aztreonam to attack by the K-1 beta-lactamase of Klebsiella oxytoca . Carumonam inhibited Richmond-Sykes type Ia and Id beta-lactamases but was a poor inhibitor of type III enzymes . It did not induce beta-lactamases.

Appl Environ Microbiol, 1986 Jul, 52(1), 124 - 7
Improved immunological membrane filter method for detection of food-borne Salmonella strains; Cerqueira-Campos ML et al.; An improved membrane filter method that involves the use of an enzyme-labeled antibody stain has been developed for the rapid detection of Salmonella species in foods . The procedure is carried out directly on a hydrophobic grid-membrane filter without requiring transfer by blotting to nitrocellulose . Pure cultures of 54 Salmonella species and 10 foods artificially contaminated with Salmonella colindale gave a positive reaction in which Salmonella colonies were visible as purple dots . Of 11 nonsalmonella organisms, only Citrobacter freundii reacted with Spicer-Edwards antiserum . Of 22 naturally contaminated food samples, 10 were positive for both the hydrophobic grid-membrane filter procedure of the Association of Official Analytical Chemists and the improved enzyme-labeled antibody stain method, and there was perfect agreement between the methods . Of these 10 positive samples, one was negative by the Health Protection Branch method; of the negative samples, two were positive by this latter method . The improved enzyme-labeled antibody stain method allows detection of Salmonella spp . in foods within 48 h, requires little equipment, and is inexpensive, easy to perform, and suitable for automated detection.

J Appl Bacteriol, 1986 Jul, 61(1), 19 - 24
Growth of salmonellas in different enrichment media; Patil MD et al.; The usefulness of selenite-F (S-F), tetrathionate (MKT) and Rappaport-10 (R-10) broths as enrichment media to support growth of salmonellas either alone or in the presence of other competing organisms was studied . Their ability to support the growth of stressed salmonellas from water was also investigated . It was observed that R-10 was more inhibitory to competing organisms than MKT and S-F . It strongly inhibited the growth of Pseudomonas aeruginosa, Citrobacter freundii and Proteus vulgaris though not of Escherichia coli and Enterobacter aerogenes . It was more toxic, however, to small numbers of salmonellas than MKT and S-F . Tetrathionate was strongly inhibitory for E . coli and Ent . aerogenes but much less so for Proteus and Pseudomonas species . Selenite-F was much less inhibitory than MKT to Ps . aeruginosa and it did not inhibit growth of E . coli and Ent . aerogenes as much as MKT . Salmonellas were inhibited by all three enrichment media and none of them is ideally suited for direct use . Of the three media, R-10 was much more inhibitory to stressed organisms than S-F or MKT.

Am J Med, 1986 Jun 30, 80(6B), 195 - 203
Antibiotics in the second half of the 1980s . Areas of future development and the effect of new agents on aminoglycoside use; Neu HC; Articles in this supplement have examined in detail the role of aminoglycosides in the therapy of infections, addressing problems of resistance, toxicity, and efficacy . This article discusses other agents and their potential utility and effect on aminoglycosides . Penem antibiotics, which have activity against only aerobic gram-negative bacteria, have recently been synthesized . These agents have proved effective in animal experiments; to date, however, results of human clinical trials are not available . Carboxypenicillins and ureidopenicillins will still have to be administered with aminoglycosides in patients with serious life-threatening infections or in those institutions in which organisms such as Klebsiella, Enterobacter, and Pseudomonas exhibit high levels of resistance . What will be the role of aminothiazolyl cephalosporins? In some institutions, these agents might be used as sole therapy, particularly if they become less costly as a result of competition . In other settings, concern over the resistance of organisms, such as Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa, will result in the use of aminoglycosides with these relatively beta-lactamase-stable cephalosporins . It will be necessary to monitor the development of resistance to the new antibiotics and to determine whether the use of aminoglycosides plus third-generation cephalosporin combinations results in decreased resistance . Other agents to be considered include the directed therapy monobactams aztreonam and carumonam, the broad-spectrum carbapenem imipenem, and the penems under development . It is unclear whether these compounds might be used with aminoglycosides in critically ill, infected patients . It is also unclear what role oral beta-lactamase-stable cephalosporins will have in the therapy of nosocomial infections, since they probably will not be effective against many of the urinary or cutaneous infections that are treated with aminoglycosides . Quinolone agents can be used successfully against many infections . However, the likelihood of bacterial resistance developing and their potential for toxicity are still unknown . Thus, despite the emergence of many new agents, it appears that the time-tested aminoglycosides will continue to play an important role in antimicrobial therapy for some time to come.

Am J Med, 1986 Jun 30, 80(6B), 126 - 37
Aminoglycosides plus beta-lactams against gram-negative organisms . Evaluation of in vitro synergy and chemical interactions; Giamarellou H; Combination antibiotic therapy has been used mainly to broaden the antibacterial spectrum and prevent the development of resistance . Antibiotic combinations proven to be synergistic in vitro are associated with a significantly better in vivo response, particularly in the compromised host in whom traditional treatment combines an antipseudomonal penicillin plus an aminoglycoside . Several investigators have examined combining new agents, such as the third-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefoperazone, and moxalactam), aztreonam, or the ureidopenicillins, with amikacin . When compared with combinations of an older cephalosporin, carbenicillin or ticarcillin, plus gentamicin or tobramycin, these newer combinations produce higher rates of clinically meaningful synergy and rapid enhancement of in vitro bactericidal activity against the difficult-to-treat Enterobacteriaceae (i.e., Serratia, Citrobacter, Enterobacter, Providencia, and indole-positive Proteus species) . This effect, without any evidence of antagonism, has been reported even for strains moderately or completely resistant to the former antibiotics . Unsatisfactory and unpredictable synergistic interactions against both resistant and susceptible strains of Pseudomonas aeruginosa--the most difficult nosocomial pathogen to treat--have been noted with combinations of tobramycin or gentamicin plus cefotaxime, moxalactam, or cefoperazone . Conversely, the use of amikacin plus various beta-lactams against multi-resistant strains is more frequently synergistic . Agents have been observed to exhibit such synergy in the following order of activity, from most to least synergistic: ceftazidime, ceftriaxone, moxalactam, aztreonam, cefotaxime, azlocillin, cefoperazone, cefsulodin, and carbenicillin . The combination of amikacin plus imipenem or ciprofloxacin against strains of P . aeruginosa resistant to the former and moderately resistant to the latter was recently reported to have a low probability of synergy; the combination of two of the newer beta-lactams had mostly an unpredictable or even antagonistic result . In vitro studies have also demonstrated that high concentrations of the antipseudomonal penicillins can inactivate the aminoglycosides . Among the latter compounds, the inactivation order, from most to least inactivated, was as follows: tobramycin, gentamicin, netilmicin, and amikacin . To date, the reports of aminoglycoside inactivation by the newer cephalosporins have been rather contradictory; only moxalactam has been shown produce a significant decrease in activity.

Antimicrob Agents Chemother, 1986 Jun, 29(6), 1067 - 72
In vitro activity of Ro 15-8074 and Ro 19-5247, two orally administered cephalosporin metabolites; Wise R et al.; The activity of two iminomethoxy aminothiazoly cephalosporins, Ro 15-8074 and Ro 19-5247, was compared with that of other beta-lactams against a total of 491 bacterial strains . Both were highly active (MIC for 90% of the strains tested {MIC 90}, less than or equal to 2 micrograms/ml) against the majority of the members of the family Enterobacteriaceae, Haemophilus influenzae, Neisseria spp., and Streptococcus pneumoniae, being at least 16-fold more active than cephalexin and 8-fold more active than cefuroxime . There was no activity against Pseudomonas aeruginosa and poor activity against Morganella morganii (in the case of Ro 15-8074), Enterobacter sp., and Citrobacter sp . Staphylococcus aureus was moderately susceptible to Ro 19-5247 (MIC90, 8 micrograms/ml), but Ro 15-8074 was eightfold less active . The protein binding of the two compounds at 5 micrograms/ml was 9.1% for Ro 15-8074 and 69.9% for Ro 19-5247 . The major target site for the two cephalosporins was PBP 3.

Pathol Biol (Paris), 1986 Jun, 34(5 Pt 2), 554 - 8
{Bactericidal activity of ceftriaxone, amikacin and their combination}; Juvin ME et al.; Third-generation cephalosporins such as ceftriaxone are often used alone; however, with Enterobacter (ENT), Citrobacter (CIT), Serratia (SER) and Morganella (MOR), a combination of two drugs is advisable . Aminoglycoside-beta-lactam combinations are often synergistic . However, results are not consistent with the new cephalosporins . We determined the killing kinetics of ceftriaxone (C) alone, amikacin (A) alone and both drugs in combination (AC) . The antibiotics were tested in the following concentrations: 0.25, 1, 4 and 16 X MIC for C, 0.5, 2 and 8 X MIC for A, and, for AC, 0.5-0.25 X MIC (1), 0.5-1 X MIC (2) and 2-0.25 X MIC (3) . Surviving bacteria were enumerated at 0 h, 1 h, 3 h, 5 h and 24 hours . Amikacin showed a strong, dose-dependent bactericidal activity . Maximal activity of ceftriaxone was observed at 1 or 4 X MIC . Time of contact had a significant influence, indicating a time-dependent activity . In 5 hours, the killing effect of the AC combination rarely exceeded that of each antibiotic alone . Higher killing rates were observed with AC and; the killing effect of AC (3) was similar to amikacin's maximal killing effect . In 24 hours, the AC (3) combination was clearly synergistic with inhibition of late regrowths.

Presse Med, 1986 May 31, 15(22), 1037 - 40
{Synergism or antagonism in combinations of beta-lactam antibiotics}; Joly-Guillou ML et al.; Several examples of antagonistic combinations between cefoxitin and other beta-lactam antibiotics have been reported in the literature . This phenomenon may occur especially with Enterobacter spp, Pseudomonas aeruginosa, Citrobacter spp, and Serratia marcescens . In these species, induction of chromosomally mediated beta-lactamases by certain potent inducers, such as cefoxitin, has been suggested as the main mechanism of antagonism . These in vitro interactions may have clinical relevance; however, although studies in animal models have shown a few examples of in vivo antagonism, the actual clinical significance of interactions between beta-lactam antibiotics requires further thorough and controlled clinical studies.

Am J Med, 1986 May 30, 80(5C), 21 - 9
Synergism and antagonism in double beta-lactam antibiotic combinations; Gutmann L et al.; Combinations of two beta-lactam antibiotics may be advantageous in certain clinical situations, providing a synergistic activity against specific organisms or a broad spectrum of antibiotic coverage . Depending on the combination and the bacteria, synergism, indifference, or antagonism can be observed . Synergism may occur when two beta-lactam antibiotics, acting on different penicillin-binding proteins, are combined or when a penicillinase-susceptible beta-lactam antibiotic is protected by another beta-lactam antibiotic acting as a beta-lactamase inhibitor in strains producing a penicillinase (chromosomal or plasmidic) . With different species, such as Enterobacter, Citrobacter, indole-positive Proteus, Serratia, Aeromonas, and Pseudomonas, which produce an inducible chromosome-encoded cephalosporinase, antagonism will appear if one of the two combined antibiotics causes induction of the beta-lactamase and the other becomes inactivated by the increased amount of the enzyme . Although most combinations of new beta-lactam antibiotics (ureido-penicillins, third-generation cephalosporins, monobactams) appear to be indifferent, antagonism and possible selection of resistant mutants are the drawbacks of such combinations . Nevertheless, highly active compounds, if used at doses above the minimal inhibitory concentrations, especially in the case of potential cephalosporinase-inducers, may be safe in vivo as far as avoiding antagonism is concerned, but not necessarily with respect to the selection of resistant mutants.

Eur J Biochem, 1986 May 2, 156(3), 441 - 5
Sequence of the Citrobacter freundii OS60 chromosomal ampC beta-lactamase gene; Lindberg F et al.; The Citrobacter freundii OS60 ampC beta-lactamase gene was sequenced and found to encode a 380-amino-acid-long precursor with a 19-residue signal peptide . The mature protein has a predicted molecular mass of 39781 Da . The first 60 residues of the purified enzyme, as determined by sequential Edman degradation, are identical to the amino acid sequence inferred from the gene sequence . Also, the amino acid composition determined for the purified beta-lactamase and that given by the gene sequence are in good agreement . 77% of the amino acid positions hold identical residues in the C . freundii and Escherichia coli K12 chromosomal AmpC beta-lactamases . This clearly puts the C . freundii enzyme into the class C of beta-lactamases . Of the 68 amino-terminal residues determined for the Enterobacter cloacae P99 beta-lactamase, 44 are identical to the corresponding residues of the C . freundii enzyme . All three enzymes, as well as that of Pseudomonas aeruginosa 18S/H are highly similar around the active-site serine at position 64 of the mature protein.

J Antimicrob Chemother, 1986 May, 17 Suppl C, 7 - 15
Susceptibility of ticarcillin-resistant gram-negative bacilli to different combinations of ticarcillin and clavulanic acid; Verbist L et al.; The susceptibility of ticarcillin-resistant and of ticarcillin-susceptible Gram-negative bacilli to different combinations of ticarcillin and clavulanic acid has been investigated . Susceptibility to ticarcillin has been restored in ticarcillin-resistant isolates in proportion to the amount of clavulanic acid in the combination and depending upon the species . The decrease in the MICs of ticarcillin was excellent to good in Proteus, Morganella, Providencia, Escherichia coli and Klebsiella, moderate in Enterobacter, Citrobacter and Serratia, but poor in Pseudomonas aeruginosa . An unfavourable effect of clavulanic acid on the MICs of ticarcillin was observed in some isolates belonging to species with inducible beta-lactamases.

Pathol Biol (Paris), 1986 May, 34(5), 494 - 7
{Ofloxacin (RU 43280): clinical evaluation in urinary and prostatic infections}; Guibert J et al.; Ofloxacin, a new fluoroquinolone, was given to fifty patients (29 females and 21 males) aged 25 to 86 years with urinary tract infection or prostatitis . Urinary tract infections usually chronic and associated with urologic anomalies, included 17 cases of cystitis and 19 cases of pyelonephritis . 14 patients had prostatitis . Pathogens recovered from the urine were 26 E . coli, 2 Citrobacter, 4 Proteus mirabilis, 2 Klebsiella, 2 Enterobacter, 3 Serratia, 3 Staphylococcus aureus and 11 Pseudomonas . Minimal inhibitory concentrations of ofloxacin ranged from 0.03 to 0.12 microgram/ml (mean MIC: 0.6 microgram/ml) for 27 nalidixic acid-sensitive strains, and from 0.25 to 4 micrograms/ml (mean MIC: 1 microgram/ml) for 26 nalidixic acid-resistant strains . Ofloxacin was given as single drug therapy in all patients, in a daily dosage of 200 mg b.i.d . in 46 patients and 400 mg b.i.d . in 4 patients, for 7 to 97 days (average 40 days) . Follow-up after discontinuation of treatment was 3 to 12 months . Therapeutic results were as follows: 17 cures for the 17 cystitis patients, 17 cures and 2 failures by relapse for the 19 cases of pyelonephritis, and 11 cures, 1 failure by persistence of bacteriuria and failure by relapse for the 14 cases of prostatitis . Digestive disorders, i.e . nausea, abdominal pain, constipation, occurred in 6 patients and required withdrawal of the drug in 1; candidiasis of the tongue was recorded in one patient and digestive complaints with neuropsychic disorders in another . Two patients had short-lived, moderate leukopenia with granulopenia and one had transient worsening of preexisting renal failure . Hepatic tolerance was good.

Pathol Biol (Paris), 1986 May, 34(5), 390 - 8
{Multicenter study of ofloxacin activity on bacteria isolated from a hospital environment}; Soussy CJ et al.; Minimal inhibitory concentrations (MICs) of ofloxacin were evaluated by agar dilution for 1508 bacterial strains isolated in five hospitals . For Enterobacteriaceae sensitive to nalidixic acid, MICs ranged from 0.008 to 1 microgram/ml (mode MIC: 0.12); the different species of Enterobacteriaceae exhibited similar mode MICs (0.12) with the exception of E . coli (0.06-0.12), P . mirabilis (0.5) and Providencia (0.25) . Among strains intermediate and resistant to nalidixic acid, most of which were Serratia, Providencia and Citrobacter, 41% had a MIC within the susceptibility range, while the others had a MIC of 2 to 8 micrograms/ml, or even 64 micrograms/ml in a few instances . Ofloxacin also exhibited satisfactory activity against P . aeruginosa, with MICs ranging from 0.25 to 16 micrograms/ml (mode MIC: 2) for 87% of strains, and A . calcoaceticus, with MICs from 0.25 to 2 micrograms/ml (mode MIC: 1) . Haemophilus sp . (MIC: 0.008 to 0.06 microgram/ml; mode MIC: 0.03), Gonococci (mode MIC: 0.008), and Meningococci (mode MIC: 0.016) were very sensitive to ofloxacin . The spectrum of ofloxacin included Gram positive cocci: MICs of Staphylococci were 0.06 to 2 micrograms/ml (mode MIC: 0.5); Enterococci, other Streptococci and Pneumococci were less sensitive, with MICs of 2 to 4 micrograms/ml for the majority of strains . As for anaerobic bacteria, ofloxacin proved more active against Clostridium (0.5 to 2 micrograms/ml) than Bacteroides (0.5 to 16 micrograms/ml).

Antimicrob Agents Chemother, 1986 May, 29(5), 955 - 7
Comparative evaluation of a new beta-lactamase inhibitor, YTR 830, combined with different beta-lactam antibiotics against bacteria harboring known beta-lactamases; Gutmann L et al.; YTR 830, a new beta-lactamase inhibitor, combined with amoxicillin or carbenicillin, showed a synergistic effect similar to that observed with clavulanic acid, and generally better than that with sulbactam, against strains harboring chromosome-encoded penicillinases and broad-spectrum beta-lactamases or plasmid-determined beta-lactamases . With ampicillin, YTR 830 showed the best synergistic activity of the inhibitors against Proteus morganii, Citrobacter freundii, and Enterobacter cloacae and their mutants with a derepressed chromosome-encoded cephalosporinase.

Antimicrob Agents Chemother, 1986 May, 29(5), 833 - 7
Transfer of amikacin resistance by closely related plasmids in members of the family Enterobacteriaceae isolated in Chile; Van Nhieu GT et al.; During a 9-month period when amikacin was the sole aminoglycoside used clinically in a hospital in Santiago, Chile, resistance to amikacin and other antibiotics was encountered in 42 strains of the family Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Serratia liquefaciens . Amikacin resistance was transferable by conjugation and carried by IncM plasmids ranging in size from ca . 48.4 to 58.1 kilobase pairs . The plasmids had ca . 70 to 80% of their structure in common, as judged after digestion with restriction endonucleases . The resistance was mediated by a 6' aminoglycoside acetyltransferase . We conclude that selective pressure has favored the dissemination of a wide-host-range amikacin resistance plasmid and its derivatives.

Antimicrob Agents Chemother, 1986 Apr, 29(4), 707 - 9
Mutation of Escherichia coli capable of expressing gene(s) for beta-lactamase production of Citrobacter freundii; Murayama SY et al.; A mutation in a chromosomal gene of Escherichia coli, designated reb, acted in trans to increase the expression of the cloned beta-lactamase gene of Citrobacter freundii . The reb gene was located around 99 min . Deletion mutants in the cloned gene(s) which had lost the regulatory region for induction were also constructed.

