guide for herpes virus diseases differential diagnosis with proper treatment plan with drug dose frequency route duration per kg dose all with clinical pearls for clinic

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Here is the complete clinical guide, synthesized from Harrison's Principles of Internal Medicine 22E, Goldman-Cecil Medicine, Andrews' Diseases of the Skin, Fitzpatrick's Dermatology, Goodman & Gilman's Pharmacology, Red Book 2021, and Tintinalli's Emergency Medicine.

Herpesvirus Diseases: Differential Diagnosis & Treatment Guide

The 9 Human Herpesviruses - Quick Reference

Virus	Common Name	Primary Disease	Latency Site
HHV-1 (HSV-1)	Herpes simplex 1	Orolabial herpes	Trigeminal ganglion
HHV-2 (HSV-2)	Herpes simplex 2	Genital herpes	Sacral ganglia (S2-S4)
HHV-3 (VZV)	Varicella-zoster	Chickenpox / Shingles	Dorsal root ganglia
HHV-4 (EBV)	Epstein-Barr	Infectious mononucleosis	B lymphocytes
HHV-5 (CMV)	Cytomegalovirus	CMV disease	Myeloid progenitors
HHV-6A/6B	Roseola virus	Roseola infantum	T lymphocytes
HHV-7	-	Roseola (2nd agent)	T lymphocytes
HHV-8 (KSHV)	Kaposi sarcoma HV	Kaposi sarcoma	B lymphocytes

1. HSV-1 - Orolabial Herpes (Cold Sores / Herpes Labialis)

Differential Diagnosis

Primary gingivostomatitis (child): Fever, drooling, painful vesicles/ulcers on gingiva, buccal mucosa, tongue, lips. Can mimic hand-foot-mouth disease (HFMD), herpangina, aphthous ulcers, or Stevens-Johnson syndrome.
Recurrent herpes labialis: Grouped vesicles on vermilion border. DDx: impetigo (honey-crusted, no prodrome), angular cheilitis (Candida), fixed drug eruption, lichen planus.
Herpes keratitis: Dendritic corneal ulcer on slit-lamp. DDx: Acanthamoeba keratitis, bacterial ulcer, recurrent corneal erosion.
Herpes whitlow: Vesicles on fingertip (HCW exposure). DDx: paronychia, felon, contact dermatitis.

Clinical Pearls

Prodrome of tingling/burning 6-48 h before vesicles = optimal antiviral window
Primary infection has systemic symptoms (fever, lymphadenopathy); recurrence does not
Tzanck smear shows multinucleated giant cells but cannot distinguish HSV-1 from HSV-2 or VZV
PCR swab from vesicle base is gold standard for confirmation
Steroid creams on undiagnosed facial lesions can cause eczema herpeticum - always rule out HSV first

Treatment

Setting	Drug	Route	Dose	Duration
Primary episode	Acyclovir	Oral	200 mg 5x/day OR 400 mg TID	7-10 days
	Valacyclovir	Oral	1 g BID	7-10 days
	Famciclovir	Oral	1 g BID	7-10 days
Recurrence (episodic)	Acyclovir	Oral	400 mg BID x5 d or 800 mg TID x2 d	2-5 days
	Valacyclovir	Oral	2 g BID x1 day (start at prodrome)	1 day
	Famciclovir	Oral	1500 mg single dose	1 day
Suppression (≥6 recurrences/year)	Acyclovir	Oral	400 mg BID	Continuous (review annually)
	Valacyclovir	Oral	500 mg-1 g once daily	Continuous
	Famciclovir	Oral	500 mg BID	Continuous
Primary gingivostomatitis (child)	Acyclovir	Oral	600 mg/m² 4x/day (or ~15 mg/kg/dose 4x/day)	10 days
Herpes keratitis	Acyclovir	Topical ophthalmic	3% ointment 5x/day	Until healed + 3 days
	Trifluridine	Topical ophthalmic	1% drops 9x/day	Up to 21 days

Clinical Pearl: Short-term high-dose valacyclovir (2 g BID x1 day) shortens healing by 1-2 days if started at prodrome - this is the most practical option for episodic therapy in clinic. Never prescribe topical acyclovir cream for orolabial herpes - oral bioavailability of cream is negligible.

