Characters of phages from coagulase-negative staphylococci.
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Biomedical subjects
Publications and source records attributed to J Verhoef.
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We previously demonstrated that ciprofloxacin prevents infections caused by gram-negative bacilli in patients with granulocytopenia. However, in patients with intensive cytotoxic treatment leading to severe mucosal damage a high incidence of bacteremias caused by alpha-hemolytic streptococci was seen. In the present study 45 consecutive patients undergoing intensive cytotoxic treatment received a short course of roxithromycin (10 days) in addition to ciprofloxacin for prevention of bacteremias caused by alpha-hemolytic streptococci. The results of this study were compared with the results obtained in previous comparable patients receiving ciprofloxacin alone. During the days with addition of roxithromycin no infections caused by alpha-hemolytic streptococci occurred, while in the control group of 80 patients 16 bacteremias (20%) were seen. Although roxithromycin was shown to antagonize bactericidal action of ciprofloxacin on gram-negative bacilli in vitro, in vivo study based on serum bactericidal titers and on results of surveillance cultures showed no antagonistic interactions.
In a previous study we demonstrated that trimethoprim-sulfamethoxazole decreases the prevalence of infection in patients with severe granulocytopenia. However, treatment was accompanied by a relatively high incidence of multiresistant microorganisms. We therefore conducted this study to determine whether the addition of colistin to the trimethoprim-sulfamethoxazole regimen prevents the emergence of these resistant bacteria. Thirty consecutive adult patients with acute non-lymphocytic leukaemia received trimethoprim-sulfamethoxazole plus colistin p.o. prophylactically. The results of this study were compared with the results of our previously published controlled study. Trimethoprim-sulfamethoxazole plus colistin was as effective as trimethoprim-sulfamethoxazole in preventing infection. However, the addition of colistin significantly reduced the acquisition of and infection by gram-negative bacilli which were resistant to trimethoprim-sulfamethoxazole. Only two patients were colonized with resistant strains, and no infections with these strains were observed. We have concluded that patients with acute non-lymphocytic leukaemia should receive a combination of trimethoprim-sulfamethoxazole plus colistin prophylactically during remission induction treatment.
In a randomized study, 42 patients undergoing extensive maxillo-facial surgery (correction of the position of the mandible or maxilla by using autologous bone transplants) received prophylactically ten-day courses of either flucloxacillin or amoxicillin with clavulanic acid. Patients were comparable with regard to age and type of surgery. During the prophylactic treatment the effect of antibiotics used on the microbial flora of the alimentary tract was studied. Patients receiving flucloxacillin showed increased numbers of Klebsiella spp. isolated from the faeces (59% of the patients versus 19% of the patients receiving amoxicillin with clavulanic acid). Patients receiving amoxicillin with clavulanic acid showed higher colonization rates of oropharynx with Enterobacteriaceae than patients receiving flucloxacillin (ten patients versus five patients). 60% of those strains isolated from patients receiving amoxicillin with clavulanic acid were resistant to this combination, as compared to 20% of gram-negative bacilli isolated from patients receiving flucloxacillin. In 50% of patients receiving amoxicillin with clavulanic acid, colonization of the gut with yeast occurred, as compared to 18% of patients receiving flucloxacillin. Only one infection leading to a partial loss of the graft was seen in the group of patients receiving flucloxacillin.
In an open, randomized study, the effect of pefloxacin (400 mg b.i.d.) was compared with that of cefotaxime (1 g t.i.d.) in the treatment of complicated urinary tract infections. In total 87 patients entered the study under the clinical diagnosis of complicated urinary tract infection, of whom 49 were eligible for evaluation. Most isolates (90%) belonged to the family of Enterobacteriaceae. Isolates were eradicated from 96% (28/29) of patients treated with pefloxacin and 89% (16/18) of those receiving cefotaxime 48 h after the end of therapy. After one week a total of 92% (22/24) of patients treated with pefloxacin were culture negative, while in the group treated with cefotaxime a total of 82% (9/11) were culture negative. After four to six weeks, 68% (13/19) in the pefloxacin and 80% (8/10) in the cefotaxime study group showed a negative urine culture (difference non-significant; p greater than 0.5). Clinical cure at the end of treatment was 97% (30/31) in the pefloxacin group vs. 89% (16/18) in the cefotaxime group. Both groups showed similar relapse and reinfection rates at 48 h and one week after therapy. Adverse effects were mild and reversible for both drugs. It is concluded that pefloxacin is a safe and effective alternative for treatment of complicated urinary tract infection.
