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PubMed1985

Review of amikacin usage in the EORTC trials.

Four trials have been conducted by the European Organization for Research and Treatment of Cancer's International Antimicrobial Therapy Project Group. These studies involve the randomized assignment of febrile neutropenic patients to receive various antibiotic combinations. The past three trials have utilized amikacin in combination with a variety of beta-lactam antibiotics to provide activity against the most commonly isolated pathogenic bacteria in this clinical setting. Amikacin in combination with expanded-spectrum beta-lactam agents is likely to remain useful in treating infections in granulocytopenic patients.

Agranulocytosis↗
PubMed1985

Aspects of clinical trials with ceftazidime worldwide.

Overall results from worldwide clinical studies of ceftazidime in open and comparative trials conducted over a four-year period in North America, Europe, and elsewhere are presented. Data from 3,570 patients treated with ceftazidime in open studies and from 1,340 patients receiving ceftazidime and 1,180 patients receiving other antibiotics in comparative studies are discussed. The comparative antibiotics consisted of aminoglycosides alone in 14.2 percent of patients, aminoglycosides combined with one or two beta-lactams in 43 percent, beta-lactams alone in 34 percent, and other antibiotic combinations in 8.8 percent. In comparative studies, bacterial clearance rates were 80.6 percent for ceftazidime and 72.5 percent for other antibiotics. Clinically, 92.6 percent of the infected sites in ceftazidime-treated patients in open studies were cured or improved, and 91.1 percent were cured or improved in comparative studies; 84.8 percent of the infected sites were cured or improved in patients treated with other antibiotics. Data indicate that ceftazidime monotherapy is as effective as combination antibiotic therapy in the empiric treatment of febrile non-neutropenic patients. The role of ceftazidime monotherapy in the treatment of febrile neutropenic patients is not yet firmly established. Superinfections were reported in 2.6 percent of the patients treated with ceftazidime alone in open trials, in 4.2 percent of the patients treated with ceftazidime alone in comparative trials, and in 8.5 percent of the patients treated with other antibiotics. During treatment, the sensitivity of bacteria to ceftazidime decreased in 2.5 percent of the pathogens isolated. Adverse events occurred in 10.2 percent of patients treated with ceftazidime in open studies, in 8.4 percent of those treated with ceftazidime in comparative studies, and in 8.8 percent of those treated with other antibiotics. The adverse events in both ceftazidime- and control-treated patients were thought by the investigators to be drug-related in about 40 percent of cases, not drug-related in 20 percent of cases, and of unknown etiology in the remaining cases.

Bacterial Infections↗
PubMed1987

Treatment of urinary tract infection with norfloxacin. Analysis of cost.

Twenty-five patients with urinary tract infection were treated with norfloxacin, a fluoroquinolone antibacterial with a wide spectrum of activity for an oral agent. Of 22 patients who were evaluable, 20 had complicated urinary tract infection; infection was cured in 19 patients at one week after treatment. Optimal alternative treatments were also selected in norfloxacin's stead, based on each patient's characteristics and the results of susceptibility testing for each isolated pathogen. Direct costs for alternative treatment ranged from $7 to $970. The results indicated that for those patients with suspected or proven urinary tract infection caused by multiresistant bacteria, therapy with norfloxacin may represent a cost-effective choice.

Adult↗
PubMed1987

Osteomyelitis in the feet of diabetic patients. Long-term results, prognostic factors, and the role of antimicrobial and surgical therapy.

Fifty-one diabetic patients with osteomyelitis of the foot were studied to determine potential prognostic factors and the role of antimicrobial therapy. Most of the patients were elderly, with diminished pulses, a sensory neuropathy, and a polymicrobial infection. Twenty-seven patients had a good outcome, defined as clinical resolution at the time of the last follow-up examination, without the need for amputation. The mean duration of follow-up for these patients was 19 months. Fifteen patients had a below-knee amputation, and nine had a toe amputation. The absence of necrosis and/or gangrene, the presence of swelling, and the use of antimicrobial therapy active against the isolated pathogens for at least four weeks intravenously, or combined intravenously and orally for 10 weeks, predicted a good outcome. Diabetic foot osteomyelitis, in the absence of extensive necrosis or gangrene, usually responds to antimicrobial therapy without the need for an ablative surgical procedure.

Amputation, Surgical↗
PubMed1989

Ciprofloxacin (intravenous/oral) versus ceftazidime in lower respiratory tract infections.