2. HSV-2 - Genital Herpes

Differential Diagnosis

Feature	HSV Genital	Syphilis (Primary)	Chancroid	LGV	Behcet's
Lesion	Vesicles → painful ulcers	Single painless ulcer	Painful, ragged ulcers	Papule → ulcer	Recurrent oral + genital
Pain	Yes (severe 1st episode)	No	Yes	Variable	Yes
Lymph nodes	Bilateral tender	Firm, non-tender	Tender, fluctuant	Inguinal bubo	Absent
Systemic	Fever, myalgia (1st)	Rash, fever (2°)	No	Fever	Uveitis, pathergy
Test	PCR swab, IgG serology	Dark field, RPR/TPHA	Culture, PCR	PCR (L1-L3 strains)	Clinical criteria

Clinical Pearls

57% of new HSV-2 infections are symptomatic; 25% of "initial" clinical episodes are actually recurrences
In women under 25, HSV-1 causes >50% of genital herpes - critical for counseling on recurrence risk (HSV-1 recurs much less often)
Asymptomatic shedding occurs from multiple sites simultaneously even with intact skin - condoms reduce but do not eliminate transmission
Suppressive valacyclovir reduces partner transmission by 48-50%
Severe first episode (bilateral erosions, systemic illness, inability to void) = hospitalize for IV acyclovir
Rectal herpes (proctitis) mimics inflammatory bowel disease - sigmoidoscopy shows discrete ulcers
HSV-2 serology (type-specific IgG) is useful to identify asymptomatic carriers and counsel partners

Treatment

Setting	Drug	Route	Dose	Duration
First episode	Acyclovir	Oral	400 mg TID or 200 mg 5x/day	7-10 days
	Valacyclovir	Oral	1 g BID	7-10 days
	Famciclovir	Oral	250 mg TID	7-10 days
Recurrence (episodic)	Acyclovir	Oral	800 mg TID x3-4 d or 1 g daily x5 d	3-5 days
	Valacyclovir	Oral	500 mg BID x2 d or 1 g daily x5 d	2-5 days
	Famciclovir	Oral	1000 mg BID x1 day or 500 mg stat then 250 mg BID x2 d	1-2 days
Suppression	Acyclovir	Oral	400 mg BID	Continuous
	Valacyclovir	Oral	500 mg once daily (1 g if >10 recurrences/year)	Continuous
	Famciclovir	Oral	250 mg BID	Continuous
Severe/disseminated	Acyclovir	IV	5-10 mg/kg q8h	5-7 days then switch oral
Pediatric (≥12 y)	Acyclovir	Oral	40-80 mg/kg/day in 3-4 divided doses (max 1000 mg/day)	7-10 days
Pregnancy (1st episode)	Acyclovir	Oral	400 mg TID	7-10 days
Pregnancy (suppression from 36 wk)	Acyclovir	Oral	400 mg TID or Valacyclovir 500 mg BID	Until delivery

3. HSV Encephalitis

Differential Diagnosis

Bacterial meningitis (CSF PMN, low glucose), Tuberculous meningitis (subacute, high protein), limbic encephalitis (autoimmune, anti-NMDAR, anti-LGI1), HSV-2 meningitis (benign, self-limited), VZV encephalitis, CMV encephalitis (immunocompromised), EBV encephalitis, rabies, ADEM.

Diagnostic Triad

Fever + focal neurological signs + CSF pleocytosis (lymphocytes, RBCs)
MRI: temporal lobe T2/FLAIR hyperintensity (pathognomonic)
EEG: periodic lateralizing epileptiform discharges (PLEDs) over temporal lobe
HSV PCR CSF = gold standard (sensitivity 96%, specificity 99%)

Clinical Pearls

Start IV acyclovir immediately on suspicion - DO NOT wait for PCR results. Mortality falls from ~70% to ~10% with prompt treatment; delay until coma = poor outcome
LP must be done before acyclovir only if no mass lesion on CT; if CT shows herniation risk, start acyclovir first, LP second
Treat for a full 21 days - shorter courses carry risk of relapse
Post-encephalitis: ~80% of survivors have neurological sequelae; fewer than 20% return to work
Check repeat PCR at Day 14 to confirm clearance; some authorities give 3 months of suppressive valacyclovir after acute treatment

