Evaluation of clinical and biological parameters in marastic Kwashiorkor children treated by parenteral nutrition.

Reduction of hospital stay and mortality rate due to dehydration and electrolyte imbalance in children suffering from severe marasmic Kwashiorkor was attempted. A program of parenteral nutrition providing 70 to 100 milliliters water, 30 to 40 kilocalories, and 3 to 4 grams amino acids per kilogram daily was given. Seventy-seven African children suffering from protein deficiency and calorie deficiency were given an intravenous perfusion of casein hydrolysate or cristalloid amino acids for a mean period of 6 days. An oral supplement of tea and sugar, boiled rice, and palm oil was also given. The total mortality has not been modified in comparison with that in children given an oral diet (semi-liquid) consisting of low fat milk and locally available proteins. In more than half of the cases, the parenteral nutrition has favored water and salt retention and the development of cardiac failure possibly due to adynamic circulatory state. Weight curve, serum albumins, serum and urine amino acids were followed closely for 1 month. In eleven patients, nitrogen balance studies were done. All were positive independently of the coexisting infectious pathology. Correlating the increase in serum proteins with the cumulative nitrogen balance allowed us to consider casein hydrolysate as particularly useful for hepatic protein synthesis while cristalloid amino acids seem to favor muscular protein synthesis. The introduction of parenteral nutrition as a therapeutic regimen for standard use in the malnourished child seems less favorable than oral realimentation programs and does not seem desirable in developing countries.

[Infectious agents : current concepts and perspectives]. / L'agent infectieux : notions actuelles et perspectives.

The authors present a detailed discussion on infectious agents and their development in the immediate future and the anti-microbial strategies which need to be developed. After describing a series of new diseases and the suspected microbial aetiology of little known syndromes, they describe the major lines of development of chemotherapy: new products which need to be developed; microbial enzyme inhibitors; selective transport. The proper use of the range of drugs already available should not be underestimated. Finally, the authors review recent developments and the prospects for the future in the immunological field: new vaccines or the improvement of existing vaccines and the immense possibilities of immunological techniques of identification.

Differentiation of resistance determinants to cefamandole and cefoxitin in Enterobacter cloacae strains.

The mechanism of resistance to cefamandole and cefoxitin was investigated in Enterobacter cloacae with the aid of cefamandole-resistant variants and their derived beta-lactamase-deficient mutants. Cefamandole-resistant variants were easily obtained from clinical isolates by direct selection. Massive beta-lactamase production seemed to be the underlying resistance mechanism, although lack of penetrability may further substantiate this resistance. The mechanism of resistance to cefoxitin in parent, variant and mutant strains on the other hand was more complex, and probably due to a complex interrelation of parameters. Apart from relative instability to beta-lactamases and lack of penetrability, the high beta-lactamase-inducing power of cefoxitin is perhaps the most important determinant in the resistance of Enterobacter to this compound.

Comparative in vitro activity and beta-lactamase stability of moxalactam and other selected cephalosporin antibiotics.

(6R, 7R)-7-[[Carboxy(4-hydroxyphenyl)-acetyl]amino]-7-methoxy-3[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-oxa-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (moxalactam, LY 127 935), a novel 1-oxa-beta-lactam, was proved to display similar antibacterial activity as cefotaxime against a number of beta-lactamase-producing gram-negative strains. The outstanding activity proved to be bactericidal in most cases and was only slightly influenced by variation of the inoculum size. The activity of cefotaxime and especially cefamandole on the contrary had rather a high inoculum-dependence. Moxalactam had equal stability to gram-negative beta-lactamases as has cefoxitin. Like cefotaxime and cefoxitin, the compound proved to be a potent inhibitor of cephalosporinases but not of broad spectrum beta-lactamases.

In vitro comparison of norfloxacin with nalidixic acid, cinoxacin and oxolinic acid.

1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarbo xylic acid (Norfloxacin, MK-0366), a new nalidixic acid analog was shown to be significantly more active against Enterobacteriaceae than nalidixic acid and cinoxacin and about four times as active as oxolinic acid. The compound was highly effective against Pseudomonas aeruginosa (MIC less than or equal to 1 microgram/ml). In contrast to the other compounds, norfloxacin inhibited group B and D streptococci, whereas against staphylococci, both norfloxacin and oxolinic acid were shown to be active. The new compound proved to be bactericidal at minimum inhibitory concentrations. Nalidixic acid-resistant strains of various species were less sensitive to norfloxacin than nalidixic acid-sensitive bacteria, although the MICs for these strains remained well within therapeutically obtainable levels. Variants with decreased sensitivity could easily be obtained in vitro with all compounds; however, high-level resistance was not observed with norfloxacin in contrast to the other three compounds.

