Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions

Training on Clinical Care of HIV, AIDS and Opportunistic Infections

Unit 7:

Respiratory Conditions


Learning Objectives

• Use empirical antibiotics for respiratory conditions

• Evaluate the specific cause of respiratory conditions when empirical antibiotics are not successful

• Describe appropriate use of sputum gram stains, direct microscopy for acid fast bacilli (AFB) and chest x-rays

• Explain specific therapy for HIV- related respiratory conditions

Unit 7: Respiratory Conditions, Slide 2


Respiratory Condition:Case History

• Angula, a 33 year old HIV positive man, presents today with 1 week of nonproductive cough and fevers. The symptoms have been gradually worsening. He feels short of breath with exertion, but not at rest.

• Angula had a CD4 count of 35 three months ago. He recently completed his pre-HAART assessment and counselling and was going to start ART in a few weeks.



• Angula has been feeling generally weak for the past year and had to quit his job 6 months ago.

• His only opportunistic infection was a case of herpes zoster 3 months ago.

• He was prescribed Cotrimoxazole for PCP prophylaxis 3 month ago but it gave him a rash so he stopped it.

Respiratory Condition: Case History (2)



• On exam, Angula has a Temperature of 39°C, BP 110/70, Pulse 90, RR 24. He appears thin, but not emaciated. He appears calm and comfortable. Chest exam shows deep inspirations but no retractions, there are diffuse crackles. The exam is otherwise normal.

Respiratory Condition: Case Exam



First, Assess the Severity of the Illness

• Severe Dyspnea• Subjective• At rest or minimal exertion

• Respiratory Distress• Objective• RR > 30• Hypoxemia• Tachycardia• Signs of ventilatory effort



Consider the Differential Diagnosis

• Bacterial Infection• Bacteria, TB, Mycobacteria other than TB (MOTT)

• Fungal Infection• Pneumocystis (PCP)• Cryptococcus, Histoplasmosis, Aspergillus

• Viral Infection• Varicella, Cytomegalovirus

• Malignancy• Kaposi’s Sarcoma, Lymphoma



Effect of CD4 on Differential

• Any CD4 Count• Bacterial pneumonia (Pneumococcus, Hemophilus,

Staphylococcus), ‘atypical’ pneumonia (Mycoplasma, Chlamydia), TB

• CD4 < 200• PCP, KS, Lymphoma

• CD4 < 100• Cryptococcus, Histoplasma, Mycobacterium kansasii

(MOTT)

• CD4 < 50• Mycobacterium avium complex (MOTT),

Cytomegalovirus, Aspergillus



General Approach to Hospital Evaluation

• Assess hydration and need for oxygen• History and physical exam

• Make/confirm diagnosis• assess immune status

• FBC• Sputum for MCS

• Microscopy, culture, sensitivity

• For chronic cough: 3 sputum specimens for AFB

• If not done previously: HIV test Unit 7: Respiratory Conditions, Slide 9


Hospital Evaluation

• As indicated in patients severely ill:• Chest x-ray• Creatinine• ALT• Bilirubin• Blood culture• CD4 count (if not done previously)



Bacterial Pneumonia

• Common at all CD4 counts• Often purulent sputum, pleuritic chest

pain, focal abnormalities on chest exam, increased WBC

• Usual pathogens may be seen on MCS (gram stain):• Streptococcus pneumoniae• Hemophilus influenza• Staphylococcal aureus• Klebsiella pneumoniae or another gram negative

organism


Bacterial Pneumonia (2)

• Left lower lobe+ RML infiltrates+ air bronchogram

• Volume loss causes raised left hemi-diaphragm

Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions, Slide 12

Streptococcus pneumoniae

• Gram stain: Polys and gram-positive diplococci

• Treatment:• IV - penicillin• PO - amoxycillin

250-500 mg tds or doxycycline 100 mg bd


Hemophilus influenza

• Gram-negative diplococci

• Treatment:• IV - ampicillin,

cefuroxime, or ceftriaxone

• Depends on availability and cost

• PO – amoxycillin, azithromycin or doxycycline


Staphylococcus aureus

• Gram positive cocci in clusters

• Treatment:• IV – cloxacillin,

cefuroxime, ceftriaxone, cephalothin

• PO – cloxacillin or clindamycin


Pseudomonas aerogenosa

• Gram negative bacilli

• Treatment:• IV –

pipiracillin/tazobactam, ciprofloxacin or gentamicin depending on the culture sensitivity



