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Enterobacter hormaechei, a new species of the family Enterobacteriaceae formerly known as enteric group 75.

The name Enterobacter hormaechei is proposed for a new species of the family Enterobacteriaceae, formerly called Enteric Group 75, which consists of 23 strains, 22 of which were isolated from humans. DNAs from 12 E. hormaechei strains tested were highly related to the type strain (ATCC 49162) by DNA hybridization, using the hydroxyapatite method (80 to 97% in 60 degrees C reactions; 80 to 90% in 75 degrees C reactions). The strains were most closely related (50 to 63%) to Enterobacter cloacae, Enterobacter dissolvens, Enterobacter taylorae, and Enterobacter nimipressuralis. E. hormaechei strains were positive within 48 h for the following: Voges-Proskauer test; citrate utilization (Simmons and Christensen); urea hydrolysis (87%); ornithine decarboxylase; growth in potassium cyanide (KCN); malonate utilization; production of acid from D-glucose, L-arabinose, cellobiose, dulcitol (87%), D-galactose, maltose, D-mannitol, D-mannose, L-rhamnose, sucrose, trehalose, and D-xylose; acid production from mucate; nitrate reduction; and o-nitrophenyl-beta-D-galactopyranoside. Delayed positive reactions were seen in tests for arginine dihydrolase, gas from D-glucose, acid from alpha-methyl-D-glucoside, and acetate utilization. E. hormaechei was negative in tests for indole production; H2S production; phenylalanine deaminase; lysine decarboxylase; gelatin hydrolysis; acid production from D-adonitol, D-arabitol, erythritol, glycerol, i(myo)-inositol, melibiose, raffinose, and D-sorbitol; esculin hydrolysis; DNase; lipase; and tyrosine clearing. Variable reactions occurred in tests for methyl red, motility, and tartrate. All strains tested were susceptible or moderately susceptible to amikacin, azlocillin, cefotaxime, ceftazidime, ceftriaxone, chloramphenicol, gentamicin, mezlocillin, moxalactam, piperacillin, trimethoprim-sulfamethoxazole, sulfisoxazole, thienamycin, tobramycin, and trimethoprim. All strains tested were resistant to nitrofurantoin; the majority were resistant to ampicillin, cefoxitin, and cephalothin. Four isolates were from blood; most other isolates were from wounds or sputum.

Adolescent↗

Improved recovery of mycobacteria from respiratory secretions of patients with cystic fibrosis.

Pulmonary colonization and infection of patients with cystic fibrosis by Mycobacterium spp. has recently been recognized as a potentially important clinical problem. However, frequent contamination of mycobacterial cultures by pseudomonads has hampered efforts to define the extent of this problem. This study was done to evaluate current techniques and to establish a more efficient method of recovering mycobacteria from respiratory secretions of patients with cystic fibrosis. Decontamination of respiratory specimens (n = 121) with 0.25% N-acetyl-L-cysteine and 1% sodium hydroxide (NALC-NaOH) was associated with a high rate of pseudomonas overgrowth for both Lowenstein-Jensen slants (74%) and BacTec vials supplemented with PANTA (polymyxin B [50 U/ml], amphotericin B [5 micrograms/ml], nalidixic acid [20 micrograms/ml], trimethoprim [5 micrograms/ml], azlocillin [10 micrograms/ml]) (36%). This overgrowth limited recovery of mycobacteria to only 64% (9 of 14) of specimens positive by smear for acid-fast bacilli (AFB). Decontamination of specimens (n = 441) with NALC-NaOH, followed by 5% oxalic acid treatment, resulted in contamination of only 5% of Lowenstein-Jensen slants and 3% of BacTec vials. AFB were recovered from all 90 AFB smear-positive specimens following the use of this decontamination technique. We recommend that respiratory secretions be decontaminated with NALC-NaOH and oxalic acid to decrease the incidence of Pseudomonas aeruginosa overgrowth.