Treatment

Setting	Drug	Route	Adult Dose	Pediatric Dose	Duration
HSV Encephalitis	Acyclovir	IV	10 mg/kg q8h	10-15 mg/kg q8h	21 days
Step-down (mild-moderate)	Valacyclovir	Oral	1 g TID	-	Complete to 21 days

4. Neonatal Herpes

Differential Diagnosis

Sepsis (bacterial), enterovirus disease, congenital CMV/toxoplasmosis/rubella (TORCH), varicella, impetigo neonatorum, epidermolysis bullosa, incontinentia pigmenti.

Three Clinical Forms

Form	Timing	Features	Mortality (untreated)
SEM (Skin/Eye/Mouth)	Days 1-12	Vesicles, no CNS	Low (~0%)
CNS	Days 10-28	Encephalitis, seizures, bulging fontanelle	~15% treated
Disseminated	Days 5-12	Multi-organ, liver failure, DIC, vesicles	~30% treated

Clinical Pearls

70% of neonatal HSV occurs when mother has NO known genital herpes history - seronegative mothers who acquire primary infection near delivery carry highest risk (30-50% transmission)
SEM can progress to CNS or disseminated if untreated - all SEM cases get IV acyclovir
CSF PCR may be initially negative in SEM - repeat at Day 2-3 if suspicion persists
After acute IV course, give 6 months oral suppressive therapy to prevent CNS relapse

Treatment

Setting	Drug	Route	Dose	Duration
All forms (acute)	Acyclovir	IV	20 mg/kg/dose q8h (60 mg/kg/day)	SEM: 14 days; CNS/Disseminated: 21 days
Oral suppression (post-acute)	Acyclovir	Oral	300 mg/m² TID	6 months
Neonatal conjunctivitis with HSV	Acyclovir	IV	20 mg/kg/dose TID + topical trifluridine	14-21 days

5. Varicella-Zoster Virus (VZV) - Chickenpox

Differential Diagnosis

HFMD (Coxsackie A16, EV71): vesicles on hands/feet/mouth, not centripetal
Impetigo: pustules not vesicles, no stages
Eczema herpeticum: underlying eczema, Kaposi varicelliform eruption
Smallpox (historical)/Monkeypox: lesions all same stage, centrifugal, palms/soles involved
Disseminated zoster: similar morphology but older or immunocompromised patient
Drug eruption, insect bites: no systemic prodrome

Clinical Pearls

Classic: centripetal distribution, "dewdrop on rose petal" vesicles, simultaneous multi-stage lesions (macule + papule + vesicle + crust)
Infectious from 1-2 days before rash until ALL lesions are crusted (typically day 5-6)
Highest-risk: neonates (born to non-immune mothers), immunocompromised, adults (10x more severe), pregnant women (risk of neonatal varicella and varicella pneumonia)
Treat adults and high-risk groups within 24-72 h of rash onset for maximum benefit
Varicella pneumonia (adults): fever, dyspnea, hemoptysis - check CXR for bilateral nodular infiltrates; admit and give IV acyclovir

Treatment

Setting	Drug	Route	Adult Dose	Pediatric Dose (per kg)	Duration
Healthy child >2 y	Acyclovir	Oral	-	20 mg/kg/dose QID (max 800 mg/dose)	5 days
Adult/adolescent (immunocompetent)	Acyclovir	Oral	800 mg 5x/day	-	7 days
	Valacyclovir	Oral	1 g TID	-	5-7 days
Immunocompromised	Acyclovir	IV	10-12 mg/kg q8h	10 mg/kg q8h	7-10 days
Varicella pneumonia	Acyclovir	IV	10-12 mg/kg q8h	-	7 days
Pregnant (varicella)	Acyclovir	Oral	800 mg 5x/day	-	7 days; IV if pneumonia
Neonatal varicella exposure (VZIG)	VZIG/VariZIG	IM	-	125 IU/10 kg (max 625 IU) within 96 h	-

6. Herpes Zoster (Shingles)

Differential Diagnosis (Pre-rash Phase = Preeruptive Zoster)

