Biomedical subjects

M L Corrado

Publications and source records attributed to M L Corrado.

At least 19 recordsLinked to original sources

PubMed1992

Evaluation of new anti-infective drugs for the treatment of acute infectious diarrhea. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline includes diarrhea causing infantile mortality in which a bacterial pathogen is recovered and for which oral rehydration therapy is an important component of care as well as traveler's diarrhea (with or without recovery of a pathogen). Diarrhea is defined as the passage of three or more unformed stools per day plus--in all patients except infants--one or more signs or symptoms of enteric infection. The preferred study design is prospective and randomized, with an active concurrent control and (when possible) blinding. Placebo-controlled trials may be performed if the severity of disease is judged by the investigator to be mild or moderate. It is desirable that both clinical and microbiological outcome be determined. Microbiological eradication is paramount.

Acute Disease↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of typhoid fever. Infectious Diseases Society of America and the Food and Drug Administration.

Typhoid fever is an acute febrile illness caused by Salmonella typhi. The evidence of blood-borne infection required for study entry includes clinical signs and symptoms plus confirmation of the presence of S. typhi in blood or other tissues or body fluids. The preferred study design is prospective and randomized with an active concurrent control. It is preferred that the investigator or an evaluator be blinded to therapy. In general, treatment should be administered for 2 weeks until it is demonstrated that a shorter course is as efficacious and as safe. Follow-up cultures of specimens from sites originally shown to be infected with S. typhi should be performed unless the diagnostic procedure places the patient at unnecessary risk.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of cholera. Infectious Diseases Society of America and the Food and Drug Administration.

Cholera is an acute gastrointestinal infection caused by Vibrio cholerae. It is characterized by watery diarrhea that may lead to massive fluid loss, which in turn may result in hypotension, shock, and death within hours. Key to the treatment of cholera is fluid replacement. Anti-infective therapy decreases the severity and duration of diarrhea and the duration of shedding of V. cholerae. Enrolled patients should have diarrhea that is moderate to severe and a culture that ultimately yields V. cholerae. A prospective, randomized, active-controlled clinical trial is preferred. Studies should be double-blinded or evaluator-blinded. The rapidity with which the organism is eliminated from stool may be assessed. Both clinical and microbiological outcome should be determined. Assessment of microbiological eradication is paramount, since fluid replacement may suffice for treatment of signs and symptoms.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Giardia lamblia. Infectious Diseases Society of America and the Food and Drug Administration.

Giardia lamblia is a flagellate protozoan that produces symptoms by infecting the small bowel and biliary tract in the trophozoite form. Diagnosis is currently established by microscopic visualization of the organism in appropriate intestinal contents (stool, small-bowel contents, or biopsy specimen). Adult patients with diarrhea and one or more enteric symptoms may be enrolled in clinical trials of new drugs for the treatment of giardial disease. A randomized, double-blind, active-concurrent-control design is recommended. Post hoc stratification by age, immune status, chronicity of disease, and ease of establishing diagnosis (organism load) may be performed. Microbiological assessment 48 hours to 7 days after the completion of therapy is paramount for determining final outcome.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Cryptosporidium. Infectious Diseases Society of America and the Food and Drug Administration.

Cryptosporidium is a coccidian protozoan that produces symptoms by infesting the small bowel. The illness is characterized by watery stools, anorexia, weight loss, and abdominal pain. Diagnosis is made by visualization of the organisms on microscopic examination of stool. There currently is no approved therapy for this infection. A randomized, double-blind, placebo-controlled study design is recommended. Stratification of patients by age and immune status should be considered. Two stool samples obtained 48 hours to 7 days after completion of therapy should be negative for Cryptosporidium oocysts. Assessment of microbiological outcome is paramount.

Adolescent↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Entamoeba histolytica. Infectious Diseases Society of America and the Food and Drug Administration.

Entamoeba histolytica causes colonic infection that ranges from asymptomatic carriage to invasive disease with infection of extraintestinal organs, particularly the liver. The disease occurs in both sporadic and epidemic forms. Diagnosis requires visualization of trophozoites or cysts by microscopic examination of stool, colonic scrapings, or biopsy specimens. Patients with either asymptomatic or symptomatic disease may be eligible for clinical trials. A prospective, randomized, double-blind, placebo-controlled study design is recommended for asymptomatic carriers and an active-concurrent-control study design for symptomatic patients. Final outcome should be assessed 48 hours to 7 days after completion of therapy. Assessment of microbiological outcome is paramount.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of chronic carriage of Salmonella. Infectious Diseases Society of America and the Food and Drug Administration.

