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The Therapy of Opportunistic Infections

 

 

Direct links
OI Diagnosis Treatment
Pneumocystis carinii pneumonia (PCP) Dx Tx
Toxoplasma gondii encephalitis Dx Tx
Cryptococcus neoformans Dx Tx
cytomegalovirus infection Dx Tx
histoplasmosis Dx Tx
aspergillosis Dx Tx
cryptosporidiosis Dx Tx
nocardiosis Dx Tx
coccidioidomycosis Dx Tx
acyclovir-resistant herpes simplex Dx Tx
severe refractory human papilloma virus (HPV) Dx Tx
progressive multifocal leukoencephalopathy (PML) Dx Tx
late stage Pseudomonas aeruginosa pneumonia Dx Tx

 

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Pneumocystis carinii pneumonia (PCP)
Drug Dosing Adverse Effects  
sulfamethoxazole / trimethoprim Oral: 15-20 mg/kg/day according to the trimethoprim component divided into three doses per day or 5 mg/kg tid

IV: same dose as oral but usually divided into 4 doses q6h per day; used only when oral route not feasible

Duration: usually 21 days

 Nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever Drug of choice

Consider "desensitization" if patient allergic
Switch to alternative if no response in first 3-5 days of therapy
Adjust dose for renal dysfunction, but not recommended for end-stage renal disease

 
pentamidine isoethionate IV/IM: 4 mg/kg/day
Duration: 14-21 days		 Dysglycemia which may be severe, renal dysfunction, hepatitis, thrombocytopenia, bone marrow suppression, pancreatitis Equally efficacious and tolerated as sulfamethoxazole / trimethoprim according to published studies, but parenteral only route and anecdotally increased toxicity relegates this therapy to third line.
aerosalized pentamindine 600 mg per day Cough, bitter taste, systemic absorption possible with side effects listed above  
atovaquone 750 mg po bid with food Nausea, rash, diarrhea Indicated only for mild to moderate PCP
primaquine + clindamycin primaquine: 30 mg base po daily
clindamycin: 300-450 mg po q8h

Duration: 21 days

 Diarrhea, pseudomembranous colitis, rash Primaquine is contraindicated with G6PD deficiency.  Check G6PD levels before initiation.

 

 

 

Toxoplasma gondii encephalitis
Drug Dosing Adverse Effects  
sulfadiazine + pyrimethamine sulfadiazine: 1-2 grams q6h PO

pyrimethamine: 200 mg followed by 50-75 mg PO daily
folinic acid: 10-20 mg daily PO

Duration: usually indefinite

 Nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, renal cystalluria/obstruction/renal dysfunction Drugs of choice

Consider densensitization if patient allergic to sulfa
Adjust dose for renal dysfunction, but not recommended for end-stage renal disease
Assure good hydration to prevent sulfadiazine crystalluria
clindamycin + pyrimethamine clindamycin: 600-1200 mg PO or IV q6-8h
pyrimethamine: 200 mg followed by 50-75 mg PO daily
folinic acid: 10-20 mg daily PO
Duration: usually indefinite		 Diarrhea, rash, fever, hepatitis, leukopenia, thrombocytopenia Possible higher incidence of relapse than sulfadiazine-based regimen.
sulfamethoxazole / trimethoprim sulfa/tmp: 5 mg/kg IV or PO q12hours
folinic acid: 10-20 mg daily PO
Duration: usually indefinite		 Diarrhea, rash, hepatitis, leukopenia, thrombocytopenia, nausea, fever, renal dysfunction Trimethoprim is not active against Toxoplasma gondii
azithromycin + pyrimethamine azithromycin: 1200-1500 mg PO daily

pyrimethamine: 200 mg followed by 50-75 mg PO daily

folinic acid: 10-20 mg daily PO

 Hepatitis, GI upset, diarrhea, rash, fever, leukopenia, thrombocytopenia Only one study to support use of this regimen; relapse rate reported at 47%
atovaquone +
pyrimethamine		 atovaquone: 1500 mg PO bid with food
pyrimethamine: 200 mg followed by 50-75 mg PO daily
folinic acid: 10-20 mg daily PO		 Nausea, GI upset, diarrhea, rash, leukopenia, thrombocytopenia Possibly less efficacious than other options above

 

 

 