Pleuritis, pericarditis, acute MI (thoracic dermatome)
Renal colic, appendicitis, biliary colic (abdominal dermatome)
Radiculopathy, sciatica (lumbar/sacral)
Trigeminal neuralgia, dental abscess (V1/V2/V3)
Cellulitis, contact dermatitis (once rash appears)

Post-rash DDx

HSV zosteriform: check serology/PCR - HSV can cause zosteriform rash
Zosteriform RCMP (rickettsia), impetigo, contact dermatitis

Clinical Pearls

Pain precedes rash by 2-3 days (preeruptive phase) - keep zoster on DDx for unilateral dermatomal pain with no visible rash
Zoster ophthalmicus (V1): any involvement of tip/side of nose (Hutchinson's sign) = high risk for eye involvement - urgent ophthalmology consult
Ramsay Hunt syndrome (HHV-3 reactivation in geniculate ganglion): ear pain + facial palsy + vesicles in external auditory canal / soft palate - treat aggressively with acyclovir + prednisolone
Zoster sine herpete: dermatomal pain without vesicles - confirm by VZV PCR of skin or CSF
Post-herpetic neuralgia (PHN): pain >3 months after healing. Risk factors: age >60, severe acute pain, ophthalmic distribution. Prevent by starting antivirals within 72 h of rash
Treat within 72 h of rash onset (or at any time if new vesicles still appearing or in immunocompromised)
PHN treatment: gabapentin, pregabalin, tricyclic antidepressants, lidocaine 5% patch, high-dose capsaicin 8% patch, opioids

Treatment

Setting	Drug	Route	Adult Dose	Pediatric Dose	Duration
Immunocompetent adult	Acyclovir	Oral	800 mg 5x/day	-	7 days
	Valacyclovir	Oral	1 g TID	-	7 days
	Famciclovir	Oral	500 mg TID	-	7 days
Immunocompromised / disseminated	Acyclovir	IV	10 mg/kg q8h	10 mg/kg q8h	7-10 days then switch oral
Zoster ophthalmicus	Acyclovir	Oral	800 mg 5x/day	-	7-10 days (IV if immunocompromised)
	Acyclovir	Topical ophthalmic	3% ointment	-	7-10 days + urgent ophthalmology
Ramsay Hunt	Acyclovir	Oral	800 mg 5x/day + Prednisolone 60 mg/day	-	7 days antiviral; taper steroid over 10 days
Pediatric (immunocompromised)	Acyclovir	IV	-	10-12 mg/kg q8h	7-10 days
PHN adjuncts	Gabapentin	Oral	300 mg at night → titrate to 1800-3600 mg/day in 3 divided doses	-	Ongoing
	Pregabalin	Oral	75 mg BID → 150-300 mg BID	-	Ongoing
	Amitriptyline	Oral	10-25 mg at night → up to 75 mg	-	Ongoing

Vaccination Pearl: Recombinant zoster vaccine (Shingrix, RZV) - 2 doses, 2-6 months apart - >90% efficacy against zoster and PHN. Preferred over live Zostavax. Give to all adults ≥50 y including those with prior zoster. Cannot be given within 12 months of post-herpetic neuralgia onset.

7. Epstein-Barr Virus (EBV) - Infectious Mononucleosis

Differential Diagnosis

Feature	EBV Mono	CMV Mono	Strep Pharyngitis	HIV Seroconversion	Toxoplasmosis
Exudative pharyngitis	++	+	+++	+	+/-
Lymphadenopathy	Cervical + posterior	Cervical	Anterior cervical	Generalized	Posterior cervical
Splenomegaly	50-75%	Less common	No	Yes	Yes
Heterophile Ab	+	Negative	Negative	Negative	Negative
Atypical lymphocytes	++	++	Absent	+	+
Rash with amoxicillin	>80%	Rare	No	No	No
Age	Teens/young adults	Any	Any	Young adults	Any