Acetylcysteine↗

Substances interfering with direct detection of Mycobacterium tuberculosis in clinical specimens by PCR: effects of bovine serum albumin.

Interfering substances have been reported to inhibit PCR assays for the direct detection of Mycobacterium tuberculosis in clinical specimens. Using an internal control, we determined that 52% of respiratory specimens interfered with our PCR assay. On the basis of these findings, we tried to circumvent the problem by simply diluting prepared sediments. With sediment from a routinely processed sputum known to be inhibitory to PCR, one aliquot was prepared in a routine manner for PCR. Remaining sediment was diluted in phosphate-buffered saline, Middlebrook 7H10 broth, or BACTEC 12B broth; an internal control was added to all reaction mixtures and controls. Internal control was detected only in the sample diluted with BACTEC 12B medium. Components of the BACTEC 12B medium including PANTA reagent (polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin), reconstituting fluid, 0.2% glycerol, 0.05% Tween 80, and 0.05% bovine serum albumin (BSA) were tested in a similar manner. Only 0.05% BSA resulted in amplification of the internal control DNA. Varying concentrations of BSA were added to 11 aliquots of a respiratory sediment known to be inhibitory to the PCR. Internal control was detected in all reaction mixtures containing 0.00038 to 0.1% BSA. To determine the ability of BSA to override inhibition, respiratory specimens were run in triplicate: undiluted, diluted 1:2 with BACTEC 12B medium, or diluted with 0.026% BSA. For 21 of 22 inhibitory specimens, BSA was able to override the presence of interfering substances. These data suggest that the presence of BSA in a PCR assay is critical for the direct detection of M. tuberculosis in respiratory specimens.

Animals↗

Isolation of blood-borne Mycobacterium avium by using the nonradioactive BACTEC 9000 MB system and comparison with a solid-culture system.

We conducted a 12-month prospective study comparing two approaches to the detection of Mycobacterium avium in the blood of human immunodeficiency virus type 1-infected patients, namely, a lytic centrifugation system combined with Middlebrook solid culture medium (the conventional procedure) and the nonradiometric BACTEC 9000 MB system. Species identification relied on 16S rRNA probe hybridization and cell wall fatty acids chromatography. M. avium was isolated in 17 of 345 (5%) blood specimens by the BACTEC 9000 MB automated system and in 14 of 345 (4%) blood specimens by the conventional procedure (nonsignificant, chi2 test). Detection time was 16 +/- 6 days by the BACTEC 9000 MB automated system and 27 +/- 3 days by the conventional procedure (P < 0.001, Student t test). Non-M. avium mycobacteria were not recovered during the study period. Contamination rate was 8% (30 specimens) by the BACTEC 9000 MB system and 0% by the conventional procedure, indicating the necessity of using an antibiotic mixture (PANTA, consisting of polymyxin B, amphotericin B, nalidixic acid, trimethoprim, and azlocillin). Working time was 1 min 30 s by the BACTEC 9000 MB system and 8 min by the conventional procedure, which was 1.8 times more expensive than the BACTEC system. Use of the BACTEC 9000 MB system increased the sensitivity of M. avium detection and reduced detection time in blood culture.

Acquired Immunodeficiency Syndrome↗

Pseudomonas arthritis treated with parenteral and intra-articular ceftazidime.

A 73-year-old diabetic presented with septic arthritis of the knee; Pseudomonas aeruginosa was isolated. She was successfully treated with a combination of parenteral and intra-articular ceftazidime, after failure to eradicate the organism with adequate serum levels of gentamicin and full doses of azlocillin.

Aged↗

Short-course intravenous antibiotics with oral quinolone prophylaxis in the treatment of neutropenic fever in autologous bone marrow or peripheral blood progenitor cell transplant recipients.