J Clin Microbiol, 1986 Apr, 23(4), 755 - 9
Effect of inoculum size on ampicillin and amoxycillin susceptibility determined by gas-liquid chromatography for members of the family Enterobacteriaceae; Hayward NJ; Inoculum size had only a small effect on the results for ampicillin and amoxycillin susceptibility testing of Escherichia coli . In contrast, a difference in inoculum size from 10(6) to 10(8) CFU/ml profoundly affected the results for ampicillin and amoxycillin susceptibility testing of Proteus mirabilis, causing a change from susceptibility to complete resistance . These different effects of inoculum size were observed both when susceptibility was determined by the suppression of a characteristic metabolic product analyzed by head-space gas-liquid chromatography (HS-GLC) and when it was determined by MIC testing in broth . Inoculum size affected the results for ampicillin susceptibility of P . mirabilis determined concurrently with the rapid HS-GLC urine test, because 10(8) CFU/ml may occur in urine specimens . In the rapid test, significant numbers of Escherichia, Klebsiella, Citrobacter, Proteus, Morganella, and Providencia spp . in urine specimens are detected within 4 h by HS-GLC analysis for characteristic metabolic products in cultures . Most P . mirabilis in urine specimens appeared to be ampicillin resistant in the rapid HS-GLC test but were reported to be ampicillin susceptible in hospital laboratory agar dilution tests 2 days later . However, ampicillin susceptibility results for Escherichia, Klebsiella, and Citrobacter spp . agreed with hospital laboratory reports . It was concluded that reports of ampicillin susceptibility or resistance for the commonest cause of urinary tract infections, E . coli, within 4 h of receipt of the specimen would be clinically valuable and that a provisional report of ampicillin resistance for P . mirabilis would not lead to ineffective therapy.

J Antimicrob Chemother, 1986 Apr, 17(4), 441 - 52
The activity of BMY 28142 a new broad spectrum beta-lactamase stable cephalosporin; Neu HC et al.; The in-vitro activity of BMY 28142, an iminomethoxy, aminothiazolyl cephalosporin containing a methyl pyrrolidinio C-3 was compared with that of cefotaxime, ceftazidime, aztreonam, imipenem and tobramycin against various bacteria . BMY 28142 was the most active agent tested against the Enterobacteriaceae inhibiting 90% at less than or equal to 1 mg/l . The in-vitro activity of BMY 28142 was equal to or superior to cefotaxime against the highly susceptible members of the Enterobacteriaceae and several-fold superior to ceftazidime and aztreonam . BMY 28142 inhibited many Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cefotaxime, ceftazidime and aztreonam . BMY 28142 was more active than imipenem against Proteus, Providencia and Morganella species . Ceftazidime and imipenem were more active than BMY 28142 against Pseudomonas aeruginosa, but it inhibited piperacillin and tobramycin-resistant isolates . BMY 28142 inhibited beta-lactamase producing Haemophilus influenzae and Neisseria gonorrhoeae . BMY 28142 was more active than ceftazidime against streptococcal and staphylococcal species, but it did not inhibit or kill most methicillin-resistant Staphylococcus aureus . BMY 28142 did not inhibit most Bacteroides species . BMY 28142 was not hydrolyzed by common plasmid and chromosomal beta-lactamases, but it bound poorly to Enterobacter beta-lactamase, was a poor inhibitor of the TEM plasmid beta-lactamase and was a poor inducer of beta-lactamases.

Eur J Clin Microbiol, 1986 Apr, 5(2), 220 - 5
Clinical experience with ciprofloxacin in the USA; Arcieri G et al.; This interim analysis of the efficacy and safety of ciprofloxacin is based on case reports of 1241 adult patients treated primarily in the USA; 1026 were suitable for analysis of drug efficacy . The daily dose ranged from 500 to 1500 mg, the unit dose being given every 12 h . Duration of treatment ranged from 5 to 211 days (mean 12.6 days) . In 1046 cases of infection the site was the urinary tract (514), skin structures (218), respiratory tract (215), blood (43), bone (27), abdomen (13), gastrointestinal tract (13) and pelvis (3) . Organisms responsible for infection were Escherichia coli (282), Pseudomonas aeruginosa (238), Staphylococcus spp . (149), Streptococcus spp . (107), Klebsiella spp . (105), Proteus spp . (97), Haemophilus spp . (71), Enterobacter spp . (58), Salmonella spp . (44), Citrobacter spp . (27), and Serratia spp . (22) . Signs and symptoms of infection resolved in 84% of all cases; 12.6% improved and 3.4% failed to improve . Pathogens were eradicated in 91% of urinary tract infections and in 87% of all other cases of infection combined; superinfections occurred in 5.3% of all patients . At the four-week follow-up 83% of patients with urinary tract infection still had sterile urine . Adverse reactions during therapy were considered probably or possibly drug-related in 166 patients . Nausea (37), diarrhea (25), vomiting (15), nervousness (28), and rash (9) were the most frequent; in only 2% of cases was it necessary to discontinue the drug . Results of ophthalmologic studies were generally unremarkable . Occasional elevations of SGOT and SGPT, and rare elevations of NPN related to ciprofloxacin therapy were seen.

J Clin Microbiol, 1986 Mar, 23(3), 600 - 3
Selective and differential medium for the primary isolation of members of the Proteeae; Hawkey PM et al.; A new differential and selective medium for the isolation of members of the Proteeae, PIM (Proteeae isolation medium) agar, was developed and evaluated . The medium relies on the ability of all members of the Proteeae (with the exception of a very few Morganella morganii strains) to produce a dark brown pigment in medium containing DL-tryptophan . An additional differential property, tyrosine degradation, was also demonstrated by the medium . Members of the Proteeae appeared as dark brown colonies with a halo of clearing of fine tyrosine crystals when cultured on PIM agar . Occasional strains of Citrobacter sp . and Pseudomonas aeruginosa may degrade tyrosine, but none has the ability to produce dark brown pigmentation on PIM agar . Quantitative recovery studies showed that the addition of 5 mg of clindamycin per liter suppressed gram-positive bacteria without inhibiting any strains of the Proteeae . The addition of 100 mg of colistin per liter made the medium highly selective for strains of the Proteeae, but approximately 10% of the strains were not isolated, thus making this formulation unsuitable for general surveys of the occurrence of members of the Proteeae . PIM agar should aid the investigation of episodes of cross infection caused by members of the Proteeae and the isolation of the new species of the Proteeae recently described.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 456 - 60
Isolation, characterization, and mode of action on Escherichia coli strains of microcin D93; Martinez JL et al.; Microcin D93 is an antibiotic substance produced by Escherichia coli strains which harbor the 5.5-kilobase plasmid pMccD93 . Its production is unaffected by the use of different carbon and ammonia sources, different phosphate concentrations, or mitomycin C . We developed a method for purifying this microcin based on gel permeation chromatography and reverse-phase high-pressure liquid chromatography . The antibiotic appears to be a small, hydrophilic, basic peptide, active on E . coli and Proteus, Citrobacter, and Pseudomonas species and much more active on recA strains than on their isogenic wild type . Diminution of the rate of DNA biosynthesis without any apparent effect on other macromolecules appears to be a primary effect in the action of microcin D93.

Diagn Microbiol Infect Dis, 1986 Mar, 4(3), 223 - 30
Antimicrobial activity and beta-lactamase stability of SK&F 88070 compared with other agents; Neu HC et al.; The in vitro activity and beta-lactamase stability of SK&F 88070 (7-{{2-amino-4-thiazolyl)(methoxyimino)acetyl}amino}-3-{{ {1-(2-sulfaminoethyl)-1H-tetrazol-5-yl}thio}methyl}-3- cephem-4-carboxylic acid) a new parenteral cephalosporin was investigated against 780 types of bacteria . SK&F 88070 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, Shigella species, Morganella morganii, and Citrobacter diversus at less than or equal to 0.5 micrograms/ml . Its activity against these species was similar to cefotaxime and moxalactam and superior to cefoperazone and piperacillin . It was less active than cefoperazone against Pseudomonas aeruginosa and less active than cefotaxime or cefoperazone against Staphylococcus aureus . SK&F 88070 inhibited hemolytic streptococci and Streptococcus pneumoniae at less than or equal to 0.12 micrograms/ml . Enterobacter species, Citrobacter freundii, and Serratia, which were resistant to cefotaxime and moxalactam were resistant to SK&F 88070 . It was not hydrolyzed by plasmid beta-lactamases, but was hydrolyzed by the Proteus vulgaris type 1c enzyme . SK&F 88070 inhibited Richmond-Sykes type 1a beta-lactamases.

Zh Mikrobiol Epidemiol Immunobiol, 1986 Feb, (2), 27 - 30
{Isolation and properties of Citrobacter bacteriophages}; Gabrilovich IM et al.; Four phages differing in their antigenic properties, thermosensitivity and spectrum of action have been obtained from Citrobacter lysogenic cultures . To prepare the suspension of Citrobacter phages, phagolysates may be treated with chloroform 1:10 for 30 minutes . The isolated phages have proved to be highly specific . The possibility of distinguishing Citrobacter cultures by means of the phages under study has been shown.

J Bacteriol, 1986 Jan, 165(1), 324 - 7
Conservation of DNA sequences for plasmid-mediated citrate utilization within the enterobacteria; Hirato T et al.; Southern blot DNA-DNA hybridization experiments with a cloned Cit+ DNA fragment as a probe showed that the plasmid-mediated Cit+ determinants from four Cit plasmids (R726, pOH3001, pOH3035, and pOH30221) were all homologous . Sequences homologous to the plasmid-borne Cit+ gene were also found in total bacterial DNA isolated from Salmonella paratyphi B, Salmonella enteritidis, Salmonella typhimurium LT-2, Citrobacter freundii, ATCC 8090, Citrobacter amalonaticus ATCC 25405, Klebsiella pneumoniae I and IID 977, and Enterobacter aerogenes ATCC 13048 . The DNA digest from C . amalonaticus ATCC 25405 contained a 1.4-kilobase BamHI-HincII DNA fragment that was strongly homologous with and identical in size to the plasmid Cit+ probe.

Vutr Boles, 1986, 25(4), 32 - 8
{Treatment of urologic infections with cefamandole (Pharmachim)--the microbiological and clinical results}; Minkov N et al.; The authors study the possibilities of cephalosporin antibiotic cefamandol, new for our clinical practice, in the treatment of uroinfections . The microbiological study on a total of 2301 bacterial strains, isolated from patients with uroinfections, reveals that cefamandol excels in its action against gram-positive microorganisms, all beta-lactam antibiotics, used in our country . As regards E . coli, Citrobacter, Klebsiella, Enterobacter, P . mirabilis and indole positive pro cefamandol is better than ampicillin, carbencillin and cefalotin . A resistance to the preparation showed the majority of the isolates of Enterococcus, Serratia, Acinebacter and Pseudomonas aeruginosa . Excellent result was attained in 60% of all the 35 patients with uroinfections treated, manifested in "sterilization" of urine and in 5.71% bacteruiria became insignificant . In parallel, the clinical and laboratory symptoms of uroinfection were favourably influenced . The preparation has a good tolerance . Finally it should be underlined that this antibiotic must be introduced in the routine clinical practice for the treatment of adequate forms of uroinfections.

Antonie Van Leeuwenhoek, 1986, 52(2), 117 - 20
Salmonellae and other enteropathogenic bacteria in the intestines of wall geckos in Nigeria; Gugnani HC et al.; The aerobic bacterial flora of the intestine of 150 wall geckos (Hemidactylus brookei) was investigated . A variety of bacteria was recovered including 35 isolates of Salmonella and several other species of Enterobacteriaceae, viz . Shigella sonnei - 2, Edwardsiella tarda - 4, Enterobacter spp - 8, Citrobacter freudii - 3, Serratia marcescens - 3, Proteus spp - 35, Klebsiella pneumoniae - 13, and Escherichia coli - 17, isolates . Eight Salmonella serotypes were identified, the predominant ones being S . hvittingfoss and S . typhimurium . The significance of these findings for the spread of human enteropathogens is discussed.

Scand J Infect Dis Suppl, 1986, 49, 38 - 45
Chromosomal beta-lactam resistance in enterobacteria; Normark S et al.; Most enterobacterial species carry a chromosomal ampC beta-lactamase gene . In Escherichia coli and Shigella, expression from ampC is non-inducible and the beta-lactamase is synthesized at low levels . Mutations leading to increased beta-lactamase synthesis occur rather infrequently, making resistance to modern cephalosporins a rare event in these species . In other enterobacteria and Pseudomonas, ampC beta-lactamase synthesis is induced by beta-lactams . In Enterobacter cloacae, Citrobacter freundii and probably also in other species with inducible beta-lactamase expression, ampC is regulated by at least two genes, ampR and ampD . Mutations affecting ampR abolish beta-lactamase inducibility, and mutants devoid of ampR, produce ampC beta-lactamase at low constitutive levels . Mutations in ampD lead to constitutive overproduction of inducible beta-lactamase if an intact ampR protein is present in the cell . The latter type of mutations occur at a high frequency and result in clinical resistance to several third-generation cephalosporins.

Arch Immunol Ther Exp (Warsz), 1986, 34(1), 135 - 8
The use of normal filter paper for "dot-immunobinding assay" of some antibodies; Rapak A et al.; Normal filter papers were used for specific detection of tiny amounts of antibodies against two penicillin amidase molecular forms from Escherichia coli, monoclonal antibodies of IgG and IgM class against lipopolysaccharide from Citrobacter O36 and IgM antibody against glycoprotein N from human red blood cells . For colour detection of antibodies bound to proper antigens adsorbed on the paper, second antibody-horse radish peroxidase conjugates and hydrogen peroxide with 4-chloronaphthol were applied . The use of filter paper for dot-immunobinding assay of antibodies gave similar results to those obtained with expensive nitrocellulose sheets used by other authors.

Scand J Infect Dis, 1986, 18(1), 3 - 13
The antimicrobial activities of trimethoprim and sulfonamides; Burman LG; The folate inhibitor trimethoprim (TMP) is active against and potentially cidal to a few higher microorganisms and a wide spectrum of pathogenic bacteria except for Bacteroides, Branhamella, Brucella, Chlamydia, Clostridium, Mycobacterium, Mycoplasma, Nocardia, Neisseria, Pseudomonas and Treponema . These organisms tend to be more sensitive to sulfonamides (SUL) than to TMP, whereas TMP is 10- to 100-fold more active than SUL against most other bacteria . Synergy between TMP and SUL occurs at drug concentrations equal to or less than their respective MICs and is often seen in vitro with isolates that are sensitive or moderately resistant to one or both of the components . Synergy occurs over a wide range of ratios between TMP and SUL, the optimal being that between their respective MICs when acting singly . In vitro synergy is more impaired by bacterial resistance than by suboptimal TMP:SUL ratios . The vast majority of clinical isolates of Haemophilus, staphylococci, streptococci and enteric bacteria are inhibited in vitro by the minimum concentrations of drug attained in plasma during therapy . Exceptions are found among Enterobacter, Citrobacter, Serratia, Proteus and in particular Klebsiella where SUL resistance is common and isolates with TMP MICs of 5 mg/l or more may occur and lead to failure of TMP-SUL therapy in systemic infections . In the urinary tract drug concentrations that are synergistic and therefore inhibitory in vitro against isolates moderately resistant to SUL (MIC less than or equal to 1 g/l) and/or TMP (MIC less than or equal to 0.1 g/l) are present during TMP-SUL therapy . However, whether the synergy and the bactericidal effect of TMP-SUL observed in vitro play a role in vivo is controversial.

J Antimicrob Chemother, 1986 Jan, 17(1), 51 - 61
Inducible type I beta-lactamases of gram-negative bacteria and resistance to beta-lactam antibiotics; Curtis NA et al.; Mutants, showing either constitutive (depressed) or non-inducible expression of chromosomally-mediated Type I beta-lactamase were obtained from clinical isolates of Enterobacter cloacae, Ent . aerogenes, Citrobacter freundii, Providencia stuartii, Morganella morganii, Serratia marcescens and Pseudomonas aeruginosa . The wild-type and mutant strains were compared for susceptibility to a range of beta-lactam antibiotics . Derepression of beta-lactamase synthesis generally, but not always, resulted in a marked reduction in susceptibility to the agents tested, including the '3rd generation' cephalosporins . In many cases, the observed resistance would preclude, or severely compromise, the therapeutic efficacy of the drugs . In this context, depressed mutants of Enterobacter spp., Citro . freundii and Ps . aeruginosa could be of primary concern although those of Ser . marcescens, Prov . stuartii and Morg . morganii often exhibited equally high resistance levels to older beta-lactams . Comparison of the susceptibilities of the non-inducible mutants with that of their inducible parents suggested variation in the beta-lactamase inductive potency of different compounds in different organisms . For example, cefoxitin was a powerful inducer in Ent . cloacae, Citro . freundii and one strain of Ps . aeruginosa; similarly cefazolin and cefuroxime were good beta-lactamase inducers in Ser . marcescens and Morg . morganii . Aminothiazolyl-oxime cephalosporins and ureido-penicillins were generally poor inducers . From such comparisons, the contribution of inducible Type I beta-lactamase to resistance phenotype could be ascertained.

Scand J Infect Dis Suppl, 1986, 49, 100 - 5
Selection of beta-lactamase producers during cephalosporin and penicillin therapy; Wiedemann B; Treatment failures due to beta-lactamase producing strains of Enterobacter cloacae, Proteus vulgaris, Citrobacter freundii and Pseudomonas aeruginosa are frequently reported . It is difficult, however, to determine the underlying mechanism of resistance development . Different beta-lactam drugs, such as cephalosporins and penicillins have different ecological impacts on the infections and physiological flora of patients . They select in different ways although the mutation frequency of strains towards beta-lactamase production is not affected by these drugs . Thus in a specific process of selection one has to consider the mechanism and frequency of changes in the beta-lactamase production, the selective power of the different drugs (relation of drug concentration to the MIC for possible mutants or induction of beta-lactamase), selection of resistance in the physiological flora of patients, spread of such mutants to other patients and in the hospital environment, and the stability of beta-lactamase production . As each antibiotic has the potential of selecting mutants and in the case of beta-lactam drugs the more powerful ones select for mutants which produce a beta-lactamase that is more stable against less powerful drugs, a careful selection of drugs together with an effective infection control is mandatory.

J Hyg Epidemiol Microbiol Immunol, 1986, 30(4), 455 - 63
Properties of free and bound Citrobacter freundii lipopolysaccharides; Bartkova G et al.; Culture medium content of free lipopolysaccharide (LPS) components spontaneously released from a Citrobacter freundii culture grown in minimum synthetic medium was determined during early (8-hr culture) and late (24-hr culture) phases of growth . As judged by Limulus-lysate test, free LPS occurred in the medium as early as after 8 hrs of incubation, i.e . at the beginning of log growth phase . As the culture continued to grow the LPS amount released into culture medium kept rising, reaching 30% of endotoxin present in 24-hr Citrobacter culture . The released LPS complex was isolated by separation and its physicochemical, immunochemical and biological properties were determined and compared with those of cell-bound endotoxin recovered from cells by phenol extraction . Comparisons revealed distinct differences in the chemical composition and the degree of heterogeneity; free LPS was less heterogeneous . Immunologically, free LPS differed from bound LPS in the structure of macromolecules, but was identical with it in some antigenic determinants . The biological activity of free LPS preparation was greater than that of cell-bound LPS.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Dec, 93(6), 407 - 10
Rapid identification of Escherichia coli from routine urine specimens based on macroscopic criteria; Jenum PA; In our laboratory, selected strains of Gram-negative rods from urine samples are identified as Escherichia coli on the basis of smell and morphology on lactose agar . To investigate the accuracy of this routine practice, 211 consecutive strains were tested in the urea-indole tube of the Three-tube method (3-TM), in the PGUA test detecting beta-glucuronidase activity and in the Simmons' citrate test, to select the strains that were non-E . coli . Additional 1022 strains were tested by the indole and urease tests of the 3-TM only . The identification of E . coli based on the macroscopic evaluation of colonies on lactose agar gave correct results for 99.1% of the strains . Citrobacter freundii was the most frequent cause of erroneous identification.

