8.4. Culture-negative Pulmonary Tuberculosis CONTENTS in Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 650 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604 8.5. Radiographic Evidence of Prior Tuberculosis: Inactive Tuberculosis . . . . . . . . . . . . . . . . . . . . . 650

American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.

Gram-negative bacteremia: IV. Re-evaluation of clinical features and treatment in 612 patients

In an examination of the relationships among plasma aminoglycoside concentrations, the minimal inhibitory concentration (MIC) for the infecting organism, and therapeutic outcome, data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin, tobramycin, and amikacin. Clinical response to therapy occurred in 188 (80%) patients. Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response (P less than .00001 and P less than .0001, respectively). A graded dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response. By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response. These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy.

Clinical Response to Aminoglycoside Therapy: Importance of the Ratio of Peak Concentration to Minimal Inhibitory Concentration

Pseudomonas aeruginosa has emerged as an important pathogen during the past two decades. It causes between 10% and 20% of infections in most hospitals. Pseudomonas infection is especially prevalent among patients with burn wounds, cystic fibrosis, acute leukemia, organ transplants, and intravenous-drug addiction. P. aeruginosa is a common nosocomial contaminant, and epidemics have been traced to many items in the hospital environment. Patients who are hospitalized for extended periods are frequently colonized by this organism and are at increased risk of developing infection. The most serious infections include malignant external otitis, endophthalmitis, endocarditis, meningitis, pneumonia, and septicemia. The likelihood of recovery from pseudomonas infection is related to the severity of the patient's underlying disease process. The introduction of the antipseudomonal aminoglycosides and penicillins has improved substantially the prognosis of these infections. Ticarcillin and carbenicillin have been especially beneficial in neutropenic patients; however, prompt institution of therapy is mandatory for optimal benefit. Many new drugs with antipseudomonal activity, including penicillins, cephalosporins, and other beta-lactams, have been introduced in recent years and offer the potential for new approaches to therapy for these infections.

Infections Caused by Pseudomonas aeruginosa

Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors

Infectious complications of human bone marrow transplantation.

https://www.amjmed.com/article/0002-9343(77)90669-6/pdf

Comparative efficacy and toxicity of amikacin/carbenicillin versus gentamicin/carbenicillin in leukopenic patients: A randomized prospective trail

The size and molecular composition of circulating immune complexes depend on various factors, including the concentrations and valences of antigens and antibodies and the antigen-antibody ...

Circulating Immune Complexes: Their Immunochemistry, Detection, and Importance

Simultaneous antibiotic levels in “breakthrough” gram-negative rod bacteremia☆

Amikacin was used in 77 treatment courses at a dosage of ≥7.5 mg/kg every 8 h, and patients were monitored for ototoxicity by following serial audiograms, serum creatinine, and amikacin blood levels. Patients were leukopenic (58), were infected by gentamicin-resistant organisms (11), or had cystic fibrosis (8). Three patients developed tinnitus, but none had vertigo or nystagmus. Of 55 courses with pre- and post-treatment audiogram, 13 (24%) were associated with development of high-frequency hearing loss, which was usually bilateral. No patient had conversational hearing loss, and audiograms reverted to normal in three patients. Onset of cochlear damage occurred in one patient after therapy was stopped. The group with high-tone hearing loss, in comparison to the group without audiographic changes, received a larger mean total dose (24 versus 9.6 g), were treated for a longer duration (19 versus 9 days), and more frequently had previous aminoglycosides. Fifty-seven percent of patients with a “peak” serum level exceeding 32 μg/ml and 55% of patients with “trough” levels exceeding 10 μg/ml developed cochlear damage. There was no difference between the groups in age, body weight, previous cochlear damage, renal disease before or during therapy, or average daily dose. Both monitoring of blood levels and limiting duration of therapy may prevent amikacin ototoxicity.

https://aac.asm.org/content/aac/9/6/956.full.pdf

Lowell S. Young

Papers

Infectious complications of human bone marrow transplantation.

Comparative efficacy and toxicity of amikacin/carbenicillin versus gentamicin/carbenicillin in leukopenic patients: A randomized prospective trail

Circulating Immune Complexes: Their Immunochemistry, Detection, and Importance

Simultaneous antibiotic levels in “breakthrough” gram-negative rod bacteremia☆

Ototoxicity of Amikacin