Evaluation Of New Anti-Infective Drugs Research Articles

Aztreonam and Vancomycin Use for Episodes of Febrile Neutropenia During Hematopoetic Stem Cell Transplantation

The spectrum of bacterial infections seen during febrile neutropenia(FN) in HSCT recipients continues to change, especially with the emergence of multi-drug resistant organisms. Aztreonam(AZ) plus Vancomycin (VAN) have been used successfully for FN in cancer patients, however the effectiveness of AZ plus VAN for FN during HSCT is largely unknown. A retrospective chart review was performed to determine the effectiveness of AZ in FN. 822 consecutive HSCT patient charts were reviewed(2004-2008). All patients received a minimum of 48hours of AZ/VAN treatment for FN. Patients had received ciprofloxacin as prophylaxis. The criteria for success was based upon evidence based guidelines for the evaluation of new anti-infective drugs in FN FN(CID Vol.15 Nov 1992 Suppl: 206-15) as follows:1.Unexplained fever: defervesence within 72hr without recurrence and no clinical s/s infection.2.Clinically defined infection: Clinical improvement including fever, without antibiotic change or death3.Microbiologically defined infection: All s/s and microbiological evidence of disease eradicated without recurrence for 7days. 67 AZ treated patients were identified. Demographics: age = 59(24-77), gender male = 29, Diagnosis: myeloma = 48, NHL = 10, AML = 7, HSCT type: autologous = 45. allogeneic = 22. Median time to start AZ(post-HSCT infusion): day +8(-6-12), Number of AZ treatment days = 6(2-33) Treatment Outcome1.Unexplained fever(n = 36): Success = 26/36(73%), 2 patients died2.Clinically defined(n = 12): Hospital Pneumonia(n = 9): Success = 5/9(55%-ATB changes), Typhlitis (n = 1) 0/1 (ATB change), Cellulitis(n = 1)(0/1success (ATB change)3.Microbiologically defined infection (see Table 1): 20 patients experienced 30 episodes of microbiologically confirmed infection. The majority (80%) were gram positive cocci blood stream infections and were successfully treated (80%-2 died). Gram negative BS infection overall success was 50%(1died) 6 patients developed clinical CDAD and 9 patients became VRE surveillance positive shortly after AZ treatment. A non-significant trend towards more BS infections was seen in allo-HSCT recipients(p = 0.086) AZ/VAN was effective in preventing breakthrough infections for patients with unexplained fever, but less effective for patients with documented infections, requiring change or addition of antibiotics. These results are comparable to those seen in non-HSCT cancer patients with FN(Bodey et al.Cancer 1996 Apr1 77(7)).Table 1Microbiologically Defined InfectionOrganismSourceSuccessful Outcome(%)Strept Viridansblood (n = 11)91 (1 died-polymicrobial)CONS(2 positive cx's at 2sitesblood (n = 5)80 (changed atb)Entereococcus Faecalisblood (n = 4)75 (1died-polymicrobial)MSSAblood (n = 2)50 (1 died-polymicrobialE.Coliblood = 1/urine = 1BS-1 died//Urine = successEnterobacterurine (n = 1)100Burkholderiablood = 10 ( died-polymicrobial)C.Diffstool (n = 3)66 (1 died-polymicrobial) Open table in a new tab

Urinary Tract Infections in Solid Organ Transplant Recipients

Urinary Tract Infections in Solid Organ Transplant Recipients

Randomized, Double-Blind Study of Prulifloxacin versus Ciprofloxacin in Patients with Acute Exacerbations of Chronic Bronchitis

Background: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined. Objective:To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin. Methods: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992). 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days. The study design was randomized, multicenter, double-blind, double-dummy. Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments. The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance). The microbiological response was assessed on sputum specimen. Results: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively. The 95% confidence interval proved the equivalence of treatments. Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Both treatments were well tolerated. Adverse drug reactions were always of mild or moderate intensity. Conclusion: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB.

Experience with the new guidelines on evaluation of new anti-infective drugs for the treatment of urinary tract infections

The new guidelines of Infectious Diseases Society of America (IDSA) and European guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) on evaluation of new anti-infective drugs for the treatment of urinary tract infection (UTI) were published in 1992 and 1993, respectively. The experience with these guidelines, including the recommendations for improvement published by an international expert group, are being updated and discussed. The IDSA and ESCMID guidelines define five categories of UTI. Some aspects specific for each group are discussed concerning definition, stratification and outcome. For patients with chronic bacterial prostatitis, a category of its own is proposed rather than using the general category of complicated UTI. The greatest advantage of the new guidelines in comparison with the former FDA guidelines is enrolment of patients according to intention to treat, as has always been recommended by the guidelines of the Japanese UTI Committee. Two problems arising in studies of all categories are addressed: (i) false positive bacteriuria and (ii) handling of dropouts and missing data. Compared with the former FDA guidelines, the new IDSA and ESCMID guidelines reflect much better the clinical situation of the physician taking care of individual patients. Therefore, the results of studies performed according to these guidelines are clinically more significant. A worldwide harmonization of guidelines may finally lead to valid and acceptable results in any country.

