Supportive care

For most mild mpox patients with intact immune systems and no skin lesions, supportive care will help them recover independently [9]. Regardless of disease severity, supportive care remains the cornerstone of mpox treatment, with particular attention to skin lesion care, pain management, and fluid management [2, 11]. Pain management is crucial, with primary medications including acetaminophen, ibuprofen, or topical lidocaine for mild cases. ICU patients often require more potent opioid analgesics such as morphine and oxycodone [2]. Intensivists should closely monitor dehydration in mpox patients caused by fever, reduced intake, and other systemic manifestations. Fluid resuscitation, maintenance, and electrolyte balance correction are crucial [11].

Available drug therapeutics for severe mpox

For severe mpox patients, the following medications may be considered:

Tecovirimat (TPOXX or ST-246)

Tecovirimat is an emerging antiviral drug inhibiting the highly conserved viral envelope protein p37 in orthopoxviruses. Note that the optimal bioavailability of tecovirimat depends on the concurrent intake of high-fat foods [12]. It should not be administered intravenously to patients with severe renal impairment (creatinine clearance < 30 mL/min) [11]. Disappointingly, tecovirimat has been reported to be ineffective against the clade Ib in clinical trials [13].

Cidofovir (Vistide)

This drug inhibits DNA synthesis by inserting itself into the DNA chain as replication occurs. Its dose-dependent nephrotoxicity limits its use, so it is usually administered with oral probenecid and hydration [12]. Caution is advised when using cidofovir with tenofovir disoproxil fumarate in HIV patients on antiretroviral therapy (ART). In patients with HIV infection and AKI, it may be necessary to change their ART regimen to one that does not include tenofovir disoproxil fumarate; consultation with an HIV specialist is recommended [10].

Brincidofovir (CMX001 or Tembexa)

Brincidofovir is a prodrug of cidofovir with lower nephrotoxicity but may cause elevated liver enzymes (such as transaminases and bilirubin), necessitating liver enzyme monitoring [10, 12]. However, obtaining brincidofovir can be challenging.

Vaccinia immune globulin intravenous (VIGIV)

VIGIV is primarily used for immunocompromised adults and children or those who cannot receive antiviral treatment (including tecovirimat) or for whom antiviral treatment is ineffective, or in severe cases, in combination with antiviral drugs and/or other therapies [8].

Mpox in patients with HIV

Mpox patients with HIV who have not received ART should start ART as soon as possible to improve immune function, ideally in conjunction with mpox treatment. Based on the severity of immune compromise and uncontrolled viral replication, prompt use of tecovirimat (possibly in intravenous form) may be considered, potentially in combination with cidofovir or brincidofovir and VIGIV. It is important to note that immune reconstitution inflammatory syndrome (IRIS) potentially induced by ART may worsen the condition of mpox patients [14].

Drug interactions

Medications used for severe mpox may interact with some drugs. Intensivists should be aware of these drug interactions; for example, tecovirimat can reduce the concentration of midazolam in the blood, diminishing its effectiveness. Additionally, tecovirimat can increase the concentration of repaglinide in the blood, leading to hypoglycemia [7, 15]. The drug interactions for severe mpox can be found in Table 1 [16,17,18,19].

Table 1 Drug interactions of available drug therapeutics for severe mpox