MEDICINE 2

LICEO DE CAGAYAN UNIVERSITY

COLLEGE OF MEDICINE

November 11, 2024

LAMATA, CHRISTEL
LORCA, NIÑO CHRISTIAN
MACASINDIL, HIDAYAH
MANGANDOG, JOMAILAH
MANGANDOG AMERCOSAIN
ONG, JOHN ALEXANDERS
OUANO, JOSEPH IVAN TIMOTHY
HIV
1. Describe and briefly discuss
A. What is the current CDC classification system for HIV infection and AIDS
a. The current CDC classification system for HIV infection and AIDS categorizes patients
based on clinical conditions associated with HIV infection together with the level of
the CD4+ T lymphocyte count. A confirmed HIV case can be classified in one of five
HIV infection stages (0, 1, 2, 3, or unknown). If there was a negative HIV test within 6
months of the first HIV infection diagnosis, the stage is 0 and remains 0 until 6
months after diagnosis. Advanced HIV disease (AIDS) is classified as stage 3 if one or
more specific opportunistic illness has been diagnosed
B. How do you define AIDS
a. AIDS, or Acquired Immunodeficiency Syndrome, is the most severe phase of HIV
(Human Immunodeficiency Virus) infection. It's defined by a significant weakening of
the immune system, which is measured by a low CD4 cell count or the presence of
certain opportunistic infections and cancers.
C. What are the AIDS-defining opportunistic illnesses?

D. What are the stages of CDC HIV infection based on CD4+ T LYMPHOCYTE test results and
immunologic criteria?
2. Transmission
A. How does HIV transmitted?
a. SEXUAL TRANSMISSION
b. TRANSMISSION THROUGH INJECTION DRUG USE
c. TRANSMISSION BY TRANSFUSED BLOOD AND BLOOD PRODUCTS
d. OCCUPATIONAL TRANSMISSION OF HIV: HEALTH CARE WORKERS, LABORATORY
WORKERS, AND THE HEALTH CARE SETTING
e. MOTHER-TO-CHILD TRANSMISSION OF HIV
f. TRANSMISSION OF HIV BY OTHER BODY FLUIDS
B. Describe each mode of HIV transmission
a. SEXUAL TRANSMISSION
i. HIV infection is predominantly a sexually transmitted infection (STI)
worldwide. By far the most common mode of infection, particularly in
developing countries, is heterosexual transmission, although in many
western countries male-to-male sexual transmission dominates.
ii. HIV has been demonstrated in seminal fluid both within infected
mononuclear cells and in cell-free material. The virus appears to concentrate
in the seminal fluid, particularly in situations where there are increased
numbers of lymphocytes and monocytes in the fluid, as seen in genital
inflammatory states such as urethritis and epididymitis, conditions closely
associated with other STIs
iii. The virus has also been demonstrated in cervical smears and vaginal fluid.
There is an elevated risk of HIV transmission associated with unprotected
receptive anal intercourse (URAI) among both men and women compared to
the risk associated with unprotected receptive vaginal intercourse
iv. Anal douching and sexual practices that traumatize the rectal mucosa also
increase the likelihood of infection. It is likely that anal intercourse provides
at least two modalities of infection:
1. direct inoculation into blood in cases of traumatic tears in the
mucosa; and
2. infection of susceptible target cells, such as Langerhans cells, in the
mucosal layer in the absence of trauma
b. TRANSMISSION THROUGH INJECTION DRUG USE
 i. HIV can be transmitted to injection drug users (IDUs) who are exposed to
HIV while sharing injection paraphernalia such as needles, syringes, water in
which drugs are mixed, or the cotton through which drugs are filtered.
ii. Parenteral transmission of HIV during injection drug use does not require IV
puncture; subcutaneous (“skin popping”) or intramuscular (“muscling”)
injections can transmit HIV as well.
c. TRANSMISSION BY TRANSFUSED BLOOD AND BLOOD PRODUCTS
i. HIV can be transmitted to individuals who receive HIV-contaminated blood
transfusions, blood products, or transplanted tissue.
ii. Transfusions of whole blood, packed red blood cells, platelets, leukocytes,
and plasma are all capable of transmitting HIV infection
d. OCCUPATIONAL TRANSMISSION OF HIV: HEALTH CARE WORKERS, LABORATORY
WORKERS, AND THE HEALTH CARE SETTING
i. There is a small but definite occupational risk of HIV transmission to health
care workers and laboratory personnel and potentially others who work with
HIV-containing materials, particularly when sharp objects are used
ii. The global number of HIV infections among health care workers attributable
to sharps injuries has been estimated to be 1000 cases (range, 200–5000)
per year
iii. Exposures that place a health care worker at potential risk of HIV infection
are percutaneous injuries (e.g., a needle stick or cut with a sharp object) or
contact of mucous membrane or nonintact skin (e.g., exposed skin that is
chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other
potentially infectious body fluids
e. MOTHER-TO-CHILD TRANSMISSION OF HIV
i. HIV infection can be transmitted from an infected mother to her fetus during
pregnancy, during delivery, or by breast-feeding
ii. Virologic analyses of aborted fetuses indicate that HIV can be transmitted to
the fetus during the first or second trimesters of pregnancy. However,
maternal transmission to the fetus occurs most commonly in the perinatal
period
iii. In the absence of antiretroviral therapy for the mother during pregnancy,
labor, and delivery, and for the fetus prophylactically following birth, the
probability of transmission of HIV from mother to infant/ fetus ranges from
15 to 25% in industrialized countries and from 25% to 35% in developing
countries
iv. Breast-feeding is an important modality of transmission of HIV infection in
certain developing countries, particularly where mothers continue to
breast-feed for prolonged periods.
v. The risk factors for mother-to-child transmission of HIV via breast-feeding
include detectable levels of HIV in breast milk, the presence of mastitis, low
maternal CD4+ T-cell counts, and maternal vitamin A deficiency.
vi. The risk of HIV infection via breast-feeding is highest in the early months of
breast-feeding
 f. TRANSMISSION OF HIV BY OTHER BODY FLUIDS
i. Although HIV can be isolated typically in low titers from saliva of a small
proportion of infected individuals, there is no convincing evidence that saliva
can transmit HIV infection, either through kissing or through other
exposures, such as occupationally to health care workers.
ii. Saliva contains endogenous antiviral factors; among these factors,
HIV-specific immunoglobulins of IgA, IgG, and IgM isotypes are detected
readily in salivary secretions of infected individuals
C. What is the estimated risk of HIV transmission for various types of exposures

3. Pathophysiology:- SELF STUDY

A. Discuss the pathophysiology and pathogenesis of HIV disease
● Early events in HIV infection
● Establishment of chronic and persistent infection
● Advance HIV DISEASE
● Long term survivors, long term nonprogressors and elite controllers
4. Diagnosis?
A. How do you diagnose HIV?
● Standard Blood Screening Test based on detection of:
○ Antibodies to HIV
○ p24 antigen
● Common Laboratory-based platform
○ ELISA (Enzyme immunoassay EIA)
■ Extremely good screening test (sensitivity of >99.5%)
● Commercial kits
○ Contain antigen from both HIV-1 and HIV-2
 ○ Use both natural and recombinant antigens
● Fourth Generation EIA test
○ combine detection of antibodies to HIV-1 and HIV with detection of p24 antigen
of HIV
○ Scoring
■ Positive - Highly Reactive
■ Negative - Nonreactive
■ Intermediate- Partially reactive
B. What are the different screening confirmatory tests used to diagnose HIV. Describe the
principle of each test