The effectiveness of short-course intravenous antibiotics concurrent with prophylactic oral ciprofloxacin in the treatment of neutropenic fever was studied in 81 patients undergoing autologous bone marrow or peripheral blood progenitor cell transplantation (ABMT or PBPCT). During the neutropenic period following ABMT or PBPCT, 10/81 (12%) patients did not require treatment with intravenous antibiotics. Seventy-one patients required antibiotics. Forty-seven of the 71 (66%) responded to 72 h treatment with gentamicin, azlocillin or ceftazidime, and vancomycin. Thirty-three of the 47 (70%) responders had a complete resolution of their fever with no further recurrence. Fourteen of the 47 responders developed a second fever between 2 and 25 days after stopping first-line antibiotics. Eleven of the 14 patients responded to a second course of intravenous antibiotics. Twenty-four of the 71 patients did not respond to intravenous antibiotics and were treated with intravenous amphotericin and the intravenous antibacterial agents were discontinued. Eighteen of the 24 patients responded to amphotericin. The 6 patients who had persistent fever resolved their temperature when their neutrophil count recovered. There were no deaths due to infection during the study. Short-duration intravenous antibiotics in conjuction with oral ciprofloxacin prophylaxis are a safe and effective treatment for neutropenic fever.

Adolescent↗

Antibacterial properties of Ro 13-99041, a long-acting new cephalosporin.

The antibacterial properties of the new cephalosporin RO 13-9904 were investigated in vitro and in vivo. The compound showed good activity against Entero-bacteriaceae and gram-positive cocci, except Streptococcus faecalis. Haemophilus influenzae, Neisseria gonorrhoeae and Neisseria meningitidis were extremely susceptible to Ro 13-9904. The bactericidal activity of Ro 13-9004 was comparable to that of cefotaxime. The new cephalosporin showed better therapeutic efficacy in mice against Pseudomonas aeruginosa than cefotaxime, cefoperazone, azlocillin, and piperacillin. Ro 13-9904 was highly effective in prophylactic studies, in contrast to cefotaxime, SCE-1365, cefoperazone and piperacillin. This indicates that Ro 13-9004 essentially differs from other beta-lactam compounds in showing unusually prolonged in vivo efficacy.

Animals↗

Simple screening method for gram-positive bacterial beta-lactam antibiotic tolerance on routine laboratory Bauer-Kirby antibiogram plates.

A simple screening method served to detect beta-lactam antibiotic-tolerant variants of clinical isolates and laboratory control strains of staphylococcus aureus, S. epidermis, group B beta-hemolytic streptococci, and Listeria monocytogenes. The beta-lactamase(s) of a multiple drug-resistant strain of Enterobacter cloacae (isolate No. 19) yielded most consistent results as compared with several other beta-lactamase producers; the E. cloacae beta-lactamase(s) was neutralized by clavulanic acid. Spot inocula of E. cloacae isolate No. 19, following overnight "induction" with 1 microgram/ml of ampicillin and 3 microgram/ml of cephalothin in tryptic soya broth, were applied centrally to beta-lactam antibiotic inhibition zones of Bauer-Kirby antibiogram plates (Mueller-Hinton agar, MHA, and diagnostic sensitivity test agar, DSTA) following removal of the appropriate disks. The spot-inoculated plates were incubated overnight at 35 degrees C and inspected for satellite growths of tolerant variants around the E. cloacae spot inocula. Satellite growths of less than or equal to 10 colonies were interpreted to indicate tolerance of the relevant cell wall synthesis inhibitor. The method readily permitted detection of variants tolerant for ampicillin, cephalothin, penicillin G, piperacillin, azlocillin, and mezlocillin. However, strains documented by minimal inhibitory and minimal bactericidal concentrations to be tolerant for cefotaxime, cefoxitin, fosfomycin, and vancomycin only rarely gave rise to respective satellite growths. DSTA proved superior to MHA with respect to "rescue" of inhibited tolerant staphylococcal variants; furthermore, the diameters of inhibition zones obtained on DSTA correlated well with those on MHA. Therefore, DSTA was adopted as the routine test medium for clinical staphylococcal isolates.