Evaluation of Spectrum-10 system for identification of members of the family Enterobacteriaceae.

A total of 378 isolates of the family Enterobacteriaceae were tested with conventional biochemical tests and with the Spectrum-10 identification system. Of these, 97.4% were correctly identified to the species level by using the seven-digit profile of Spectrum-10. The preliminary four-digit profile provided the correct species for 61.1% and the correct genus for 79.4% of the strains. Most misidentifications were observed with aberrant biotypes of Citrobacter freundii.

In vitro activity and beta-lactamase stability of N-formimidoyl thienamycin compared to that of second and third generation cephalosporins.

N-Formimidoyl thienamycin (MK0787) was found to be active against 21 gram-negative isolates, selected for their beta-lactamase production. None of the crude beta-lactamases could hydrolyze MK0787 or cefoxitin, in contrast to cefotaxime which was moderately attacked by a number of enzymes. MK0787 behaved as a moderate inhibitor of most beta-lactamases, whereas cefoxitin and cefotaxime were strong inhibitors of cephalosporinases but not of broad-spectrum enzymes. The new compound had good penetration characteristics in a strain of Enterobacter cloacae, in contrast to cefoxitin. Against a number of trained cefamandole- and cefoxitin-resistant variants, MK0787 was clearly the most active of the compounds tested.

Comparative stability of first, second and third generation cephalosporins and N-formimidoyl thienamycin against gram-negative beta-lactamases.

The susceptibility of cefamandole, cefoxitin, cefotaxime, moxalactam, and N-formimidoyl thienamycin to different gram-negative beta-lactamases was determined by the UV-spectrophotometric method and two microbiological techniques in comparison with that of first generation cephalosporins. In general, the microbiological methods were more sensitive than the UV-assay. Cefamandole was rapidly hydrolyzed by all enzymes tested. The beta-lactamase stability of the other compounds was significantly higher, but clearly proved to be not absolute. With the aid of the "double-disc technique", the most sensitive of the methods used, cefotaxime was shown to be susceptible to all enzymes, whereas cefoxitin, moxalactam and N-formimidoyl thienamycin showed some susceptibility to 6, 3 and 7 enzymes, respectively. Moxalactam appeared to be the most stable of the compounds tested.

In vitro antibacterial activity of BMY-28142, a new extended-spectrum cephalosporin.

The in vitro activity of BMY-28142 was compared with that of cefotaxime, ceftazidime, moxalactam, and imipenem against 639 clinical isolates and a number of in vitro-selected resistant mutants. BMY-28142 was the most potent compound against the members of the family Enterobacteriaceae with a MIC for 90% of the strains of 0.12 micrograms/ml. The activity against Pseudomonas aeruginosa was comparable to that of ceftazidime and imipenem. Strains of staphylococci were moderately susceptible to BMY-28142 (MIC required to inhibit 90% of strains, 4 micrograms/ml), but Streptococcus faecalis isolates were resistant. The activity of the five compounds was inoculum dependent for several gram-negative species. By a single-step selection procedure, resistant mutants were selected from strains of Citrobacter freundii, Enterobacter cloacae, and P. aeruginosa. The mutant frequencies with the cephalosporins, including BMY-28142, ranged between 10(-6) and 10(-8). BMY-28142 was the most active cephalosporin against these resistant organisms, most of them strong beta-lactamase producers. It inhibited all mutants of C. freundii and E. cloacae at 2 micrograms/ml and all mutants of P. aeruginosa at 32 micrograms/ml. Imipenem on the other hand was as active on all of these resistant organisms as on the parent strains.

Urease activity of enterobacteriaceae: which medium to choose.

Detection and intensity of urease activity in enterobacteriaceae greatly varies as a function of the media or techniques used, or both. A comparative investigation on several solid and liquid media led us to the following conclusions. (i) Detection of Proteus spp. can be adequately performed with the highly selective solid medium described by Cook (1948), as well as with the different liquid media described (Stuart standard and rapid media; Elek medium). (ii) Detection of Klebsiella should be based upon urease production on solid media with low buffer capacity (Christensen, 1946). (iii) For the identification of Yersinia, either the solid Christensen urea agar or the rapid Elek technique give optimal results.

Endotoxin testing.