Am J Med, 1985 Nov 29, 79(5B), 2 - 12
Contribution of beta-lactamases to bacterial resistance and mechanisms to inhibit beta-lactamases; Neu HC; Resistance of bacteria to beta-lactam antibiotics has become a serious problem in the past several decades . Virtually all Staphylococcus aureus, and many Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Enterobacteriaceae, and Bacteroides species possess beta-lactamases that hydrolyze penicillins and cephalosporins . The most common plasmid-mediated beta-lactamase is the TEM enzyme (Richmond-Sykes type IIIa), which is present in Hemophilus, Neisseria, and Enterobacteriaceae . One technique to overcome bacterial resistance has been the development of beta-lactamase inhibitors . Clavulanic acid is a beta-lactamase inhibitor that inhibits the beta-lactamases of S . aureus, Hemophilus, Neisseria, Branhamella, Eschericia coli, Klebsiella, and Bacteroides . Clavulanate acts as a "suicide" inhibitor, forming a stable enzyme complex that binds to serine at the active site of the enzyme . Clavulanate readily crosses the outer cell wall of most Enterobacteriaceae to interact with beta-lactamases in the periplasmic space . Clavulanate does not inhibit beta-lactamases such as the Richmond-Sykes type I enzymes found in Pseudomonas aeruginosa, Enterobacter, and Citrobacter species, which are inducible enzymes that function primarily as cephalosporinases.

Am J Med, 1985 Nov 29, 79(5B), 101 - 5
Timentin in the treatment of symptomatic complicated urinary tract infections in adult patients; Gebhart RJ et al.; The safety and effectiveness of Timentin were evaluated in 34 adult patients with symptomatic complicated urinary tract infections, principally due to multiply-drug-resistant bacteria . Although a wide variety of organisms, particularly gram-negative bacilli, were found, Escherichia coli was the most frequent, accounting for 14 of 45 (31 percent) pathogens isolated . Ten (22 percent) isolates were Pseudomonas aeruginosa; 11 (24 percent) were Proteus or Morganella species; three (7 percent) were Citrobacter; one (2 percent) was Klebsiella pneumoniae; two (4 percent) were Staphylococcus aureus; and two (4 percent) were enterococci . Ninety-three percent of all pathogens isolated produced a beta-lactamase . Eight (24 percent) infections were polymicrobial; seven (21 percent) were associated with bacteremia . Clinical improvement occurred in 30 of 34 (86 percent) patients . All bacteremias were cured . Although bacteriologic cure occurred in only 32 percent of patients, control of sepsis and temporary eradication of bacteria (bacteriologic improvement) occurred in 96 percent . Not surprisingly, the rates of relapses and reinfections were high . It was concluded that Timentin is a useful agent in the management of complicated urinary tract infection and offers clinicians an alternative to more toxic antibiotics, such as aminoglycosides.

Diagn Microbiol Infect Dis, 1985 Nov, 3(6), 469 - 78
Antibacterial activity of amifloxacin (WIN 49, 375), a new quinolone agent; Neu HC et al.; The in vitro activity of amifloxacin, a quinolone antimicrobial agent was compared with those of ciprofloxacin, enoxacin, ofloxacin and norfloxacin against gram-positive and gram-negative bacteria . Ninety percent of Escherichia coli, Klebsiella species, Aeromonas, Salmonella, Shigella, Citrobacter, Enterobacter species, Proteus mirabilis, Serratia marcescens, and Morganella morganii were inhibited by less than or equal to 0.5 microgram/ml . Amifloxacin inhibited Branhamella, Haemophilus, and Neisseria at less than or equal to 0.25 microgram/ml, and 90% of Pseudomonas aeruginosa, including gentamicin- and carbenicillin-resistant isolates, at 4 micrograms/ml . It also inhibited staphylococci, including methicillin-resistant isolates, but was less active against streptococci and Bacteroides species . Amifloxacin had in vitro activity similar to enoxacin, ofloxacin, and norfloxacin, but was less active than ciprofloxacin . Like other quinolones, it was less active at acid pH and in the presence of urine.

J Antimicrob Chemother, 1985 Nov, 16(5), 563 - 74
In-vitro activity of ofloxacin, a quinolone carboxylic acid compared to other quinolones and other antimicrobial agents; Kumada T et al.; Ofloxacin is a new quinolone carboxylic acid compound . Its activity against 900 bacterial isolates was determined . It inhibited 90% of Escherichia coli, Klebsiella sp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Citrobacter spp., Enterobacter spp., Morganella morganii, Proteus mirabilis, Yersinia enterocolitica at less than or equal to 0.8 mg/l . Branhamella catarrhalis, Haemophilus sp., Neisseria sp . were inhibited by less than or equal to 0.1 mg/l . Pseudomonas aeruginosa and other Pseudomonas species were inhibited by less than or equal to 6.3 mg/l . Although most staphylococcal species, including methicillin-resistant staphylococci were inhibited by 3.1 mg/l, many streptococcal species had higher MIC values, and most Bacteroides species were inhibited at less than or equal to 6.3 mg/l . The overall activity of ofloxacin was similar to enoxacin and norfloxacin . Ofloxacin inhibited organisms resistant to nalidixic acid, ampicillin, cephalexin, piperacillin, and gentamicin including Enterobacter spp., Citrobacter freundii and Serratia marcescens resistant to cefotaxime . The activity of ofloxacin was lower at an acid pH and in urine, but serum had no effect on MICs or MBCs . Increase in ofloxacin MICs for various bacteria could be achieved by repeated subculture in the presence of ofloxacin.

Rev Infect Dis, 1985 Nov-Dec, 7 Suppl 4, S783 - 8
Aztreonam in the treatment of bone and joint infections caused by gram-negative bacilli; Simons WJ et al.; Aztreonam was used successfully in 17 of 17 patients with orthopedic infections due to gram-negative bacilli (11, osteomyelitis; six, septic arthritis) . Duration of treatment ranged from 14 to 55 days, and the period of follow-up was four to 18 months . Causative organisms included Pseudomonas aeruginosa, Serratia marcescens, Enterobacter gergoviae, Citrobacter diversus, Proteus mirabilis, and Enterobacter aerogenes . Aztreonam was well tolerated . The only definite reactions attributable to aztreonam were asymptomatic increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) in four patients; none of these reactions interfered with completion of therapy . Adverse reactions that were possibly attributable to aztreonam included rash (two patients), diarrhea (one patient), and leukopenia (one patient) . All of these patients were receiving antibiotics active against gram-positive organisms in mixed infections in addition to aztreonam . Aztreonam is a promising new monobactam without significant toxicity . It has good activity against gram-negative aerobic bacteria, including P . aeruginosa, and is effective in the treatment of serious infections due to gram-negative aerobes.

Appl Environ Microbiol, 1985 Oct, 50(4), 755 - 62
Holding effects on coliform enumeration in drinking water samples; McDaniels AE et al.; Standard procedures for analyzing drinking water stress the need to adhere to the time and temperature conditions recommended for holding samples collected for microbiological testing . The National Drinking Water Laboratory Certification Program requires compliance with these holding limits, but some investigators have reported difficulties in meeting them . Research was conducted by standard analytical methods to determine if changes occurred when samples were held at 5 and 22 degrees C and analyzed at 0, 24, 30, and 48 h . Samples were analyzed for coliforms by the membrane filter and fermentation-tube procedures and for heterotrophs by the pour plate method . A total of 17 treated water samples were collected from a large municipal distribution system from August to December 1981, and 12 samples were collected from January to May 1983 . The samples were dosed with coliforms previously isolated from the water system, Enterobacter cloacae in 1981 and Citrobacter freundii in 1983 . The coliform counts declined linearly over time, and the rates of decline were significant at both 5 and 22 degrees C . Within 24 h at 22 degrees C, levels of E . cloacae and C . freundii decreased by 47 and 26%, respectively, and at 5 degrees C, E . cloacae numbers declined by 23% . Results from these representative laboratory-grown coliforms reinforced those previously obtained with naturally occurring coliforms under the same experimental conditions . Significantly, some samples with initially unacceptable counts (greater than 4/100 ml) met the safe drinking water limits after storage at 24 h at 5 and 22 degrees C and would have been classified as satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Pathol Microbiol Immunol Scand {B}, 1985 Oct, 93(5), 365 - 9
Population analysis of susceptibility to cefotaxime in Enterobacteriaceae; Sogaard P; Population analysis of susceptibility to cefotaxime (CTX) in eight species of Enterobacteriaceae was carried out . One strain of each species was examined . The strains represented their individual species as regards natural susceptibility to ampicillin (A) and carbenicillin (Ca) . Cephalothinase activity of the parental strains and strains selected on the plates with the highest concentration that allowed growth was determined by an ultraviolet assay . The populations of the A-susceptible/Ca-susceptible (A-s/Ca-s) species, Escherichia coli and Proteus mirabilis were homogeneous as regards susceptibility to CTX . The A-resistant/Ca-resistant (A-r/Ca-r) species, Klebsiella oxytoca and Citrobacter koseri, were less homogeneous, but in all four mentioned species no increase in cephalothinase activity was observed between the parental strains and the strains selected in the population analysis . The four A-r/Ca-s species, Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, and Morganella morganii, were heterogeneous . The frequency of CTX-r mutants was approx . 10(-6.5) . The IC50 for CTX was 2(7.5)-2(8.5) times higher for the mutants than for the parental strains . The CTX resistance was maintained in subcultures of the strains . All four species had a very high increase in cephalothinase activity from parental strains to the strains selected in the population analysis . Only the enzyme of Proteus vulgaris was able to hydrolyze CTX.

Arch Intern Med, 1985 Oct, 145(10), 1808 - 10
Bacteremias due to Citrobacter diversus and Citrobacter freundii . Incidence, risk factors, and clinical outcome; Drelichman V et al.; From 1974 to 1982, 38 patients developed Citrobacter bacteremia at two adult community-teaching hospitals in the Detroit Medical Center (incidence, 1.2 cases per 10,000 discharges) . Citrobacter accounted for 0.7% of all bacteremias during the study period . Of 31 cases reviewed, Citrobacter bacteremia frequently developed in elderly patients (65%) and was hospital acquired (77%) . Initial sites of infection included the urinary tract (39%), gastrointestinal tract (27%), wound (10%), and unknown (13%) . More bacteremias caused by Citrobacter diversus tended to arise from the urinary tract, while patients with Citrobacter freundii bacteremia had significantly more gallbladder disease . Patients with Citrobacter bacteremia were more likely than patients with Escherichia coli bacteremia to have had additional pathogens in the bloodstream, to develop bacteremia in the hospital, and to have undergone invasive procedures contributing to infection . Significant differences were not observed in demographic, host, or other epidemiologic or clinical factors examined . Of patients with Citrobacter bacteremia, 48% died.

Antibiot Med Biotekhnol, 1985 Sep, 30(9), 681 - 4
{Characteristics of the composition of the causative agents of different forms of suppurative inflammatory diseases and their antibiotic sensitivity}; Levina EN et al.; Antibiotic sensitivity of 466 clinical strains of gram-positive and gram-negative microorganisms isolated from patients with different forms of pyoinflammatory diseases was studied . Most of the staphylococcal isolates were resistant to benzylpenicillin (74.3 per cent) . The number of the isolates resistant to erythromycin amounted to 59.6 per cent . The respective figures for methicillin and dicloxacillin were 17.9 and 10.8 per cent . Staphylococci resistant to new aminoglycosides, fusidin and rifampicin were rare . It was shown that . P . aeruginosa preserved its sensitivity to the majority of the antipseudomonas antibiotics . Among Enterobacteriaceae the highest levels of antibiotic resistance were observed in Enterobacter, Citrobacter, Serratia and Klebsiella . Significant variation in the isolation frequency of different microbial species and in the proportion of gram-negative and gram-positive bacteria in the hospital departments was observed . It was noted that gram-negative causative agents predominated in the departments of chest and abdominal surgery, anesthesiology, intensive care and urology.

Vopr Pitan, 1985 Sep-Oct, (5), 51 - 5
{Biochemical properties of enterobacteria on polystyrene plates}; Kuvaeva IB et al.; The authors studied 84 strains of enterobacteria . The reliability of the results of the biochemical testing obtained by the micromethod with the use of polystyrene plates was examined comparatively to the data obtained by the classical method and API microsystems manufactured in France . Of the 84 strains of enterobacteria, 36 belonged to Proteus, 24 to Enterobacter, 8 to Klebsiella, 5 to Citrobacter, and 11 to E . coli . Of the strains tested, 50 were isolated from the intestine of children and adults, 30 from the residual microflora of foods, and 4 were museum strains . Study according to 23 tests on the conventional media with consideration of the results after 18 to 48 hours demonstrated the coincidence of the data, obtained by the methods used, for most strains . This circumstance permits recommending the micromethod for testing the biochemical properties of enterobacteria on polystyrene plates for broad-scale use.

Pharmacotherapy, 1985 Sep-Oct, 5(5), 237 - 53
Ceftriaxone: a beta-lactamase-stable, broad-spectrum cephalosporin with an extended half-life; Beam TR Jr; Ceftriaxone is an aminothiazolyl-oxyimino cephalosporin . It possesses the typical in vitro activity of a third-generation cephalosporin with excellent activity against many gram-negative aerobic bacilli: Escherichia coli; species of Proteus, Klebsiella, Morganella, Providencia and Citrobacter; and Enterobacter agglomerans . Ceftriaxone also has outstanding bactericidal action against pneumococci, group B streptococci, meningococci, gonococci and Hemophilus influenzae . In healthy volunteers, it has an exceptionally long serum half-life of 5.8-8.7 (mean 6.5) hours . It distributes well throughout all body spaces, including cerebrospinal fluid in the presence of inflammation . Dosage modification is necessary only when there is combined hepatic and renal dysfunction . Adverse reactions characteristic of cephalosporins have been observed with the administration of ceftriaxone . No unique toxicities have been identified, and hypoprothrombinemic bleeding is not part of the adverse reaction profile . Ceftriaxone has been used to treat serious bacterial infections in neonates, infants, children and adults . Bacteriologic and clinical success rates have consistently exceeded 90% . The drug has also been used as single-dose chemoprophylaxis in coronary artery bypass, biliary tract, vaginal hysterectomy and prostatic surgery . Efficacy and safety were similar to multiple-dose cefazolin . Ceftriaxone warrants special consideration because its extended half-life allows for less frequent dosing than other antimicrobials . Significant cost savings can be realized with proper use of this antibiotic.

Am J Med, 1985 Aug 9, 79(2A), 75 - 82
New beta-lactam antibiotics in granulocytopenic patients . New options and new questions; Pizzo PA et al.; Infectious complications are a frequent cause of morbidity and, at many centers, the major cause of death in patients with cancer . The increased risk and severity of infectious sequelae result from profound alterations in normal host defenses that occur secondary to the underlying malignancy and the treatment thereof . During the last decade, early empiric antibiotic therapy has become standard practice in the initial management of febrile granulocytopenic patients and has contributed significantly to the improved outcome among patients undergoing cancer therapy . Although early death due to unsuspected or inadequately treated bacterial infection has been largely overcome, new problems--also with life-threatening implications--have emerged . As the use of cancer chemotherapy continues to increase, new populations of patients are being placed at increased risk of infection . Defining the host and environmental factors that contribute to this risk assumes central importance for delineating those patients who require the most intense surveillance . Changing medical practices (e.g., increased use of indwelling catheters) have contributed to the emergence of new pathogens . Recent drug developments (e.g., the third-generation cephalosporins and extended-spectrum penicillins) offer new treatment options, as well as generate controversy and confusion . For example, authorities disagree on the optimal duration and modifications in treatment that are required by cancer patients who remain granulocytopenic and who thus are at continued risk of multiple infectious episodes or superinfections . A question of current interest is whether combination therapy with synergistic agents is important in light of the development of the third-generation cephalosporins and extended-spectrum penicillins . Several of these new antibiotics have an exceedingly broad spectrum of activity that includes Pseudomonas aeruginosa, as well as Enterobacteriaceae, Serratia, Citrobacter, indole-positive Proteus, and anaerobes (including Bacteroides fragilis) . However, the third-generation cephalosporins are not as active against staphylococci and streptococci as are the first-generation cephalosporins, and none is effective against enterococci . Nonetheless, these agents achieve serum levels that can be 10 to 100 times greater than the minimal inhibitory and bactericidal concentrations of gram-negative bacteria, raising the possibility that these drugs might be effective as single agents . The advantages of the third-generation cephalosporins are their minimal toxicity and long serum half-lives.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1985 Aug, 38(8), 2185 - 229
{Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1983) . I . Susceptibility distribution}; Kosakai N et al.; During 1979-1983 in vitro activities of antimicrobial agents against causative bacteria isolated from patients with urinary tract infections (UTI) were investigated by Microbiological Research Group of UTI including the 8 institutions in Japan . Of all strains (219) isolated from patients with simple UTI, 65.3% were E . coli, and 9.6% Klebsiella spp.; these species accounted for about 75% of all isolates in 1983 . MPC and CCL among the oral antimicrobial agents have showed potent activities against E . coli, MPC at 1.56 micrograms/ml and CCL at 3.13 micrograms/ml inhibited 80% of E . coli from simple and complicated UTI . CTM, CTX, CZX, CMX and LMOX among the parenteral antimicrobial agents, at concentrations of 0.20 micrograms/ml or less inhibited 90% of E . coli isolated from simple and complicated UTI . The frequency of isolates from patients with complicated UTI, without catheter, was as follows; E . coli 27.6%, P . aeruginosa 20.1%, Streptococcus spp . 12.6%, Serratia spp . 8.8% and Klebsiella spp . 8.0% . The frequency of isolates from patients with complicated UTI, indwelling catheter, was as follows; P . aeruginosa 22.6%, Streptococcus spp . 18.0%, Serratia spp . 15.0%, Proteus spp . 12.4%, and Enterobacter spp . and Klebsiella spp . are 6.0%, respectively, in 1983 . The antibacterial activity (MIC80) against E . coli, Klebsiella spp., P . mirabilis, Citrobacter spp . and Serratia marcescens from simple and complicated UTI was compared, for example, among third generation cephem antibiotics . Four drugs such as CMX, CZX, CTX and LMOX showed virtually comparable activities while CPZ was slightly less active against the strains tested . There have been many studies reported concerning the antibacterial activity of various drugs against clinical isolates from patients with infections, but it seems that, to our knowledge, no article has dealt with yearly surveys on antimicrobial susceptibility of bacterial isolates from defined clinical specimens with the same period of each year at the same series of institutions.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Aug, 260(1), 8 - 14
First strains of the genus Kluyvera in Czechoslovakia; Aldova E et al.; Fourteen of 21 strains isolated from stools, urine specimens and the hospital environment were identified as Kluyvera . All of these 14 strains corresponded with the literary description of the genus Kluyvera and were identical with two reference strains except that one of them failed to utilize sodium acetate within 7 days . One strain (No . 23441) produced massive growth on Jordan's tartrate, which some Kluyvera do . Important in differentiating indole- and Simmons' citrate-negative Kluyvera strains from Escherichia vulneris (two other of our 21 strains) is negative ornithin decarboxylase and negative Christensen citrate in the latter . Three strains were identified as Citrobacter, where especially indole-positive and urease-negative strains may be reminiscent of Kluyvera . An aberrant strain, No . 25115, which alone failed to grow at 42 degrees C and by some characters differed from Kluyvera, E . vulneris and Enteric Group 10, was identified as E . coli.