Cryptococcus neoformans infections
For initial or recurrent disease consider induction therapy for 14 - 42 days with amphotericin B plus flucytosine, followed by maintenance with fluconazole.
Drug Dosing Adverse Effects  
amphotericin B +/- flucytosine (5-FC)  

Ampho: 0.7-1.0 mg/kg/day
Flucytosine: 100 mg/kg/day divided q6h PO

Duration: usually 14 -42 days

 ampho B: nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, rigors, anemia, hypokalemia, hypomagnesemia, renal tubular acidosis, phlebitis; rarely lethal reactions of unclear cause (arrhythmia?)
flucytosine: bone marrow suppression, rash		 Drugs of choice

Adjust dose for renal dysfunction

Hydrate well with continuous IV fluids or bolus with 500-1000 cc NS before and after each dose
Administer 5-FC via NG tube if patient unable to take PO
liposomal
amphotericin B +/- flucytosine (5-FC)		 Ampho B liposomal: 5 mg/kg/day
Flucytosine: 		liposomal ampho B: Less (than conventional ampho B) nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, rigors, anemia, hypokalemia, hypomagnesemia, renal tubular acidosis; this form is easy to administer with a more rapid infusion rate and less rigors

flucytosine: bone marrow suppression, rash

 Use liposomal formulation for baseline renal dysfunction or other uncontrollable intolerances to conventional ampho B
Hydrate well with continuous IV fluids or bolus with 500-1000 cc NS before and after each dose

Administer 5-FC via NG tube if patient unable to take PO
fluconazole IV: 400 mg/day

PO: 400 mg/day
Up to 800-1200 mg per day in special circumstances

Duration: indefinitely or until immune reconstitution

 Rash, hepatitis, nausea/vomiting, GI upset Good alternative to ampho B for profound intolerance as well as maintaining suppression
voriconazole 400 mg per day? Visual blurring (transient), nausea, vomiting Active in vitro

 

 

 

 

cytomegalovirus (CMV) infections
Retinitis: consider intravitreal implant with ganciclovir plus systemic oral "prophylaxis" with valganciclovir (duration: indefinite or until immune reconstitution)
Encephalitis: foscarnet plus ganciclovir IV for 14-21 days
Pneumonitis: foscarnet or IV ganciclovir for 14-21 days
Esophagitis/gastritis: foscarnet or IV ganciclovir for 14-21 days
Hepatitis: foscarnet or ganciclovir IV
Colitis: foscarnet or IV ganciclovir for 14-21 days
Drug Dosing Adverse Effects  
intravitreal
ganciclovir
implant		 one implant / year Retinal detachment, infection Treatment of choice for retinitis

Well tolerated and effective; requires surgical expertise and yearly re-implantation
ganciclovir induction: IV

maintenance: 2x500 mg tid po with food

 Bone marrow suppression, rash, renal dysfunction Watch CBC closely; adjust dosing for renal dysfunction
foscarnet 90 mg/kg IV q12h or 60 mg/kg IV q8h Renal dysfunction Requires a central line and close monitoring of renal function

Adjust dosing carefully for renal dysfunction

Administer 500-1000 cc NS before and after each dose of foscarnet.
cidofovir +
probenecid		 cidofovir: 5 mg/kg weekly x 2, then every other week
probenecid: 2 grams 8 hrs before cidofovir and 1 gram 2 and 6 hours after cidofovir		 cidofovir: renal dysfunction

probenecid: rash (cross hypersensitivity with sulfa in some cases), nausea

 Check serum creatinine, CBC with differential WBC and urinanalysis the day before; check serum creatinine and U/A the day of therapy; administer NS at least 1000 cc before each dose of cidofovir and until urine protein < 30 mg/dl
Adjust dose for renal dysfunction
No central intravenous line is necessary.
valganciclovir 900 mg PO bid x 21 days, then 900 mg daily to prevent recurrence Bone marrow suppression, rash, renal dysfunction Prodrug of ganciclovir; watch CBC closely; adjust dosing for renal dysfunction
This is the preferred agent for maintenance and the oral drug preferred for induction

 

 

 

 

histoplasmosis
For initial or recurrent disease consider induction therapy for 14 - 42 days with amphotericin B or liposomal amphotericin B followed by maintenance with itraconazole
Drug Dosing Adverse Effects  
amphotericin B  

Ampho B: 0.7 - 1.0 mg/kg/day
Duration: usually 14-42 days

 ampho B: nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, rigors, anemia, hypokalemia, hypomagnesemia, renal tubular acidosis, phlebitis; rarely lethal reactions of unclear cause (arrhythmia?) Drug of choice

