Andrew M. Roecker

Objective: Summarize data on the pathophysiology, treatment, and prevention options for non–AIDS immunocompromised patients who have Pneumocystis jirovecii pneumonia (PJP); review the epidemiology of patients presenting with PJP; and discuss the first and second-line pharmacological options for treatment and prophylaxis of PJP in this population. Data Sources: MEDLINE (1989-February 2016) searched. Terms searched included combinations of Pneumocystis jirovecii, Pneumocystis carinii, non-HIV, infected, patients, prevention, prophylaxis, Bactrim, treatment, AIDS, opportunistic, immunocompromised, cancer, and pathophysiology. Study Selection and Data Extraction: Articles included had the most relevant information on PJP pathophysiology, and first-/second-line treatment and prophylactic options. Inclusion criteria were met and evaluated with 43 sources. Data Synthesis:P jirovecii has a complicated life-cycle; it seeks to find compromised immune systems in order to replicate, causing life-threatening complications. With immunosuppressive medications coming to market for immunomodulating diseases, PJP has become a prevalent opportunistic infection in the non-HIV population. CD4+ lymphocyte count <200 cells/µL is the primary risk factor for PJP presentation in these patients. With data from clinical trials, trimethoprim/sulfamethoxazole (TMP/SMX) has become the primary treatment and prophylaxis of PJP in the non-HIV population, although second-line options are available. Conclusion: PJP is a health problem that may result in an increased concern as more immunomodulating medications to treat various disease states are developed. Patients on these drugs or those with immunosuppressive diseases should have their CD4+ count monitored. Health care providers should continue to use TMP/SMX as the primary option in non-HIV, immunocompromised patients for treatment and prophylaxis of PJP.

Nelarabine is a nucleoside analog indicated for the treatment of adult and pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) that is refractory or has relapsed after treatment with at least two chemotherapy regimens. After being first synthesized in the late 1970s and receiving FDA approval in 2005, the appropriate use of nelarabine for refractory hematologic malignancies is still being elucidated. Nelarabine is the prodrug of 9-β-D-arabinofuranosylguanine (ara-G) which when phosphorylated intracellularly to ara-G triphosphate (ara-GTP), preferentially accumulates in cancerous T-cells. Dose-dependent toxicities, including neurotoxicity and myelosuppression, have been documented and may, in turn, limit the ability to appropriately treat the diagnosed malignancy. This article will summarize the pharmacologic properties of nelarabine and will address the current place in therapy nelarabine holds based upon the results of the available clinical trials to date.

Dalbavancin is a lipoglycopeptide antibacterial agent with in vitro and in vivo activity against a number of Gram-positive organisms, including some with multidrug resistance. This is a review of the available literature explaining the pertinent information regarding dalbavancin's pharmacodynamics/pharmacokinetics, clinical efficacy, adverse event profile and potential place in therapy. The aim of the study was to explain the relevant data on dalbavancin's administration, efficacy and tolerability. A PubMed/MEDLINE search was used to review data published from January 1966 through to February 2008 with the keywords dalbavancin, lipoglycopeptide or BI 397. Dalbavancin, currently pending full FDA approval, has favorable minimum inhibitory concentrations against many Gram-positive organisms as compared to currently available antimicrobials. Dalbavancin has a prolonged half-life (149 - 300 h), which may lead to a therapeutic option that is different from available antimicrobials. Its efficacy and tolerability have been established in treating complicated skin and skin structure infections. Future data are required in order to determine dalbavancin's true place in therapy, if approval is achieved.

Nelarabine is a nucleoside analog prodrug of 9-beta-D-arabinofuranosylguanine. Nelarabine is indicated for the treatment of adult and pediatric patients with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma whose disease has not responded to, or has relapsed after treatment with, at least two chemotherapy regimens. Nelarabine was granted Orphan Medical Product Status in Europe in June 2005, and accelerated approval by the US FDA in October 2005. The most common adverse events associated with nelarabine are neurotoxic in nature and have been dose-limiting.