The efficacy and safety of intravenous ciprofloxacin was compared with intravenous ceftazidime in 80 hospitalized patients with lower respiratory tract infection. There were 40 patients in each treatment group. Patients and physicians were blinded to the randomized scheme for treatment groups until patient consent was obtained. The 37 evaluable ciprofloxacin-treated patients received 200 mg every 12 hours intravenously as initial therapy and 29 completed their course receiving oral ciprofloxacin. The 34 evaluable ceftazidime-treated patients received 1 to 2 g intravenously every eight to 12 hours. The two groups did not differ with respect to patient age, infection severity, and admitting diagnosis. Clinical outcomes were similar with greater than 95 percent of treatments in each group being successful. Headache was the most commonly reported complaint (four patients) in the ciprofloxacin group. Three patients experienced substantial increases in serum theophylline concentrations while receiving ciprofloxacin. The predominant pathogens isolated were Haemophilus influenzae and Pseudomonas aeruginosa, and susceptibility rates for all organisms were similar for both drugs. The mean peak serum concentration at steady state while receiving intravenous ciprofloxacin was 2.3 micrograms/ml, and the mean trough concentration was 0.5 micrograms/ml. Patients randomly assigned to ciprofloxacin therapy received 2.6 fewer days of intravenous antibiotic therapy than those receiving ceftazidime. This 80-patient comparative trial demonstrates that ciprofloxacin and ceftazidime are similar in efficacy and safety when treating gram-negative lower respiratory tract infections. There appears to be potential for cost-reducing benefits through decreased length of intravenous therapy and earlier hospital discharge.

Administration, Oral↗
PubMed1989

Randomized, double-blind comparative study of intravenous ciprofloxacin versus ceftazidime in the treatment of serious infections.

We compared intravenously administered ciprofloxacin with ceftazidime in a randomized, double-blind study. Patients received ciprofloxacin 200 mg intravenously every 12 hours or ceftazidime 2 g intravenously every eight hours, with placebo infusions to maintain blinding. Therapy with metronidazole was added for suspected or documented intra-abdominal infection. Thirty-two of the 57 ciprofloxacin-treated patients were evaluable for determination of efficacy and had 41 bacterial isolates from 34 sites. Thirty-six of the 56 ceftazidime patients were evaluable for determination of efficacy and had 41 bacterial isolates from 38 sites. Seven of 35 bacteremic patients had no identifiable primary focus. The most commonly isolated pathogens were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Cure rates and bacteriologic eradication rates were comparable. Nine patients did not improve. Patients with treatment failures in the ciprofloxacin group included a quadriplegic patient with relapse of urinary tract infection with bacteremia (K. pneumoniae). Another patient with bacteremia (Pseudomonas aeruginosa), pneumonia (Proteus vulgaris), and urinary tract infection (P. vulgaris, Providencia sp.) died on the first treatment day. The third patient (S. aureus and Streptococcus pneumoniae pneumonia) had a new aspiration pneumonia develop on the third day; the pneumococcus also persisted. Undrained S. pneumoniae empyema caused the fourth ciprofloxacin treatment failure, and the fifth patient had a relapse of S. aureus pneumonia with bacteremia. One ceftazidime-treated patient died of pneumococcal pneumonia on the first day. Another had persistent Staphylococcus epidermidis and Listeria bacteremia despite 48 hours of treatment. Two other patients had pneumonia (S. aureus and P. aeruginosa, respectively) and completed full courses of ceftazidime therapy without improvement. Five patients had pneumococcal bacteremia; four patients were cured: one of two patients in the ciprofloxacin group and three of three patients in the ceftazidime group. Significant increases in the number of platelets (four patients with ciprofloxacin treatment, one patient with ceftazidime treatment) and declines in the number of platelets (one patient with ciprofloxacin treatment, one patient with ceftazidime treatment) were observed. Intravenously administered ciprofloxacin is comparable with ceftazidime and is a safe and effective antibiotic for the treatment of patients with serious infections, including bacteremia.

Bacterial Infections↗
PubMed1989

Intravenous ciprofloxacin and ceftazidime in serious infections. A prospective, controlled clinical trial with third-party blinding.