Adjust dose for renal dysfunction

Give a 1 mg test dose in 100 cc D5W over 1-2 hours before therapy to determine tolerance
Hydrate well with continuous IV fluids or bolus with 500-1000 cc NS before and after each dose
liposomal
amphotericin B		 Ampho B liposomal: 5 mg/kg/day
Duration: usually 14 -42 days		 liposomal ampho B: Less (than conventional ampho B) nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, rigors, anemia, hypokalemia, hypomagnesemia, renal tubular acidosis; this form is easy to administer Use liposomal formulation for baseline renal dysfunction or other uncontrollable intolerances to conventional ampho B
Hydrate well with continuous IV fluids or bolus with 500-1000 cc NS before and after each dose
itraconazole 200 mg bid
Duration: usually indefinite		 Rash, hepatitis, nausea/vomiting, GI upset Good alternative to ampho B for profound intolerance as well as maintaining suppression
voriconazole 200 mg bid Visual blurring (transient), nausea, vomiting Active in vitro

 

 

 

 

aspergillosis
Drug Dosing Adverse Effects  
amphotericin B  

Ampho: 1.0 mg/kg/day
Duration: until resolution

 ampho B: nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, rigors, anemia, hypokalemia, hypomagnesemia, renal tubular acidosis, phlebitis; rarely lethal reactions of unclear cause (arrhythmia?)  

Adjust dose for renal dysfunction

Hydrate well with continuous IV fluids or bolus with 500-1000 cc NS before and after each dose
liposomal
amphotericin B		 Ampho: 5 mg/kg/day
Duration: until resolution		 liposomal ampho B: Less (than conventional ampho B) nausea, rash, leukopenia, thrombocytopenia, hepatitis, renal dysfunction, fever, rigors, anemia, hypokalemia, hypomagnesemia, renal tubular acidosis; this form is easy to administer Use liposomal formulation for baseline renal dysfunction or other uncontrollable intolerances to conventional ampho B
Hydrate well with continuous IV fluids or bolus with 500-1000 cc NS before and after each dose
itraconazole IV: 200 mg bid x 4 doses, then 200 mg per day

PO: switch to PO form asap
Duration: until resolution

 Rash, hepatitis, nausea/vomiting, GI upset Good alternative to ampho B for profound intolerance as well as maintaining suppression
caspofungin      
voriconazole 6 mg/kg IV q12 hours x 2 doses, then 4 mg/kg IV q12 hours

Switch to PO form asap

 Visual blurring (transient), nausea, vomiting Drug of choice

 

 

cryptosporidiosis
Therapy usually continues until immune reconstitution.  Immune reconstitution is itself the best therapy for cryptosporidiosis.
Drug Dosing Adverse Effects  
nitazoxanide 500-1000 mg bid PO nausea, vomiting, anemia Drug of choice?
Not uniformly effective
paromomycin 250-500 mg po tid nausea, vomiting, diarrhea Poorly effective at best

 

 

 

acyclovir-resistant herpes simplex
Drug Dosing Adverse Effects  
cidofovir + probenecid cidofovir: 5 mg/kg every other week
probenecid: 2 grams 8 hrs before cidofovir and 1 gram 2 and 6 hours after cidofovir		 cidofovir: renal dysfunction

probenecid: rash (cross hypersensitivity with sulfa in some cases), nausea

 Drug of choice (author's opinion)
Check serum creatinine, CBC with differential WBC and urinanalysis the day before; check serum creatinine and U/A the day of therapy; administer NS at least 1000 cc before each dose of cidofovir and until urine protein < 30 mg/dl
Adjust dose for renal dysfunction
No central intravenous line is necessary.
Careful dose adjustment will be necessary as ongoing treatment usually produces renal dysfunction.
foscarnet   renal dysfunction Requires a central line and close monitoring of renal function

Adjust dosing carefully for renal dysfunction

Administer 500-1000 cc NS before and after each dose of foscarnet.
Monitor renal function carefully

 

 

 

Pseudomonas aeruginosa pneumonia (late stage AIDS)
Drug Dosing Adverse Effects  
2-3 active antipseudomonal antibiotics
(avoid aminoglycosides if possible)		 Maximum dosing of both agents Depends on agents used Administer a long course parenterally and consider continuation for 3-6 months

 

 

Updated 10.27.2004