C. What are the laboratory test used in the morning of patients with HIV infection
A. CD4+ T-CELL COUNTS
a. This is a laboratory test generally accepted as best indicator of immediate state
if immunologic competence of the patient with HIV infection
b. CD4+ T-cell counts <200/μL- high risk of disease from P. jirovecii, and patient
should be placed on a regimen for P. jirovecii prophylaxis.
c. CD4+ T-cell counts <50/μL- high risk of disease fromCMV, MAC and T. gondii.
Primary prophylaxis for MAC infection if indicated unless the patient is
immediately started on ART.

d. As with any laboratory measurement, one may wish to obtain two

determinations prior to any significant changes in patient management based
on CD4+ T-cell count alone
i. HIV infection should have CD4+ T-cell measurements performed at the
time of diagnosis
ii. 3–6 months thereafter
e. For patients who have been on ART for at least 2 years with HIV RNA levels
persistently <50 copies/ mL and CD4 counts 300-500/μL monitoring may be
decreased to every year
f. CD4 counts >500/μL- Optional monitoring
 g. HTLV-1/HIV co-infection may have elevated CD4+ T-cell counts that do not
accurately reflect their degree of immune competence
i. hypersplenism, undergone splenectomy, patients receiving
medications that suppress the bone marrow-CD4+ T-cell percentage
may be a more reliable indication of immune function than the CD4+
T-cell count
ii. CD4+ T-cell percent age of 15 is comparable to a CD4+ T-cell count of
200/μL.
B. HIV RNA DETERMINATIONS
a. Measurement of serum or plasma levels of HIV RNA has become an essential
component in the monitoring of patients with HIV infection
b. Most used technique is the RT-PCR assay, which generates data in the form of
number of copies of HIV RNA per milliliter of serum or plasma and can reliably
detect as few as 40 copies of HIV RNA per milliliter of plasma
c. undetectable- common practice to describe levels of HIV RNA below cut-offs, a
term that should be avoided as it is imprecise and leaves the false impression
that the level of virus is 0.
d. Measurements of changes in HIV RNA levels over time have been of great
value in delineating the relationship between
i. levels of virus and rates of disease progression
ii. rates of viral turnover
iii. relationship between immune system activation and viral replication
iv. time to development of drug resistance
e. Measurements of plasma HIV RNA levels
i. made at the time of HIV diagnosis
ii. every 3–6 months thereafter in the untreated patient
f. Following the initiation of therapy or any change in therapy
i. plasma HIV RNA levels should be monitored approximately every 4
weeks until the effectiveness of the therapeutic regimen is determined
by the development of a new steady-state level of HIV RNA
g. Effective antiretroviral therapy
i. plasma level of HIV RNA will drop to <50 copies/mL within 6 months of
the initiation of treatment
h. During therapy
i. levels of HIV RNA should be monitored every 3–6 months to evaluate
the continuing effectiveness of therapy
C. HIV RESISTANCE TESTING
a. HIV resistance testing can be done through either genotypic or phenotypic
measurements
b. Genotypic Assay
i. sequence analyses of the HIV genomes obtained from patients are
compared with sequences of viruses with known antiretroviral
resistance profiles
c. Phenotypic assays
 [Link] vivo growth of patient-derived viral isolates or genetically
constructed pseudoviruses is compared with the growth of reference
strains of the virus in the presence or absence of different
antiretroviral drugs
d. Resistance testing is recommended at the time of initial diagnosis and, if
therapy is not initiated at that time, at the time of initiation of ART
e. Drug resistance testing is also indicated in the setting of virologic failure and
should be performed while the patient is still on the failing regimen because of
the propensity for the pool of HIV quasispecies to rapidly revert to wild-type in
the absence of the selective pressures of ART
D. CO-RECEPTOR TROPISM ASSAYS
a. Maraviroc as the first CCR5 antagonist for the treatment of HIV infection
b. Antiretroviral agent maraviroc is effective only against CCR5-tropic viruses
c. Because the genotypic determinants of cellular tropism are poorly defined, a
phenotypic assay is necessary to determine this property of HIV
d. Trofile assay (Monogram Biosciences) is available to make this determination.
i. assay clones the envelope regions of the patient’s virus into an
indicator virus that is then used to infect target cells expressing either
CCR5 or CXCR4 as their co-receptor
ii. takes weeks to perform and is expensive
e. genotypic assay of the V3 region of HIV-1
i. less costly
ii. employ a computer algorithm to predict viral tropism from the
sequence
E. OTHER TEST

● CLINICAL MANIFESTATIONS
Discuss the clinical presentations on the different clinical spectrum of HIV infection
1. Acute HIV Infection
2. The Asymptomatic Stage-Clinical Latency
● The median time for untreated patients is ~10 years.
● Long-term nonprogressors - show little if any decline in CD4+ T-cell counts over extended
periods of time
● Elite nonprogressors - exhibits HIV RNA levels <50 copies/mL.
● During the asymptomatic period of HIV infection, the average rate of CD4+ T-cell decline
is ~50/μL per year in an untreated patient.
● When the CD4+ T-cell count falls to <200/μL, the resulting state of immunodeficiency is
severe enough to place the patient at high risk for opportunistic infections and
neoplasms and, hence, for clinically apparent disease.
3. Symptomatic Stage
A. Disease of the Respiratory System
● Acute bronchitis and sinusitis are prevalent during all stages of HIV infection. The
most severe cases tend to occur in patients with lower CD4+ T-cell counts.
○ Sinusitis presents as fever, nasal congestion, and headache.
○ The diagnosis is made by CT or MRI.
○ The maxillary sinuses are most commonly involved; however, disease is
also frequently seen in the ethmoid, sphenoid, and frontal sinuses.
● Pulmonary disease is one of the most frequent complications of HIV infection.
○ The most common manifestation of pulmonary disease is pneumonia.
○ Three of the 10 most common AIDS-defining illnesses are recurrent
bacterial pneumonia, tuberculosis, and pneumonia due to the
unicellular fungus P. jirovecii.
○ S. pneumoniae (pneumococcal) infection may be the earliest serious
infection to occur in patients with HIV disease.

● Pneumocystis pneumonia (PCP) is caused by the fungus P. jirovecii and was once
the hallmark of AIDS.
○ It is, however, still the single most common cause of pneumonia in
patients with HIV infection in the United States and can be identified as
 a likely etiologic agent in 25% of cases of pneumonia in patients with
HIV infection.
○ Otic involvement may be seen as a primary infection, presenting as a
polypoid mass involving the external auditory canal.