Atypical Pneumonia

• May be milder than classical bacterial pneumonia

• More common in younger patients• Less common among AIDS patients than

bacterial pneumonia• No organism seen on gram stain• Pathogens:

• Mycoplasma• Chlamydia• Legionella (this may be severe)

• Treatment: • Azithromycin, doxycycline, erythromycin• Ciprofloxacin may also be used for legionella



Empiric Outpatient Therapy for Bacterial/Atypical Pneumonia

• Amoxycillin 250-500 mg tds• S. pneumonia and H. influenza

• Doxycycline 100 mg bd (Tetracycline 500 mg od)• Above plus Staph and atypical pneumonia

organisms

• Azithromycin 500 mg od (3d)

• Erythromycin 500 mg qid• Like tetracycline, but doesn’t include H. influenza



Empiric Inpatient Therapy for Severe Bacterial Pneumonia• IV Penicillin plus gentamicin OR • IV Cefuroxime plus azithromycin / erythromycin

OR• IV Ampicillin plus doxycyline• Adequate initial therapy for most

Pneumococcus, Haemophilus, Staphylococus, and many gram-negative organisms• Azithromycin, erythromycin and doxycyline treat

mycoplasma, chlamydia

• Therapy should be adjusted if a specific diagnosis is made



Pulmonary TB

• Chronic cough, fever, sweats, weight loss are typical

• Must send sputum for direct microscopy if cough persisted ≥ 3 weeks

• Do not house TB suspects with general medical patients• Many general medical patients have HIV

and can very easily catch a new TB infection



Pulmonary TB (2)

• Occurs at all CD4 counts• Classic pulmonary TB at higher CD4 counts• Atypical at lower CD4 counts

• Sputum smear negative• Lack of pulmonary cavity• Pleural effusion• Hilar or mediastinal adenopathy• Lower lobe infiltrates


Pulmonary TB (3)

Perform CXR if sputum smears are negative in TB suspect


Source: International Union Against Tuberculosis and Lung Disease (IUATLD) www.tbrieder.org



Treatment of PTB

• Follow National Guidelines

• New case, smear positive or smear negative PTB• 2 HRZE / 4 HR• Directly observed therapy in hospital• Arrange for directly observed therapy on

discharge and follow-up sputum exams at 2 and 5 months

• Recommend HIV test if not previously performed



When to Start HAART in TB Patients

• CD4 > 350• May not require HAART. Re-evaluate after completion

of TB treatment

• CD4 200 – 350 • If patient is eligible for HAART, then start HAART after

TB treatment is completed

• CD4 < 200• Start HAART after completing 2 month initial phase of

TB treatment• Delay is to minimize pill burden, reduce toxicity, and

avoid immune response syndrome



HAART Selection with TB

• Main issue is rifampicin drug interactions

• Dramatically reduces drug levels of nevirapine and most protease inhibitors

• Small decrease in efavirenz levels, no dose adjustment needed

• NRTI levels not affected



HAART Selection with TB (2)

• First-line per Namibian Guidelines:

• d4T/3TC/EFV

• When patient discontinues Rifampicin, can switch EFV to NVP if desired



Pneumocystis Pneumonia (PCP)

• Causative organism now known as Pneumocystis jiroveci

• Usually progresses over several weeks

• Dyspnea

• Non-productive cough

• Fever, fatigue, weight loss

• No pleuritic pain • May have vague substernal discomfort



PCP (2)

• Occurs at CD4 count < 200

• Dyspnea may be obvious or subtle• Worsens with exercise, walking, speaking

• Lung sounds may be normal

• No organisms on sputum gram stain or AFB stain

• Probably more common than we diagnose



PCP (3)