Oral ciprofloxacin has been shown to be effective in the treatment of infections due to gram-positive cocci and gram-negative rods. The efficacy and safety of intravenous ciprofloxacin was compared with that of intravenous ceftazidime in the treatment of 59 patients with well-documented serious infections in a prospective, controlled, randomized study with a third-party blinding. Thirty-three patients were treated with intravenous ciprofloxacin (200 mg every 12 hours, plus a daily extra placebo dose); 26 patients were treated with ceftazidime (1 g every eight hours). The severity of the infections, underlying diseases, and demographic features were comparable in both groups, although there were more men in the ciprofloxacin group. For ciprofloxacin/ceftazidime treatments, respectively, the evaluated infections were: pyelonephritis (16 patients/nine patients), pneumonia (three/five), soft-tissue infections (four/zero), spontaneous peritonitis (five/two), primary bacteremia (three/eight), and other (two/two). Isolated pathogens included: Escherichia coli (22/12), Klebsiella sp. (five/four), Pseudomonas aeruginosa (two/three), Haemophilus influenzae (one/one), Proteus mirabilis (two/zero), Proteus vulgaris (one/zero), Salmonella sp. (zero/two), Plesiomonas shigelloides (one/zero), and others (one/four). The clinical responses were cure or improvement in 31 ciprofloxacin cases/21 ceftazidime cases; failure, zero/four; and indeterminate, two/one. The bacteriologic responses were eradication in 28 ciprofloxacin cases/22 ceftazidime cases; persistence, one/three; and indeterminate, four/one. Mild intolerance occurred in three ciprofloxacin cases and two ceftazidime cases. A mild increase in serum hepatic enzymes was observed in two patients in each group. Superinfections occurred in five patients: enterococcal septicemia (zero/two) and urinary tract infections (one/two). The results presented suggest that intravenous ciprofloxacin is an effective and safe antimicrobial agent for the treatment of serious infections, with an efficacy comparable with that of ceftazidime, a broad-spectrum cephalosporin. An additional advantage seems to be a lower rate of superinfections.

Adolescent↗
PubMed1990

Acute diarrhea in developed countries. A rationale for self-treatment.

Acute diarrhea is a common, nonlethal condition that causes frequent inconvenience and economic loss. People rarely consult physicians for this problem. Epidemiologic studies among adults, hospitalized adults, children attending day care centers, homosexual men, and travelers indicate a wide spectrum of etiologic agents. The clinical presentation of acute diarrhea may lead clinicians to consider certain causative agents, but it is not diagnostic of any specific cause. Clinical laboratory studies can detect or isolate pathogens in only a minority of cases. By the time this information is available, patients have usually recovered. For these reasons, early self-treatment aimed at reducing symptoms of acute diarrhea is recommended.

Antidiarrheals↗
PubMed1991

Clinical and economic evaluation of oral ciprofloxacin after an abbreviated course of intravenous antibiotics.

PURPOSE: Oral ciprofloxacin has the requisite pharmacokinetic and antibacterial properties to rival the potency of intravenous antibiotics. This study was designed to determine whether oral ciprofloxacin could abbreviate the course of intravenous antibiotics in the treatment of serious infections. PATIENTS AND METHODS: Hospitalized adult patients were eligible for enrollment if they had a serious infection that was expected to require 8 or more days of intravenous antibiotic treatment. After conventional intravenous antibiotics were administered for 3 days, informed consent was obtained and patients were randomly assigned to either continue parenteral antibiotics (n = 53) or switch to oral ciprofloxacin 750 mg taken twice daily (n = 52). Ninety-nine of the 105 patients were evaluable for the assessment of efficacy. Clinical and bacteriologic efficacy, adverse events, and costs of the two treatments were compared. RESULTS: The two treatment groups were comparable for demographic characteristics, types of infections, bacteria isolated, initial intravenous antibiotic regimens, and duration of antibiotic treatment. The most common infections were of the skin and skin structure; bacteremia and infections of the lower respiratory tract, urinary tract, and bone and joint were also represented. The most commonly isolated pathogens were Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The most frequently prescribed intravenous antibiotics before randomization included aminoglycosides, cephalosporins, vancomycin, and nafcillin; 52 evaluable patients were treated with combination therapy while 47 received monotherapy. The clinical and bacteriologic outcomes and adverse reaction frequency with oral ciprofloxacin were comparable to those of the continued intravenous antibiotic regimens. Ciprofloxacin was associated with an average cost savings of $293 per patient. CONCLUSION: When used after 3 days of intravenous antibiotics, oral ciprofloxacin was as safe and effective as full courses of intravenous antibiotics and provided substantial cost savings.

Administration, Oral↗
PubMed1991

Nosocomial infections in elderly patients in the United States, 1986-1990. National Nosocomial Infections Surveillance System.