The chronic carriage of salmonellae is defined as the shedding of a Salmonella species for > or = 1 year, as documented by an initial positive culture of a stool sample obtained at least 1 month after resolution of the acute illness and repeated positive cultures for at least 1 year. Clinical trials of investigational anti-infective drugs for the treatment of the salmonella carrier state may be conducted with a placebo control or an active concurrent control. A crossover design also may be employed for establishing efficacy. Patients should generally receive therapy for at least 6 weeks. Outcome will be assessed only by microbiological criteria. Determination of the interval required for the suppression of salmonellae and follow-up for 6 months after completion of therapy are recommended.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of antibiotic-associated colitis. Infectious Diseases Society of America and the Food and Drug Administration.

Colitis due to Clostridium difficile is diagnosed in 10%-15% of hospitalized patients who develop diarrhea after treatment with antimicrobial drugs. Diagnosis is based on the concurrence of diarrhea, one or more signs or symptoms of enteric intoxication, and stool from which toxigenic C. difficile is isolated or from which its toxins are identified. Clinical trials evaluating therapy may be placebo controlled (for mild disease) or concurrently controlled with an active drug. A randomized, double-blind study design is preferred. Outcome should be assessed by monitoring of the degree of inflammation of the bowel mucosa, the intensity and severity of diarrhea, the duration of illness, changes in stool form, and the eradication of C. difficile or its toxins from stool. Because C. difficile can be a component of the normal gastrointestinal flora, assessment of clinical outcome is paramount.

Anti-Bacterial Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of gastritis and peptic ulcer disease associated with infection by Helicobacter pylori. Infectious Diseases Society of America and the Food and Drug Administration.

Helicobacter pylori is a gram-negative, microaerophilic, spiral bacillus. Infection by this organism is currently believed to be the major cause of type B gastritis. Inflammation and infection may persist for years in the absence of therapeutic intervention. There is currently no approved antimicrobial therapy for gastritis. Clinical investigations have shown that combination regimens including bismuth salts and antimicrobial drugs result in the relief of symptoms, the resolution of histologic evidence of gastritis, the eradication of H. pylori, high rates of ulcer healing, and lower rates of ulcer relapse than have been found with other therapies (antacids and H2 antagonists). A randomized, double-blind, placebo-controlled study design is recommended for evaluation of new therapies. Study participants should have their progress monitored by endoscopy performed at enrollment, at completion of therapy, and 3 months thereafter. Assessment of microbiological outcome is paramount for final evaluation of the patient.

Anti-Bacterial Agents↗

PubMed1991

The clinical experience with ofloxacin in the treatment of sexually transmitted diseases.

Sexually transmitted diseases are an important cause of morbidity in women. Some of the common causes of sexually transmitted disease include Neisseria gonorrhoeae, Chlamydia trachomatis, and in some patients Ureaplasma urealyticum. N. gonorrhoeae has become more resistant to traditional therapies including penicillin. Resistance to penicillin is mediated by the elaboration of beta-lactamase for most organisms and by chromosomal resistance in others. Resistance to tetracycline and spectinomycin has been clearly identified, as has an increase in the minimum inhibitory concentrations to some cephalosporins. Because of the potential for concomitant infection with N. gonorrhoeae and C. trachomatis, many patients are currently treated with a combination of a single dose of ceftriaxone plus a tetracycline for 7 days. Therefore it is significant that a single agent, ofloxacin, has been introduced recently for the treatment of such mixed infections. It also has the potential for treating N. gonorrhoeae resistant to other drugs.

Chlamydia Infections↗

PubMed1991

Worldwide clinical experience with ofloxacin in urologic cases.

