Results of culture form colonoscopically obtained specimens for bacteria and fungi in HIV-infected patients with diarrhea.

BACKGROUND: The aim of our study was to determine the diagnostic yield of culture for bacteria and fungi from colonic biopsy specimens in 290 consecutive HIV-infected patients with diarrhea. METHODS: During each colonoscopy, three biopsy specimens were homogenized and cultured on media for Salmonella and Shigella and for Campylobacter and Yersinia, on Loewenstein medium and on Sabouraud medium. RESULTS: Cultures were found positive for one (n = 32) or two (n = 5) infectious agents in 37 cases, i.e., in 12.8% of the patients. Bacteria were isolated in 24 cases, and identified as Campylobacter jejunl-coli (n = 14), Salmonella (n = 2), Shigella (n = 1), or Pseudomonas aeruginosa (n = 7). Among the 14 patients with C. jejuni-coli intestinal infection, 11 had normal-appearing mucosa at colonoscopy, and 3 had a concomitant stool culture negative for Campylobacter. Mycobacterial cultures were positive for Mycobacterium avium intracellulare in 6 patients, who were already known as having a disseminated M. avium intracellulare infection from positive blood cultures. Fungal cultures were positive for Candida in 10 cases, without clear clinical significance. CONCLUSIONS: The overall yield of culture for bacterial pathogens from colonic tissue in HIV-infected patients with diarrhea is low, but some individual cases of C. jejuni-coli infections may be detected from colonic tissue culture and not diagnosed by concomitant stool culture.

Piperacillin, tazobactam, and gentamicin alone or combined in an endocarditis model of infection by a TEM-3-producing strain of Klebsiella pneumoniae or its susceptible variant.

The efficacy of tazobactam, a beta-lactamase inhibitor, in combination with piperacillin, was studied in vitro and in rabbit experimental endocarditis due to a Klebsiella pneumoniae strain (KpR) producing an extended-spectrum beta-lactamase, TEM-3, or its nonproducing variant (KpS). In vitro, piperacillin was active against KpS (MIC = 4 micrograms/ml, MBC = 8 micrograms/ml with 10(7)-CFU/ml inoculum) but not against KpR (MIC = MBC = 256 micrograms/ml). Tazobactam (1 microgram/ml) restored the activity of piperacillin against KpR (MIC = 2 micrograms/ml, MBC = 4 micrograms/ml). Gentamicin was active against both strains (MIC = 0.25 and 0.5 micrograms/ml for KpS and KpR, respectively). The piperacillin-tazobactam-gentamicin combination was synergistic in vitro. The piperacillin/tazobactam ratio in plasma and in vegetations was always lower than the 4/1 injected dose ratio. In vivo, piperacillin (300 mg/kg of body weight four times a day [QID]) was active against KpS but not against KpR. Tazobactam (75 mg/kg QID) was able to restore the in vivo effect of piperacillin (300 mg/kg QID) against KpR (-3.0 log10 CFU/g of vegetation versus that of controls). Gentamicin (4 mg/kg twice a day [BID]) was active against both strains. Compared with controls, the combination of gentamicin plus piperacillin against KpS (-5.6 log10 CFU/g of vegetation), and the gentamicin-piperacillin-tazobactam combination against KpR (-4.4 log10 CFU/g of vegetation) achieved the greatest decrease in bacterial counts in vegetations and were the only regimens that significantly increased the proportion of sterile vegetations. It is concluded that (i) tazobactam was able to restore the effect of piperacillin against a TEM-3 extended-spectrum Beta-lactamase-producing strain of K. pneumoniae, both in vitro and in a severe experimental infection with high inoculum, when used in a 4/1 piperacillin/tazobactam dose ratio; (ii) gentamicin alone was effective because of the high peak/MBC ratio in plasma; (iii) piperacillin-tazobactam-gentamicin, probably because of the effect of gentamicin in reducing bacterial inoculum in vivo, as stressed by the results obtained by piperacillin-gentamicin against KpS, may be the most effective regimen against KpR.

Clinical and bacterial features of infections caused by Streptococcus milleri.