We analyzed 101,479 nosocomial infections in 75,398 adult patients (greater than 15 years) that were reported to the National Nosocomial Infections Surveillance (NNIS) system between 1986 and 1990 by 89 hospitals using the NNIS hospital-wide surveillance component. Overall, 54% of the infections occurred in elderly patients (greater than or equal to 65 years). In the elderly, 44% of the infections were urinary tract infections (UTIs), 18% were pneumonias, 11% were surgical wound infections (SWIs), 8% were bloodstream infections (BSIs), and the remainder were infections at other sites. When we compared the infections in elderly patients with those in younger adult patients, ages 15 to 64 years, a far greater percentage of the infections in elderly patients were UTIs, and there were more pneumonias than SWIs. Elderly and younger patients with ventilator-associated pneumonia were about 1.5 times more likely to develop a secondary BSI than those with pneumonia not associated with ventilator use. When the pathogens isolated from the infections were compared to those reported to the NNIS system in 1984, the percentage that were coagulase-negative staphylococci had increased in both elderly and younger patients. The patient died in 12% of all of the infections. Surveillance personnel reported that 54% of the infections in elderly infected patients who died were related to death compared with 59% in younger infected patients who died. When the infection was related to the patient's death, it was most often pneumonia or a BSI. The risk of an infection-related death was significantly higher when the infected patient developed a secondary BSI. Infection prevention efforts should target infections that occur frequently, are amenable to intervention, and have an adverse outcome.

Age Factors↗
PubMed1990

Structure of syringotoxin, a bioactive metabolite of Pseudomonas syringae pv. syringae.

The covalent structure of syringotoxin, a bioactive metabolite of Pseudomonas syringae pv. syringae isolates, pathogenic on various species of citrus trees, has been deduced from 1D and 2D 1H- and 13C-NMR spectra combined with extensive FAB-MS data and results of some chemical reactions. Similarly to syringomicins and syringostatins, produced by other plant pathogenic strains of P. syringae pv. syringae, syringotoxin is a lipodepsinonapeptide. Its peptide moiety corresponds to Ser-Dab-Gly-Hse-Orn-aThr-Dhb-(3-OH)Asp-(4-Cl)Thr with the terminal carboxy group closing a macrocyclic ring on the OH group of the N-terminal Ser, which in turn is N-acetylated by 3-hydroxytetradecanoic acid.

Amino Acid Sequence↗
PubMed1991

Evaluation of mortality in surgical neonates over a 10-year period: nonpreventable, permissible, and preventable death.

The mortality pattern and causes of death in surgical neonates were evaluated over the period of 1980 through 1990 in order to assess whether any deaths might have been prevented. In the study period 1,010 neonates were admitted, 104 of whom died (10%). These 104 neonates formed our study population. The Clinical Classification System (CCS) and the Therapeutic Intervention Scoring System (TISS) were used to assess the severity of illness. All 104 nonsurvivors were seriously ill (CCS 3 and 4; TISS greater than 20). The mortality pattern was classified in three groups. Group A (nonpreventable death) included 56 deaths, 48 of which were due to the underlying disease. The other 8 patients died of a nonpreventable complication of treatment. Eleven of the patients in group B (permissible death) had (multiple) congenital anomalies associated with chromosomal anomalies. Three of them were not treated and in the other 8 treatment was initially started but later withdrawn. In most of the other 14 patients further treatment was withdrawn because of serious postoperative complications or inoperable cardiac anomalies. Group C (preventable death) consisted of 23 patients. Six of 10 had irreversible brain damage due to prolonged hypoxemia. In the other 13 patients of group C, death was due to sepsis acquired in the postoperative period and treated inadequately. Staphylococcus epidermidis was the most frequent isolated pathogen (7/13).

Cause of Death↗
PubMed1990

Diagnosis and management of pyogenic vertebral osteomyelitis in adults.

Management of vertebral osteomyelitis remains controversial regarding optimum duration of antibiotic therapy and the role of surgery. Forty adults with vertebral osteomyelitis were reviewed. Staphylococcus aureus was the most common pathogen isolated. Disk space narrowing with end-plate erosion was the earliest finding, followed by progressive vertebral body destruction. Magnetic resonance imaging proved extremely valuable in detecting spinal cord compression in patients with neurologic deficit. Treatment should include at least 8 weeks of intravenous antibiotics combined with immobilization for pain reduction. Surgical intervention is indicated for all patients with neurologic deficit. Serial erythrocyte sedimentation rates are valuable for following response to therapy. The value of magnetic resonance imaging in diagnosis is emphasized.

Adult↗
PubMed1992

Multicenter open-label study of parenteral ofloxacin in treatment of pyelonephritis in adults.