Ofloxacin is a quinolone carboxylic acid with a broad spectrum of activity for gram-negative pathogens that are common causes of urologic infections including cystitis, pyelonephritis, and prostatitis. The data in this publication will review clinical trials in urologic infections as well as the literature which dates from January 1983 through February 1989. The database includes over four hundred reports from nineteen foreign countries and involves data from more than 21,000 patients. The data from the United States were accumulated in clinical trials conducted between 1984 and 1988. Ofloxacin has certain attributes that make it a potentially useful drug in the treatment of urologic infections. These include the high bioavailability from oral administration and the fact that the product is excreted almost entirely by the kidney, primarily as the active parent compound. Urinary levels of ofloxacin two to four hours postadministration can achieve concentrations above 600 micrograms/mL after a single 400-mg dose. Urinary levels twenty-four hours after a single dose are noted to be typically around 50 micrograms/mL. Both of these concentrations are well above the minimum inhibitory concentration (MIC90) for uropathogens, which might be below 1 microgram/mL for many uropathogens. With respect to the prostate, ofloxacin penetrates prostatic tissues well and can achieve concentrations of approximately 4.5 micrograms per gram of prostate tissue as a mean peak level. Prostate levels ten hours postdose will typically be approximately 2.7 micrograms per gram of prostatic tissue. These levels exceed the MIC90 for the majority of prostatic pathogens as well.

Female↗

PubMed1990

Review of the efficacy of oral norfloxacin in pyelonephritis and nosocomial urinary tract infection.

One hundred thirty-eight patients with pyelonephritis were treated with norfloxacin, 400 mg twice daily. Women accounted for 74% of cases, and Escherichia coli was the predominant pathogen, accounting for 51% of organisms. Tests for antibody-coated bacteria (ACB) were performed in 48% of patients, and 72% (48 of 67) were positive. Forty percent of the patients had temperatures greater than 37.6 degrees C at the time of study entry. Patients who had both fevers and positive ACB tests had cure rates similar to those of afebrile, ACB-negative patients. Norfloxacin was also highly effective in the treatment of multiply resistant, nosocomial urinary tract infections (UTIs), in which Pseudomonas aeruginosa and E. coli predominated. It is concluded that, when used appropriately, i.e., in nonbacteremic patients who are able to absorb oral drugs, norfloxacin is a highly effective alternative modality in the therapy of certain UTIs that historically have been treated with parenteral antibiotics.

Administration, Oral↗

PubMed1990

Norfloxacin versus trimethoprim-sulfamethoxazole in the treatment of urinary tract infections.

In a controlled, randomized trial of 133 patients with proven urinary tract infections (UTIs), significantly more pathogens were found to be susceptible to norfloxacin than to trimethoprim-sulfamethoxazole (TMP-SMZ) (p less than 0.01). Among patients with pathogens susceptible to both drugs, more of those treated with norfloxacin were cured or improved (p = 0.06). When at least one patient variable, i.e., prior history of therapy, was corrected for, this difference became significant (p = 0.03). Norfloxacin eradicated 11 of 13 infections due to Pseudomonas aeruginosa and 6 of 7 due to enterococci. Five patients treated with norfloxacin and two treated with TMP-SMZ had relapses within 6 weeks. Significantly fewer adverse experiences occurred in patients receiving norfloxacin (p less than 0.01).

Adult↗

PubMed1988

Norfloxacin in the eradication of enteric infections in AIDS patients.

Recurrent episodes of salmonellosis, including recurrent life-threatening bacteremias, have been well-described in patients with AIDS. Because of the need to avoid sensitization to trimethoprim-sulfamethoxazole (TMP-SFX) in AIDS patients and the high frequency of ampicillin resistance of Salmonella isolates, alternative therapies must be sought. We report the treatment of nine AIDS patients, who had recurrent salmonellosis, with norfloxacin, a new oral fluoroquinolone which has excellent in vivo activity against Salmonella sp. Each patient had two to three prior distinct clinical episodes of salmonellosis which had failed to be eradicated with standard courses of ampicillin, TMP-SFX, ceftriaxone or cefotaxime. Microbiologic relapse had occurred in each patient within 2-4 weeks. Each of the enteric pathogens was susceptible in vitro to norfloxacin. Patients were treated with norfloxacin 400 mg bid orally for 30 days. Stool cultures were negative at 1 week in all patients. Nausea and headache were the only adverse reactions to norfloxacin noted. One patient had a clinical and microbiologic relapse of Salmonella 1 week after norfloxacin was stopped but responded to retreatment with norfloxacin. Norfloxacin appears effective in the treatment of enteric infections in AIDS patients and may be more useful than standard agents in eradicating the organism and preventing clinical and microbiologic relapse. Oral administration and twice daily dosing are significant advantages.

