Sulfonamides

Background

NoteWhat percent of the total population reports an allergy to sulfa antibiotics?

The reported global prevalence of sulfa antibiotic allergy is 3% to 6%. The prevalence is higher is individuals with hematological malignancies (12-40%) and HIV (30-70%)^{serrano-arias2024?}.

NoteWhat is the structure of sulfa antibiotics?

Sulfa antibiotics–also called sulfonylarylamines–are characterized by the presence of a sulfonamide functional group with two side chains, arylamine (aromatic amine) and an aromatic heterocyclic ring^{serrano-arias2024?}.

NoteAlthough sulfa antibiotics and non-antiobitic sulfamide both contain a sulfonamide functional group, do they cross-react?

No, they do not cross-react because non-antibiotic sulfonamides lack the same side chains as sulfa antibiotics–aryalmine and aromatic heterocyclic ring^{serrano-arias2024?}.

NoteFor what respiratory, opportunistic infection in immunocompromised patients is trimethoprim-sulfamethoxazole the preferred prophylaxis?

Trimethoprim-sulfamethoxazole is the preferred prophylaxis for Pneumocystis jirovecii pneumonia (PJP) because of its greater evidence of efficacy and lower cost compared to alternative prophylaxis, such as atovaquone, dapsone, and aerosolized pentamidine^{maertens2016?}.

Further, compared to alternative PJP prophylaxis, trimethoprim-sulfamethoxazole may also prevent other breakthrough infections such as Nocardia, Toxoplasma, Streptococcus pneumoniae, and Haemophilus species.

A Cochrane review on the efficacy of trimethoprim-sulfamethoxazole for PJP prevention in non-HIV immunocompromised patients found the number needed to treat to prevent one case of PJP is 19^stern2014?.

NoteFor what patient populations is prophylaxis for Pneumocystis jirovecii pneumonia recommended?

When considering Pneumocystis jirovecii pneumonia prophylaxis, the two main patient populations to consider are non-HIV immunocompromised and HIV immunocompromised individuals.

HIV immunocompromised:

• CD4+ T cell count < 200 cells/µL

Non-HIV immunocompromised:

• Solid organ transplant

• Bone marrow transplant

• Prednisone ≥ 20 mg (or equivalent) for more than one month

NoteWhen and in what patient population was Pneumocystis jirovecii pneumonia first described?

The first cases of Pneumocystis jirovecii pneumonia were described in malnourished children in orphanages in Europe during World War II. When initially described, it was referred to as “interstitial plasma cell pneumonia^morris2004?.

NoteWhat type of pathogen is Pneumocystis jirovecii?

Pneumocystis jirovecii is a ubiquitous fungus with infection commonly occurring at young age, with near universal positivity to Pneumocystis by two years of age^vargas2001?. In immunocompetent individuals, primary infection is largely asymptomatic. In addition, colonization with Pneumocystis jirovecii occurs in more than 50% of the general adult population and is assumed to be due to re-infection (i.e. person-to-person transmission, environmental re-exposures) rather than reactivation^{gigliotti2012?}.

NoteWhy did the nomenclature human Pneumocystis pneumonia change from Pneumocystis carinii to Pneumocystis jiroveci?

DNA sequencing improved our understanding of Pneumocystis and its different species that are associated with various host organisms. Therefore, Pneumocystis jirovecii describes the species that infects humans while Pneumocystis carinii describes the species that infects rats^{stringer2002?}.

NoteWhat primary immune deficiency is notably associated with a high risk of Pneumocystis jirovecii pneumonia?

Hyper-immunoglobulin M syndromes—the X-linked recessive version caused by defects in CD40L (expressed on the surface of T cells to induce antibody isotype switching in B cells)–is associated with a notably increased risk of Pneumocystis jirovecii pneumonia^davies2010?.

NoteWhy is trimethoprim-sulfamethoxazole sometimes referred to as “co-trimoxazole?”

Co-trimoxazole is the British Approved Name (BAN) for trimethoprim-sulfamethoxazole. BANs are assigned for both single-drug and combination preparations. The prefix of “co-” is used for denote combination drugs like trimethoprim and sulfamethoxazole. For example, the combination of amoxicillin and clavulanic acid has the BAN “co-amoxiclav.”

Figure 1: Sulfonamides and sulfone structures