Clinical Pearls

Amoxicillin/ampicillin rash (maculopapular, widespread, non-allergic) occurs in >80% of EBV mononucleosis - avoid all aminopenicillins pending monospot/EBV serology
Splenomegaly = avoid contact sports, strenuous activity until spleen normalizes (USS to confirm, typically 3-4 weeks)
Splenic rupture (rare, 0.1-0.5%) = surgical emergency - presents as acute left upper quadrant pain
Monospot (heterophile Ab) test: sensitivity 85% in adults, only 50% in children <4 years - if negative and high suspicion, send EBV-specific serology (VCA IgM/IgG, EA, EBNA)
Acyclovir reduces viral shedding but has NO clinical benefit in typical mononucleosis - do not routinely prescribe
Corticosteroids are indicated only for impending airway obstruction, severe thrombocytopenia, or autoimmune hemolytic anemia
EBV complications: hepatitis, meningitis/encephalitis, myocarditis, Guillain-Barre, hemophagocytic lymphohistiocytosis (HLH) - rare but serious

Treatment

Setting	Therapy	Dose/Notes
Typical mononucleosis (1st line)	Supportive: NSAIDs/acetaminophen, rest	Paracetamol 15 mg/kg/dose q4-6h (child) or 500-1000 mg q6h (adult)
	Avoid contact sports	Until spleen normalizes on USS
Airway obstruction / severe thrombocytopenia / AIHA (2nd line)	Prednisolone	1 mg/kg/day (max 60 mg) x 5-7 days then taper
Acyclovir	Not routinely recommended	Reduces shedding, no clinical benefit
EBV encephalitis / HLH (severe)	IV Acyclovir	10 mg/kg q8h x 14-21 days; add rituximab/IVIG for HLH

8. Cytomegalovirus (CMV)

Differential Diagnosis by Clinical Syndrome

Syndrome	CMV	Other causes
CMV mononucleosis	EBV-negative mononucleosis (heterophile-negative)	EBV, toxoplasmosis, HIV
CMV retinitis	"Brushfire" or "pizza pie" appearance (immunocompromised)	Toxoplasma retinitis, syphilitic retinitis
Congenital CMV	Petechiae, jaundice, periventricular calcifications	Congenital toxoplasmosis (diffuse calcifications), rubella, syphilis
CMV pneumonitis	Bilateral interstitial pneumonitis (transplant)	PCP, invasive fungal, RSV, adenovirus
CMV colitis	Bloody diarrhea, mucosal ulcers (HIV/transplant)	C. difficile, IBD flare, other viral colitis

Clinical Pearls

CMV mononucleosis: more prominent hepatitis, less pharyngitis than EBV; heterophile antibody NEGATIVE
Congenital CMV: 90% asymptomatic at birth but 15% develop sensorineural hearing loss later - all confirmed cases need audiologic follow-up regardless of symptoms
Periventricular calcifications on head CT/USS = congenital CMV until proven otherwise (toxoplasmosis causes diffuse/cortical calcifications)
In HIV patients: CMV retinitis occurs when CD4 <50 cells/µL - weekly fundoscopic screening recommended
Monitor CBC weekly during ganciclovir - myelosuppression (neutropenia, thrombocytopenia) is dose-limiting; hold if ANC <500 or platelets <25,000
Ganciclovir resistance (UL97 mutation): switch to foscarnet. If UL54 mutation also present: cidofovir or maribavir

Treatment

Setting	Drug	Route	Dose	Duration
CMV Disease (immunocompromised) - Induction	Ganciclovir	IV	5 mg/kg q12h	14-21 days
	Valganciclovir	Oral	900 mg BID	14-21 days (equivalent to IV)
Maintenance	Valganciclovir	Oral	900 mg once daily	Until CD4 >100 x3 months
	Ganciclovir	IV	5 mg/kg once daily	If oral not tolerated
CMV Retinitis (intravitreal)	Ganciclovir	Intravitreal	2 mg/injection	+ systemic therapy
CMV Colitis/Pneumonitis (HIV)	Ganciclovir	IV	5 mg/kg q12h	3-4 weeks
Congenital CMV with CNS involvement	Valganciclovir	Oral	16 mg/kg/dose BID	6 months
	Ganciclovir	IV	6 mg/kg/dose q12h x 6 wk then step-down	6 weeks IV → then oral
Transplant prophylaxis	Valganciclovir	Oral	900 mg once daily	Per protocol (typically 3-6 months)
Ganciclovir-resistant CMV	Foscarnet	IV	60 mg/kg q8h or 90 mg/kg q12h	14-21 days
	Cidofovir	IV	5 mg/kg weekly x2 then every 2 weeks (with probenecid + hydration)	-
	Maribavir	Oral	400 mg BID	8 weeks