● Worldwide, approximately one-third of all AIDS-related deaths are associated

with TB, and TB is the primary cause of death for 10–15% of patients with HIV
infection.
○ In patients with relatively high CD4+ T-cell counts, the typical pattern of
pulmonary reactivation occurs: patients present with fever, cough,
dyspnea on exertion, weight loss, night sweats, and a chest x-ray
revealing cavitary apical disease of the upper lobes.
○ In patients with lower CD4+ T-cell counts, disseminated disease is more
common.

B. Disease of the Cardiovascular System

● The most common form of heart disease is coronary heart disease.
● In patients with HIV infection, cardiovascular disease may be associated with
classic risk factors such as smoking, a direct consequence of HIV infection, or a
complication of ART.
● Patients with HIV infection have higher levels of triglycerides, lower levels of
high-density lipoprotein cholesterol, and a higher prevalence of smoking than
cohorts of individuals without HIV infection.
● Another form of heart disease associated with HIV infection is a dilated
cardiomyopathy associated with congestive heart failure (CHF) referred to as
HIV-associated cardiomyopathy.
● Patients present with typical findings of CHF including edema and shortness of
breath. Patients with HIV infection may also develop cardiomyopathy as side
effects of IFN-α or nucleoside analogue therapy.
● Pericardial effusions may be seen in the setting of advanced HIV infection.
Predisposing factors include TB, CHF, mycobacterial infection, cryptococcal
infection, pulmonary infection, lymphoma, and KS.

C. Disease of the Oropharynx and Gastrointestinal System

● Oral lesions, including thrush, hairy leukoplakia, and aphthous ulcers, are
particularly common in patients with untreated HIV infection.
○ Thrush, due to Candida infection, and oral hairy leukoplakia, presumed
due to EBV, are usually indicative of fairly advanced immunologic
decline; they generally occur in patients with CD4+ T-cell counts of
<300/μL.

● Esophagitis may present with odynophagia and retrosternal pain.

○ Upper endoscopy is generally required to make an accurate diagnosis.
 ○ Esophagitis may be due to Candida, CMV, or HSV. While CMV tends to be
associated with a single large ulcer, HSV infection is more often
associated with multiple small ulcers.

● Bacteria may be responsible for infections of the GI tract in patients with HIV
infection.
○ Infections with enteric pathogens such as Salmonella, Shigella, and
Campylobacter are more common in men who have sex with men and
are often more severe and more apt to relapse in patients with HIV
infection.
○ Patients with untreated HIV have approximately a 20-fold increased risk
of infection with S. typhimurium.

● Cryptosporidia, microsporidia, and Isospora belli (Chap. 224) are the most
common opportunistic protozoa that infect the GI tract and cause diarrhea in
HIV-infected patients.

● CMV colitis was once seen as a consequence of advanced immunodeficiency in

5–10% of patients with AIDS.
○ It is much less common with the advent of ART. CMV colitis presents as
diarrhea, abdominal pain, weight loss, and anorexia.
○ The diarrhea is usually nonbloody, and the diagnosis is achieved through
endoscopy and biopsy.
○ Multiple mucosal ulcerations are seen at endoscopy, and biopsies reveal
characteristic intranuclear and cytoplasmic inclusion bodies

● In addition to disease caused by specific secondary infections, patients with HIV

infection may also experience a chronic diarrheal syndrome for which no
etiologic agent other than HIV can be identified.
○ This entity is referred to as AIDS enteropathy or HIV enteropathy.
 D. Hepatobiliary Diseases

Hepatobiliary Diseases in HIV Patients

• Liver disease accounts for ~15% of deaths in HIV-infected patients.
• Primarily due to co-infection with hepatitis B (HBV) and hepatitis C (HCV) and liver injury
from ART.

Co-Infection Prevalence and Effects

• High prevalence of HBV (~90% with exposure, 6–14% chronic) and HCV (5–50%) in
HIV-positive individuals in the U.S.; HCV rates are 70–95% among IV drug users.
• HIV co-infection increases persistent HBV surface antigenemia risk threefold.
• Increased liver-related mortality in HIV-HBV co-infected patients by 4–10 times; higher
HCV levels and fivefold increased liver-related death risk in HIV-HCV co-infection.

Treatment Approaches
• HBV: Use lamivudine, tenofovir, entecavir, etc., within ART to prevent HIV resistance.
• HCV: Direct-acting antivirals yield near 100% cure rate in co-infected patients, reducing
mortality.
• Vaccinate HIV patients against HAV and HBV if not previously exposed.

Other Hepatitis Viruses

• Hepatitis A not more frequent in HIV; Hepatitis G (GB virus C) associated with slower HIV
progression.

Opportunistic Infections and Complications

• Granulomatous hepatitis: Caused by mycobacterial or fungal infections, especially MAC.
 • Liver masses: Linked to TB, peliosis hepatis, fungal infections (e.g., C. immitis, H.
capsulatum).
• Biliary tract disease: Seen in cryptosporidiosis, CMV, Kaposi sarcoma; termed AIDS
cholangiopathy when diagnosis is unclear.

Drug-Induced Hepatotoxicity
• Many ART drugs metabolized in liver; may cause hepatotoxicity, including fatal hepatic
reactions.
• Nucleoside analogues: Mitochondrial toxicity can lead to hepatic steatosis, lactic
acidosis, and liver failure.
• Nevirapine and indinavir linked to severe hepatic reactions; unexplained transaminase
rise in ART patients suggests drug toxicity.

Pancreatic Injury
• Primarily due to drug toxicity (e.g., pentamidine, dideoxynucleosides); clinical
pancreatitis in <5% of cases.

E. Diseases Of the Kidney and Genitourinary Tract

Microalbuminuria (~20% in untreated HIV patients) and significant proteinuria (~2%) increase all-cause
mortality risk.

HIV-Associated Nephropathy (HIVAN)

• Common in African-American and Hispanic populations; can lead to end-stage renal
disease (ESRD).
• Presents with proteinuria, rarely edema or hypertension; kidneys appear enlarged and
hyperechogenic on ultrasound.
• Histology shows focal segmental glomerulosclerosis (80%) and mesangial proliferation
(10–15%).
• Treatment includes ART, ACE inhibitors, and possibly prednisone.
• Decreased incidence and severity with effective ART.
Drug-Induced Renal Damage
• Common causative drugs: pentamidine, amphotericin, adefovir, cidofovir, tenofovir, and
foscarnet.

Specific Drugs:
• TDF may cause renal injury; switching to TAF is recommended.
• TMP-SMX and cobicistat can elevate serum creatinine without lowering GFR.
• Sulfadiazine can cause reversible renal shutdown; indinavir and atazanavir may form
renal stones.
• Hydration is crucial for managing and preventing kidney stone formation.

Genitourinary Infections
 • High frequency in HIV patients; symptoms include skin lesions, dysuria, hematuria, and
pyuria.

Syphilis in HIV:
• Higher risk of atypical presentations (e.g., lues maligna, nephrotic syndrome,
neurosyphilis).
• Neurosyphilis may present as meningitis, neuroretinitis, deafness, or stroke; lumbar
puncture recommended in secondary syphilis.
• Diagnosis challenging due to possible false-positive or delayed VDRL and anti-FTA
results; dark-field examination advised.
• Monitor carefully for adequate response to syphilis therapy; ~33% experience
Jarisch-Herxheimer reaction.