After intravenous dosing in dogs [3H-Lys9]-DE gamma E (Org 5878) was very rapidly eliminated from the circulation. Disappearance of the neuropeptide from blood followed a biphasic decay with half-lives of 0.6 +/- 0.1 min (+/- S.D.; alpha-phase) and 2.4 +/- 1.0 min (beta-phase). The central volume of distribution ranged between 0.05 and 0.23 l.kg-1. The mean blood clearance rate amounted to 0.15 l.min-1.kg-1, which is indicative of extensive hepatic and extrahepatic metabolism of DE gamma E. In contrast to intravenous dosing, subcutaneous injection of [3H]-DE gamma E in dogs resulted in low but relatively long-lasting peptide levels in blood. Peak values were found at 5-10 min, whereafter they declined to the limit of detection at 1.5-2 h. The bioavailability of DE gamma E for this route of administration was shown to be 20-23%.
Serum, fat and pelvic tissue levels of piperacillin or mezlocillin (patients randomly selected to receive one of both) were measured during surgery of 48 patients (mean age 55 years) with gynecologic cancer and related to the minimal inhibitory concentrations (MIC). Only during the first 3 hours the fat and pelvic tissue levels of these antibiotics were above the MIC levels (3 to 5 mg/l), while the serum reached marginal levels after 4 to 5 hours. Excessive blood loss (more than 1.500 ml) decreases the serum and fat levels; however, during the first 3 hours not below the MIC values. Single-dose prophylaxis with both antibiotics appeared fully effective in debulking surgery, total abdominal hysterectomy and radical hysterectomy. However, out of a group of 12 patients who underwent radical vulvectomy, 8 patients had postoperative infections.
Autoradiographic studies aimed at identifying target cells in the brain for ACTH-like peptides were performed using (3H-7-Phe)-4-Met(O2),8-D-Lys, 9-Phe-ACTH4--9, a behaviorally potent analog of ACTH4--9. The 3H-peptide was injected into the lateral ventricle of hypophysectomized rats that were sacrificed 5, 30, 60, 180, and 240 min later. Dry-mount autoradiograms of brain showed the highest density of silver grains in the ventricular lumen and choroid plexus. In addition, radioactivity penetrated brain tissue as far as 100 microns from the ventricles, and was distributed predominantly over neuropil. Within 5 min after the injection, an intracellular concentration of radioactivity above background levels was observed in a small proportion of cells near the ventricles in the septum, caudate-putamen, preoptic area, hypothalamus, thalamus, amygdala, and hippocampus. The cellular labeling decreased in intensity at greater distances from the injection site and at longer survival intervals, and was no longer evident 4 hr after the injection. The labeled cells were usually small, dark, and often elongated, suggesting that ACTH peptides may act preferentially upon a morphologically distinct class of cells in the brain.
Despite the dramatic decline in the infection-associated death rate as a result of advances in antimicrobial therapy, extensive diagnostic procedures, and better supportive care, morbidity from infectious disease in granulocytopenic patients remains a problem. Several approaches are used for infection prevention. The new oral fluorinated quinolones seem promising for the prevention of infections caused by gram-negative bacilli. Results from different studies showed that these compounds are more efficacious and better tolerated than are other prophylactic regimens. Prophylactic use of quinolones leads to trends in bacteriologically documented infections toward gram-positive microorganisms associated either with the presence of central intravenous catheters (Staphylococcus epidermidis) or with chemotherapy-induced mucositis (alpha-hemolytic streptococci). These changes suggest a need for the inclusion of an antibiotic effective against gram-positive organisms in the initial therapeutic regimen.