9. HHV-6 (Roseola Infantum / Exanthem Subitum)

Differential Diagnosis

Roseola is the classic diagnosis: fever 3-5 days → defervescence → macular rash
DDx during fever: otitis media, occult bacteremia, UTI, influenza
DDx of rash: rubella (lymphadenopathy, no high fever), measles (Koplik spots, cephalocaudal spread, coryza), drug reaction (rash before defervescence), enteroviruses

Clinical Pearls

Most common in infants 6-18 months (maternal antibody wanes)
Febrile seizures occur in up to 10-15% during rapid temperature rise - counsel parents
In immunocompromised (post-transplant): HHV-6 encephalitis = most common viral encephalitis after allogenic SCT; presents as amnesia, confusion, SIADH
HHV-6 PCR in CSF for transplant patients with acute encephalitis
Chromosomally integrated HHV-6 (ciHHV-6): causes falsely elevated HHV-6 plasma viral loads - suspect if consistently very high levels without symptoms

Treatment

Setting	Drug	Route	Dose	Notes
Roseola (immunocompetent child)	Supportive	-	Antipyretics (paracetamol 15 mg/kg q4-6h)	Antiviral NOT indicated
HHV-6 Encephalitis (immunocompromised)	Ganciclovir	IV	5 mg/kg q12h	First-line
	Foscarnet	IV	60 mg/kg q8h	Alternative; less myelosuppression
	Valganciclovir	Oral	900 mg BID	Step-down/maintenance

10. HHV-8 - Kaposi Sarcoma Herpesvirus

Differential Diagnosis of Kaposi Sarcoma Lesions

Bacillary angiomatosis (Bartonella - look-alike in HIV, PCR distinguishes)
Pyogenic granuloma, angiosarcoma, melanoma, dermatofibroma, ecchymosis (purpuric lesions)

Clinical Pearls

Classic KS (Mediterranean elderly men), Endemic KS (sub-Saharan Africa), Iatrogenic KS (transplant immunosuppression), Epidemic KS (HIV with CD4 <200)
Pulmonary KS mimics PCP - bronchoalveolar lavage and bronchoscopy with direct visualization needed
Primary treatment for HIV-associated KS = antiretroviral therapy (ART) + immune reconstitution
Localized cutaneous disease: radiotherapy, intralesional vinblastine, topical alitretinoin
Systemic/advanced KS: pegylated liposomal doxorubicin (PLD) is first-line chemotherapy

Setting	Therapy	Dose
HIV-KS (all stages)	Optimize ART	Core treatment
Systemic/advanced KS	Pegylated liposomal doxorubicin	20 mg/m² IV q3 weeks
	Paclitaxel	100 mg/m² q2 weeks (2nd line)
Localized	Intralesional vinblastine	0.1-0.2 mg/cm² lesion
	Topical alitretinoin 0.1% gel	Apply BID-QID
HHV-8 Castleman's disease	Siltuximab or tocilizumab (anti-IL-6)	Per oncology protocol

Key Antiviral Drug Summary Table

Drug	Spectrum	Key Mechanism	Renal Dose Adjustment	Major Toxicity
Acyclovir	HSV-1, HSV-2, VZV (weak CMV)	Viral TK phosphorylation → inhibits viral DNA polymerase	Yes (CrCl <50)	Nephrotoxicity (IV), neurotoxicity (high dose), phlebitis
Valacyclovir	HSV-1, HSV-2, VZV	Prodrug of acyclovir (3-5x bioavailability)	Yes	Same as acyclovir; TTP/HUS at very high doses in immunocompromised
Famciclovir	HSV-1, HSV-2, VZV	Prodrug of penciclovir	Yes	Well tolerated; headache, nausea
Ganciclovir	CMV, HSV, VZV, HHV-6/8	UL97 kinase phosphorylation → DNA polymerase inhibition	Yes	Neutropenia, thrombocytopenia (monitor CBC weekly)
Valganciclovir	Same as ganciclovir	Prodrug of ganciclovir (similar plasma levels to IV GCV)	Yes	Same as ganciclovir
Foscarnet	CMV, HSV, VZV (resistant)	Direct pyrophosphate binding to DNA polymerase (no TK needed)	Yes (nephrotoxic)	Nephrotoxicity, electrolyte disturbances (Ca, Mg, K, PO4), genital ulceration
Cidofovir	CMV, resistant HSV/VZV	Cellular kinase phosphorylation	Yes (nephrotoxic)	Nephrotoxicity (must use with probenecid + IV hydration)
Maribavir	CMV (resistant)	UL97 kinase inhibitor	No	GI symptoms, taste disturbance