Vulvovaginal Candidiasis in Women with HIV

• Symptoms: pruritus, discomfort, dyspareunia, dysuria, and rash extending to the thighs.
• Diagnosis via microscopic exam showing pseudohyphae; treat mild cases with topical
therapy and severe cases with fluconazole.
• Other causes of vaginitis include Trichomonas and bacterial infections.

F. Diseases Of the Endocrine System and Metabolic Disorders

Lipodystrophy Syndrome:
• Affects 33–75% of patients on thymidine analogues or protease inhibitors.
• Symptoms: Elevated triglycerides, cholesterol, apolipoprotein B, hyperinsulinemia, and
hyperglycemia.
• Physical changes: Truncal obesity, dorsocervical fat pad (“buffalo hump”), breast
enlargement, and peripheral wasting (notable in face and buttocks).
• Around 20% meet metabolic syndrome criteria.
• Management includes NCEP guidelines, switching from thymidine analogues and specific
protease inhibitors, and using lipid-lowering agents like gemfibrozil or atorvastatin.
• Lactic acidosis, particularly with nucleoside analogues, can occur and may be fatal.

Electrolyte Imbalances:
• Hyponatremia due to SIADH or adrenal insufficiency (evident by high potassium).
• Hyperkalemia from adrenal insufficiency, nephropathy, or drugs like trimethoprim and
pentamidine.
• Hypokalemia can be linked to tenofovir or amphotericin therapy.

Adrenal and Thyroid Disorders:

• Adrenal insufficiency may arise from mycobacterial, CMV, cryptococcal infections,
histoplasmosis, or ketoconazole.
• Iatrogenic Cushing’s syndrome may develop from glucocorticoid use with ritonavir or
cobicistat, causing prolonged steroid effects.
 • Thyroid abnormalities in 10–15% of HIV patients, mainly subclinical hypothyroidism;
immune reconstitution with ART may cause elevated TSH or Graves’ disease.

Hypogonadism:
• Seen in 20–50% of men with HIV, more common without ART.
• Associated with underlying illness or as a side effect of ganciclovir.
• Symptoms: Decreased libido, erectile dysfunction; consider androgen replacement for
symptomatic hypogonadism.
• Minimal effect on menstrual cycle except in advanced disease.

G. Immunologic And Rheumatologic Diseases

Drug Allergies:
• Common in advanced HIV, especially with TMP-SMX (up to 65%).
• Symptoms: Erythematous, pruritic, morbilliform eruptions with fever.
• Abacavir hypersensitivity is HLA-B5701-linked and contraindicates rechallenge.
• Desensitization is effective for some drugs, except abacavir.

Autoimmunity and B-cell Activation:

• Elevated antiphospholipid and antinuclear antibodies without increased lupus or
rheumatoid arthritis.
• Diffuse infiltrative lymphocytosis syndrome (DILS): Resembles Sjogren’s but differs in cell
type and HLA profile (CD8+ predominant in HIV).

Arthralgias and Arthritis:

• ~33% experience arthralgias; 5–10% have reactive arthritis (Reiter’s syndrome, psoriatic
arthritis).
 • HIV-associated arthropathy: Oligoarticular arthritis, mainly knees and ankles, lasting
weeks to months.
• Painful articular syndrome: Severe, acute pain in joints, often requiring analgesics.

Fibromyalgia:
• 11% in HIV-infected cohorts experience chronic musculoskeletal pain, supporting a
musculoskeletal link with HIV.

Septic Arthritis and Opportunistic Infections:

• Septic arthritis is rare but mostly caused by Staphylococcus aureus or mycobacterial
infections.

Bone and Joint Complications with ART:

• Osteonecrosis (hip and shoulders) observed in 4.4% of asymptomatic patients, linked
with glucocorticoids, testosterone, and lifestyle factors.
• Osteoporosis in 7% of women with HIV, and bone mineral density declines of 2–6% in
the first 2 years on ART, especially with tenofovir.

H. Immune Reconstitution Inflammatory Syndrome

Immune Reconstitution Inflammatory Syndrome (IRIS):

• Paradoxical worsening of preexisting, untreated, or partially treated infections, or
development of autoimmune conditions after ART initiation.

Types:
• Paradoxical IRIS: Exacerbation of known pre-existing infections or neoplasms.
• Unmasking IRIS: Manifestation of previously undiagnosed conditions.
• Immune Reconstitution Disease (IRD): IRIS specific to opportunistic diseases versus
autoimmune IRIS.

Incidence: Occurs in 10–30% of patients on ART, especially with CD4+ counts <50 cells/μL and rapid HIV
RNA decrease.

Symptoms: Localized lymphadenitis, prolonged fever, pulmonary infiltrates, hepatitis, increased

intracranial pressure, uveitis, sarcoidosis, Graves’ disease.

Onset: 2 weeks to 2 years post-ART initiation.

Mechanism: Resembles type IV hypersensitivity due to rapid immune recovery.

Treatment: Severe cases may require immunosuppressive drugs (e.g., glucocorticoids) alongside specific
antimicrobial therapy.
 I. Disease Of the Hematopoietic System

Lymphadenopathy:
• Persistent generalized lymphadenopathy is an early clinical sign.
• Caused by follicular hyperplasia in lymph nodes; nodes are typically movable and
discrete.
• Reduction in lymph node size may indicate disease progression.
• Common causes: TB, KS, Castleman’s disease, lymphoma, atypical mycobacterial
infection, toxoplasmosis, systemic fungal infections, bacillary angiomatosis.

Anemia:
• Most common hematologic abnormality in HIV; can predict poor prognosis.
• Causes: drug toxicity (e.g., zidovudine), systemic infections, nutritional deficiencies,
parvovirus B19 infection.
• Treatment: erythropoietin for low levels, IVIg for parvovirus-induced anemia.

Neutropenia:
• Seen in ~50% of patients; may increase risk of bacterial infections.
• Linked to advanced HIV disease or myelosuppressive therapies.
• Treatment: G-CSF or GM-CSF to raise neutrophil counts.

Thrombocytopenia:
• Occurs early in HIV infection; increases with lower CD4 counts.
• May resemble idiopathic thrombocytopenic purpura; caused by immune complexes or
direct effect on megakaryocytes.
• Treated effectively with ART, IVIg or anti-Rh Ig for severe cases, rituximab for refractory
cases.
• Splenectomy is a last-resort treatment, requiring vaccinations for encapsulated
organisms.

Venous Thromboembolic Disease:

• Incidence ~1% per year, higher than the general population.
 • Risk factors: age >45, history of opportunistic infection, low CD4 count, estrogen use.
• Associated with coagulation abnormalities (e.g., decreased protein S, anticardiolipin
antibodies).

J. Dermatologic Diseases
● 90% of HIV patients experience dermatologic issues.
● Cutaneous manifestations vary from acute rashes to end-stage Kaposi’s Sarcoma (KS).

Common Non-Neoplastic Skin Conditions

● Seborrheic Dermatitis: Affects up to 50% of HIV patients, worsens with lower CD4+ counts.
Treated with antifungal agents.
● Folliculitis: Seen in ~20% of HIV patients, common with CD4+ <200 cells/μL. May improve with
ART.
● Pruritic Papular Eruption: Common pruritic rash in HIV, appears on face, trunk, and extensor
surfaces.