Anti-Bacterial Agents↗

Activity of cefsulodin, other beta-lactams, and aminoglycosides against Pseudomonas aeruginosa.

Cefsulodin was the most active of the cephalosporins and exhibited 4-16 times more activity than carbenicillin or ticarcillin against 50 clinical isolates of Pseudomonas aeruginosa. Azlocillin and piperacillin showed good activity, while tobramycin was the most effective aminoglycoside. The activity of cefsulodin was unaltered by increases in inocula, but resistance was induced easily. When combined with gentamicin, no synergistic or antagonistic activity was observed against multiply resistant isolates.

Aminoglycosides↗

Comparative in vitro activity of ciprofloxacin and other antimicrobial agents against aminoglycoside-resistant gram-negative rods and microorganisms isolated from patients with bacteremia.

The comparative in vitro activity of ciprofloxacin, norfloxacin, aztreonam, cefotaxime, ceftazidime, mezlocillin, azlocillin, and tobramycin was evaluated against 188 isolates from bacteremic patients and 161 aminoglycoside-resistant gram-negative rods. Although some streptococcal (particularly enterococcal) blood isolates, Pseudomonas spp., and nonfermentative gram-negative rods were not inhibited by ciprofloxacin, it was nevertheless the most active compound tested against both microorganism groups.

Aminoglycosides↗

Comparison of inhibitory and bactericidal activity of antipseudomonal antibiotics against Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Using a broth microtiter dilution method, the minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of so-called antipseudomonal antibiotics were determined against 79 Pseudomonas aeruginosa isolates from cystic fibrosis patients. On the basis of the MIC values and using DIN breakpoints, the percentual susceptibilities led to the following rank order: imipenem (91%), ciprofloxacin (90%), tobramycin (87%), amikacin (87%), ceftazidime (82%), cefsulodin (76%), piperacillin (71%), azlocillin (62%), followed by gentamicin, ceftriaxone, mezlocillin, netilmicin, and cefotaxime (less than 50%). However, evaluating MBC values according to DIN breakpoints, only ciprofloxacin (82%), tobramycin (77%), amikacin (58%), and imipenem (57%) showed a pronounced antipseudomonal effectiveness. The data indicate that MBC determinations are necessary to evaluate the antibiotic susceptibility of P. aeruginosa rather than MIC determinations, at least in patients with impaired defence mechanisms which require bactericidal therapy.

Amikacin↗

Netilmicin plus ceftriaxone versus amikacin plus ceftriaxone in the treatment of infections in granulocytopenic patients.

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Adult↗

Pseudomonas cepacia: the sensitivity of nosocomial strains to new antibiotics.

Pseudomonas cepacia, considered a phytopathogenic organism for many years, has been shown recently to be widely distributed geographically. The hospital environment has become an important source of this organism but the resistance of Ps. cepacia to most antibiotics has made the treatment of infections a problem. One hundred per cent of the strains tested have proved to be sensitive to the sulphonamides and to novobiocin, 93.0% to the combination of trimethoprim and sulfamethoxazole (co-trimoxazole); 85.2% to minocycline; 77.8% to chloramphenicol and dibekacin and 44.4% to nalidixic acid. One hundred per cent of the strains exhibit resistance to ampicillin, cephalothin, cefamandole, cefoxitin, colistin, cefuroxime, tetracycline and cefazolin; 88.9% to amikacin, tobramycin and sisomycin; 85.2% to carbenicillin. The new beta-lactams, apalcillin, ceftazidime, N-formimidoyl-thienamycin, piperacillin, cefotaxime and azlocillin proved to be the most potent of the molecules tested, inhibiting 90% of the strains, at concentrations of 4, 8, 8, 8, 32 and 16 mg/l and 100% of the strains at 8, 16, 16, 32, 32 and 64 mg/l, respectively. In contrast to the usual sensitivity patterns of Pseudomonas spp, Ps. cepacia has been shown to be resistant to colistin, cefsulodin and the aminoglycosides. However, unlike Ps. aeruginosa, Ps. cepacia has been shown, by the dilution method, to be sensitive to co-trimoxazole, 92.3% of the strains being inhibited by 16 mg/l.