Jpn J Antibiot, 1985 Aug, 38(8), 2243 - 312
{Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1983) . III . Secular changes in susceptibility}; Kosakai N et al.; The in vitro antimicrobial activities of antibiotics against causative pathogens isolated from patients with urinary tract infections (UTI) in the 8 institutions in Japan during the period from 1980 to 1983 were compared . A number of new beta-lactam antibiotics with broad spectrum of activity have become available for clinical use in recent years . Some of them, in particular so-called third generation cephems, are reported to be responsible for developing microbial-cross resistance to multiple beta-lactam antibiotics . We have been making survey in recent years to explore changes in susceptibility to various antimicrobial agents of clinical isolates . All bacterial isolates from clinical specimens were submitted to the Department of Clinical Pathology, Juntendo University School of Medicine, where they were tested for antimicrobial susceptibility with MIC 2000 apparatus . Of all pathogens from patients with simple UTI, the majority of the isolates was E . coli and Klebsiella spp . In cases of complicated UTI, on the other hand, Pseudomonas spp . were most frequent, followed in order by Proteus spp., Klebsiella spp., Serratia spp., Citrobacter spp . and E . coli . Conspicuous changes in antimicrobial activity of antibiotics against E . coli and Klebsiella spp . from simple UTI have not been found in our survey . Against strains of Citrobacter spp., even the third generation cephems proved to be not remarkably active and there was a significant decrease in susceptibility of isolates to the drugs test-showed MIC values of 50 micrograms/ml and the proportion increased to 50% (22/44) with isolates obtained in 1982 . The antimicrobial activity of cefsulodin and gentamicin against P . aeruginosa was decreased in 1982 compared with that in 1980 and 1981 . However, resistant strains were slightly more frequent with gentamicin . In 1983, the antimicrobial activity of third generation cephems against Serratia spp . was significantly reduced from that in 1982.

J Bacteriol, 1985 Aug, 163(2), 669 - 76
Purification and characterization of selenocysteine beta-lyase from Citrobacter freundii; Chocat P et al.; The purification and characterization of bacterial selenocysteine beta-lyase, an enzyme which specifically catalyzes the cleavage of L-selenocysteine to L-alanine and Se0, are presented . The enzyme, purified to near homogeneity from Citrobacter freundii, is monomeric with a molecular weight of ca . 64,000 and contains 1 mol of pyridoxal 5'-phosphate as a cofactor per mol of enzyme . L-Selenocysteine is the sole substrate (Km, 0.95 mM) . L-Cysteine is a competitive inhibitor of the enzyme (Ki, 0.65 mM) . The enzyme also catalyzes the alpha, beta elimination of beta-chloro-L-alanine to form NH3, pyruvate, and Cl- and is irreversibly inactivated during the reaction . The physicochemical properties, e.g., amino acid composition and subunit structure, of the bacterial enzyme are fairly different from those of the pig liver enzyme (Esaki et al., J . Biol . Chem . 257:4386-4391, 1982) . However, the catalytic properties of both enzymes, e.g., substrate specificity and inactivation by the substrate or a mechanism-based inactivator, beta-chloro-L-alanine, are very similar.

Vopr Pitan, 1985 Jul-Aug, (4), 56 - 9
{Dependence of the dynamics of the multiplication of bacteria in the genus Citrobacter on the temperature factor and on the product type in experimental contamination}; Sakimbaeva SD; A study was made of the time course of the reproduction of bacteria of the Citrobacter genus in milk, sausage meat and vermicelli during experimental contamination, with incubation of cultures at 3 temperature regimens (24, 37 and 44 degrees C) . Estimation of the results of experiments was performed by counting the number of the colonies on the surface of 2% beef-extract agar . It was established that within the first 6 h, at 24 and 37 degrees C there was an identical growth of the number of microorganisms in all the foods under study . During incubation at 44 degrees C (for 4-8 h), there was a slower reproduction of bacteria in milk as compared with sausage meat . It was revealed that food consistency had an effect on the intensity of the reproduction of bacteria of the Citrobacter genus depending on the time of incubation and temperature.

J Foot Surg, 1985 Jul-Aug, 24(4), 251 - 4
An unusual mixed infection in a diabetic patient: Citrobacter freundii and Peptococcus magnus; Notari MA et al.; A case of an unusual mixed infection of the foot involving Citrobacter freundii and Peptococcus magnus is presented . Characteristics and treatment of infections caused by these organisms are reviewed . The possible effects of an infection of this type in a compromised patient are also presented.

Hinyokika Kiyo, 1985 Jul, 31(7), 1159 - 70
{Clinical and experimental studies on the pathogenicity of clinical isolated Citrobacter freundii}; Harada M; Clinical and fundamental studies were performed using Citrobacter freundii isolated from urine specimens of in- and out-patients between January 1980 and July 1981 . The C . freundii (greater than 10(4)/ml) isolated from urine was closely related to chronic complicated urinary tract infection . MICs of pyridonecarbonic acids (ENX, OFLX and NFLX) and CMX against C . freundii were low . Pyridonecarbonic acids (ENX, OFLX and NFLX) and CMX showed good therapeutic effects against the experimental ascending pyelonephritis of mice according to their MICs . Against the experimental ascending pyelonephritis of cyclophosphamide-treated mice, pyridonecarbonic acids (ENX, OFLX and NFLX) showed good therapeutic effects . Experimental intraperitoneal infection of mice was made easily with a low inoculation dose by adding mucin . Pyridonecarbonic acids (ENX, OFLX and NFLX) and CMX showed good therapeutic effects against this experimental model . Experimental respiratory tract infection could not be made in the mice with the organism isolated from urine.

Proc Natl Acad Sci U S A, 1985 Jul, 82(14), 4620 - 4
Regulatory components in Citrobacter freundii ampC beta-lactamase induction; Lindberg F et al.; Citrobacter freundii encodes an inducible chromosomal beta-lactamase similar to the constitutively expressed ampC beta-lactamase of Escherichia coli . In the latter species the ampC gene is located next to the fumarate reductase (frd) operon, whereas in C . freundii the ampC gene is known to be separated from frd by 1100 base pairs . This intervening DNA segment carries a gene, ampR, coding for a 31-kilodalton polypeptide . The cloned C . freundii OS60 ampC gene is inducible by beta-lactam antibiotics in E . coli, but only in the presence of an intact ampR gene . In the absence of inducer the AmpR protein represses C . freundii ampC synthesis 2.5-fold . Addition of beta-lactams induced expression from the cloned ampC beta-lactamase gene 11-fold . Thus, the AmpR protein has a positive effect on ampC expression in the presence of inducing beta-lactams . Two spontaneous mutants of C . freundii were isolated that constitutively overproduce the ampC beta-lactamase . The mutations in both these strains occurred outside the frd-amp region, suggesting that there is at least one additional component in the regulatory system . With the cloned C . freundii ampC gene in E . coli, mutants with the same phenotype could be obtained . These mutations were located on the E . coli chromosome . The constitutive beta-lactamase overproduction in these mutants requires the presence of an intact ampR gene.

Antimicrob Agents Chemother, 1985 Jun, 27(6), 982 - 4
In vitro comparative antimicrobial activity of cefpimizole against clinical isolates from five medical centers; Jones RN et al.; Cefpimizole was compared with cefoperazone and cefotaxime against 6,599 clinical bacterial isolates from five medical centers . Cefoperazone and cefotaxime were both more active and provided a greater spectrum of antimicrobial coverage than cefpimizole . Some of the cefpimizole minimum concentrations inhibiting 50% of tested strains were as follows: Citrobacter freundii and Enterobacter cloacae, 16 micrograms/ml; Escherichia coli and Klebsiella pneumoniae, 2.0 micrograms/ml; Proteus mirabilis, 1.0 microgram/ml; Pseudomonas aeruginosa, 16 micrograms/ml; Staphylococcus spp., 32 micrograms/ml; and the enterococci, greater than 32 micrograms/ml.

Pathol Biol (Paris), 1985 Jun, 33(5 Pt 2), 482 - 6
{HR 810 (cefpirome) . Experimental evaluation of the in vitro and in vivo antibiotic activity of a new amino-2-thiazole methoxy- imino cephalosporin}; Chantot JF et al.; HR 810 or cefpirome is a new amino thiazole cephalosporin whose specific characteristic is a cyclopentenopyridinium group in position 3 of the cephem nucleus . This structure is responsible for a broad spectrum of activity, covering Enterobacteriaceae, including cephalosporinase-producing Enterobacter spp . and Citrobacter spp., Staphylococcus aureus, Pseudomonas aeruginosa and group D Streptococci.

Jpn J Antibiot, 1985 Jun, 38(6), 1603 - 18
{Distribution and changes in the susceptibility of bacteria isolated from clinical samples . III}; Deguchi K et al.; This report presents data concerning in vitro activity of antimicrobial agents against Citrobacter freundii, Enterobacter spp., Serratia marcescens and Proteus vulgaris isolated from patients with complicated urinary tract infections and against Pseudomonas aeruginosa isolated from surgical wounds with postoperative infection and exudate from superficial abscesses . There was a marked increase of resistant strains of C . freundii, Enterobacter spp . and S . marcescens to penicillins, CEPs or GM . The isolates of these species obtained in 1983 showed MIC values of 100 micrograms/ml or more for the so-called new CEPs (CTX, CMX, CZX, LMOX and CPZ) . The P . vulgaris isolates exhibited an increasing incidence of strains resistant to penicillins, and data on P . vulgaris isolates in 1983 indicated increase of strains resistant to CEPs . GM-resistant organisms were also noted to be increasing among the isolate of this species . The analysis did not reveal any appreciable change with calendar years among P . aeruginosa in respect of frequency of strains resistant to SBPC or CEPs (except CPZ) . The data obtained in 1983, however, showed an indication of increasing incidence of organisms resistant to CPZ and GM . The increasing tendency of emergence of organisms resistant to new CEPs designed to expand activity against C . freundii, Enterobacter spp., S . marcescens and P . vulgaris, observed among the isolates of these species is considered probably to be the consequence of bacterial selective acquisition of R plasmid that carry drug resistant genes against CEPs . These are exactly reflected in the present data obtained in studies initiated in 1981 when the new CEPs became commonly prescribed in the daily clinics . It is concluded, accordingly, that organisms of these species resistant to CEPs have been increasing throughout the country.

J Antimicrob Chemother, 1985 Jun, 15 Suppl C, 15 - 23
Sch 34343: in-vitro antibacterial activity and susceptibility to beta-lactamases; Shannon K et al.; The in-vitro activity of the penem Sch 34343 was assessed in comparison with third-generation cephalosporins, aztreonam and imipenem . Sch 34343 was active, with MICs generally 2 mg/1 or less, against a broad spectrum of organisms amongst which were staphylococci (including methicillin-resistant strains), streptococci (though enterococci were less susceptible with Sch 34343 MICs mostly 4-8 mg/1), anaerobes (including the Bacteroides fragilis group), Haemophilus influenzae and Neisseria gonorrhoeae . It was also active against the Enterobacteriaceae though Enterobacter cloacae and Serratia spp . were somewhat less susceptible than other members of this group . Sch 34343 lacked useful activity against most species of Pseudomonas (including Ps . aeruginosa) but was active against Ps . acidovorans and some isolates of Ps . cepacia . Sch 34343 showed a high degree of resistance to plasmid-determined and most chromosomally-determined beta-lactamases; however, it was hydrolysed rapidly by enzymes from some isolates of Aeromonas hydrophila and more slowly by enzymes from Ps . maltophilia and Bact . melaninogenicus subspecies intermedius . We did not observe any reduction in sensitivity to Sch 34343 for most beta-lactamase-producing organisms, including strains of Enterobacter spp . and Citrobacter freundii that were resistant to most other beta-lactams.

J Antimicrob Chemother, 1985 Jun, 15 Suppl C, 147 - 54
Sch 34343 activity against streptococci and beta-lactam-resistant Enterobacteriaceae; Gutmann L et al.; The in-vitro activity of Sch 34343 was compared with that of cefotaxime, ceftazidime, latamoxef (moxalactam), aztreonam and ampicillin . Against pneumococci, Sch 34343 was as active as ampicillin, whereas against the other streptococci it was less active than ampicillin but significantly better than the other antibiotics against enterococci . With clinical isolates of Enterobacteriaceae resistant to cefotaxime, Sch 34343 had MICs generally less than 2 mg/l . After introduction of plasmid-mediated beta-lactamases into Escherichia coli Cla . there were no significant changes in the MICs of Sch 34343 . Mutants of Enterobacter cloacae, Citrobacter freundii and Morganella morganii with derepressed cephalosporinases had susceptibilities equal to or less than 1 mg/l, which were generally lower than those of the other compounds tested . Comparison of parental strains and permeability mutants of E . coli, Ent . cloacae, and Serratia marcescens showed that the increase in MICs of Sch 34343 were lower than those found for the other antibiotics.

J Hyg (Lond), 1985 Jun, 94(3), 245 - 62
Rapid and automated detection of salmonella by electrical measurements; Easter MC et al.; A rapid method for determining the presence of salmonella in food is described . It consists of pre-enrichment in buffered peptone water modified by the addition of dulcitol and trimethylamine oxide, followed by selective enrichment in a selenite-cystine broth with similar modifications . Changes in the conductance of the selective enrichment broth are monitored continuously using a suitable impediometric instrument . Most of the Salmonella spp . tested gave a fast (approximately 100 microS/h) and large (greater than 600 microS) change in conductance, other enteric bacteria much less or no change . The assay is usually complete within 24 h . Samples of foodstuffs, naturally and artificially contaminated with Salmonella spp., were all correctly classified . Some strains of Citrobacter freundii produced a false positive conductance response, and they could not be selectively eliminated using antibiotics or cyanide . The conductance method is simple and easy to use, gives rapid results and involves less media and subculturing than is required for traditional methods.

Acta Pathol Microbiol Immunol Scand {B}, 1985 Jun, 93(3), 243 - 7
Population analysis of susceptibility to cefotaxime and desacetyl-cefotaxime in Staphylococcus and Enterobacteriaceae; Hansen BG et al.; Population analyses of susceptibility to cefotaxime (CTX) and desacetyl-cefotaxime (DCTX) of strains of Staphylococcus and some genera of Enterobacteriaceae were carried out . DCTX, which is the main metabolite of CTX, has antimicrobial activity . The penicillinase-producing strains of S . aureus and S . epidermidis were homogeneous as regards susceptibility to both agents . CTX was about 4-8 times more active than DCTX . The methicillin-resistant strains contained a sub-population of resistant bacteria with both CTX and DCTX . The frequency of resistant bacteria was 10(-6) - 10(-5) . The E . coli strain was homogeneous to both agents . The strains of Enterobacter cloacae and Citrobacter freundii had a sub-population of resistant bacteria with both agents . The frequency of resistant bacteria was 10(-7) - 10(-4.5) . In Klebsiella pneumoniae no resistant sub-population was found . CTX was about four times more active than DCTX with the strains of the Enterobacteriaceae . DCTX had no advantage over CTX as regards homogeneity of susceptibility of the populations examined . CTX seems applicable for treatment of infections with E . coli, Klebsiella pneumoniae, and penicillinase-producing, methicillin-susceptible Staphylococcus, but should not be used alone in treatments of infections with Enterobacter cloacae or Citrobacter freundii.

J Antimicrob Chemother, 1985 Jun, 15 Suppl C, 25 - 37
In-vitro activity and beta-lactamase stability and inhibitory properties of a new penem antibiotic, Sch 34343; Neu HC et al.; Sch 34343 is a new penem antibiotic . Its in-vitro activity was determined against Gram-positive and -negative aerobic and anaerobic isolates . Sch 34343 inhibited 90% of strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella spp, Citrobacter spp . and Shigella spp . at less than 1 mg/1 . Ninety per cent of strains of Enterobacter, Morganella and Providencia spp . were inhibited by less than 4 mg/1 . Sch 34343 did not inhibit Pseudomonas spp., and it had slightly less activity against Enterobacteriaceae than did cefotaxime or latamoxef (moxalactam), but it inhibited organisms resistant to cefoxitin, cefoperazone and piperacillin . Sch 34343 inhibited methicillin-susceptible Staphylococcus aureus at less than or equal to 0.25 mg/1, and it inhibited haemolytic streptococci at less than or equal to 0.06 mg/1 . Sch 34343 inhibited Bacteroides fragilis at 0.06 mg/1, including some cefoxitin-resistant isolates . Sch 34343 was not hydrolysed by plasmid- or chromosomally-mediated beta-lactamases, was an excellent inhibitor of Richmond-Sykes type Ia beta-lactamases, and also inhibited, although less effectively, the common plasmid beta-lactamases . It induced beta-lactamases, but inhibited Enterobacter and Citrobacter spp . in which it induced beta-lactamase activity.

J Antimicrob Chemother, 1985 Jun, 15 Suppl C, 137 - 46
Comparative activity of the penem antibiotic Sch 34343 against gram-negative and gram-positive bacteria with special reference to multiresistant strains; Kayser FH et al.; A new penem antibiotic, Sch 34343, was shown to be active against a large number of Gram-positive bacteria . The drug inhibited penicillinase-positive and -negative staphylococci equally well, being five times more active than cefamandole and ten times more active than methicillin . Most methicillin-resistant staphylococci were inhibited by concentrations between 0.25 and 4 mg/l, but a small group of highly resistant strains were observed . Sch 34343 was eight times less active than ampicillin and penicillin G, but as active as piperacillin against enterococci . The drug showed excellent activity against various streptococci . Sch 34343 was as bactericidal as flucloxacillin, ampicillin and penicillin G against staphylococci, enterococci and streptococci, respectively, in killing kinetic tests . Enterobacteriaceae susceptible to third-generation cephalosporins were approximately five times less susceptible to Sch 34343, but MICs were far below the susceptibility breakpoint . Sch 34343 was equally active against Citrobacter and Enterobacter strains that were highly resistant to third-generation cephalosporins and to aztreonam . Together with thienamycin, this drug seems to be a good alternative for the treatment of infections caused by bacteria resistant to third-generation cephalosporins and to aztreonam.

Mol Biol (Mosk), 1985 May-Jun, 19(3), 671 - 8
{Effect of monovalent cations on the catalytic and spectral properties of tyrosine-phenol-lyase from Citrobacter intermedius}; Miagkikh IV et al.; The action of monovalent cations Li+, Na+, K+, Rb+, Cs+, NH4+ on catalytic and physico-chemical properties of bacterial tyrosine--phenol-lyase was investigated . It was shown that K+, Rb+, Cs+, NH4+ were the noncompetitive activators of the enzyme, Na+ was an inhibitor, Li+ did not influence the catalytic activity . The values of KA and Vmax were determined for the activators in the reaction of alpha, beta-elimination of L-tyrosine . Monovalent cations affect the absorption and CD spectra of the enzyme and its complex with the quasi-substrate--L-alanine . It was suggested that an activation of tyrosine phenollyase by monovalent cations was connected with the increase of the active protonated form of the holoenzyme (lambda max 420 mm) induced by the cations-activators.

Prikl Biokhim Mikrobiol, 1985 May-Jun, 21(3), 342 - 8
{Synthesis of tyrosine and 3,4-dihydroxyphenylalanine by Citrobacter freundii bacteria from lactic acid}; Kupletskaia MB; A possibility of using lactic acid as a precursor for the synthesis of L-tyrosine and L-3,4-dihydroxyphenylalanine (DOPA) by Citrobacter freundii 62 and 63 was established . The synthesis of tyrosine from lactic acid occurs at a phenol concentration of less than 0.6% . The conditions were found which enable C . freundii 62 and 63 to synthesize from lactic acid tyrosine and DOPA with the yield of 35-38 g/l and 32-33 g/l, respectively.

Infection, 1985 May-Jun, 13(3), 146 - 55
The in vitro activity and beta-lactamase stability of cefpirome (HR 810), a pyridine cephalosporin agent active against staphylococci, Enterobacteriaceae and Pseudomonas aeruginosa; Neu HC et al.; The in vitro activity of cefpirome, a new cyclopyridinium cephalosporin, was evaluated against 947 aerobic and anaerobic bacteria . Cefpirome inhibited 90% of Escherichia coli, Klebsiella spp., Citrobacter diversus, Morganella morganii, Proteus vulgaris, Proteus mirabilis, Aeromonas spp., Salmonella spp., Shigella spp . and Haemophilus and Neisseria species at less than or equal to 0.4 mg/l . It had activity comparable to that of cefotaxime, ceftizoxime, ceftazidime, aztreonam, and moxalactam against these species . Only a few Citrobacter freundii, Enterobacter spp . and Serratia marcescens had MICs above 3.1 mg/l . The activity of cefpirome against Pseudomonas aeruginosa, 90% MIC of 12.5 mg/l, was superior to piperacillin, moxalactam, cefotaxime and cefoperazone . The 90% MIC against Staphylococcus aureus was 0.8 mg/l, but methicillin-resistant staphylococci were not inhibited . Cefpirome was not significantly hydrolyzed by most plasmid beta-lactamases (TEM, SHV-1, PSE, OXA) nor by chromosomal enzymes (P99, Branhamella catarrhalis, K1) . Cefpirome did not inhibit chromosomal or plasmid beta-lactamases . Mice systemically infected with E . coli, Klebsiella pneumoniae, P . aeruginosa and S . aureus were protected by concentrations of cefpirome ranging from 0.85 mg/kg for K . pneumoniae to 4.467 mg/kg for P . aeruginosa.

