In practice the total daily dose may be divided either qid or tid

In practice the total daily dose may be divided either qid or tid. The intravenous route is preferred for severe disease [39]. For mild–moderate PCP [PaO2>9.3 kPa (>70 mmHg)], dosing is either via the oral route (TMP-SMX 1920 mg tid or 90 mg/kg/day

tid) or using the iv regimen described above [40–42]. The dose reduction from 120 mg/kg/day to 90 mg/kg/day, in severe disease, has equivalent efficacy but a lower incidence of adverse events than continuous use of higher-dose therapy [36]. Individuals with a PaO2<9.3 kPa (<70 mmHg) or SpO2<92%, should receive prednisolone 40 mg bd po, days 1–5, 40 mg od po, days 6–10, 20 mg od po, days 11–21 [43,44]; or if unable to take oral medications, methylprednisolone at 75% of this dose [45]. The benefit of corticosteroid therapy is documented only where it has been commenced within 72 h of starting specific anti-PCP therapy. A favourable treatment Birinapant clinical trial response may take 7 days or more. The decision to switch from one drug to another is driven by either treatment-limiting toxicity or lack of efficacy.

Sulphamethoxazole inhibits dihydropteroate synthase (DHPS). DHPS mutations have been associated with duration of prior TMP-SMX prophylaxis and also geographical factors, which may influence patient-to-patient transmission [46,47]. Although DHPS mutations may be found in subjects with failure of primary prophylaxis [48] it remains controversial whether these mutations influence the efficacy of treatment with TMP-SMX based regimens. Some early studies reported an association with treatment failure [47,48], while more recent work has not shown this [49–51]. One recent study suggests that the frequency of DHPS mutations may be falling this website in the HAART era in association with less long-term exposure to PCP prophylaxis [52]. Overall the outcome of PCP is more influenced by the severity of PCP than by the presence of DHPS mutations [49]. There is currently no evidence to support the routine determination of DHPS mutations; or that if

they are detected early in treatment, patients should not receive TMP-SMX (category III recommendation). In many studies salvage treatment is defined as the regimen given after a change of the primary drug regimen on the grounds of suspected treatment failure and occurring after at least 5 days of anti-PCP therapy. It is reported to Gefitinib in vitro occur in up to one-third of subjects on treatment [40–42,53,54]. Current evidence suggests that for a given level of PCP severity there is little to choose in terms of efficacy between the different second-line drugs [40–42,53]. The choice of treatment is therefore determined by patient tolerance and ability to take either oral or iv medication. For severe PCP, treatment options are clindamycin 600–900 mg qid/tid iv or 300–450 mg tid/qid po and primaquine 15–30 mg od po or pentamidine 4 mg/kg od iv for 21 days. Many clinicians favour clindamycin-based therapy in view of the toxicity profile of iv pentamidine [38,55].

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