Other Skin Issues

● Psoriasis & Ichthyosis: Severe forms in HIV patients.

● Herpes Zoster: Reactivates in 10-20% of HIV patients, may indicate immune decline.
● Herpes Simplex Virus (HSV): Causes recurrent orolabial, genital, and perianal lesions in
advanced HIV.
● Molluscum Contagiosum: Diffuse skin eruptions in advanced HIV, often regress with ART.

Neoplastic Conditions

● Kaposi’s Sarcoma (KS), more common in immunocompromised individuals.

Skin Infections

● Fungal Infections: Mycobacteria, Acanthamoeba, Bartonella.

● Aspergillus: Noted in IV catheter sites.

Drug-Related Skin Reactions

 ● Severe reactions: Erythroderma, Stevens-Johnson syndrome, Toxic Epidermal Necrolysis
(especially from sulfa drugs, NNRTIs, abacavir, etc.).

Cosmetic Changes

● Yellowing of nails, hair straightening (common in African-Americans).

● Zidovudine: Elongation of eyelashes, bluish nail discoloration.

Treatment

● Antifungals, antivirals (Valacyclovir, Acyclovir), and ART are key to managing skin conditions in
HIV.
K. Neurologic Diseases

Neurological Disease in HIV:

● HIV infection leads to significant neurological morbidity, either through direct viral effects or
secondary opportunistic infections (e.g., toxoplasmosis, cryptococcosis, progressive multifocal
leukoencephalopathy).
● ART has reduced the frequency of secondary CNS diseases, but primary HIV-related neurological
issues persist.
HIV-Associated Neurocognitive Disorders (HAND):

● Range from asymptomatic impairment to severe dementia (HIV-associated dementia or HAD).

● HAD is a common AIDS-defining illness with cognitive decline, motor abnormalities, and
behavioral changes.
● 50% of ART-treated patients may experience mild to moderate cognitive impairment.

Cerebrospinal Fluid (CSF) Abnormalities:

● In ~90% of untreated HIV patients, CSF shows abnormal findings, such as pleocytosis, elevated
protein, and viral RNA presence, even without symptoms.

Aseptic Meningitis and Encephalitis:

● Can occur at any stage, often immune-mediated. Acute meningitis presents with headache,
fever, and photophobia, but usually resolves within weeks.

Fungal and Other Infections:

● Cryptococcal meningitis is common in patients with AIDS, especially in those with CD4+ <100
cells/μL.
● Primary CNS lymphoma and other rare infections (e.g., CMV, syphilis) are seen in later stages.

HIV-Associated Dementia:

● A late complication of HIV, characterized by cognitive decline, motor abnormalities, and

behavioral changes. Can occur in patients with higher CD4 counts.
PML (Progressive Multifocal Leukoencephalopathy):

● A rare and fatal complication of AIDS caused by JC virus. MRI reveals characteristic lesions, and
JC virus DNA in CSF aids diagnosis.

Spinal Cord Disease and Myelopathy:

● Seen in 20% of AIDS patients. Vacuolar myelopathy, dorsal column disease, and sensory ataxia
are common. CMV myelopathy may also occur.

Peripheral Neuropathy:

● Includes distal sensory polyneuropathy (DSPN), often due to HIV or ART side effects, leading to
painful sensations and sensory loss in the feet.

Treatment and Prognosis:

● ART helps manage neurocognitive issues but does not fully prevent neurological complications.
Prompt treatment for infections like CMV and cryptococcosis is crucial for improving outcomes.
L. Additional Disseminated Infections and Wasting Syndrome
○ In patients with advanced HIV infection, several disseminated infections and
wasting syndromes are commonly observed:
1. Bartonella infections (e.g., bacillary angiomatosis, cat-scratch disease, trench fever) are frequent
in those with CD4+ T-cell counts <100/μL. Bacillary angiomatosis, caused by B. henselae,
presents with vascular skin lesions and systemic symptoms. Diagnosis is challenging, often
relying on PCR or biopsy, and treatment includes doxycycline or erythromycin.
2. Histoplasmosis is an opportunistic fungal infection mainly in areas like the Mississippi and Ohio
River valleys. It presents as disseminated disease in HIV patients, often with fever, weight loss,
hepatosplenomegaly, and bone marrow involvement. Diagnosis involves tissue cultures or
antigen detection, and treatment includes amphotericin B followed by itraconazole.
3. Penicillium marneffei is a fungal infection endemic in Southeast Asia, particularly among HIV
patients. It causes fever, lymphadenopathy, and papular skin lesions. Treatment involves
amphotericin B followed by itraconazole.
4. Visceral leishmaniasis occurs in HIV-infected individuals in endemic areas, presenting with fever,
hepatosplenomegaly, and hematologic issues. Diagnosis is through PCR and bone marrow
culture, and treatment typically includes amphotericin B or pentavalent antimony.
5. Malaria risk is higher in HIV-positive patients, especially those with CD4+ T-cell counts <300/μL.
Malaria treatment efficacy is lower in these patients, and TMP-SMX prophylaxis may reduce the
risk.
6. Generalized wasting syndrome (involuntary weight loss >10%) is an AIDS-defining condition,
characterized by muscle wasting, fatigue, and chronic diarrhea or fever. It was more common
before the widespread use of antiretrovirals but is less frequent today. Treatments like
glucocorticoids, anabolic steroids, growth hormone, and parenteral nutrition have shown
variable success.
M. Neoplastic Disease
 ○ Neoplastic diseases in HIV-infected individuals include AIDS-defining
conditions such as Kaposi's sarcoma (KS), non-Hodgkin’s lymphoma, and
invasive cervical carcinoma, as well as a higher incidence of
non-AIDS-defining malignancies like Hodgkin’s disease, multiple myeloma,
and various cancers (e.g., melanoma, testicular, and lung cancers). ART has
significantly reduced the incidence of KS, but non-AIDS-defining cancers now
account for more morbidity and mortality in HIV patients, with KS and
non-Hodgkin’s lymphoma being the most common.

○ Kaposi’s sarcoma, linked to HHV-8, is characterized by vascular nodules on

skin, mucous membranes, and internal organs, with a varied clinical course
from indolent to aggressive. It often affects sun-exposed areas, and its
treatment primarily involves ART, with additional therapies like radiation,
intralesional vinblastine, or chemotherapy for more advanced cases.

○ Lymphoma is more common in HIV patients, especially in those with low

CD4+ counts, and includes immunoblastic lymphoma, Burkitt’s lymphoma,
and primary CNS lymphoma. Treatment often involves chemotherapy, with
ART improving survival outcomes. CNS lymphoma, which presents with focal
neurologic symptoms, has a poor prognosis due to the advanced stage of HIV
at diagnosis.

○ Multicentric Castleman’s disease (MCD), often associated with KSHV and

occurring more frequently in the ART era, shares features with lymphoma but
is treated with chemotherapy, and survival has improved with ART.