J Infect Dis, 1985 May, 151(5), 790 - 5
An outbreak of antibiotic-resistant Salmonella enteritidis in Liberia, West Africa; Hadfield TL et al.; Between October 1980 and August 1982, 100 patients in the pediatric population at Curran Lutheran Hospital, Zorzor, Liberia were identified as having multiple drug-resistant Salmonella enteritidis serotype enteritidis . The illness usually presented as an enteric fever but also as meningitis, gastroenteritis, empyema, subcutaneous abscesses, chronic otitis media, or a combination of these conditions . Predisposing factors were young age and debilitation from malnutrition or measles . The mortality of infected patients was 27.8% . The organism was originally misidentified as a Citrobacter species because of a delayed reaction on lysine decarboxylase medium . Incubation of the medium for five days resulted in a positive reaction that identified the organism as a Salmonella species . The isolates were resistant to multiple antibiotics . Genes mediating resistance were located on a 120-megadalton conjugative plasmid . A cryptic nonconjugative 40-megadalton plasmid was also present in several isolates.

Antimicrob Agents Chemother, 1985 May, 27(5), 727 - 32
Covalent binding of moxalactam to cephalosporinase of Citrobacter freundii; Murakami K et al.; The inhibition of Citrobacter freundii cephalosporinase activity by moxalactam is shown to be due to the formation of a transiently stable covalent complex, probably acyl enzyme . The covalent complex formed was identified by coelution of {14C} moxalactam with the enzyme by using Sephadex G-25 gel filtration in the presence of 5.7 M guanidine hydrochloride and by analytical isoelectric focusing . Both the side-chain carboxyl group and the 7 alpha-methoxy group of moxalactam were necessary to stabilize the complex . Moxalactam is racemic with respect to the alpha carbon of the 7 beta-acylamino side chain, and the complex with the R epimer (half-life, 4.6 min) decomposed much more rapidly than that formed with the S epimer (half-life, 130 min) . For other beta-lactam antibiotics that were stable to beta-lactamase, the half-lives of enzyme-antibiotic complexes were less than 4 min.

Antimicrob Agents Chemother, 1985 Apr, 27(4), 473 - 8
In vitro and in vivo activities of DN-9550, a new broad-spectrum cephalosporin; Une T et al.; DN-9550 {(6R, 7R)-7-{(Z)-2-(2-aminothiazol-4-yl)-2-(1H-imidazol-4-yl) methoxyiminoacetamido}-3-{(1-pyridinio)methyl}-8-oxo-5-thia -1-azabicyclo methyl}-8-oxo-5-thia-1-azabicyclo{4.2.0}oct-2-ene-2-carboxylate hydrochloride} is a new semisynthetic cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria . The activity of DN-9550 against most species of the family Enterobacteriaceae was roughly comparable to that of ceftazidime, slightly lower than that of cefotaxime, and far exceeded that of cefoperazone . Against Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens, DN-9550 was more active than ceftazidime and cefotaxime . DN-9550 and ceftazidime were significantly more active than cefotaxime against Pseudomonas aeruginosa, but DN-9550 and cefotaxime were clearly more active than ceftazidime against staphylococci and streptococci . Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DN-9550, but Bacteroides fragilis was generally not susceptible to the compound . DN-9550 was stable to various types of beta-lactamases and had high affinities for penicillin-binding protein 3 of both Escherichia coli and P . aeruginosa . When DN-9550 was administered subcutaneously to mice experimentally infected with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, or Pseudomonas aeruginosa, its efficacy well reflected its in vitro potency.

Jpn J Antibiot, 1985 Apr, 38(4), 1029 - 36
{Evaluation of ceftizoxime in the treatment of respiratory tract infections}; Shimokata K et al.; Ceftizoxime (CZX) was used for 33 patients with respiratory tract infections; 22 patients with pneumonia, 3 patients with pulmonary abscess, 4 patients with diffuse panbronchiolitis and 4 patients with acute exacerbation of bronchiectasia . Clinical effects of CZX were evaluated in 33 patients; excellent in 16 and good in 14 patients . The efficacy rate was 91% . Bacteriological effects of CZX were prominent in 7 patients infected with S . pneumoniae, H . influenzae, K . pneumoniae and Citrobacter, but not in a patient infected with P . aeruginosa . The elimination rate was 92% (12/13) . As the side effects, exanthema in 1 patient and gastrointestinal symptoms (nausea and vomiting) in 1 patient were observed . However, they improved without any treatment by cessation of CZX use . Abnormal laboratory findings were observed in 2 patients with elevated GOT and/or GPT . They normalized after cessation of drug . The usefulness of CZX was 82% (27/33) . Therefore, CZX is a very useful drug and its effects are promising in clinical management of respiratory tract infections.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Apr, (4), 26 - 30
{Protective action of a corpuscular polyvalent Pseudomonas aeruginosa vaccine against representative enterobacteria}; Vetkova LG et al.; Animal experiments have demonstrated that P . aeruginosa vaccine is capable of protecting animals from experimental P . aeruginosa infection, as well as rendering a protective effect with respect to some representatives of the family Enterobacteriaceae . The comparative study of the antigenic spectra of the vaccine strains and some representatives of Enterobacteriaceae (Enterobacter, Serratia, Citrobacter and Klebsiella) has revealed no direct relationship between the degree of this protective effect and the presence of common antigenic determinants in them.

FEBS Lett, 1985 Mar 25, 182(2), 509 - 13
Characterization of restriction-modification enzymes Cfr13 I from Citrobacter freundii RFL13; Bitinaite JB et al.; This communicatiopn describes some properties of RCfr13 I and MCfr13 I, isolated from Citrobacter freundii RFL13 . RCFfr13 I restriction enzyme recognizes the 5'-G GNCC sequence and cleaves, as indicated by the arrow . MCfr13 I methylase modifies the internal cytosine producing m5C (5'-GGNm5CC) . RCfr13 I is sensitive not only to this type of substrate modification but also to hemimethylation in overlapping sites by MCfr10 I (internal cytosine of RCfr13 I recognition is methylated) and MHpa II (external cytosine is methylated) . From these results the sensitivity of RCfr13 I to methylation by dcm methylase of E.coli in overlapping sites is deduced.

J Urol, 1985 Mar, 133(3), 443 - 6
Ureolytic Citrobacter freundii infection of the urine as a cause of dissolution of cystine renal calculi; Gutierrez Millet V et al.; We report a case of cystinuria with staghorn renal lithiasis in a solitary right kidney and chronic renal failure . Right nephropyelolithotomy was performed and although 29 renal calculi were extracted many stones remained in situ . A permanent nephrostomy was left in the kidney . Several months later the urine was infected chronically with a ureolytic Citrobacter freundii bacteria and urinary pH oscillated between 8.0 and 9.2 . Spontaneous dissolution of the cystine calculi was observed and many tiny fragments of cystine were expulsed through the nephrostomy, following which renal function improved . Despite the conditions favoring struvite calculi, formation did not occur.

Prikl Biokhim Mikrobiol, 1985 Mar-Apr, 21(2), 161 - 6
{Enzymatic synthesis of 3,4-dihydroxyphenyl-L-alanine by free and immobilized Citrobacter freundii cells}; Voivodov KI et al.; The Citrobacter freundii 62 cells immobilized in PAAG and possessing the tyrosine-phenol-lyase (TPL) activity catalyse the synthesis of 3,4-dihydroxyphenyl-L-alanine (DOPA) from pyrocatechol and ammonium pyruvate . The synthesis of DOPA was studied using both free and immobilized bacterial cells . When the concentration of pyrocatechol is over 0.1 M the TPL activity of the cells is inhibited . The concentration of pyrocatechol can be increased up to 0.3 M by using an equimolar mixture of pyrocatechol and boric acid . The addition of ascorbic acid as an antioxidant results in a lower TPL activity of both free and immobilized bacterial cells.

Am J Med, 1985 Feb 8, 78(2A), 27 - 30
Treatment of gram-negative infections with aztreonam; Simons WJ et al.; Twenty-one patients with serious gram-negative infections were treated with aztreonam . Twenty of these were clinical and microbiologic cures; there was one clinical improvement with microbiologic persistence . No bacteria became resistant . Cure rates were: bone and joint (11 of 11); skin and soft tissue (six of six); pneumonia (two of two); perinephric abscess (one of one); and intra-abdominal abscess (zero of one) . The bacteria responsible for these infections included Pseudomonas aeruginosa (12), Serratia marcescens (two), Enterobacter gergoviae (three), Enterobacter aerogenes (two), Escherichia coli (one), Citrobacter diversus (one), and Hemophilus influenzae (one) . Aztreonam was well tolerated . Significant serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase elevations developed in three patients, but none was symptomatic and all resolved after therapy was stopped . Two patients in whom a rash developed were receiving other antibiotics (vancomycin and metronidazole), making the cause of the rash unclear . Diarrhea developed in a single patient with Pseudomonas osteomyelitis, who also was receiving cefazolin for Staphylococcus aureus superinfection of his decubitus ulcer . Aztreonam was highly effective against gram-negative bacilli, including P . aeruginosa . The only clear-cut side effect was an asymptomatic rise in serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase levels in three patients.

Chemioterapia, 1985 Feb, 4(1), 90 - 4
The emergence of resistance and the therapy of septicaemia; Phillips I et al.; There were 658 positive blood cultures in St . Thomas' Hospital during 1982-1984, from which 301 Enterobacteriaceae were isolated . Most were of species that do not usually produce inducible class I beta-lactamases but 39 of the isolates were of species that do . Many of these strains were resistant to the older cephalosporins but resistance to cefuroxime was uncommon and resistance to ceftazidime or cefotaxime was confined to five isolates of Enterobacter cloacae (four of which were from patients who had been previously treated with beta-lactams) . In only two cases did initially cefuroxime-sensitive strains unambiguously develop resistance during treatment (one strain each of Enterobacter aerogenes and Citrobacter freundii--both treated with amoxycillin).

Eur J Clin Microbiol, 1985 Feb, 4(1), 34 - 40
Evidence for nonspecific induction of beta-lactamase in overproducing variants of Enterobacter cloacae and Citrobacter freundii; Cullmann W et al.; Induction of chromosomally mediated beta-lactamases was studied in clinical isolates of Enterobacter cloacae and Citrobacter freundii . Whereas isolates resistant to ampicillin and cefoxitin exhibited an inducible enzyme, those sensitive to both agents did not . Cefoxitin and above all imipenem proved the most efficacious enzyme inducers . Variants among these inducible isolates which produced large amounts of beta-lactamase could be selected in the presence of cefamandole . In each of these selected variants constitutive enzyme production was markedly enhanced by induction, even with compounds lacking induction potency for the corresponding wild strains . Moreover, these variants could also be induced non-specifically, i.e . by non-beta-lactam compounds . Production of large amounts of enzyme was associated with resistance to all available beta-lactam compounds.

Chemioterapia, 1985 Feb, 4(1), 63 - 70
A perspective on the present contribution of beta-lactamases to bacterial resistance with particular reference to induction of beta-lactamase and its clinical significance; Neu HC et al.; Resistance of bacteria to beta-lactam antibiotics has become a serious problem in the past several decades . Virtually all Staphylococcus aureus, many Haemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, many Enterobacteriaceae, many Pseudomonas aeruginosa and Bacteroides species possess beta-lactamases which hydrolyze to varying degree penems, penams, carbapenems, cephems, cephamycins and monobactams . The most common plasmid-mediated beta-lactamase is the so-called TEM beta-lactamase (Richmond Sykes type IIIa) which exists in Haemophilus, Neisseria and many of the Enterobacteriaceae . Techniques to overcome this resistance have been the development of beta-lactamase stable compounds and of beta-lactamase inhibitors . However, inducible chromosomally mediated beta-lactamases in species such as Enterobacter, Pseudomonas, Citrobacter and some Serratia have become an increasing problem with more widespread use of beta-lactamase stable cephalosporins.

Chemioterapia, 1985 Feb, 4(1), 47 - 52
Mechanisms and clinical relevance of antagonism between beta-lactam antibiotics; Bergogne-Berezin E; The author discussed the problem of antagonism between combined antibiotics . Several examples of antagonistic combinations between cefoxitin plus moxalactam, or carbenicillin were cited in the literature . This phenomenon may occur especially with Enterobacter spp., Pseudomonas aeruginosa, Citrobacter spp . and Serratia marcescens: in these species induction of chromosomally mediated beta-lactamase by certain potent inducers such as cefoxitin has been suggested as the main mechanism of antagonism . Competition for binding sites (PBPs) or diminished permeability that alter susceptibility to beta-lactams, may be less likely acceptable hypotheses for double beta-lactam combination antagonism . These in vitro interactions may have clinical relevance; however even if studies in animal models showed a few examples of in vivo antagonism, the actual clinical significance of interactions between beta-lactams requires further thorough controlled clinical studies.

Eur J Biochem, 1985 Feb 1, 146(3), 641 - 7
Citrobacter lipopolysaccharides: structure elucidation of the O-specific polysaccharide from strain PCM 1487 by mass spectrometry, one-dimensional and two-dimensional 1H-NMR spectroscopy and methylation analysis; Gamian A et al.; Structural studies on the O-specific polysaccharide of Citrobacter PCM 1487 lipopolysaccharide, using methylation analysis, Smith degradation and 1H-NMR spectroscopy, indicate that it consists of the trisaccharide repeating units (formula, see text) In this structure, 4-deoxy-D-araHex stands for 4-deoxy-D-arabino-hexose.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Feb, 259(1), 11 - 9
Comparison of the exoproducts of gram-negative bacteria by SDS-Page; Euteneuer B et al.; The protein exoproducts released during exponential growth of Gram-negative bacteria were analysed and compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-Page) . The following bacterial strains were tested: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia liquefaciens, Serratia rubidaea, Proteus mirabilis, Proteus vulgaris, Salmonella minnesota, Pseudomonas aeruginosa and Pseudomonas fluorescens . It is demonstrated by SDS-Page that members of one species show identical protein pattern, whereas different species show besides comparable protein bands a species characteristic pattern . All members of Enterobacteriaceae were shown to release proteins whose molecular weights fell into the following size regions: Each strain was shown to synthesize a polypeptide of molecular weight 34,000 and one or more polypeptides within the molecular weight range 25,000-29,000 . This profile was shown to be clearly different from that of Pseudomonas strains where 20 or more distinct polypeptides ranging from 12,500 to 160,000 Mr were detectable.

Vutr Boles, 1985, 24(5), 46 - 53
{Pipemidinic acid as a urinary antiseptic--microbiological and clinical study}; Minkov N et al.; The authors present the results from the microbiological and clinical studies about the potentialities of pipemidinic acid in the treatment of uroinfections . Pipemidinic acid was established with the study on 375 bacterial strains, isolated from the urine of urological patients to have a very good in vitro effect as regards E . coli, Citrobacter, Proteus retgeri, Proteus mirabilis, Klebsiella and Enterobacter, and in case of those microorganisms, it gives way only to some aminoglucoside antibiotics . The admit that with those causative agents of uroinfections, the pipemidinic acid could be the agent of choice . The percentage of susceptible strains is low in case of Seratia, Proteus vulgaris, Pseudomonas and Acunetobacter . Sanation of the uroinfection was attained in 56.2 per cent of the patients from the 32 patients treated with persistent, most often nosocomial uroinfection, by the pipemidinic acid (in the form of the preparation palin), and a reduction of the bacterial number to insignificant values--in 12,6% . Obvious clinical improvement was established in almost all patients treated, manifested with fading or considerable reduction of the subjective and physical symptoms of the uroinfection, in parallel with a normalization or improvement of the paraclinical laboratory indices as well . In conclusion, it was emphasized that the introduction of that uroantiseptic in the practice will broaden the possibilities of effective treatment of uroinfections.

Drugs, 1985, 29 Suppl 5, 24 - 31
Comparative in vitro activity of temocillin; Gobernado M et al.; The antibacterial activity of temocillin, a novel beta-lactam antibiotic, was tested against 796 clinical isolates . We also conducted a comparative study against 8 other antibiotics . Temocillin exhibited good activity against Gram-negative organisms including Escherichia coli, and the genera Proteus, Enterobacter, Serratia, Klebsiella, Citrobacter, Providencia, Salmonella, Shigella and Haemophilus: 98% of the strains were inhibited by concentrations less than or equal to 16 mg/L . The results of this in vitro study and temocillin's favourable pharmacokinetic properties suggest that temocillin is a very promising penicillin for the treatment of hospital infections caused by Gram-negative organisms.

Nahrung, 1985, 29(4), 375 - 80
Bacteria and food poisoning organisms in milk; Abo-Elnaga IG et al.; Individual milk samples of 50 goats, 50 ewes and 50 cows were examined for the total viable count, coliform bacteria, staphylococci and salmonellae . Growth of enterotoxin A producing Staphylococcus aureus NCTC 10652 in the milk of the three animal species was also studied . The average total count was 1.9 X 10(7) cells/ml for cow's, 7.7 X 10(6) for goat's and 2.7 X 10(6) for ewe's milk with micrococci staphylococci, rods and streptococci being the predominant organisms in the three milks, respectively . Goat's milk contained the lowest numbers of coliforms and ewe's milk the highest numbers . Staphylococcus aureus could not be detected in goat's milk, whilst 16 and 26% of the ewe's and cow's milk samples contained 100 and 80 cells/ml, respectively . Out of 39 coagulase positive staphylococci, 27 were thermonuclease positive, 18 produced lecithinase and 15 fermented mannitol . Red blood cells of sheep origin were much more resistant to lysis by ewe's strains compared to bovine strains . Growth curves of Staphylococcus aureus were nearly linear at 17 degrees C but exponential at 31 degrees C without lag phase . Hazardous numbers of about 10(6) cells/ml were readily reached at 31 degrees C after 6 h and at 17 degrees C after 18 h . Salmonellae could not be detected in any of the samples examined . Out of 19 enterobacteria suspected to be salmonellae 11 proved to be Proteus and 8 Citrobacter.

J Hyg Epidemiol Microbiol Immunol, 1985, 29(4), 427 - 34
Toxic exoproducts of citrobacter freundii; Majtan V et al.; A strain of Citrobacter freundii isolated from the feces of a patient with diarrhoea was examined for growth kinetics and toxic exoproduct formation using the complete (BHI) and synthetic culture media . It was found that the test organism in synthetic medium grew distinctly slower than in BHI . Fractionations on Sephadex G-100 column yielded 3 fractions from the complete medium culture filtrate and 2 fractions from the culture filtrate obtained from synthetic medium . The first culture filtrate fractions (F1) were represented by components of the molecular weight over 100,000, the respective second fractions (F2) from complete and synthetic medium were of the molecular weights of about 40,000 and 10,000 . In the early skin test on rabbits the toxicity of culture filtrates and their fractions manifested itself by an increased permeability of blood vessels, in the late skin test by a hemorrhagic reaction associated with dilatation of blood vessels and induration of the skin tissue . In a test on mouse foot pad all separated filtrate fractions gave a positive edematous reaction . In cultured Vero cells samples of synthetic medium fractions gave a distinct cytotoxic reaction . Immunochemically, the presence of LPS in culture filtrates as well as some variations in the antigenicity of components from the complete and synthetic medium fractions were found . Apart from LPS some additional high-molecular-weight components were also present in the toxic complex of both first filtrate fractions (F1) . Much more attention should be given to analysis of these first fraction complexes as well as to toxinogenicity of second fractions (F2) using some additional tests.