Foscarnet Clinical Pearls

Does NOT require viral thymidine kinase for activation - covers acyclovir-resistant HSV/VZV and ganciclovir-resistant CMV
Mandatory IV saline pre-hydration (1 L NS before each infusion) to reduce nephrotoxicity
Monitor electrolytes daily - causes hypocalcemia, hypomagnesemia, hypokalemia, hypophosphatemia/hyperphosphatemia
Genital/perianal ulceration from foscarnet in urine = reduce dose, increase hydration

Pediatric Per-kg Dosing Quick Reference

Drug / Indication	Age	Dose	Route	Frequency	Duration
Acyclovir - Neonatal HSV	0-3 months	20 mg/kg/dose	IV	q8h (60 mg/kg/day)	14-21 days
Acyclovir - HSV Encephalitis	All ages	10-15 mg/kg/dose	IV	q8h	21 days
Acyclovir - Chickenpox (immunocompromised)	All ages	10 mg/kg/dose	IV	q8h	7-10 days
Acyclovir - Chickenpox (immunocompetent child)	2-12 y	20 mg/kg/dose (max 800 mg)	Oral	QID	5 days
Acyclovir - Genital HSV 1st episode (peds)	≥12 y	40-80 mg/kg/day in 3-4 doses (max 1000 mg/day)	Oral	-	7-10 days
Acyclovir - Post-neonatal oral suppression	0-3 months	300 mg/m² /dose	Oral	TID	6 months
Acyclovir - Primary gingivostomatitis	Child	600 mg/m² /dose or ~15 mg/kg/dose	Oral	4x/day	10 days
Valganciclovir - Congenital CMV	Neonate	16 mg/kg/dose	Oral	BID	6 months
Ganciclovir - Congenital CMV	Neonate	6 mg/kg/dose	IV	q12h x 6 wk	6 weeks
VZIG - Varicella post-exposure prophylaxis	All	125 IU per 10 kg (max 625 IU)	IM	Single dose	Within 96 h

Special Populations Summary

Pregnancy

Acyclovir (category B equivalent) - safe in all trimesters, use for primary varicella or HSV
Suppressive acyclovir/valacyclovir from 36 weeks reduces clinical recurrence and HSV shedding at delivery
Avoid valacyclovir at very high doses (3g/day+) in first trimester
VZIG for VZV-seronegative exposed pregnant women within 96 h

Immunocompromised (HIV, transplant, chemotherapy)

Lower threshold to use IV antivirals
Longer courses needed
Resistance more common - send viral resistance testing early if no response at Day 5-7
All HSV/VZV antiviral courses should be followed by suppressive therapy
Monitor CBC weekly on ganciclovir; G-CSF if neutropenia develops

Renal Impairment

All herpetic antivirals need dose adjustment - check CrCl before prescribing
Acyclovir IV: if CrCl 10-25 mL/min → q12h; if <10 → q24h
Ensure adequate hydration for IV acyclovir to avoid crystal nephropathy

Sources: Harrison's Principles of Internal Medicine 22E (2025) - Antiviral Chemotherapy Ch.96; Goldman-Cecil Medicine - Antivirals Ch.328; Andrews' Diseases of the Skin; Fitzpatrick's Dermatology 9E; Goodman & Gilman's Pharmacological Basis; Red Book 2021 (AAP); Tintinalli's Emergency Medicine; Creasy & Resnik's Maternal-Fetal Medicine

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