○ HPV-related cancers, including cervical and anal cancers, are more common
in HIV patients. HPV can cause intraepithelial dysplasia leading to invasive
cancer, and regular screenings (Pap smears and anal exams) are
recommended for HIV-infected individuals. Though ART does not significantly
reduce HPV-related cancer risks, vaccination is recommended.

● TREATMENT
A. What are the General Principles of Patient Management

General Principles of Patient Management

● Routine HIV Testing: The CDC recommends HIV testing as part of routine medical care, with
patients informed and given the option to "opt out." Around 13% of HIV-infected individuals in
the U.S. are unaware of their status.
● Pretest Counseling: Counseling before testing is essential to prepare patients for the possibility
of a positive result, helping to emotionally stabilize them and activate support systems.
● Initial Care: After an HIV diagnosis, healthcare providers should immediately initiate ART
(antiretroviral therapy) and offer emotional and social support. Local HIV support centers can
assist in this process.
Comprehensive Management

● Medical Knowledge: Successful management requires expertise in internal medicine, as HIV can
mimic conditions related to accelerated aging and requires up-to-date knowledge of ART and
other interventions.
● Role of ART: ART has transformed HIV from a fatal condition into a manageable chronic illness,
and effective use of ART is critical for long-term health.
● Patient Education: Educating patients about transmission, viral load, ART effectiveness, and safer
practices (e.g., safe sex, not sharing needles) is crucial. Patients should understand that an
"undetectable" viral load does not mean the virus is absent, and it is still transmissible.

Patient-Centered Care

● Therapeutic Decisions: Decisions should be made in consultation with the patient, or a proxy if
the patient cannot decide. Those with CD4+ counts <200/μL should designate a durable power
of attorney for medical decisions.

Initial Evaluations and Baseline Studies

● Comprehensive Assessments: Upon diagnosis, a range of tests and screenings should be done,
including routine labs (lipid profiles, liver enzymes, glucose), HIV resistance testing, CD4+ count,
and plasma HIV RNA levels. Imaging and additional screenings (Pap smear, chest X-ray, etc.) are
also necessary.
● Vaccinations: Patients should be vaccinated against pneumococcal, influenza, HPV, hepatitis A,
and B, depending on their immunity status.
● Hepatitis C and Other Screenings: Hepatitis C status should be determined, and counseling on
sexual practices and needle sharing should be offered.
Ongoing Management and Education

● Adaptation to New Information: The field of HIV care evolves rapidly, so staying updated with
the latest treatment guidelines and research is essential. Patients should receive continuous
counseling, especially regarding transmission risks and lifestyle adjustments.
B. What is the Mainstay of Management of Patients with HIV Infection
● Antiretroviral therapy (ART)
○ Combination antiretroviral therapy (ART), also known as highly active
antiretroviral therapy (HAART), is central to HIV management and
should be started as soon as possible after diagnosis, except in cases
with conditions like cryptococcal or TB meningitis, where a delay in ART
initiation is recommended
○ (Benefits) ART has significantly reduced the incidence of AIDS-defining
conditions by suppressing HIV replication, which extends the patient’s
 life expectancy, improves quality of life, and reduces HIV transmission
risks.
○ Effective suppression requires strict adherence to ART regimens, made
easier with coformulated drugs and options for daily or monthly dosing.
C. What are the Different Antiretroviral Drugs Most Commonly Used in the
Treatment of Infection
● HIV treatment drugs fall into four main classes:
○ Reverse Transcriptase Inhibitors (both nucleoside/nucleotide and
non-nucleoside types)
■ Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
(NRTIs):
● Tenofovir Disoproxil Fumarate (TDF) and Tenofovir
Alafenamide (TAF)
● Emtricitabine (FTC) and Lamivudine (3TC)
● Abacavir (ABC)
■ Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
● Efavirenz (EFV)
● Rilpivirine (RPV)
● Doravirine (DOR)

○ Protease Inhibitors
■ Darunavir (DRV)
■ Atazanavir (ATV)
■ Boosting Agents
● Ritonavir and Cobicistat

○ Integrase Strand Transfer Inhibitors

■ Dolutegravir (DTG)
■ Bictegravir (BIC)
■ Raltegravir (RAL)
■ Cabotegravir (CAB)

○ Entry Inhibitors
■ Maraviroc (MVC)
■ Enfuvirtide (T-20)
■ Ibalizumab
■ Fostemsavir

D. Discuss the Principles of Therapy of HIV Infection

● An approach centered on lifelong adherence to antiretroviral therapy (ART), the
individualized choice of medications, and strategic management based on
monitoring viral load and CD4+ cell counts. The main goals of ART are to
suppress HIV replication, improve immune function, and prevent disease
progression and transmission
 ●

E. When Do You Consider Changing Antiretroviral Therapy in Patients with HIV

Infection
● Following the initiation of therapy, one should expect a rapid, at least 1-log
(tenfold) reduction in plasma HIV RNA levels within 1–2 months and then a
slower decline in plasma HIV RNA levels to <50 copies/mL within 6 months.

● During this same time there should be a rise in the CD4+ T-cell count of
100–150/cells μL that is also particularly brisk during the first month of therapy.
Subsequently, one should anticipate a CD4+ T-cell count increase of 50–100
cells/year until numbers approach normal.

● Many clinicians feel that failure to achieve these endpoints is an indication for a
change in therapy. Other reasons for a change in therapy include a persistently
declining CD4+ T-cell count, a consistent increase in HIV RNA levels to >200
copies/mL, clinical deterioration, or drug toxicity
 ●
● PREVENTION: What are the Strategies to Prevent Acquisition and HIV Infection?