The clinical and bacteriological features of 51 infections due to Streptococcus milleri observed in 43 patients over a 2-year period were reviewed. Clinical syndromes included bacteremia in 6 cases, endocarditis in 4 cases, cellulitis and subcutaneous abscesses in 8 cases, pleural empyema in 8 cases, brain abscesses in 5 cases, abdominal infections in 5 cases, and other miscellaneous infections in 15 cases. An underlying condition was associated with infection in 33/43 patients (77%). S. milleri was the only pathogen isolated in 19 patients (44%). All strains of S. milleri were susceptible to penicillin. Surgery was combined with antimicrobial therapy in 27 (63%) patients. Nine patients died during hospitalization, and death was directly related to S. milleri infection in 4 patients (9%). These results confirm that S. milleri frequently causes serious suppurative infections and that species identification is a clinically useful procedure.

Ceftriaxone-sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae producing extended-broad-spectrum TEM-3 beta-lactamase.

We studied the activity of the combination of sulbactam and ceftriaxone against a Klebsiella pneumoniae strain producing TEM-3, a new extended-broad-spectrum beta-lactamase, in an endocarditis model. In vitro, ceftriaxone was strongly inactivated in the presence of TEM-3 (MBC, 128 micrograms/ml with an inoculum of 5 x 10(5) CFU/ml). A marked inoculum effect was demonstrated with sulbactam: effective concentrations of inhibitor needed to reduce the MIC and MBC of ceftriaxone to similar levels increased from 1 microgram/ml in the presence of an inoculum of 5 x 10(5) CFU/ml to 20 micrograms/ml in the presence of an inoculum of 1 x 10(7) CFU/ml. In vivo, sulbactam given at 200 mg/kg of body weight every 12 h, a dosage higher than that previously reported to be effective against rabbit endocarditis caused by other microorganisms, was not sufficient to restore the complete activity of ceftriaxone given at 30 mg/kg once daily for 4 days. This insufficient activity may be correlated with the presence of a high level of beta-lactamase inside the vegetations, as indicated by a quantitative in vitro assay of beta-lactamase activity in the cardiac vegetation, suggesting an insufficient inactivation of the extended-broad-spectrum beta-lactamase in vivo.

[HIV infection and "malignant" strongyloidiasis]. / Infection VIH et anguillulose "maligne".

Disseminated Strongyloides stercoralis infection occurs in immunocompromised patients. Despite the epidemiological overlap of HIV infection and strongyloidiasis observed in certain parts of the world, only six cases of dissemination have been reported in AIDS patients. The clinical presentation has no special features, except for the frequency of other opportunistic infections. The prognosis is poor. This lack of association between disseminated strongyloidiasis and HIV infection had led to the exclusion of extra-intestinal forms of this paraistosis from the revised classification of AIDS.

Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta-lactamase.

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Vancomycin-aminoglycoside combinations in therapy of endocarditis caused by Enterococcus species and Streptococcus bovis.

Between 1974 and 1986, five patients with enterococcal endocarditis (three of whom had a prosthetic valve) and three patients with Streptococcus bovis endocarditis were treated with a combination of vancomycin and an aminoglycoside for a mean duration of 40 days. This regimen was prescribed because of allergy to beta-lactam (n = 7) and/or failure of previous treatment (n = 4). Three of the eight patients underwent valve replacement. In the six evaluable patients cure was achieved with the vancomycin-aminoglycoside combination. An increase of the creatinine serum levels was observed in all cases but it was never necessary to discontinue treatment, adjustment of the vancomycin and aminoglycoside dosage according to the serum and/or serum creatinine levels allowing continuation of therapy.

[A fosfomycin-gentamicin combination in the treatment of experimental endocarditis caused by Klebsiella pneumoniae producing type TEM-3 beta-lactamase]. / Association fosfomycine-gentamicine dans le traitement d'une endocardite expérimentale à Klebsiella pneumoniae produisant une beta-lactamase de type TEM-3.

The authors studied the activity of fosfomycin (FOS) and/or gentamicin (GEN) against a Klebsiella pneumoniae strain resistant to all beta-lactams--except cephamycins and imipenem--by production of a plasmid mediated extended broad-spectrum beta-lactamase-TEM-3, to all aminoglycosides--except gentamicin--by production of a plasmid mediated 6' aminoglycoside acetyltransferase IV, to sulfonamides and to tetracyclines. In vitro, the combination FOS (MIC = MBC = 32 mg/l) + GEN (MIC = MBC = 2) appeared indifferent (FIC = 0.75; FBC = 1). In vivo, on experimental endocarditis in rabbits, FOS alone was ineffective, GEN alone was active but only at high dose regimen, FOS - GEN combination was active as compared with controls. Fosfomycin - gentamicin combination may be an alternative in the therapy of severe infections due to multiresistant Enterobacteriacae.