Parenterals, sterile preparations intended to be injected in man or animal, should be free from pyrogenic substances which are able to raise the thermostatic setting in the hypothalamus. This article gives an up-to-date review of the principal detection and quantification methods for these agents, with special attention on the chromogenic Limulus Amebocyte Lysate assay.

Plasmid-mediated beta-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli resistant to ceftazidime.

Low-level transferable resistance to ceftazidime was detected in seven strains of Klebsiella pneumoniae and one strain of Escherichia coli. Six of the Klebsiella strains and the E. coli strain were shown to produce a novel beta-lactamase (CAZ-lo) with a pI of 5.6 that hydrolyzed broad-spectrum cephalosporins at low but comparable levels. One strain of K. pneumoniae was of a serotype different from that of the other strains and produced a plasmid-encoded cefuroximase (FUR) with a pI of 7.5 that mediated moderate levels of resistance to different broad-spectrum cephalosporins. High-level resistance to ceftazidime was detected in one other strain of K. pneumoniae, which produced a beta-lactamase with a pI of 6.5 (CAZ-hi). Apart from its pI, this enzyme differed from CAZ-lo by a specific and high hydrolytic activity against ceftazidime. The epidemiological context suggested that CAZ-hi may be a mutant of CAZ-lo, and this hypothesis was supported by the isolation of laboratory mutants of CAZ-lo showing properties identical to those of the clinical CAZ-hi enzyme.

In vitro activity of BL-s640 against gram-negative bacilli and Staphylococcus aureus compared with activity of four other semisynthetic cephalosporins.

The in vitro activity of BL-S640 (cefatrizine) was determined against 674 recent clinical isolates of Staphylococcus aureus and Enterobacteriaceae. Activity against S. aureus was less than that of cephapirin, cephalothin, and cefazolin, but greater than that of cephalexin. Activity against gram-negative isolates was variable: BL-S640 was slightly less potent than cefazolin against Escherichia coli and Klebsiella, but more active than the other compounds. As for the more resistant gram-negative genera, BL-S640 was significantly superior to the control cephalosporins. The effect of inoculum size on the antibacterial activity was moderate for most organisms except Enterobacter, Providencia stuartii, and indole-positive Proteus, the median minimal inhibitory concentrations of which were 6 to 27 times lower when determined with a 10(-4)-diluted culture compared with the undiluted one. The stability in aqueous solution at 37 C was remarkably high at the lower pH values, but low at the neutral point.

Selection of resistant mutants of Citrobacter freundii by second and third-generation cephalosporins and imipenem.

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.

Plasma amino acid patterns, one and two hours after continuous naso-gastric alimentation of low birth weight infants fed two types of milk during the first month of life.

Plasma amino acid concentrations were determined in the morning, 1 and 2 h after discontinuing any naso-gastric feeding on the 3rd, 5th, 15th and 30th days of life, in order to establish their course according to the moment of sampling and to the type of diet given. Two types of conventional naso-gastric feeding were given in 12 infants with a birth weight of 1,500 g or less. The diets supplied either 1.2 g proteins/100 ml (pooled human milk) or 1.8 g proteins/100 ml ("humanized formula' with an albumin/casein ratio of 60/40) from the 3rd h to the 30th day of life. No statistically significant difference appeared between the amino acid concentrations 1 and 2h after discontinuation of naso-gastric alimentation on the 3rd, 5th and 15th days whichever milk was used, but a significant difference appeared for two amino acids on day 30 (phenylalanine and lysine) when fed the humanized formula. It is concluded that caution might be necessary when interpreting amino acid results: the moment of sampling induced a statistically significant difference on day 30 of life only for phenylalanine and lysine in children fed on a "humanized formula'.

Investigation of the ability of newer beta-lactam antibiotics to select resistant mutants from Serratia marcescens after mutagenesis with nitrosoguanidine.

Resistant mutants could easily be selected from a nitrosoguanidine-treated culture of Serratia marcescens with piperacillin, cefotaxime, cefoxitin, cefotetan, latamoxef (moxalactam) and aztreonam. Imipenem on the other hand was significantly less effective in mutant selection. Resistant clones broadly fell into two distinct classes. Most mutants did not show increased beta-lactamase; their resistance seemed to be due to changed outer membrane proteins. Other mutants had strongly increased cephalosporinase activity, although the derepression was only partial. Piperacillin, cefotaxime and aztreonam preferentially selected the derepressed phenotype, whereas mutants selected with cefoxitin, cefotetan, moxalactam and imipenem were exclusively of the non-derepressed phenotype. There was a significant degree of cross-resistance between the beta-lactam antibiotics except imipenem which was only slightly less active against the membrane-altered mutants.