● Education, Counseling, and Behavior Modification

○ A significant proportion of new HIV infections are transmitted by individuals who
are unaware of their HIV status. In the U.S., an estimated 13% of the 1.2 million
people living with HIV are unaware of their infection.
○ The CDC recommends that HIV testing become part of routine medical care for
individuals between the ages of 13 and 64 years, with a "one-time" test being
recommended for everyone in this age range. High-risk individuals should be
tested more frequently.
● Condom Use and Safe Sexual Practices
○ Condom use is recommended to reduce the chance of HIV transmission, but
they are not 100% effective. The failure rate of condoms used for contraceptive
purposes is approximately 10%. The most common failures occur due to
breakage or improper use, such as not using the condom throughout
intercourse.
○ Latex condoms are preferred over natural skin condoms, which are less effective
at preventing HIV transmission. Petroleum-based lubricants should be avoided,
as they increase the likelihood of condom rupture.
● Microbicides for Women
○ Microbicides, such as the dapivirine vaginal ring, have shown variable efficacy in
preventing HIV acquisition, with the variability largely due to poor adherence to
usage. However, the World Health Organization (WHO) has recommended the
dapivirine ring as an additional prevention method for women at substantial risk
of HIV infection.
● ART as Prevention
○ The HPTN 052 clinical trial demonstrated that starting ART immediately for
HIV-positive individuals in heterosexual HIV-discordant couples reduced HIV
transmission by 96% compared to delayed ART initiation.
○ The final results of the study published in 2016 showed no HIV transmissions
among couples when the partner with HIV maintained a suppressed viral load
(defined as <400 copies/mL).
 ○ In several studies involving over 125,000 sex acts among HIV-discordant couples,
transmission did not occur when the HIV-positive partner had an undetectable
viral load (viral suppression).
● Pre-Exposure Prophylaxis (PrEP)
○ PrEP, when taken consistently (one pill daily), is 99% effective in preventing HIV
acquisition in men who have sex with men and heterosexual individuals at high
risk.
○ PrEP with emtricitabine + tenofovir disoproxil fumarate is recommended for
those at substantial risk. Studies have shown that the efficacy is similar with
cabotegravir injections given every two months as maintenance.
○ The CDC estimates that approximately 1.2 million people in the U.S. are at high
risk for HIV infection and should be counseled about PrEP use.
● Male Circumcision
○ Male circumcision has been shown to reduce the risk of acquiring HIV by 50-65%
in circumcised individuals. This intervention is especially recommended in
regions with high HIV prevalence, such as parts of sub-Saharan Africa.
● Interventions for Injection Drug Users (IDUs)
○ For injection drug users, stopping injectable drug use is the most effective way
to prevent HIV transmission. However, for those who continue to inject drugs,
harm reduction practices like needle exchange programs have been shown to
significantly reduce HIV transmission without increasing drug use.
○ PrEP has been shown to be effective in preventing HIV acquisition in people who
inject drugs (PWID), further supporting its use in high-risk populations.
● Prevention in Medical and Maternal Contexts
○ Prevention of mother-to-child transmission of HIV is crucial. With proper
antiretroviral treatment (ART) during pregnancy and delivery, the risk of
transmission to the infant can be reduced to below 1%.
○ Screening of blood and blood products, along with ART interventions for people
living with HIV, continues to be a major preventive strategy in clinical settings.

URINARY TRACT INFECTION

A. Describe and distinguish the following to include its approach
1. Asymptomatic Bacteriuria (ASB)
● occurs in the absence of symptoms attributable to the bacteria in the urinary tract
● and usually does not require treatment
● ASB (Asymptomatic Bacteriuria) diagnosis:
○ Can only be considered if the patient lacks local or systemic symptoms related to the urinary tract.
○ Typically detected incidentally during a screening urine culture for an unrelated reason.
● Systemic signs or symptoms (e.g., fever, altered mental status, leukocytosis):
○ In the presence of a positive urine culture, these are nonspecific.
○ Do not justify a diagnosis of symptomatic UTI unless other potential causes have been ruled out.
2. CYSTITIS
● symptomatic infection of the bladder
● Typical symptoms of cystitis:
○ Dysuria (painful urination)
 ○ Urinary frequency
○ Urgency
○ Nocturia (frequent urination at night)
○ Hesitancy
○ Suprapubic discomfort
○ Gross hematuria (visible blood in urine)
● Symptoms indicating more serious infection:
○ Unilateral back or flank pain: Suggests involvement of upper urinary tract, inconsistent with
uncomplicated cystitis.
○ Fever: Indicates potential invasive infection (e.g., kidney, prostate, bloodstream).
3. PROSTATITIS
● Prostatitis: Includes both infectious (bacterial) and noninfectious (e.g., chronic pelvic pain syndrome)
prostate gland abnormalities.
● Acute Bacterial Prostatitis:
○ Symptoms: Dysuria, frequency, pain in prostatic, pelvic, or perineal area.
○ Fever, chills, and bladder outlet obstruction are common.
● Chronic Bacterial Prostatitis:
○ Presents insidiously with recurrent cystitis episodes.
○ Associated with pelvic and perineal pain.
○ Recurrent cystitis in men should prompt evaluation for a prostatic source and urinary retention.

4. PYELONEPHRITIS
● symptomatic infection of the kidneys
● occurs when the infec- tion involves the renal parenchyma
● Mild Pyelonephritis: Presents with low-grade fever and possibly lower-back or costovertebral-angle pain.
● Severe Pyelonephritis: Manifests with high fever, rigors, nausea, vomiting, and flank or loin pain.
● Symptom Onset: Acute, with fever as the distinguishing feature from cystitis.
○ Fever typically shows a "picket-fence" pattern and resolves within 72 hours of treatment.
● Bacteremia: Occurs in 20–30% of pyelonephritis cases.
● Diabetic Patients: May present with obstructive uropathy due to acute papillary necrosis, which can obstruct
the ureter.
● Papillary Necrosis: Can also occur with obstruction, sickle cell disease, analgesic nephropathy, or
combinations thereof.
○ Bilateral Necrosis: May present with a rapid increase in serum creatinine.
● Emphysematous Pyelonephritis: Severe form involving gas production in renal/perinephric tissues, primarily
in diabetics.

● Xanthogranulomatous Pyelonephritis: Linked to chronic obstruction (often staghorn calculi) and chronic
infection, leading to destruction of renal tissue.
 ○ Characterized by yellow-colored renal tissue with lipid-laden macrophages.
● Intraparenchymal Abscess: Suspected when fever or bacteremia persists despite antibacterial therapy.

5. UNCOMPLICATED URINARY TRACT INFECTION (UTI)

● refers to an infection confined to the bladder, or acute cystitis
6. RECURRENT URINARY TRACT INFECTION
● is not necessarily complicated;
● individual episodes can be uncomplicated and treated as such
7. COMPLICATED URINARY TRACT INFECTION
● is accompanied by symptoms that suggest the infection extends beyond the bladder,
○ such as a fever or signs or symptoms of systemic illness
● presents as a systematic illness with an infectious focus in the urinary tract and frequently occurs in patients
with an anatomic predisposition to infection, such as a foreign body in the urinary tract, or with factors
predisposing to a delayed response to therapy.

B. Pathogenesis of UTI (FIG 135-1)

C. Diagnostic Approach to UTI (Fig 135-4)

D. Give the management of the following

1. Uncomplicated cystitis
● Uncomplicated Cystitis Management: Can often be managed over the phone for healthy women at low
complication risk.
● Initial Guidelines (1999): TMP-SMX was recommended as first-line treatment; however, increased resistance
and collateral damage now necessitate alternative approaches.
● Collateral Damage: Refers to the unintended adverse effects on normal flora and resistance patterns.
 ○ Drugs with minimal impact: pivmecillinam, fosfomycin, nitrofurantoin.
○ Drugs with significant impact: trimethoprim, TMP-SMX, quinolones, ampicillin (linked to rising
resistance).
● Treatment Selection: Focus on agents with urinary-specific activity for the shortest effective duration to
minimize resistance.
● Recommended Agents:
○ First-Line: TMP-SMX, nitrofurantoin, fosfomycin (increasingly popular, especially for resistant E.
coli).
○ Second-Line: β-lactams (e.g., oral cephalosporins like cefpodoxime) as resistance grows to other
drugs.
○ Fluoroquinolones: Effective but discouraged due to resistance risk and serious side effects (e.g.,
tendon rupture, neuropathy).
● TMP-SMX: Still viable in regions with <20% resistance; however, resistance leads to prolonged symptoms
and higher failure rates.
● Nitrofurantoin: Low resistance and effective against E. coli; however, ineffective for Proteus, Pseudomonas,
and pyelonephritis.
● Fosfomycin: Effective as a single dose; remains highly effective against E. coli, though not reliable for
Klebsiella.
● Fluoroquinolone Advisory: FDA recommends avoiding for uncomplicated cystitis if alternatives are available
due to potential adverse effects.
● β-Lactams: Less effective for cystitis, but increasingly used due to TMP-SMX resistance and to limit
fluoroquinolone use.
● Urinary Analgesics: Phenazopyridine and combination products for bladder discomfort, though
phenazopyridine can cause nausea.
● Antibiotic-Sparing Approaches:
○ Placebo and analgesics alone are less effective than antibiotics.
○ Delayed Therapy: Prescription given but filled only if symptoms persist; avoids unnecessary
antibiotic use but may increase discomfort.
○ Correct Duration: Ensures effective treatment; prolonged courses beyond guidelines are
discouraged.