TEM-4, a new plasmid-mediated beta-lactamase that hydrolyzes broad-spectrum cephalosporins in a clinical isolate of Escherichia coli.

A clinical isolate of Escherichia coli, strain CB-134, recovered in 1986 from an abdominal abscess, exhibited resistance to penams, oxyimino-beta-lactams including broad-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime), and aztreonam but remained susceptible to cephamycins (cefoxitin, cefotetan) and to moxalactam and imipenem. Clavulanate (2 micrograms/ml) restored the susceptibility of the strain to broad-spectrum cephalosporins and aztreonam. A beta-lactamase with an isoelectric point (pI) of 5.9 was detected in strain CB-134, and the corresponding gene was transferred by conjugation to E. coli together with the associated aminoglycoside resistance determinant [AAC(3)-II] and tetracycline, trimethoprim, and sulfonamide resistance. The beta-lactamase efficiently hydrolyzed cefotaxime and ceftriaxone but only moderately hydrolyzed ceftazidime and was inhibited by clavulanate and sulbactam (1 microM) and by anti-TEM-1 and anti-TEM-2 sera. This extended-spectrum beta-lactamase, conferring resistance to cefotaxime, ceftriaxone, ceftazidime, and aztreonam, was comparable to CTX-1 (TEM-3) but differed from it by pI. Agarose gel electrophoresis of the plasmid DNA indicated that this new enzyme was coded by pUD16, a plasmid of 220 kilobases which belongs to the Inc6 incompatibility group. Hybridization with an intragenic probe for TEM-1 revealed that this beta-lactamase derives from TEM-type beta-lactamases and hence it was named TEM-4.

[In vitro antibacterial effect of a new oral cephalosporin, cefixime. Results of a multicenter study]. / Activité antibactérienne in vitro d'une nouvelle céphalosporine orale, le céfixime. Résultats d'une étude multicentrique.

Minimal inhibitory concentrations (MIC) of cefixime (CXM) were evaluated by agar dilution against 2,469 bacterial strains isolated in 10 hospitals. For Enterobacteriaceae, MIC 50 and 90% micrograms/ml were respectively: (I) naturally non beta lactamase producing species: E. coli and Shigella 0.25-0.5; Salmonella 0.06-0.25; P. mirabilis 0.008-0.032. (II) chromosomal penicillinase producing species: Klebsiella 0.06-2. (III) chromosomal cephalosporinase producing species: E. cloacae and C. freundii 1-greater than 128; S. marcescens 0.25-16; indole + Proteus 0.06-4; P. stuartii 0.032-0.5. Activity of CXM was not modified against plasmid-mediated penicillinase producing strains, but CXM was inactive on cephalosporinase hyperproducing strains and on broad spectrum beta lactamases producing strains. CXM was inactive on P. aeruginosa (MIC 50 and 90%: 64-128) and on A. baumannii (16-128). Haemophilus and Gonococci, regardless of beta-lactamase production status, and Meningococci were very susceptible to CXM (MIC 0.008-0.12). B. catarrhalis was generally inhibited by 0.03 to 0.5. CXM was poorly active on methicillin susceptible Staphylococci (MIC 50 and 90%: 1-64) and inactive on methicillin resistant strains. Enterococci were generally resistant whereas Streptococci and Pneumococci were inhibited by low concentrations: 0.008 to 1. These antibacterial properties place CXM in excellent position among oral cephalosporins.

Detection of extended broad-spectrum beta-lactamases in Enterobacteriaceae in four French hospitals.

In 210 strains of Enterobacteriaceae which were isolated in four hospitals and which showed reduced susceptibility to cefotaxime, high synergy was demonstrated between amoxicillin (20 micrograms) + clavulanate (10 micrograms) and cefotaxime (30 micrograms) using a simple double-disk test. Isoelectric focusing on gel and specific iodometric detection using ceftriaxone identified four extended broad-spectrum beta-lactamases (isoelectric points 7.6, 6.3, 7.0 and 5.9) produced by the strains.

Characterization of the plasmid genes blaT-4 and blaT-5 which encode the broad-spectrum beta-lactamases TEM-4 and TEM-5 in enterobacteriaceae.

