First-line Antimicrobials Research Articles

Does Initial Choice of Antimicrobial Therapy Affect Length of Stay for Patients with Complicated Intra-abdominal Infections?

Outcomes for complicated intra-abdominal infection are influenced by operation for source control, patient-related factors, and medical management, including antibiotic treatment. We analyzed length of stay (LOS) at 33 hospitals for 2,150 patients discharged between February 2002 and June 2003, who were > 18 years, had intra-abdominal infection, and received one of 6 first-line antimicrobials. A regression tree analysis selected important variables, their interactions, and their order of significance in explaining LOS. A linear mixed model evaluated the difference in LOS between treatment groups. Adjusted LOS was calculated by the least squares means from the model and was used to assess treatment differences. Mean LOS analyzed by initial antimicrobial therapy and stratified by diagnosis showed LOS for ampicillin/sulbactam and ertapenem to be significantly shorter from levofloxacin, ceftriaxone, and piperacillin/tazobactam (all P < 0.05). Adjusting for all other factors, the variables associated with severity (e.g., diagnosis, ICU stay, and comorbidities) had the greatest impact on adjusted LOS (all P < 0.001). Our findings indicate ampicillin/sulbactam and ertapenem were associated with shorter hospital stays, which may be explained by unaccounted for underlying severity of infection and/or by surgeons stratifying antimicrobial selection according to severity of illness.

Pneumocystis jiroveci Pneumonia in Adult Patients with AIDS

Pneumocystis jiroveci (P. carinii) is an opportunistic pathogen that has gained particular prominence since the onset of the AIDS epidemic. Among several important advances in diagnosis and management, appropriately targeting chemoprophylaxis to HIV-infected patients at high clinical risk for P. jiroveci pneumonia and the introduction of effective combination anti-retroviral therapy (including highly active antiretroviral therapy [HAART]) have contributed to the reduced incidence of P. jiroveci pneumonia. Despite the success of these clinical interventions, P. jiroveci pneumonia remains the most common opportunistic pneumonia and the most common life-threatening infectious complication in HIV-infected patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) remains the first-line agent for effective therapy and chemoprophylaxis, and corticosteroids represent an important adjunctive agent in the treatment of moderate-to-severe P. jiroveci pneumonia. However, problems of chemoprophylaxis and treatment failures, high rates of adverse drug reactions and drug intolerance to first-line antimicrobials, high rates of relapse or recurrence with second-line agents, and newer concerns about the development of P. jiroveci drug resistance represent formidable challenges to the management and treatment of AIDS-related P. jiroveci pneumonia. With the expanding global problem of HIV infection, the intolerance or unavailability of HAART to many individuals and limited access to healthcare for HIV-infected patients, P. jiroveci pneumonia will remain a major worldwide problem in the HIV-infected population. New drugs under development as anti-Pneumocystis agents such as echinocandins and pneumocandins, which inhibit beta-glucan synthesis, or sordarins, which inhibit fungal protein synthesis, show promise as effective agents. Continued basic research into the biology and genetics of P. jiroveci and host defense response to P. jiroveci will allow the development of newer antimicrobials and immunomodulatory therapeutic agents to more effectively treat life-threatening pneumonia caused by this organism.

Therapeutic options for Gram-positive infections

Gram-positive infections impose a major burden on patients and the healthcare systems globally. The need to treat these infections correctly in an empirical fashion is of paramount importance. Further complicating this changing aetiology is the emergence of resistant strains which are no longer predictably susceptible to standard first-line antimicrobials such as oxacillin or vancomycin. Thus new agents such as linezolid have been developed to assist with initial empirical prescribing in infections where Gram-positive pathogens may be present. The characteristics of linezolid, including spectrum of activity, pharmacodynamic profile, tolerablility and overall efficacy should strengthen confidence when considering initial antimicrobial therapy in patients in risk areas. Future agents also being developed to fight multiresistant Gram-positive infections include oritavancin, daptomycin and the glycylcyclines; however, these are still in the development phase.

Review of the Sulfonamides and Trimethoprim

Review of the Sulfonamides and Trimethoprim