Evaluation of New Anti-Infective Drugs for the Treatment of Infection with Human Immunodeficiency Virus

This guideline describes the preclinical documentation required for a new drug active against human immunodeficiency virus (HIV) and offers suggestions regarding the design and implementation of phase 1, 2, and 3 clinical trials. Drugs with a low level of potential toxicity, especially those that are not nucleoside analogues, should be evaluated in healthy individuals who are not infected with HIV before trials in HIV-infected patients commence. The guideline also discusses possible clinical and laboratory end points for efficacy and emphasizes the need for careful validation of all laboratory end points used. The approach of the guideline is deliberately general: more specific recommendations would soon become outdated in this field, which is characterized by extremely rapid developments.

Evaluation of New Antiinfective Drugs for Helicobacter pylori Infection: Revisited and Updated

Evaluation of New Antiinfective Drugs for Helicobacter pylori Infection: Revisited and Updated

Evaluation of New Anti-Infective Drugs for the Treatment of Infections of Prosthetic Hip Joints

Infections of a prosthetic hip are of three types: acute contiguous, chronic contiguous, and hematogenous. Acute contiguous infections result from contamination of the operative field at the time of surgery; clinical manifestations of infection become apparent within 6 months. Chronic contiguous infections are diagnosed 6-24 months postoperatively and are believed to be caused by intraoperative contamination. Hematogenous seeding of prosthetic joints accounts for infections that develop > or = 2 years after surgery. Fever and pain or dysfunction of the joint may be the only signs or symptoms of prosthetic hip joint infection. Definitive diagnosis is established by culture of a needle aspirate from the joint space or by intraoperative culture. Prospective, randomized, double-blind or evaluator-blinded, active-control comparative studies are preferable to open trials. Success rates 10-14 weeks after completion of a 4- to 6-week course of antimicrobial therapy should be > or = 90%.

Evaluation of New Anti-Infective Drugs for the Treatment of Acute Hematogenous Osteomyelitis in Children

Most children with acute hematogenous osteomyelitis have no preceding illness. Their early symptoms are pain and fever. A bacterial etiology is established in approximately 75% of cases by needle aspiration of the affected site or blood culture. Clinical trials should be limited to cases of bacterial origin. The antimicrobial agents studied should be active against Staphylococcus aureus and streptococci. If children < 5 years of age are included, the drug should also be active against beta-lactamase-negative and -positive strains of Haemophilus influenzae. Randomized, prospective, double-blind comparative studies are preferable to open, evaluator-blinded trials. Clinical outcome is appraised by physical signs and symptoms. A successful microbiological outcome consists of presumptive eradication. The final assessment should be made 1 year after completion of therapy.

Evaluation of New Anti-Infective Drugs for the Treatment of Acute Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is a syndrome unrelated to pregnancy or surgery and characterized by lower abdominal pain and tenderness, cervical motion tenderness, and adnexal tenderness. Fever, leukocytosis, and the results of laboratory tests are used to support the diagnosis. Participants in clinical trials should be stratified into two groups: those with and those without tubo-ovarian abscess--i.e., those with complicated and those with uncomplicated PID. Diagnostic studies and treatment should be directed at four major groups of pathogens: Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobic bacteria, and facultative bacteria such as Escherichia coli. Women requiring hospitalization should generally be treated as inpatients for at least 4-7 days; outpatient therapy should then be instituted to complete a 14- to 21-day course. Clinical and laboratory evaluations should be conducted daily during hospitalization and both 2-4 days and 2-4 weeks after the completion of therapy.

Evaluation of New Anti-Infective Drugs for the Treatment of Syphilis

Syphilis is caused by Treponema pallidum, a spirochetal bacterium pathogenic only for humans. The clinical course of disease is divided into three stages interspersed by periods of latency. Penicillin remains the treatment of choice for all stages of infection; tetracycline or erythromycin may be used as therapeutic alternatives in defined circumstances. Patients enrolled in clinical trials should be evaluated clinically, microscopically, and serologically for the presence of the spirochete. All participants, after undergoing counseling and giving informed consent, should be tested for infection with human immunodeficiency virus. Specific criteria exist for diagnosis of syphilis and response to therapy. It may be desirable to perform a small, uncontrolled, open trial of a new anti-infective drug for the collection of preliminary evidence of efficacy. A larger-scale, randomized, active-control comparative clinical trial is necessary to prove efficacy.

Evaluation of New Anti-Infective Drugs for the Treatment of Infectious Arthritis in Adults

This guideline describes clinical trials of new anti-infective drugs for the treatment of septic arthritis due to bacteria other than Neisseria gonorrhoeae in adults. Septic arthritis is associated with fever and with physical findings at the affected joint. Diagnosis is established by culture of synovial fluid. Treatment includes the administration of antimicrobial drugs and drainage of the joint by needle aspiration or surgery. Multicenter, randomized comparative clinical trials that are single-, double-, or evaluator-blinded should be performed. However, an open trial of a new antimicrobial agent with historical controls is acceptable. Patients should receive treatment for at least 2-3 weeks. After 5 days of antimicrobial therapy, synovial fluid should be sterile and clinical signs and symptoms should have diminished. Patients should be followed for 2-4 weeks after completion of therapy.