We have determined the nucleotide sequence of the plasmid genes blaT-4 and blaT-5 which encode the broad-substrate-range beta-lactamases TEM-4 and TEM-5, respectively. The TEM-4 enzyme, which confers high-level resistance to cefotaxime (Ctx) and ceftazidime (Caz), differed from the TEM-1 penicillinase by four amino acid substitutions. Two of the mutations are identical to those responsible for the wide substrate range of the TEM-3 beta-lactamase which hydrolyses Ctx and Caz. The amino acid sequence of TEM-5, which confers higher levels of resistance to Caz than to other recently developed cephalosporins, differed from that of TEM-1 by three mutations distinct from those of TEM-4. Analysis of the location of the mutations in the primary and tertiary structures of class A beta-lactamases suggests that interactions between the substituted residues and beta-lactam antibiotics non-hydrolysable by TEM-1 and TEM-2 allow TEM-4 and TEM-5 to hydrolyse efficiently novel broad-spectrum cephalosporins such as Ctx and Caz.

Ceftriaxone-netilmicin combination in single-daily-dose treatment of experimental Escherichia coli endocarditis.

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.

[Comparative study of the penetration of penicillin V, amoxicillin, cefaclor and josamycin in the tonsils]. / Etude comparée de la pénétration de la pénicilline V, de l'amoxicilline, du céfaclor et de la josamycine dans les amygdales.

Fourty patients undergoing tonsillectomy for recurrent tonsillitis were administered penicillin V, amoxicillin, cefaclor or josamycin. Antibiotic concentrations in serum and tonsillar tissues were determined by microbiological assay. Cefaclor demonstrated a superior diffusion than penicillin V and amoxicillin, but nevertheless inferior to that of josamycin.

Dissemination in five French hospitals of Klebsiella pneumoniae serotype K25 harbouring a new transferable enzymatic resistance to third generation cephalosporins and aztreonam.

A strain of Klebsiella pneumoniae K25 resistant to newer beta-lactam drugs was isolated in clusters in five hospitals in the Paris area. The MICs of ceftazidime and aztreonam (greater than or equal to 128 mg/l) were higher than that of cefotaxime (16 mg/l) for the strain but, when measured in the presence of clavulanic acid, they were less than or equal to 1 mg/l. The donor strains and derivatives produced a beta-lactamase with a pI of 7.75-7.8 and hydrolysing activity against a wide spectrum of beta-lactams similar to that of SHV-2 and SHV-3, but with significant hydrolysis of ceftazidime. This new enzyme could be designated SHV-4.

[Retrospective bacteriological study of mycobacterial infections in patients with acquired immunodeficiency syndrome]. / Etude bactériologique rétrospective des infections à mycobactéries chez les malades atteints de syndrome immunodéficitaire acquis.

The main species of mycobacteria isolated in 62 of the 316 acquired immunodeficiency syndrome patients admitted to the Claude Bernard Hospital, Paris, between January, 1983 and October, 1986 were studied retrospectively according to their site of isolation and their pathogenic role. Mycobacterium tuberculosis was isolated in 19 cases (from pulmonary specimens in 17 cases); this species was present in 59 percent of our African patients as against 20 percent of our European patients. M. avium intracellulare was isolated in 33 cases (17 from blood, 12 from the lung and 11 from the gastrointestinal tract) and was found in 55 p. 100 of our European patients. Other species that were isolated less frequently were M. xenopi (5 cases), M. kansasii (3 cases), M. aurum, M. chelonae, M. fortuitum, M. gordonae, M. simiae and M. terrae (1 case each). Post mortem specimens obtained from 110 acquired immunodeficiency syndrome patients were cultivated during the same period. In 20 patients, at least one specimen was positive for a mycobacterium: M. tuberculosis in 2 cases, M. avium intracellulare in 18 cases. Twenty-nine of the 33 patients in whom M. avium intracellulare was isolated were considered a posteriori as being infected by this organism. The therapeutic approach varies according to the species involved. No treatment seems to be truly effective against M. avium intracellulare. Pending the results of cultures, no direct bacteriological examination can provide information on the mycobacterial species concerned; however, a conventional antituberculosis treatment may be instituted, particularly in patients from Africa or Haiti.

Bactericidal activity against Haemophilus influenzae of cerebrospinal fluid of patients given amoxicillin-clavulanic acid.

Patients with purulent meningitis received amoxicillin-clavulanic acid (200/20 mg/kg [body weight] per day). Clavulanic acid levels in cerebrospinal fluid were less than or equal to 0.05 micrograms/ml in 5 of 18 samples and ranged from 0.1 to 0.8 micrograms/ml in the others. Of 12 cerebrospinal fluid samples tested, 10 lacked bactericidal activity in vitro against a beta-lactamase-producing strain of Haemophilus influenzae.