Anti-Bacterial Agents↗

Effect of ten new beta-lactam antibiotics on urine glucose test methods.

The effect of ten new beta-lactam antibiotics (cefoperazone, cefotaxime and its metabolite desacetylcefotaxime, ceftazidime, ceftizoxime, ceftriaxone, aztreonam, azlocillin, mezlocillin, piperacillin, and ticarcillin) on the accuracy of Clinitest, Diastix, and Tes Tape determinations of glycosuria was investigated. Solutions of each of the antibiotics were prepared in urine over a range of clinically obtainable drug concentrations. Urine samples from a healthy subject were used to prepare simulated diabetic urine by adding dextrose to achieve concentrations of 0.5%, 1%, and 2%. With penicillin derivatives, falsely elevated Clinitest readings generally were observed at lower glucose concentrations. When no glucose was present, cephalosporins and the monobactam, aztreonam, gave a dark green-black color that could only be interpreted as 0% on the Clinitest color chart. At higher urine glucose concentrations (1% and 2%), no interaction with Clinitest could be demonstrated, with the exception of a few falsely reduced readings. All urine solutions containing beta-lactam antibiotics were estimated accurately by both Diastix and Tes Tape. The unpredictability of the Clinitest-beta-lactam antibiotics interaction should discourage the use of this urine glucose test in patients who receive these drugs. The glucose-oxidase tests, Diastix and Tes Tape, may be used as qualitative tests for glycosuria in patients treated with beta-lactam antibiotics.

Adult↗

Natural antibiotic susceptibility of Enterobacter spp., with special reference to Enterobacter aerogenes and Enterobacter intermedius strains.

The natural susceptibility to 71 antibiotics of 44 strains of Enterobacter aerogenes and 12 strains of Enterobacter intermedius was examined using a microdilution procedure in Isosensitest broth (for all strains) and cation-adjusted Mueller Hinton broth (for some strains). Both species were naturally sensitive or sensitive and intermediate to tetracyclines, all tested aminoglycosides, several penicillins and cephalosporins, carbapenems, aztreonam, quinolones, folate-pathway inhibitors, chloramphenicol and nitrofurantoin. Uniform natural resistance was found to cefoxitin and to antibiotics to which most other Enterobacteriaceae are also intrinsically resistant, e.g. several macrolides, lincosamides, streptogramins and glycopeptides. Major species-specific differences in susceptibility affecting clinical assessment criteria were found with amoxycillin, amoxycillin-clavulanate, some narrow-spectrum cephalosporins and fosfomycin. With the exception of penicillin G, oxacillin and cefoxitin, E. intermedius was naturally sensitive or naturally sensitive and intermediate (azlocillin) to all beta-lactams tested. Natural antibiotic susceptibility patterns of E. aerogenes and E. intermedius were analyzed with regard to the underlying mechanisms. The data were compared with the results from two recent studies dealing with natural susceptibilities of other clinically-relevant Enterobacter spp. With reference to beta-lactam susceptibility patterns, it can be assumed that all human-affecting Enterobacter species examined produce species-specific, chromosomally-encoded beta-lactamases of the AmpC type. The naturally-expressed amount of enzyme depends on the species.

Anti-Bacterial Agents↗

The effect of heat upon the interaction between aminoglycosides and semi-synthetic penicillins in human serum: a consideration for HIV infectious serum.