Acquired Immunodeficiency Syndrome↗

PubMed1988

The tolerability profile of prophylactic norfloxacin in neutropenic patients.

Norfloxacin has been compared to placebo (136 patients), sulfamethoxazole plus trimethoprim (SXT, 72 patients) and oral vancomycin plus colistin (V/C, 61 patients) for the prevention of alimentary tract-associated infections during and after induction chemotherapy. These patients were evaluated for the safety and tolerability of each regimen by clinical and laboratory means. Most neutropenics involved, regardless of the regimen, experienced at least one adverse experience. The majority were felt to be unrelated to prophylactic study drug therapy. Of 139 patients who received norfloxacin, only two had drug-related adverse experiences, compared to two of 35 receiving SXT, five of 28 for VC, and none of 67 receiving placebo. In evaluating adverse experiences considered possibly drug related, 19 occurred on norfloxacin compared to 13 for placebo. Among neurologic adverse experiences, only one possibly related to norfloxacin occurred (confusion), while three occurred on placebo (confusion, decreased auditory acuity and hallucinations). Generally, no significant differences were seen between any of the regimens except for a higher frequency of diarrhea in those receiving V/C.

Agranulocytosis↗

PubMed1987

Norfloxacin: review of safety studies.

The tolerability profile of norfloxacin, the first of a new generation of fluoroquinolone carboxylic acid antibacterials, has been defined in numerous laboratory animal and human trials. Whether administered for moderate or protracted periods, norfloxacin has been relatively safe in animals over a wide range of doses. There has been no evidence of a teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at six to 50 times the human dose (400 mg twice daily). However, norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times the maximal human dose, resulting in peak plasma levels that are two to three times those obtained in humans. Although there are no adequate and well-controlled studies in pregnant women, norfloxacin is not recommended for use in this population because it, like other drugs in this class, causes arthropathy in immature animals. In animals, norfloxacin is neither mutagenic nor carcinogenic, and, in clinical trials, norfloxacin-related adverse experiences have been uncommon. Those that have occurred have been generally mild, requiring discontinuation of therapy in less than 1 percent of patients. The most frequently reported side effects have been nausea, dyspepsia, headache, and dizziness. Administration of 400 mg of norfloxacin at two or three times a day has been associated with reasonably good gastrointestinal tolerance.

Animals↗

PubMed1987

Norfloxacin in the treatment of urinary tract infections in men with and without identifiable urologic complications.

A retrospective analysis of data from the treatment of 95 men with nonbacteremic urinary tract infections (UTIs) (clean-catch urinary bacterial count greater than or equal to 10(5) colony-forming units/ml) who received norfloxacin (400 mg orally twice daily) was performed. Treatment duration ranged from a required minimum of seven days to a maximum of 30 days. If an underlying anatomic or functional condition existed that might decrease the likelihood of a favorable medical response and/or require prolonged treatment, the patient's UTI was considered "complicated." In addition to eight patients with polymicrobic UTIs (usually involving enterococci or Pseudomonas aeruginosa), 48 men (i.e., 51 percent of the total population) had an identifiable complication. Complications included benign prostatic hypertrophy in 13 patients; prostatic cancer in four; urethral stricture in four; quadriplegia/paraplegia with indwelling urinary catheter in four; prostatism in three; and other conditions commonly recognized as altering the response to antibiotic treatment. Among the 95 patients treated, 76 (80 percent) were considered to have had a cure and five (5 percent) showed improvement. Fourteen patients (15 percent) failed to show a response to treatment. Of the 48 patients with UTI and defined complications, 36 (75 percent) had a cure, three (6 percent) showed improvement, and therapy failed in nine (19 percent). Ninety-seven percent (105 of 108) of the pretreatment bacterial isolates were susceptible to norfloxacin. In addition to the three resistant organisms that were present prior to therapy, three organisms (two P. aeruginosa and one Enterobacter) persisted and acquired resistance during therapy. Five adverse clinical experiences and six adverse laboratory experiences were noted. Only one of the former (mild heartburn) was thought to be drug related, and no adverse experience was considered serious or required discontinuation of treatment. Gastrointestinal tolerability of oral norfloxacin was good.

Adolescent↗

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↗