Arch Immunol Ther Exp (Warsz), 1985, 33(5), 625 - 8
Studies on specificity of protection induced by immunization with outer membrane proteins of Shigella; Witkowska D et al.; Immunization of C3H/HeJ mice with outer membrane proteins (OMP) and with peptidoglycan associated proteins (PGP) isolated from Shigella flexneri 3a and from Shigella sonnei phase I protected the animals against lethal dose of homologous and heterologous bacteria and against various serotypes of Shigella flexneri . Neither of the protein preparations protected the animals against challenge with Escherichia, Klebsiella, Citrobacter, Salmonella, Serratia, Proteus and Pseudomonas . OMP preparations however, isolated from these species protected the animals not only against challenge with homologous bacteria but also against Shigella flexneri 3a.

Drugs, 1985, 29 Suppl 5, 194 - 6
Therapeutic experience with temocillin in peritonitis; Pfeiffer M et al.; The therapeutic efficacy of the new beta-lactam antibiotic, temocillin, was studied in 30 critically ill patients with peritonitis, abscesses, bronchopneumonia, and serious soft tissue infections . Patients were treated with temocillin Ig intravenously twice daily . The isolated pathogens comprised mainly Escherichia coli and Proteus, but enterococci, Pseudomonas species, Klebsiella pneumoniae, Citrobacter species, Bacteroides species, streptococci and peptococci were also implicated . Temocillin was effective in 21/22 patients with peritonitis, as well as in 6/8 patients with long-lasting infections due to temocillin-sensitive pathogens . No adverse reactions to temocillin were observed . The indications for temocillin in patients undergoing abdominal surgery are discussed.

Chemotherapy, 1985, 31(3), 200 - 3
Inhibitory activity of cefpiramide on beta-lactamase; Fu KP et al.; The beta-lactamase stability and inhibitory activity of cefpiramide were investigated . Cefpiramide was found to be stable to hydrolysis and inhibited beta-lactamase produced by Citrobacter freundii, Enterobacter cloacae, Morganella morganii, and Escherichia coli . Kinetic studies showed that cefpiramide is a competitive inhibitor of cephaloridine hydrolysis by E . cloacae beta-lactamase.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 241 - 9
Application of in-vitro models: development of resistance; Seeberg AH et al.; The development of chromosomal beta-lactam resistance of Escherichia coli, Enterobacter cloacae and Citrobacter freundii was observed by following the bacterial kill-kinetics in an in-vitro model simulating human serum antibiotic concentrations . From sensitive Escherichia coli cells mutants arose resistant to aminopenicillins, and to first and second generation cephalosporins, whereas with the Ent . cloacae and Citro . freundii mutants were also resistant to cefotaxime . Resistant mutants from all three species could also be selected on antibiotic-containing agar plates . With E . coli they occurred in two steps, the first mutation being stable but the second mutation reverting spontaneously . In Ent . cloacae, and apparently also in Citro . freundii, the mutation changes the cephalosporinase production from an inducible to a constitutive one . The different mutation rates, and the rate was extremely high for some Ent . cloacae strains, were correlated with a corresponding reduction of viable cell count and with the time of re-growth observed in the model.

J Clin Microbiol, 1985 Jan, 21(1), 46 - 76
Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens; Farmer JJ 3rd et al.; In 1972 there were only 11 genera and 26 species in the family Enterobacteriaceae . Today there are 22 genera, 69 species, and 29 biogroups or Enteric Groups . This paper is a review of all of the new organisms . It has a series of differential charts to assist in identification and a large chart with the reactions of 98 different organisms for 47 tests often used in identification . A simplified version of this chart gives the most common species and tests most often used for identification . The sources of the new organisms are listed, and their role in human disease is discussed . Fourteen new groups of Enterobacteriaceae are described for the first time . These new groups are biochemically distinct from previously described species, biogroups, and Enteric Groups of Enterobacteriaceae . The new groups are Citrobacter amalonaticus biogroup 1, Klebsiella group 47 (indole positive, ornithine positive), Serratia marcescens biogroup 1, and unclassified Enteric Groups 17, 45, 57, 58, 59, 60, 63, 64, 68, and 69.

Chemotherapy, 1985, 31(4), 272 - 8
The interaction of beta-lactam compounds with chromosomally mediated enzymes: relations to the molecular structure; Cullmann W; The interaction of 25 beta-lactam compounds with both chromosomally mediated beta-lactamases from Enterobacter cloacae and Citrobacter freundii was studied by enzyme kinetics . All the penams, cephems, and the penem Sch 29482 revealed 'competitive inhibition' of both enzymes . The penem required a preincubation period of approximately 5 min before reaching a state of equilibrium between the active and the inactive enzyme . Except for the recently developed compound HR 810, newer cephalosporins generally exhibited a high affinity for both enzymes . Consistent with earlier findings latamoxef, N-formimidoyl thienamycin, aztreonam and clavulanic acid showed a time dependent inhibition of the enzyme activity . These findings suggest a more complex reaction scheme including a second reversible complex . The last-mentioned compounds share one structural property: the modification or even the loss of the ring fused to the beta-lactam ring . Among these compounds, clavulanic acid exhibited the lowest affinity for the enzymes . It seems likely that the affinity of beta-lactam compounds is mainly influenced by the nature of the substituents.

J Antibiot (Tokyo), 1985 Jan, 38(1), 83 - 93
Conversion of cloxacillin into a progressive inhibitor of beta-lactamases by sulfonation and its activity against various types of these enzymes; Yamaguchi A et al.; On the assumption of the theory that the sulfone of a penam derivative should effectively act as a suicide substrate against beta-lactamases to which the parent compound is a poor substrate, the action of cloxacillin sulfone on four different types of beta-lactamases was studied . As we expected, cloxacillin sulfone showed strong mechanism-based irreversible inactivation against type Ib penicillinase and Proteus vulgaris cephalosporinase whereas it showed no progressive inactivation against cloxacillin-hydrolyzing type II penicillinase . However, an unexpected result was that cloxacillin sulfone could not inactivate Citrobacter freundii cephalosporinase which itself could hardly hydrolyze the parent cloxacillin . The number of hydrolytic events which occurred before inactivation of type Ib penicillinase, and P . vulgaris cephalosporinase, by the inactivator was 190 and 13, respectively . These values indicate that cloxacillin sulfone is far more effective as a suicide substrate against the two types of beta-lactamases than penam sulfones so far reported . The inactivation proceeded via the formation of an irreversible enzyme-inhibitor complex which could be detected by isoelectric focusing.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 207 - 19
Mezlocillin, ceftizoxime, and amikacin alone and in combination against six Enterobacteriaceae in a neutropenic site in rabbits; Gerding DN et al.; Closed-space, locally neutropaenic infection sites were simulated in rabbits by implanting subcutaneous semipermeable chambers inoculated with 5 X 10(4) cfu/ml of Escherichia coli (one strain), Citrobacter diversus (one strain), Klebsiella pneumoniae (two strains) or Serratia marcescens (two strains) . Four hours after inoculation, treatment was begun with amikacin (15 mg/kg), mezlocillin (100 mg/kg), or ceftizoxime (50 mg/kg) alone or in two-drug combinations . Antibiotics were given intramuscularly every 6 h for 16 doses . Chambers were sampled for bacterial counts at the start of therapy, and 20, 44, and 92 h thereafter . Blood and chamber antibiotic levels were determined during the treatment course . In-vivo results were compared to in-vitro tests of inhibition, killing and synergism . Ceftizoxime alone was successful in vivo (greater than 6 log reduction in count) against the three strains of klebsiella and citrobacter, mezlocillin against one serratia strain, and amikacin alone against none of the strains . The best in-vitro correlation was with the minimum inhibitory concentration (MIC) at a high (10(8} inoculum for the beta-lactams and with the anaerobic MIC for amikacin . Among combinations, amikacin plus mezlocillin alone was successful against the three strains of klebsiella and serratia, but neither amikacin nor mezlocillin added to ceftizoxime were more successful than ceftizoxime alone . In-vitro chequerboard synergism was not predictive of in-vivo success . Mezlocillin alone was inactivated in vivo by all the strains except Ser . marcescens, and the E . coli strain inactivated both mezlocillin and ceftizoxime alone and in combination.

Drugs, 1985, 29 Suppl 5, 49 - 56
Temocillin . In vitro antibacterial activity; Slocombe B et al.; Temocillin, a 6-alpha-methoxy penicillin derivative, was tested in vitro against 516 recent clinical isolates of Enterobacteriaceae . The compound exhibited good antibacterial activity, with 95% of isolates inhibited by a range 2 to 16 mg/L . Further studies, against selected isolates resistant to ticarcillin, piperacillin and cefuroxime (Klebsiella oxytoca, 25; Enterobacter species, 34; and Citrobacter species, 5), showed about half of the isolates of K . oxytoca (11/25) to be resistant to aztreonam (MIC range 16-greater than or equal to 128 mg/L), but susceptible to temocillin, cefotaxime and latamoxef . In general, the resistant strains of Enterobacter species tested were not susceptible to cefotaxime (MIC range 16-128 mg/L), or aztreonam (MIC range 1.0-64 mg/L), and many exhibited reduced susceptibility to latamoxef (MIC range 2-128 mg/L) . In contrast, all the strains were susceptible to temocillin (MIC range 4-16 mg/L) . The bactericidal activity of temocillin was confirmed against selected aztreonam-resistant strains of K . oxytoca and Enterobacter cloacae by conventional time-kill studies, and against a strain of E . cloacae in an in vitro model system designed to simulate the temocillin concentration profiles attained in extravascular fluid such as peripheral lymph . In the time-kill studies, temocillin concentrations of 16 and 32 mg/L were shown to effectively reduce the numbers of viable bacteria by 99 and 99.9%, respectively, within 12 hours . In the in vitro model system the numbers of bacteria were reduced 99.9% over the initial 4-hour period . In combination with aminoglycoside antibiotics, temocillin exerted a synergistic or partially synergistic effect (sigma FIC less than or equal to 0.75) against the majority of strains of Pseudomonas aeruginosa tested . When combined with piperacillin, cefotaxime or latamoxef, temocillin, unlike cefoxitin, exhibited no antagonism against strains of Enterobacteriaceae producing inducible cephalosporinases.

Chemotherapy, 1985, 31(2), 112 - 8
In vitro antibacterial activity of norfloxacin and other agents against ocular pathogens; Shungu DL et al.; 302 clinical isolates representing 16 bacterial species most often implicated in ocular infections were tested in vitro against norfloxacin and a panel of antibacterial agents . On the basis of the 90% minimal inhibitory concentration (MIC90) data, norfloxacin was 4-32 times more active than the next best antimicrobial tested against Citrobacter freundii, Escherichia coli, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae, Neisseria gonorrhoeae and Staphylococcus epidermidis, with overall MIC90 less than or equal to 1 mg/l . Norfloxacin was equal in activity to polymyxin B against Klebsiella pneumoniae (MIC90 = 1 mg/l), and it ranked second to both polymyxin B against Pseudomonas aeruginosa and cotrimoxazole against Staphylococcus aureus, (MIC90 = 2 mg/l in each case) . Along with neomycin and cotrimoxazole, norfloxacin (MIC90 = 1 mg/l) ranked second to gentamicin and tetracycline against Moraxella species . Compared to erythromycin (MIC90 less than or equal to 0.125 mg/l), norfloxacin (MIC90 less than or equal to 16 mg/l) was considerably less active against streptococci . Overall, norfloxacin was the most active agent in both potency and antibacterial spectrum against the test organisms . These results suggest the potential use of norfloxacin in the treatment of superficial bacterial infections of the eye.

Ann Neurol, 1984 Dec, 16(6), 655 - 9
Neonatal Citrobacter meningitis: pathogenesis of cerebral abscess formation; Foreman SD et al.; In 2 premature infants with brief survival, the major pathological feature of Citrobacter meningitis consisted of vasculitis and infarction with necrosis and liquefaction of large portions of the white matter of the hemispheres . Areas of decreased density demonstrated on computed tomographic head scan represented infarction with necrosis, liquefaction, and cavitation and not a classic abscess . This finding has clinical significance, because surgical drainage of liquefied infarcts is rarely indicated and could further damage the relatively preserved cortex.

J Clin Microbiol, 1984 Dec, 20(6), 1180 - 5
Monoclonal antibody-based enzyme-linked immunosorbent assays for identification and serotyping of Vibrio cholerae O1; Gustafsson B; Monoclonal antibodies directed against O-specific antigens of Vibrio cholerae O1 lipopolysaccharide were used in two different enzyme-linked immunosorbent assays (ELISAs), designed for identification and serotyping of V . cholerae O1 . In the sandwich ELISA, a monoclonal antibody against the group-specific antigen was used as capture antibody, whereas peroxidase-conjugated monoclonal antibodies directed against group- and type-specific antigens were used as the second antibodies . Monoclonal antibodies were also used in ELISA inhibition tests with whole bacteria as inhibitors in microtiter trays coated with V . cholerae O1 lipopolysaccharide . In addition, the monoclonal antibodies were shown to be useful in slide agglutination tests . The enzyme immunoassays were equally sensitive, showing positive reactions with all V . cholerae O1 strains tested, whereas all V . cholerae non-O1 as well as strains of Escherichia coli, Shigella sonnei, Salmonella spp., Citrobacter freundii, and Brucella abortus were negative . The microtiter application makes the immunoassays suitable with low consumption of reagents for screening of samples from suspected cases as well as from the environment.

Acta Pathol Microbiol Immunol Scand {B}, 1984 Dec, 92(6), 319 - 24
Beta-lactamase production in Enterobacter cloacae and Citrobacter freundii; Sogaard P; The beta-lactamase activity with ampicillin (A) and cephalothin (Ce) as substrate was examined in 28 strains of Ent . cloacae and 24 strains of C . freundii by a micro-iodometric-(MIA) and an ultraviolet assay (UVA) . Carbenicillin resistance (Ca-R) was present in 32 strains (16 of each species) . All Ca-resistant (Ca-r) strains had elevated amounts of beta-lactamase . The conditions were very similar in the two species . The Ca-r strains could be divided into two subgroups . One group had very high ampicillinase activity and lower cephalothinase activity in MIA . In UVA the cephalothinase activity was equal to that in MIA . The strains could transfer their A- and Ca-R . The reaction velocity increased with time in MIA . The Ca-R was probably plasmid mediated . The other group had no or low ampicillinase activity in MIA . The cephalothinase activity in UVA was much higher than in MIA . Velocity decreased with time in MIA, probably due to inhibition by iodine . The strains were very Ce-r and could not transfer A-R . The Ca- and Ce-R was probably chromosomally mediated . The acquisition of Ca-R in Ent . cloacae and C . freundii was analogous to acquisition of A-R in E . coli . The fraction of strains with high ampicillinase activity (plasmid mediated among all strains with acquired beta-lactam resistance was the same in Ent . cloacae and C . freundii, viz . 0.63 . In E . coli the corresponding value is 0.61 . This fraction thus seems rather constant between the different genera.

Isr J Med Sci, 1984 Nov, 20(11), 1056 - 60
Citrobacter koseri isolated in Israel, 1972-83; Altmann G et al.; Cultures of Citrobacter koseri (syn . C . diversus), an opportunistic pathogen that was isolated in Israel during 1972-83, were studied by sero- and biotyping and for susceptibility to antibacterial agents . Of 1,172 cultures, 96% were isolated from adults, more than half from urinary tract infections . Other frequent sources were superficial wounds and discharges from the respiratory and genital tracts . Seventeen strains originated from blood cultures of patients with sepsis and four from the cerebrospinal fluid of newborns with meningitis . The isolates belonged to 17 O groups, 60 serotypes and 5 biotypes . The most frequent serotypes were 15:a:{2}, first identified in Israel, and 1:a:{2} . The most frequent biotypes were c and a . No correlation was found between sero- or biotypes and source of isolation or type of disease . Of 720 cultures tested for sensitivity, all were resistant to ampicillin and carbenicillin, but only 9.3% were resistant to one or more of nine other antibacterial agents tested.

Clin Orthop, 1984 Nov, (190), 50 - 64
Cephalosporin antibiotics as applied in surgery of bones and joints; Neu HC; New cephalosporin antibiotics will continue to be discovered as old forms are found to lose effectiveness . Cephalosporins currently account for a major part of any hospital pharmacy budget . They are often used inappropriately in treatment of both community and hospital infections . Cephalosporins should be used when penicillins are not effective and for particular infections . A major use of cephalosporins is in prophylaxis; cephalosporin antibiotics will not prevent infections caused by organisms that are resistant to these compounds . Infections caused by Enterobacter cloacae, Citrobacter freundii, and Pseudomonas aeruginosa, which are resistant to even third-generation cephalosporins and the monobactams and thienamycins, have been encountered . Wound infections with a deficient blood supply provide situations in which such organisms will grow . It is hoped that proper application of each generation of cephalosporins combined with careful surgical procedures will prevent rapid development of resistance and make it possible to have these drugs as a useful part of our armamentarium for more than just a few years.

Infection, 1984 Nov-Dec, 12(6), 402 - 4
Selection of resistant mutants of Citrobacter freundii by second and third-generation cephalosporins and imipenem; del Rosario Valencia AM et al.; Using a single-step selection procedure, resistant mutants could be obtained from three clinical isolates of Citrobacter freundii with two second-generation and four third-generation cephalosporins but not with imipenem . All mutants showed a drastically increased beta-lactamase activity and were cross-resistant to all the cephalosporins examined . Combinations of cloxacillin with the cephalosporins were markedly synergistic, suggesting the principal role of the cephalosporinase in the resistance of these mutants.

J Antibiot (Tokyo), 1984 Nov, 37(11), 1414 - 22
Synergism of PS-5 with penicillins and cephalosporins in antimicrobial activity against beta-lactam-resistant gram-negative microorganisms; Sakamoto M et al.; The in vitro synergism of PS-5 combined with various penicillins and cephalosporins in antimicrobial activity was examined in detail against beta-lactam-resistant Gram-negative bacteria . PS-5 showed a highly significant synergism in antimicrobial action against Escherichia coli RGN238 in combination with penicillins; and against Proteus vulgaris GN76 and Serratia marcescens T55 in combination with cephalosporins . It was moderately synergistic against Citrobacter freundii GN346, Enterobacter cloacae 45, Proteus morganii 111 and Enterobacter aerogenes E19, whereas no synergism was observed against Pseudomonas aeruginosa E2 and Klebsiella pneumoniae 130.

J Infect Dis, 1984 Nov, 150(5), 688 - 98
A virulence plasmid in Escherichia coli enterotoxigenic for humans: intergenetic transfer and expression; Yamamoto T et al.; We studied the colonization-factor antigen I (CFA/I) fimbriae- and heat-stable enterotoxin (ST)-coding plasmid of enterotoxigenic Escherichia coli (strain H10407, serotype O78:H11) pathogenic for humans . With use of conjugal-transfer system of E . coli H10407 and transposon-labeling techniques, the virulence plasmid was shown to be transferable to many species of the family Enterobacteriaceae, including the enteropathogens, Shigella and Salmonella species, and the opportunistic pathogens, Klebsiella, Enterobacter, Citrobacter, Edwardsiella, Serratia, and Proteus species . The virulence plasmid-carrying transconjugants produced both CFA/I fimbriae and ST (exotoxin) . Moreover, most of the transconjugants stably inherited the virulence plasmid, although plasmid stability was greatly dependent on culture temperature . Finally, administration of the virulence plasmid-carrying living bacterial cells of Klebsiella, Enterobacter, and Citrobacter species and E . coli K12 resulted in fluid accumulation in both infant-mouse and rabbit ileal-loop tests.