All adult patients with acute nonlymphocytic leukemia--either first diagnosed or in relapse--who were admitted to University Hospital (Utrecht) between 1 December 1978 and 1 November 1980 were randomly assigned to a control group or to a group that received trimethoprim-sulfamethoxazole (TMP-SMZ) prophylactically; those admitted between 30 November 1980 and 1 December 1981 received a regimen of TMP-SMZ plus colistin; those admitted from 1 December 1981 to 1 December 1983 were randomized to receive TMP-SMZ plus colistin or neomycin plus colistin; and those admitted after 1 December 1983 were randomized to receive either ciprofloxacin alone or TMP-SMZ plus colistin. All agents were capable of preventing infections. However, the use of TMP-SMZ alone led to an increase in the number of infections caused by multiresistant microorganisms. The combination of TMP-SMZ plus colistin was superior to that of neomycin plus colistin. The new quinolone derivative ciprofloxacin was more effective than TMP-SMZ and was well tolerated. Antimicrobial prophylaxis with agents that provide adequate levels of drug in tissue prevents infections in granulocytopenic patients and is superior to that with nonabsorbable agents.
During the years 1979 to 1981 we experienced an increasing incidence of septicemia due to coagulase-negative staphylococci in the neonatal intensive care unit (NICU). A detailed analysis was performed for the 1981 NICU population. More than 90% of cases occurred in premature infants of low birth weight (less than 2500 g). All septicemic infants were receiving intravenous therapy and total parenteral nutrition (TPN) solutions had been administered to nearly 80% just before or during the septic episode. A case-control study performed for the 1981 NICU population, which included 26 proved cases of coagulase-negative staphylococcal septicemia and 26 matched controls, did not uncover any differences in underlying diseases or modes of treatment between cases and controls. However, the infusion of contaminated TPN fluids was identified as a significant risk factor. Random bacteriological checks of TPN fluids revealed that nearly 20% of these solutions were contaminated, mainly with coagulase-negative staphylococci. The incidence of staphylococcal septicemia in infants who had received contaminated TPN fluids was 10-fold higher than in infants who had received sterile solutions (P less than 0.0005). The majority of coagulase-negative staphylococci isolated from the blood cultures from the NICU were multiply resistant to antibiotics although all isolates were susceptible to cephalothin. Treatment, consisting of removal or replacement of the intravenous devices and the administration of cephalothin and fresh plasma, was universally successful.
The respiratory tract is continuously exposed to inhaled particles. The mucous membrane and the mechanisms of sneezing, coughing, and mucociliary clearance are the first line of defense. For the bronchioli and alveoli, the phagocytic cells are the cornerstone of defense against invading microorganisms. Alveolar macrophages and polymorphonuclear leukocytes are responsible for phagocytosis. For optimal phagocytosis, antibodies and complement are needed; phagocytic cells possess receptors for the Fc fragment of the immunoglobulin (IgG) molecule and complement. Receptors for cytokines are also present. These cytokines are important for activating the alveolar macrophage and recruiting other phagocytic cells and lymphocytes to the site of infection. Alveolar macrophages also contain cytophilic antibodies, IgG molecules that are bound to the cell via the F(ab)2 fragments. These cytophilic antibodies can interfere with the process of phagocytosis. They can bind to bacteria containing an Fc receptor (eg, Staphylococcus aureus protein A) and therefore provide the alveolar macrophage with a means to bind and digest staphylococci. Pulmonary surfactant proteins enhance the uptake of bacteria and viruses by alveolar macrophages and viruses. Thus surfactant contributes to the defense mechanisms of the lung. Phagocytic cells can injure alveoli. During the process of phagocytosis, toxic oxygen species and enzymes, needed for killing bacteria, are produced. These toxic substances may leak out of the cell and damage the surrounding tissues. All these phenomena contribute to the processes of inflammation. The function of phagocytic cells is decreased in smokers and by certain air pollutants. Phagocytic cells are crucial for the elimination of microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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