The efficacy and safety of parenteral ofloxacin were evaluated in an open, multicenter study of hospitalized patients with pyelonephritis. The patients received ofloxacin 400 mg IV as an initial dose followed by ofloxacin 200 mg IV b.i.d. for a minimum of three days. The patients could then continue ofloxacin orally 200 mg b.i.d. for a total of seven to fourteen days. The most common pathogens isolated were Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. Microbiologic eradication was achieved in 65 of 66 evaluable patients (98%), and clinical cure or clinical improvement was noted in all patients. Of 82 patients evaluable for safety, 12 (15%) reported drug-related adverse events, the most frequent of which was pruritus or rash. None of the patients experienced drug-related central nervous system symptoms. Ofloxacin is well tolerated and highly effective in the treatment of pyelonephritis.

Administration, Oral↗
PubMed1994

Arabidopsis mutants simulating disease resistance response.

We describe six Arabidopsis mutants, defining at least four loci, that spontaneously form necrotic lesions on leaves. Lesions resemble those resulting from disease, but occur in the absence of pathogen. In five mutants, lesion formation correlates with expression of histochemical and molecular markers of plant disease resistance responses and with expression of genes activated during development of broad disease resistance in plants (systemic acquired resistance [SAR]). We designate this novel mutant class Isd (for lesions simulating disease resistance response). Strikingly, four Isd mutants express substantial resistance to virulent fungal pathogen isolates. Isd mutants vary in cell type preferences for lesion onset and spread. Lesion formation can be conditional and can be induced specifically by biotic and chemical activators of SAR in Isd1 mutants.

Arabidopsis↗
PubMed1990

Life threatening Branhamella catarrhalis pneumonia in young infants.

Branhamella catarrhalis is a common nasopharyngeal commensal organism but is also a recognised pathogen. Lower respiratory tract infections caused by this organism have been reported in adults but not, to our knowledge, in otherwise healthy infants. Two infants, born prematurely, suffered near fatal pneumonia. Branhamella catarrhalis was the only microbial pathogen isolated in each case. We suggest that initial antibiotic therapy for severe pneumonia in young infants should be tailored to cover B. catarrhalis infection.

Humans↗
PubMed1992

Urinary-tract infections in African neonates.

During a 4-year period between January 1987 and December 1990, 41 high-risk neonates with proven urinary tract infections (UTIs) were studied prospectively and compared with 55 control neonates. An incidence of 2.6 UTIs per 1000 live births was noted, amongst whom no obvious radiological abnormalities of the urinary tract were found. Significantly, more males than females developed UTIs, the ratio being 4.5:I. Low-birth-weight babies were significantly more often affected than those of normal weight (P less than 0.05). Staphylococcus aureus and Klebsiella spp. were the predominant pathogens isolated. Aetiologically, bacteraemia from sepsis was important. Most of the infants presented with a significantly higher incidence of pyrexia, abdominal distension, lethargy and jaundice (P less than 0.01). The overall mortality rate of 17.1% was closely related to these associated problems. The relatively high incidence of UTI and the rarity of radiological abnormalities of the urinary tract in the African neonate contrast with previous reports in the literature and the reason is worthy of consideration. Despite the rarity of urinary-tract anomalies, a continuous surveillance of the trend of neonatal UTI and its outcome is recommended.

Bacterial Infections↗
PubMed1988

Presence of natural suppressor cells in the chicken embryo spleen and the effect of virus infection of the embryo on suppressor cell activity.

Spleen cells but not the thymus or the bursa cells of chicken embryos suppressed the in vitro mitogenesis of spleen cells of adult syngeneic or allogeneic chickens. The natural suppressor cell activity of embryo spleen was present at embryonation day 16, reached peak levels at embryonation day 18 and disappeared at hatch. The embryo spleen cells did not by themselves respond to phytohemagglutinin stimulation in vitro. The suppressive effect of embryonic spleen cells on adult spleen cells was present when the embryonic cells were added at the time of or after initiation of the adult spleen mitogenic cultures. When the embryonic cells were added to the cultures of adult spleen cells after the blastogenic response of the adult cells had peaked, the embryonic cells inhibited the incorporation of the label into adult spleen cell blasts. The suppressive activity of the embryonic spleen cells was mediated by soluble suppressor product(s) secreted by these cells, and direct cell-to-cell contact between embryonic and adult spleen cells was not necessary for suppression to occur. Infection of embryos with turkey herpesvirus and Marek's disease virus reduced the suppressor cell activity of embryonic spleen, although substantial residual suppressor cell activity remained in virus-infected embryos. Several pathogenic or non-pathogenic isolates of infectious bursal disease virus did not appreciably alter the suppressor cell activity of embryonic spleen cells.

Animals↗