Jpn J Antibiot, 1984 Nov, 37(11), 2131 - 40
{Laboratory and clinical studies of ceftriaxone in the pediatric field}; Nishimura T et al.; The authors have carried out the laboratory and clinical studies of ceftriaxone (Ro 13-9904, CTRX) and obtained the following results . The antibacterial activities of CTRX against the clinical isolates of S . aureus, E . coli, K . pneumoniae, E . cloacae, E . aerogenes, S . marcescens, Citrobacter sp . and P . aeruginosa were measured by the agar dilution method with inoculum size of 10(6) cells/ml . The susceptibility distribution of S . aureus to CTRX ranged from 0.2 to 12.5 micrograms/ml, and the peak of distribution was 3.13 micrograms/ml . The peak of susceptibility distribution of E . coli and K . pneumoniae were 0.1 microgram/ml or lower, and the distribution of E . aerogenes and E . cloacae ranged from 0.1 to 100 micrograms/ml, Citrobacter sp . and S . marcescens, from 0.1 to 12.5 micrograms/ml and that of P . aeruginosa, from 0.39 to 100 micrograms/ml or more . For pharmacokinetic study, CTRX was given in a single dose of 10 mg/kg in 1 child and 20 mg/kg in 2 children by drip infusion for 1 hour . After drip infusion of CTRX in a single dose of 10 mg/kg, the peak serum level was 61.4 micrograms/ml on completion of the infusion, and 8.43 micrograms/ml at 12 hours . Half-life time was 4.6 hours . With drip infusion of CTRX in a single dose of 20 mg/kg, the peak serum level was 105.5 micrograms/ml on completion of the infusion, and 19.1 micrograms/ml at 12 hours . Half-life time was 8.7 hours . CTRX was effective all cases out of 8 cases with bacterial infection . No side effect was observed except for elevation of serum GOT in 2 cases and eosinophilia in 1 case.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Oct, 258(1), 32 - 7
Degradation of Citrobacter O-Serogroup Ci23Vi+ murein with Vi phages; Jastrzemski KB et al.; Dialysable products resulting from the digestion of the Citrobacter O-Serogroup Ci23Vi+ murein with Vi phages show a decrease of their reducing power/muropeptides . It is accompanied with an increase of free amino groups amount/muropeptide when compared to the one obtained after the lysozyme treatment . It leads to a suggestion, that Vi phage particles possess two enzyme activities: "lysozyme-like" and deacetylase which might be a transacetylase.

Acta Pathol Microbiol Immunol Scand {B}, 1984 Oct, 92(5), 261 - 4
Evaluation of Rosco diagnostic beta-glucuronidase tablets in the identification of urinary isolates of Escherichia coli; Dibb WL et al.; Rosco diagnostic beta-glucuronidase tablets have been evaluated as a method for the identification of urinary isolates of Escherichia coli . Results were compared with those from traditional biochemical testing . A total of 539 isolates were employed, representing a variety of Gram-negative species . Reproducibility testing was also performed . After 4h incubation, 86% of E . coli isolates (both lactose-positive and lactose-negative) gave a positive reaction . Some Salmonella, many Shigella and one Citrobacter freundii isolate also gave positive reactions . All other organisms gave negative reactions . Results were highly reproducible and not influenced by choice of primary medium . The tablets are suitable for routine use in the diagnostic laboratory for the identification of lactose-positive E . coli . A suitable diagnostic table has been suggested.

Jpn J Antibiot, 1984 Oct, 37(10), 1898 - 918
{Fundamental and clinical studies of sulbactam/cefoperazone in the pediatric field}; Motohiro T et al.; To 6 cases of children in 2 groups of 3 each, newly developed sulbactam/cefoperazone (SBT/CPZ) was given at 20 and 40 mg/kg by intravenous bolus injection, respectively, and the serum and urinary concentrations and recoveries of SBT and CPZ were determined . To 1 case of purulent meningitis, this drug was given at 40 mg/kg by intravenous bolus injection, and the cerebrospinal fluid and serum concentrations of SBT and CPZ were determined . Susceptibility tests to SBT/CPZ and CPZ of total 289 strains were conducted; Gram-positive cocci tested consisted of 26 S . aureus strains, 20 S . pyogenes strains and 21 S . pneumoniae strains, and Gram-negative bacilli consisted of 24 H . influenzae strains, 22 E . coli strains, 26 K . pneumoniae strains, 24 E . cloacae strains, 21 E . aerogenes strains, 19 Citrobacter sp . strains, 20 S . marcescens strains, 23 P . mirabilis strains, 23 indole-positive Proteus sp . strains and 20 P . aeruginosa strains . SBT/CPZ was given to total 43 cases at a mean daily dosage of 80.4 mg/kg, in 3 or 4 divided doses (6 cases in 3 and 37 cases in 4), 1 case receiving the drug by drip infusion over 30 minutes (in 3 divided doses) and all the other 42 cases by intravenous bolus injection, for 7 days on an average . They consisted of 2 cases of tonsillitis, 1 case of otitis media, 1 case of otitis media associated with mastoiditis, 30 cases of pneumonia, 1 case of suspected septicemia, 1 case of purulent meningitis, 5 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of submaxillaritis . And the clinical and bacteriological effects were evaluated . Also, side reactions and laboratory examinations for abnormal values due to administration of this drug were made on 47 cases including 4 drop-outs . The following results were obtained: After administration of this drug to 2 groups of 3 children each at 20 and 40 mg/kg by intravenous bolus injection, mean serum concentrations of both SBT and CPZ reached the peaks in 5 minutes; SBT levels were 60.9 and 124.7 micrograms/ml for the 2 groups and CPZ levels were 105.0 and 214.1 micrograms/ml, respectively . In either group, CPZ levels were 1.7 times as high as SBT levels, and there was observed a dose-response in both . In the 20 mg/kg group, mean half-lives of SBT and CPZ were 0.96 and 1.24 hours, respectively, and in the 40 mg/kg group, they were 1.01 and 1.32 hours, CPZ values tending to be longer.(ABSTRACT TRUNCATED AT 400 WORDS)

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 59 - 65
Survey of the phenotypes of susceptibility to beta-lactams in Enterobacteriaceae at the Pitie-Salpetriere Hospital; Jarlier V et al.; The phenotypes of susceptibility to ampicillin, carbenicillin, cephalothin, cefamandole, cefoxitin and cefotaxime were determined by the disc-diffusion method in 10,994 Enterobacteriaceae consecutively isolated from in-patients during 18 months . The susceptible phenotypes were much more frequent among Escherichia coli, Proteus mirabilis and Klebsiella (67.4 to 84.8%) than among Serratia, Enterobacter and Citrobacter (8.8 to 35.5%) . In all species the most common resistance phenotypes were to ampicillin and carbenicillin: E . coli (28%), Pr . mirabilis (15.2%), Klebsiella (23.8%), indole-positive Proteus (33.3%), Serratia (74.4%), Enterobacter (61.4%) and Citrobacter (74.8%) . Among E . coli 4.6% of the strains were resistant to ampicillin and cephalothin but susceptible to carbenicillin . Among E . coli, Pr . mirabilis and Klebsiella the strains susceptible only to cefotaxime represented 0.3 to 5% and no cefotaxime-resistant strain was isolated; whereas among Serratia, Enterobacter and Citrobacter the former represented 28.3 to 58.3% and the latter 7.5 to 18.5% . Some important differences in the distribution of the phenotypes according to the type of ward were observed.

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 1 - 12
Do we need the third-generation cephalosporins?
Neu HC.
Third-generation cephalosporins have been available for the past 5 years . The continued increase in resistance of bacteria to older antimicrobial agents and the safety profile of a number of the third-generation agents have established situations in which these compounds are useful . Upper respiratory infections such as epiglottitis, lower respiratory tract infections due to Enterobacteriaceae are examples of illnesses in which third-generation cephalosporins would be preferred to older drug programmes . Bone and joint infections due to Enterobacteriaceae can be treated with third-generation cephalosporins with less risk of toxicity than that associated with aminoglycoside use . But this is an area in which resistance may develop . Meningitis in the elderly due to Escherichia coli or Klebsiella pneumoniae are best treated with cefotaxime and the third-generation cephalosporins are alternative therapy for neonatal and the other forms of meningitis except Listeria or Pseudomonas . These drugs have proved extremely useful in treatment of penicillinase-producing Neisseria gonorrhoeae . Hospital-acquired urinary tract infections in the elderly can be treated with these agents since they provide excellent urinary levels and have a low risk of nephrotoxicity . The need for third-generation cephalosporins in gynaecological and intra-abdomonal infections is less clear . Selected patients will benefit from their use . Closer attention to the excellent in vitro activity and pharmacological activity of third-generation cephalosporins should establish other areas of need for these compounds, but it will be necessary to follow closely the development of resistance to these compounds since species such as Enterobacter, Serratia and Citrobacter can become resistant.

J Bacteriol, 1984 Sep, 159(3), 1074 - 6
Intergeneric homology of the speC gene encoding biosynthetic ornithine decarboxylase in Escherichia coli; Wright JM et al.; A 32P-labeled fragment of DNA containing the speC gene, which encodes the biosynthetic enzyme ornithine decarboxylase of Escherichia coli, was used as a hybridization probe for homologous sequences in the genomes of gram-negative and gram-positive bacteria . The speC probe detected homologous sequences in the DNA of only four members of the Enterobacteriaceae (Citrobacter freundii, Salmonella typhimurium, Klebsiella pneumoniae, and Enterobacter aerogenes); no homology was detected with the DNA of other representative members of the Enterobacteriaceae and gram-negative and gram-positive bacteria.

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 307 - 10
Single-dose cefotaxime in the treatment of urinary tract infections in children: a randomized clinical trial; Repetto HA et al.; Thirty-seven patients with a median age of 5 years with symptomatic lower or upper urinary tract infection, documented by a clean-catch midstream urine culture and sediment examination, completed a randomized study comparing the effectiveness of a single dose of cefotaxime with 10-day treatment with an antibiotic chosen by in-vitro sensitivities . Eighteen patients were randomly assigned to the cefotaxime group (50 mg/kg/im route) and 19 patients were placed in the 10-day therapy group . In the cefotaxime group 4/18 patients had an upper urinary tract infection and 11/18 had a history of recurrences . The causal organisms were Escherichia coli (16 cases) and Klebsiella pneumoniae (two cases) . All patients had sterile urine 48 hours after therapy, and 2/18 cases had recurred 28 days later . In the 10-day treatment group, 7/19 patients had an upper urinary tract infection, 6/19 had a history of recurrences, 17 cases were caused by E . coli, one case by Citrobacter freundii and one case by K . pneumoniae . Eighteen of 19 patients had sterile urine 48 hours after therapy and 1 case remained symptomatic with positive culture . The other 18 patients had no recurrences . Rates of cures and recurrence in the compared groups were not statistically different (P greater than 0.05).

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 195 - 202
Treatment of 160 cases of acute bacterial meningitis with cefotaxime; Lecour H et al.; One hundred and sixty cases of acute bacterial meningitis were treated with cefotaxime . Patients were between 9 days and 79 years old: 7 new borns, 37 infants, 43 children, 19 adolescents and 54 adults . Fifty-eight patients (36%) were in coma when admitted . Aetiology was determined in 110 patients (68.8%): Neisseria meningitidis in 42, Streptococcus pneumoniae in 36, Haemophilus influenzae in 16, Salmonella spp . in 7, Staphylococcus aureus in 2, Enterobacter spp . in 2 and Haemophilus parainfluenzae, pseudomonas aeruginosa, Escherichia coli, Citrobacter freundii and Klebsiella pneumoniae in one patient each . All isolates were sensitive to cefotaxime, with MIC's for 26 strains ranging from 0.01 to 0.50 mg/l . One hundred and fifty-six of the 160 patients were treated with cefotaxime alone and the four others with cefotaxime in association with an aminoglycoside in three and rifampicin in one . Cefotaxime was administered by intravenous infusion, in a daily dose 100 to 300 mg/kg . Duration of treatment ranged from 8 days to 6 weeks, with a mean of 15 days . One hundred and forty-nine patients (93.1%) were cured, two after a relapse . Three patients had sequelae . Most (88.5%) had sterile CSF within 72 h after starting treatment . Eleven patients (6.9%) died, eight within the first 48 h . The only side-effects observed were mild transient eosinophilia in some patients and rash and leukopenia in 2 each . The study demonstrates that cefotaxime is effective in the treatment of acute bacterial meningitis.

J Bacteriol, 1984 Sep, 159(3), 1063 - 4
Correction of the nucleotide sequence of the Citrobacter freundii tryptophan operon regulatory region; Kuroda MI et al.; We present a correction of the previously reported nucleotide sequence of the Citrobacter freundii trp operon regulatory region . The original sequence analyses were performed with a plasmid designated pCF2 . We repeated the cloning of the trp regulatory region of C . freundii and concluded from the determined sequence that a DNA rearrangement had occurred within the leader region of the cloned trp DNA of pCF2 . The correct sequence is homologous to the Escherichia coli sequence.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Aug, 257(3), 400 - 8
Survey of resistance to metals and volatilization activity of Hg-resistant R plasmids in Citrobacter isolated from clinical lesions in Japan; Nakahara H et al.; Clinical isolates of Citrobacter (277 strains) were studied for the resistance to four metals and four drugs . The distribution patterns of their susceptibility to Hg, Cd and As clearly revealed two peaks, but only a single peak of resistance to Pb . The frequencies of resistance to Hg, Cd, As, SM, TC, CP and KM were 31.8, 94.2, 57.8, 51.3, 44.8, 35.7 and 28.9%, respectively . And we selected 88 mercury resistant strains, and they were tested for their ability to transfer the resistance to the mercury and drug sensitive recipients of E . coli K12-ML1410-Nx and E . coli JE17-Rif . Among 88 strains of Hg resistant Citrobacter, 80 R plasmids with Hg resistance could be demonstrated . It should be noted that transferable R plasmids with Hg resistance were demonstrated in 91% of the Hg-resistant isolates . Furthermore, we tested the volatilization of mercury by strains containing these mercury resistance plasmids, by using radioactive 203Hg2+ . All of these isolates of Citrobacter have volatilization activity of Hg2+ . Also, all of these volatilization activity is inducible.

J Infect Dis, 1984 Aug, 150(2), 229 - 35
Nosocomial meningitis due to Citrobacter diversus in neonates: new aspects of the epidemiology; Williams WW et al.; Two term neonates born within four days of each other at a small hospital developed sepsis and meningitis caused by a unique strain of Citrobacter diversus not previously reported to cause meningitis . Eleven (27.5%) of 40 other infants admitted to the nursery during the epidemic period developed rectal or umbilical colonization by C . diversus . Contact soon after birth with either of two nurses was more common among infected or colonized infants than among infants who were not infected or colonized . Hand cultures of both nurses and a rectal culture of one of the nurses yielded the epidemic strain . C . diversus may have been introduced into the nursery by the rectal carrier and spread person to person . Six weeks later continued surveillance identified a second cluster (of four colonized infants) associated with a mother who was a carrier of C . diversus and whose newborn infant became colonized at birth . The outbreak ended after strict control measures were used.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Aug, (8), 32 - 4
{Enterotoxigenicity and neuraminidase activity of bacteria of the genus Citrobacter}; Balanin NV et al.; The data obtained in the study of Citrobacter strains isolated from patients with diarrheal diseases and from healthy persons are presented: enterotoxigenicity was studied in 68 strains, while neuraminidase activity in 41 strains . Among the strains of these groups 9 strains with active enterotoxin and 2 strains producing active neuraminidase were detected . The criteria for subdividing Citrobacter strains according to the activity of their thermolabile enterotoxin are proposed.

Arch Intern Med, 1984 Aug, 144(8), 1585 - 8
Bacterial changes in the urine samples of patients with long-term indwelling catheters; Breitenbucher RB; The bacterial flora in the urine samples of 15 nursing home patients with long-term, indwelling catheters were examined monthly for one year . There was a rapidly changing polymicrobial flora averaging 2.0 changes per month in species with colony counts greater than 100,000/mL, and 3.2 changes per month when changes in species, biogram, and quantity of bacteria were considered . The flora changed significantly more frequently, and cultures of Pseudomonas aeruginosa, Providencia stuartii, and Citrobacter diversus were significantly more frequent in those receiving sulfamethoxazole and trimethoprim prophylaxis than in those who did not . There was no difference in incidence of urinary tract infection (UTI) between those patients who received sulfamethoxazole and trimethoprim prophylaxis and those who did not . Ampicillin or gentamicin was effective against 99% of species cultured that are of established UTI pathogenicity . Owing to the rapidity of bacterial flora changes, routine monthly cultures are of little predictive value in patients with indwelling catheters . This study does not support the efficacy of sulfamethoxazole and trimethoprim prophylaxis in such patients.

Clin Pharm, 1984 Jul-Aug, 3(4), 351 - 73
Third-generation cephalosporins: a critical evaluation; Barriere SL et al.; Six third-generation cephalosporins--cefotaxime, moxalactam, cefoperazone, ceftizoxime, ceftriaxone, and cefmenoxime--are reviewed; covered are chemistry and structure-activity relationships, mechanism of action, spectra of activity, pharmacokinetics, clinical utility, adverse effects, and cost effectiveness . The third-generation cephalosporins have a similar mechanism of action to that of other beta-lactam antibiotics . None of the agents is particularly active against certain gram-positive bacteria, including methicillin-resistant Staphylococcus aureus; the drugs are effective against gonococci, Haemophilus influenzae, and Neisseria meningitidis . Several common gram-negative pathogens are susceptible to the third-generation cephalosporins, including Escherichia coli, Klebsiella, Citrobacter diversus, Proteus, and Morganella . About 50% of Pseudomonas aeruginosa isolates are susceptible . Only moxalactam has good activity against Bacteriodes fragilis . The pharmacokinetic profiles of the six agents reveal some important differences . The half-life of ceftriaxone allows once-daily dosing in many patients; the half-lives of ceftizoxime and cefoperazone permit dosing every 8-12 hours . Cefoperazone and ceftriaxone are highly protein bound, but the clinical relevance of this is unknown . Generally, the agents penetrate most body tissues and fluids well . Moxalactam and cefotaxime and possibly ceftriaxone effectively penetrate into the cerebrospinal fluid well . The third-generation cephalosporins have become the accepted drugs of choice for the treatment of adult gram-negative bacillary meningitis; as more experience is gained, they are likely to become the drugs of first choice for neonatal (with ampicillin) and childhood (except for moxalactam) meningitis . Serious infections of Enterobacteriaceae can be treated with these agents, thereby avoiding use of the aminoglycosides . Moxalactam is comparable with combination therapy in treating intra-abdominal infections . Adverse effects associated with use of the third-generation cephalosporins are generally similar to those that occur with other beta-lactam antibiotics with the exception of coagulopathies and the disulfiram reaction seen with moxalactam and cefoperazone . Despite the relatively high cost of the third-generation cephalosporins, they are often cost effective because of their reduced dosing frequencies, broad spectra of activity, and effectiveness in serious infections for which more toxic antibiotics have been required in the past.

Appl Environ Microbiol, 1984 Jul, 48(1), 142 - 8
Effect of noncoliforms on coliform detection in potable groundwater: improved recovery with an anaerobic membrane filter technique; Franzblau SG et al.; A total of 529 well and distribution potable water samples were analyzed for total coliforms by the most-probable-number and membrane filter (MF) techniques . Standard plate count bacteria and MF noncoliform bacteria were also enumerated . Frequency of coliform detection, turbidity in most-probable-number tubes, and extensive overgrowth by noncoliforms on MF filters were directly proportional to standard plate counts . Recovery of coliforms was greatest by the MF method at low (less than 100 CFU/ml) standard plate count densities and better by the most-probable-number method (confirming gas and turbid tube) at high (greater than 500 CFU/ml) standard plate count densities . In the latter case, overgrowth by noncoliforms on MF filters suppressed sheen development and, in turn, masked coliform detection . Of 341 atypical (no sheen) MF colonies verified by parallel inoculation of lauryl sulfate broth and billiant green-bile broth, 156 were aerogenic in the latter medium . Of atypical isolates, 84% were identified as either Citrobacter or Enterobacter species . A 4.3-fold reduction in numbers of overgrown MF filters and an 2.2-fold increase in numbers of coliforms recovered from 127 water samples was accomplished by anaerobic incubation of MF cultures . This anaerobic modification of the standard MF technique significantly reduced overgrowth and enhanced recovery of coliforms from potable groundwater . This technique is simple, cost effective, and suitable for monitoring of untreated ground water common to some small water systems and private water supplies.