We conducted 2 experiments to study the effect of heat on the interaction between aminoglycosides and semi-synthetic penicillins in human serum. In one experiment, human serum spiked with either gentamicin or tobramycin at a concentration of 4.7 mg/l plus carbenicillin, ticarcillin, piperacillin, mezlocillin, or azlocillin at concentrations of either 50 mg/l or 150 mg/l was subjected to a 30-min, 56 degrees C waterbath incubation. In the second experiment, randomly selected sera from patients receiving either gentamicin or tobramycin were also heat-treated. Two methods, the Abbott TDx and the Syva Emit, were used for each aminoglycoside assay. The difference between pre- and post-heat treatment aminoglycoside concentration was less than 10% in approximately 92% of the patient sera and in 93% of the spiked sera containing an aminoglycoside plus a semi-synthetic penicillin at 50 mg/l. For sera spiked with an aminoglycoside plus a semi-synthetic penicillin at 150 mg/l, post-heat treatment concentrations were 5-19% lower than pre-heat treatment concentrations. In most instances, heat treatment of sera does not alter aminoglycoside concentrations to any clinically significant degree.

Aminoglycosides↗

Pseudomonas aeruginosa infection in cancer patients.

Pseudomonas aeruginosa is an important cause of infection in immunosuppressed patients, particularly those with cancer. However, it is being recognized with greater frequency in patients who appear to be immunocompetent. Changes in modern lifestyles have led to the appearance of some new manifestations of pseudomonas infection including corneal ulceration and keratitis associated with contact lenses, and hot-tub- or whirlpool-associated folliculitis. These represent additional hazards to patients with cancer. Many studies, both in animals and humans, have contributed to our knowledge of the pathogenesis, immunology, treatment, and prevention of pseudomonas infections. Although the aminoglycosides represented a significant step forward in the treatment of these infections, of greater importance was the discovery of the antipseudomonal penicillins. These antibiotics are more effective than the aminoglycosides in neutropenic patients, who are especially susceptible to pseudomonal infections. The older antipseudomonal penicillins (carbenicillin, tircarcillin) have largely been replaced by newer ones (mezlocillin, azlocillin, pipercillin) which are more potent in vitro against P. aeruginosa. Although the accepted therapeutic practice has been to utilize a penicillin in combination with an aminoglycoside, the introduction of newer beta lactam agents and fluoroquinolones with antipseudomonal properties offers the possibility of other approaches to combination therapy. These include the combination of a penicillin or a cephalosporin or the combination of a quinolone with an aminoglycoside or a betalactam antibiotic. However, the development of newer antimicrobial agents is not likely to be a lasting solution to the problem of pseudomonas infections. Since pseudomonas infection often progresses rapidly, optimal results will always depend upon the prompt initiation of appropriate therapy in febrile patients, particularly those who are at high risk. The use of granulocyte transfusions has proved to be of limited benefit. Early data with the use of monoclonal antibodies is promising, and the results of large-scale trials are eagerly awaited. It is hoped that continuing investigation of pseudomonas vaccines will lead to the discovery of effective prophylaxis for highly susceptible patients. It is also hoped that with the availability of GM-CSF it will become possible to reduce the period of risk for serious infections. Finally, a reduction in the frequency of microbiologically proven P. aeruginosa infections in cancer patients should not lead to the assumption that these organisms do not constitute a problem in such patients anymore. The use of prophylactic antibiotics and prompt empiric antibiotic coverage for therapy has resulted in this decline. Cultures are therefore unlikely to be positive with the same frequency as they were before antimicrobial prophylaxis and empiric antibiotic therapy became standard practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Novel inhibitors of enkephalin-degrading enzymes. IV: Structure-activity relationships within the penicillins as enkephalinase inhibitors.

A range of penicillins have been examined as competitive reversible inhibitors of enkephalinase (neutral endopeptidase; EC 3.4.24.11). Carfecillin (Ki = 0.18 microM) was the most potent inhibitor in the series, whereas cloxacillin (27.5 microM), ampicillin (41.0 microM), nafcillin (58.7 microM) and carbenicillin (158 microM) had moderate potency and benzyl penicillin (885 microM), mezlocillin (473 microM) and azlocillin (556 microM) were weak inhibitors. Structure-activity relationships within the series have been rationalised from a consideration of molecular graphics analysis of the match between receptor binding groups with thiorphan as well as log P values.

Computer Graphics↗