2. PYELONEPHRITIS
● First-line Therapy: Fluoroquinolones are preferred due to high rates of TMP-SMX-resistant E. coli.
○ Choice between oral or IV depends on patient’s ability to tolerate oral intake.
○ Recommended regimen: 7-day course of oral ciprofloxacin (500 mg twice daily, with or without an
initial 400-mg IV dose).
● Alternative Option: TMP-SMX (one double-strength tablet twice daily for 14 days) if the pathogen is known
to be susceptible.
○ If susceptibility unknown: Start with a 1-g IV dose of ceftriaxone.
● Oral β-lactams: Less effective; should be used cautiously with close monitoring.
● Parenteral Therapy Options:
○ Fluoroquinolones
○ Extended-spectrum cephalosporins (with or without an aminoglycoside)
○ Carbapenems
 ● For Patients with Complicated Histories or Resistance Concerns:
○ Combination therapies like β-lactam/β-lactamase inhibitors (e.g., ampicillin-sulbactam) or
carbapenems.
○ Consult infectious disease specialist for highly resistant infections and newer broad-spectrum
agents.
● Transition to Oral Therapy: Switch from IV to oral therapy once clinical improvement is observed.

3. UTI in Pregnant women

● Safe Antibiotics in Early Pregnancy: Nitrofurantoin, ampicillin, and cephalosporins.
○ Nitrofurantoin: Safe, though one study suggested a possible (unconfirmed) association with birth
defects.
● Avoided in Pregnancy:
○ Sulfonamides: Avoid in the first trimester (teratogenic risk) and near term (risk of kernicterus).
○ Fluoroquinolones: Avoid due to potential effects on fetal cartilage development.
● Preferred Drugs for UTI in Pregnancy:
○ Ampicillin and cephalosporins are the drugs of choice for asymptomatic or symptomatic UTI.
○ Treatment Duration: Asymptomatic bacteriuria (ASB) typically treated for 4–7 days; single-dose
therapy is not recommended.
● Overt Pyelonephritis in Pregnancy: Standard care involves parenteral β-lactam therapy, with or without
aminoglycosides.

4. UTI in Men
● Primary Goal in Men with Febrile UTI: Eradicate both prostatic and bladder infections.
● Recommended Treatment for UTI: 7- to 14-day course of fluoroquinolone or TMP-SMX if the pathogen is
susceptible.
○ Current Trend: Preference for a shorter 7-day course to minimize antibiotic exposure.
● If Acute Bacterial Prostatitis is Suspected:
○ Start antibiotics after obtaining urine and blood cultures.
○ Tailor therapy to culture results and continue for 2–4 weeks.
● Chronic Bacterial Prostatitis:
○ Requires a 4- to 6-week course of antibiotics.
○ For Recurrences: Often treated with a 12-week course.

5. Complicated UTI
● Complicated UTI: Occurs in patients with structural or functional urinary tract/kidney abnormalities.
● Pathogen Diversity: Wide range of species with varied antimicrobial susceptibilities.
● Individualized Therapy: Based on urine culture results.
○ Empiric Therapy: Prior urine-culture data may guide initial therapy while awaiting current culture
results.
● Specific Conditions:
○ Xanthogranulomatous Pyelonephritis: Treated with nephrectomy.
○ Emphysematous Pyelonephritis: Initial treatment with percutaneous drainage, followed by
elective nephrectomy if needed.
○ Papillary Necrosis with Obstruction: Requires intervention to relieve obstruction and preserve
renal function.

6. ASB
● ASB Treatment Benefits: Generally does not reduce symptomatic infections or complications.
○ Exceptions: Pregnant women, individuals undergoing urologic surgery, and possibly neutropenic
patients and renal transplant recipients.
 ● Guided Treatment: In pregnancy and urologic procedures, ASB treatment should be based on urine culture
results.
● Screening and Treatment: Discouraged in all other populations.
● Catheter-Associated Bacteriuria: Typically asymptomatic and does not require antimicrobial therapy.

7. CAUTI
● CAUTI Definition: Bacteriuria (≥10³ CFU/mL) with urinary or systemic symptoms in a catheterized patient;
ASB threshold is ≥10⁵ CFU/mL.
● Signs and Symptoms: Typical UTI signs (pain, urgency, fever) are less predictive in catheterized patients;
fever may not indicate CAUTI.
● Diagnosis and Treatment:
○ Diverse causes; urine cultures essential for guiding therapy.
○ Catheter Change: Recommended during treatment to remove biofilm-associated bacteria.
○ Recommended Duration: 7–14 days of antibiotics; further research needed.
○ Spinal Cord Injury Patients: Relapse less common with 14 days of treatment than with 3 days.
● Prevention Strategies:
○ Avoid unnecessary catheters; remove catheters promptly when no longer needed.
○ Quality-improvement efforts focusing on technical protocols and team communication reduce
CAUTI rates.
○ Antimicrobial Catheters: Silver or nitrofurazone-impregnated catheters lack significant benefit in
preventing symptomatic UTI.
○ Alternative Catheterization: Insufficient evidence to recommend suprapubic or condom catheters
over indwelling catheters; intermittent catheterization may be preferred in certain cases (e.g.,
spinal cord injury) to reduce infection and complications.

8. CANDIDURIA
● Candida in Urine: Common in patients with indwelling catheters, especially ICU patients, those on
broad-spectrum antibiotics, and diabetics.
● Species: Over 50% of urinary Candida isolates are non-albicans species.
● Clinical Presentation: Ranges from asymptomatic lab finding to pyelonephritis and sepsis.
● Catheter Removal: Resolves candiduria in over one-third of asymptomatic cases.
● Treatment:
○ Not recommended for asymptomatic cases, as it doesn’t prevent recurrence.
○ Therapy Indicated for symptomatic cystitis, pyelonephritis, or high-risk patients (e.g., neutropenic,
undergoing urologic manipulation, clinically unstable, or low-birth-weight infants).
● First-Line Treatment: Fluconazole (200–400 mg daily for 7–14 days) due to high urinary levels.
● Alternative Agents: Newer azoles and echinocandins not recommended due to low urinary excretion.
○ For Fluconazole-Resistant Candida: Oral flucytosine or parenteral amphotericin B are options.
● Bladder Irrigation: Amphotericin B bladder irrigation is generally not recommended.