Jpn J Antibiot, 1984 Jul, 37(7), 1306 - 12
In vivo antibacterial activity of cefodizime, a new cephalosporin antibiotic; Kasai K et al.; The in vivo activity of cefodizime (HR 221) was compared with that of cefotaxime (CTX), cefmenoxime, latamoxef, cefazolin and cefmetazole (CMZ) . The protective effects of HR 221 on experimental infections in mice caused by Staphylococcus aureus Smith, Escherichia coli C-11, Proteus vulgaris GN-76 and Serratia marcescens No . 2 were directly related to its in vitro activity against these strains . In contrast, the compound showed the smallest ED50 values, among the 5 antibiotics tested (not including CMZ), for Klebsiella pneumoniae 3K-25 and Pseudomonas aeruginosa PI 67 against which it had relatively low in vitro activity, and its ED50 for Citrobacter freundii GN-346 was as small as 1.821 mg/mouse in spite of its MIC of greater than 100 micrograms/ml . HR 221 exerted potent bactericidal activity against Streptococcus pneumoniae Sp-1 inoculated into the mouse lung; the duration of action was prolonged . When tested against the E . coli Ec-89 infection induced in the rat uterus, the activity of HR 221 given to rats once daily was equal to that of CTX or CMZ given at the same dose twice daily.

Tex Heart Inst J, 1984 Jun, 11(2), 216 - 7
Endocarditis due to citrobacter freundii; Reyes CV et al.; The etiologic association of acute bacterial endocarditis with the Citrobacter species has been rare, although it is one of the opportunistic organisms that afflicts the elderly, neonates, the debilitated and immunocompromised . We report a case of endocarditis due to Citrobacter freundii.

Chemioterapia, 1984 Jun, 3(3), 163 - 6
In vitro antibacterial activity of thiamphenicol; Ravizzola G et al.; This in vitro study of thiamphenicol activity against 247 strains of Gram-positive and 195 strains of Gram-negative pathogenic bacteria showed no significant changes from past activity . Of the 442 strains involved, thiamphenicol proved: - Effective (MIC = less than or equal to 0.5-4 micrograms/ml) against 131 strains, mostly streptococci, pneumococci and enterococci . - Moderately effective (MIC = 8-64 micrograms/ml) against 252 strains, mostly staphylococci, Salmonella, Citrobacter, K . pneumoniae, Enterobacter, E . coli and Proteus . - Ineffective (MIC = 64 micrograms/ml) against 59 strains, mostly Proteus, E . coli and K . pneumoniae . Against 23 strains of Neisseria gonorrhoeae, thiamphenicol generally proved as effective as penicillin G and cefuroxime and more effective than spectinomycin.

Arch Microbiol, 1984 Jun, 138(2), 131 - 9
Microbial aspects of the cockroach hindgut; Cruden DL et al.; The cockroach hindgut has a complex, active microbiota, a large portion of which is associated with the chitinous gut wall . It provides a different environment from that of termites and other insects which are dependent on their hindgut microbiota for the digestion of cellulose . The pH of the midgut of Eublaberus posticus was not as high as it is in insects with a primarily cellulolytic nutrition . The hindgut of E . posticus was highly methanogenic, normal adults producing typically 10-25 mumol of methane per hour . The hindgut contained large amounts of the storage products polyphosphate and poly-beta-hydroxybutyrate . Dilution series on nonselective medium yielded 100 times more obligately anaerobic colonies than facultatively anaerobic colonies . The most common facultative isolates were Klebsiella oxytoca, Citrobacter freundii and Enterobacter agglomerans . Treatment of E . posticus with metronidazole caused a dedifferentiation of the different regions of the hindgut . One region of the hindgut is characterized by its visibly black color, a unique microbiota, and electron dense deposits in electron micrographs . Chemical determinations showed high concentrations of ferrous and sulfide ions in the region . X-ray microprobe analysis showed that some of the electron dense deposits consisted of iron, sulfur and lower amounts of copper, aluminium, and chromium associated with ruthenium red staining material . Spectra of other deposits revealed only silicon, which was not associated with ruthenium red.

Pathol Biol (Paris), 1984 Jun, 32(5 Pt 2), 563 - 6
{Dibekacin in the treatment of urinary infections in the elderly}; Lopitaux R et al.; Urinary tract infections in the elderly are severe and intractable, often justifying the use of aminoglycosides . We studied the effects of dibekacin in 28 patients, with no vesical catheter, whose average age was 78 +/- 6.1 years . The drug was given for ten days, in an average dose of 2.1 mg/kg/day divided into two injections . Serum concentration was measured after one hour on day 1 and after eight hours on days 1 and 10 . Causative pathogens, all susceptible to dibekacin, were: 18 E . coli, 3 Proteus mirabilis, 3 Klebsiella, 1 Enterobacter cloacae, 1 Citrobacter and 2 Staphylococci . MIC and MBC of dibekacin were determined for each microorganism . Dibekacin was discontinued in four cases on day three because of persistent bacteriuria . Ten days after treatment end, 19 patients were cured, 4 had a relapse and 1 was reinfected . Average serum concentration of dibekacin, measured after eight hours, increased from 0.77 +/- 0.48 micrograms/ml on day 1 to 1.78 +/- 1.22 microgram/ml on day 10 (t = 4.42; p less than 0.0005), while, over the same period, there was no significant change in serum creatinine.

Pharmacotherapy, 1984 May-Jun, 4(3), 122 - 36
Amoxicillin and potassium clavulanate: an antibiotic combination . Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects; Weber DJ et al.; The combination of amoxicillin and potassium clavulanate will soon be marketed in 2:1 and 4:1 fixed ratio dosage forms . In vitro and in vivo evidence suggests that clavulanic acid, a potent inhibitor of many bacterial beta-lactamase enzymes, will increase the spectrum of amoxicillin to include, at achievable serum concentrations, Haemophilus influenzae, H . ducreyi, Neisseria gonorrhoeae, Staphylococcus aureus and Branhamella catarralis and, at achievable urine levels, many beta-lactamase-producing strains of E . coli, Klebsiella, Proteus and Citrobacter . Both amoxicillin and clavulanic are well absorbed after oral administration, reach peak serum levels in 40-120 min and have similar half-lives of 45 to 90 min . This combination will be suitable for the treatment of complicated urinary tract infections, otitis media, sinusitis and respiratory tract infections . However, precise recommendations for its use will need to await further clinical trials that compare amoxicillin/clavulanate to alternative therapies.

Antimicrob Agents Chemother, 1984 May, 25(5), 591 - 5
Development of resistance to cephalosporins in clinical strains of Citrobacter spp; Gootz TD et al.; The predominant beta-lactam antibiogram of Citrobacter freundii resembles that of Enterobacter cloacae in demonstrating resistance to cephalothin and cefoxitin with susceptibility to the newer cephalosporins . Four representative strains of C . freundii were reversibly induced to high-level beta-lactamase production by cefoxitin, and mutants with stable, high-level production were selected with cefamandole . The mutants were resistant to several second- and third-generation cephalosporins . Comparisons of isoelectric points and substrate profiles of beta-lactamases from wild-type, induced wild-type, and mutant organisms suggested a close relationship to those from E . cloacae and indicated that C . freundii mutants, like those of E . cloacae, were derepressed for production of beta-lactamase . One primary isolate of C . freundii resembled the mutants in all characteristics . In contrast, most strains of Citrobacter diversus were susceptible to all cephalosporins, and two representative strains showed neither inducible nor mutational resistance . Cefoxitin induction to enhanced beta-lactamase production was demonstrated in a cephalothin-resistant isolate, and a derepressed mutant was selected with cefotaxime . The beta-lactamase from this C . diversus strain differed substantially in substrate profile from that of E . cloacae and C . freundii.

Pathol Biol (Paris), 1984 May, 32(5), 393 - 5
{Resistance of Enterobacteria to cefotaxime and lamoxactam at the Pitié-Salpêtrière Hospital in 1982}; Nicolas MH et al.; Systematic collection of data on every Enterobacteriaceae clinical isolate cultured in the Central Bacteriology Laboratory allowed comparison of the percentage of cefotaxim (CTX) and moxalactam ( MOX ) intermediate or resistant (IR) strains among the 8 199 Enterobacteriaceae isolated in 1982 and the 5 032 Enterobacteriaceae isolated in 1980 . In 1982, IR rates were 2% to CTX and 0.6% to MOX . Among the 166 strains IR to CTX, 28% were also IR to MOX . Two strains only were IR to MOX but not to CTX . No E . coli, P . mirabilis or Klebsiella strains IR to CTX or MOX were isolated . On the opposite, percentages of strains IR to CTX or MOX were respectively 2.5 and 0 for indole positive Proteus, 6 and 3.6 for Enterobacter, 7.4 and 0.5 for Serratia and 17.2 and 2.5 for Citrobacter . Strains IR to CTX or MOX represented 3.3%, 2.5% and 1% of Enterobacteriaceae isolated from pus, urine and blood cultures, and 4.7%, 2.2% and 1.3% of those isolated in urology, surgery and medicine . Between 1980 and 1982, there was a simultaneous increase in the consumption of CTX and MOX (10 fold) and in the percentage of Enterobacteriaceae IR to CTX (2 fold); this last involved Serratia (9 fold) more than Citrobacter (3 fold) and spared Enterobacter.

J Clin Microbiol, 1984 May, 19(5), 699 - 702
Specific identification of Salmonella serogroup E antigen O3 by immunofluorescence and coagglutination with antiserum elicited by a synthetic trisaccharide-bovine serum albumin glycoconjugate; Ekwall E et al.; Antiserum specific for Salmonella O3 antigen was raised by immunization of rabbits with an artificial glycoconjugate consisting of the synthetic trisaccharide beta-D- Manp (1----4)-alpha-L- Rhap (1----3)-alpha-D-Galp covalently linked to bovine serum albumin (beta- MRG -BSA) . Enzyme immunoassays showed that only lipopolysaccharides extracted from Salmonella serogroup E (O3 antigen-containing) bacteria bound the antiserum . The usefulness of the beta- MRG -BSA antiserum for rapid and accurate identification of Salmonella isolates of serogroup E was shown by indirect immunofluorescence tests in which 50 Salmonella strains of serogroup E 1-4 were correctly identified from among 651 intestinal strains investigated . The finding that one strain of Citrobacter freundii was positive in immunofluorescence tests with this antiserum is readily explained by the known cross-reactivity between some C . freundii strains and Salmonella spp . strains of serogroup E . As expected, the specificity of the antiserum for the O3 antigen could further be demonstrated in coagglutination tests with staphylococci sensitized with beta- MRG -BSA antiserum.

Surgery, 1984 Apr, 95(4), 398 - 403
Intra-abdominal Citrobacter infections: association with biliary or upper gastrointestinal source; Lew PD et al.; The clinical records of 46 patients with intra-abdominal and/or bacteremic infections caused by Citrobacter organisms were reviewed to determine whether the isolation of Citrobacter organisms from these sites could be used to determine its portal of entry . The isolation of Citrobacter organisms from intra-abdominal or pleural fluid cultures was associated with a biliary tract or upper gastrointestinal source in 36 of 41 patients . The biliary tract or small bowel was likewise the portal of entry for 8 to 13 patients with Citrobacter septicemia . Thus, the isolation of these organisms from the blood, pleural space, or abdominal cavity strongly suggests that the upper gastrointestinal (or biliary) tract is the site of significant pathologic disease . Of the antibiotics tested, moxalactam, cefotaxime, and amikacin were most effective against Citrobacter.

Jpn J Antibiot, 1984 Apr, 37(4), 723 - 33
{Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1982) . II . Background of patients}; Kosakai N et al.; The frequency of the causative strains in urinary tract infections was investigated from the point of view of the patient's background such as age, sex administration of antibiotics and so on . Especially, the frequency of the causative strains isolated from patients within 3 days after the administration of antibiotics has markedly decreased . However, the frequency of the resistant strains such as P . aeruginosa, Enterobacter spp., Citrobacter spp . and Serratia spp . has increased after 8 days' administration of antibiotics.

Jpn J Antibiot, 1984 Apr, 37(4), 734 - 74
{Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1982) . III . Secular changes in susceptibility}; Kosakai N et al.; In vitro susceptibilities have been investigated against several species isolated from patients with simple and complicated urinary tract infections (UTI) during 1980-1982 . Antimicrobial activities of the third generation cephems against E . coli isolated from patients with complicated UTI were found to decrease slightly in 1982 . And those against Klebsiella spp . isolated from patients with simple and complicated UTI were also found to decrease similarly . Against P . mirabilis, all the drugs tested have showed relatively potent activities and slight changes in the susceptibility . The marked decrease of susceptibility against Citrobacter spp . isolated from UTI have been found even in the third generation cephems . Especially, Citrobacter spp . exhibited a greater degree of resistant to CZX and CPZ . Strains of P . aeruginosa were on the whole susceptible to the drugs tested, CFS, GM, TOB and AMK, inhibiting 50-80% of the strains tested at 1.56 micrograms/ml . CTX, CZX and CMX seemed most effective against S . marcescens among the third generation cephems, inhibiting 50-90% of the strains tested at 3.13 micrograms/ml.

Acta Pathol Microbiol Immunol Scand {B}, 1984 Apr, 92(2), 79 - 83
Resistance types in Citrobacter freundii . Occurrence and resistance to ampicillin, carbenicillin, cephalothin and mecillinam . Transfer of ampicillin resistance; Sogaard P; The resistance types of Citrobacter freundii were investigated . The strains were divided into three groups according to susceptibility to penicillin derivatives . Group 1, comprising the ampicillin-carbenicillin sensitive strains (A-s/Ca-s), constituted 22% . Group 2 (ampicillin-resistant (A-r)/Ca-s) constituted 45% and group 3 (A-r/Ca-r) 32% . Two strains (1%) were recorded as A-s/Ca-r . Group 3 contained a higher proportion of multi-resistant strains than groups 1 and 2 . The log2IC50 with ampicillin, carbenicillin, cephalothin and mecillinam in the tube-dilution method were determined for 32 strains . Groups 1 and 2 differed only as regards cephalothin resistance . The strains of group 3 were more A-r than the group 2 ones . The mecillinam susceptibility did not differ between the three groups . No strains in group 2 could transfer A-resistance . In group 3 ten out of 16 strains were able to transfer A-resistance . Resistance to sulphonamide, tetracycline, and streptomycin was also transferred, but with low frequency . The A-r/Ca-r strains could be divided into two subgroups, probably reflecting different modes of developing beta-lactam resistance . One group was very A- and Ca-r, less cephalothin-r, more mecillinam-r and could transfer A-resistance . The other group had very high cephalothin-resistance and could not transfer A-resistance . Citrobacter freundii and Enterobacter cloacae are very similar as regards resistance conditions.

Mikrobiologiia, 1984 Mar-Apr, 53(2), 246 - 50
{Enzyme activity of the formate hydrogenlyase complex in Citrobacter freundii}; Zatsepin SS et al.; Citrobacter freundii 62 can grow in the absence of oxygen in media containing glucose, peptone, fumarate or malate . When the medium contained fumarate or malate, the culture could grow under anaerobic conditions only in the presence of molecular hydrogen, formate or nitrate . The highest activity of formatehydrogenlyase and hydrogenase was found when C . freundii grew in a medium with glucose and formate . The activity was lower in media with other organic substrates, particularly, in the absence of formate or H2 . The activity of hydrogenase was very low in cells grown under aerobic conditions or in the presence of nitrates while the activity of formatehydrogenlyase was not found at all for all practical purposes . The activity of formate dehydrogenase assessed in the presence of methylene blue was rather high irrespective of the conditions under which the culture was grown . However, when the activity of formate dehydrogenase was determined in the presence of benzyl viologen, it was high only in cells grown in the medium with glucose and formate.

Antimicrob Agents Chemother, 1984 Mar, 25(3), 348 - 53
Novel carbapenem derivative SF2103A: studies on the mode of beta-lactamase inactivation; Yamaguchi A et al.; A novel carbapenem, SF2103A, is a strong inhibitor of various types of beta-lactamase . Equimolar concentrations of SF2103A completely inactivated the cephalosporinases of Proteus vulgaris and Citrobacter freundii and type Ib and type II penicillinases mediated by R plasmids in a progressive manner . The inactivation of the two penicillinases and P . vulgaris cephalosporinase was apparently irreversible; however, when the inactivated enzymes were separated from excess SF2103A by gel filtration, they showed very slow reactivation . The hydrolysis of SF2103A by these three beta-lactamases was below the limit of detection . It is concluded that SF2103A acts as a tight-binding competitive inhibitor for the penicillinases and P . vulgaris cephalosporinase . In contrast, the inactivation of C . freundii cephalosporinase by SF2103A was evidently reversible . The rate constant of reactivation of the enzyme was compatible with the turnover rate of the enzyme in the steady state of SF2103A hydrolysis . Thus, SF2103A simply acts as a poor substrate for C . freundii cephalosporinase.

J Clin Microbiol, 1984 Feb, 19(2), 301 - 2
Use of the Autobac IDX system for rapid identification of Enterobacteriaceae and nonfermentative gram-negative bacilli; Costigan WJ et al.; The Autobac IDX system was evaluated for its ability to accurately identify 290 gram-negative bacilli from 18 different genera . Excluding isolates with a low identification probability, the overall sensitivity of the system was found to be 95.8% . Late lactose-fermenting Escherichia coli, Citrobacter freundii, and Proteus mirabilis accounted for over 90% of the misidentifications . The Autobac IDX system offers a rapid and reliable method for the identification of gram-negative bacilli.

Vet Med Nauki, 1984, 21(3), 58 - 61
{Rapid method for the simultaneous determination of bacterial urease and phenylalanine desaminase}; Pavlov A et al.; Tested was an accelerated method for the evaluation of urease and phenylalanine desaminase of a total of 327 strains of E . coli, S . typhimurium, S . enteritidis, S . braenderup, S . tennessee, P . vulgaris, P . mirabilis, Yersinia enterocolitica, and Citrobacter that were subjected to a preliminary identification with routine methods . It was established that the method tested had the following advantages as compared to the classical methods employed up to then in the laboratory practice: --100% positive results were obtained up to the 4th hour, i . e . the method appeared 6 times more rapid, and the overall result was obtained one day earlier; --the two enzymes were studied simultaneously; --the expenditures in connection with the use of nutrient medium per one test were several times lower . Suggested is the timely adoption of the accelerated method in the laboratory practice.

J Gen Microbiol, 1984 Jan, 130 ( Pt 1), 53 - 62
Cadmium accumulation by a Citrobacter sp; Macaskie LE et al.; Cadmium accumulation by a Citrobacter sp . growing in the presence of the metal occurred as a sharp peak during the mid-exponential phase of growth, but cultures showed considerable inhibition of growth compared to cadmium-free controls . This problem was overcome by pregrowing the cells in cadmium-free medium and subsequently exposing them to the metal in the resting state, under which conditions higher concentrations of cadmium were tolerated and metal uptake was enhanced . This ability was retained when the cells were immobilized and then challenged with a flow containing Cd2+; 65% of the metal presented was removed from solution . The influence on uptake of the composition of the exposure buffer and of various cell treatments were investigated and the results are discussed with respect to the anticipated speciation of the cadmium presented to the cells and also with respect to the probable mechanism of metal uptake . This is thought to occur through the activity of a cell-bound phosphatase, induced during pre-growth by the provision of glycerol 2-phosphate as sole phosphorus source . Continued enzyme function in resting cells would then precipitate the metal as cell-bound cadmium phosphate.

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