PCP Diagnosis

• Consider diagnosis when bacterial pneumonia and TB are not present, especially if CD4 < 200 or patient has signs of immunodeficiency• Oral candidiasis or oral hairy leukoplakia

• Special sputum stains and bronchoscopy to prove diagnosis • not available in Namibia



PCP Treatment

• Cotrimoxazole 80/400mg, 4 tabs q8hrs for 21 days• IV dose: TMP 15mg/kg, SMX 75mg/kg divided 6-8

hourly

• Add prednisone only for severe dyspnea • pO2 < 70• O2 saturation < 92%• Prednisone dose

• 40 mg bd x 5 days then• 40 mg daily x 5 days then• 20 mg daily for 11 days



Respiratory Condition: PCP Treatment

• If Cotrimoxazole allergy was not severe:• Consider rapid desensitization

• If Cotrimoxazole allergy was severe:• Dapsone 100mg po daily plus • Trimethoprim 5mg/kg po tds for 21 days (not

currently available)



Rapid Cotrimoxazole Densensitisation

Hour Dose (mg)

0 0.004/0.02

1 0.04/0.2

2 0.4/2

3 4/20

4 40/200

5 160/800

Respiratory Condition: PCP Treatment (2)

See Handout 7.1 Successful in 86% of HIV+ Patients. Source: Gluckstein and Ruskin, CID. 1995; 20:849

Slide 33


Fungal Pneumonia

• May present like TB:• Chronic cough, fever, night sweats, weight

loss• Chest xray may show focal abnormalities,

diffuse infiltrates, miliary pattern, rarely cavities

• Sputum smears for AFB negative• No response to TB therapy



Cryptococcal Pneumonia

• Other than PCP, most common • Lung is portal of entry for organism• May occur before, during, or after meningitis• In absence of meningitis, difficult to diagnose

• Blood culture may be positive• Serum cryptococcal antigen is usually positive• Sputum fungal culture or lung biopsy would

demonstrate organism



Cryptococcal Pneumonia (2)

• Treat like cryptococcal meningitis• Amphotericin B x 2 weeks if available• Fluconazole 400 mg daily 8-10 weeks• Fluconazole 200 mg daily for life long

suppressive therapy



Histoplasma Pneumonia

• Histoplasma capsulatum is present worldwide• H. capsulatum var. dubosii is present in sub-

Saharan Africa• AIDS patients get disseminated infection

presenting like disseminated TB• Hepatosplenomegaly• Typical skin lesions and oral ulcers

• Case reports in AIDS patients from Congo, Kenya, South Africa, Zimbabwe



Fungal Pneumonia



Oral ulcer of Histoplasmosis



Haematology Lab Finds the Pathogen

Wright-stained peripheral blood smear shows intracellular Histoplasma organisms



Treatment of Histoplasmosis

• If severely ill, best to start with 1-2 weeks of Amphotericin, followed by

• Itraconazole 200 mg bd for 10-12 weeks, followed by

• Lifetime suppression with itraconazole 200 mg daily

• Alternative• Ketoconazole 200 mg bd with food or orange

juice• Fluconazole is not effective



Aspergillus

• Causes severe necrotizing pneumonia

• Associated with low CD4 count and low WBC

• May cause pleural-based wedge shaped infiltrates and/or cavities anywhere in lung

• Treated with high dose amphotericin for weeks to months



Opportunistic Viral Pneumonia

• Herpes simplex may occur with HSV disease at other sites• Acyclovir 800 mg 5x daily

• Varicella occurs during primary chicken pox or with disseminated zoster• Acyclovir 800 mg 5x daily

• CMV pneumonia may occur with retinal or GI disease• Ganciclovir IV



Kaposi’s Sarcoma

• Lung disease represents visceral spread

• Skin lesions and often oral lesions precede lung lesions

• Treatment of fit patients:

• HAART

• Palliative chemotherapy

• Unfit patients

• Symptomatic treatment



Kaposi’s Sarcoma



Chest CT Scan: KS nodules in Lung



Lymphoma

• Can cause

• Hilar adenopathy

• Pleural and pericardial effusions

• Focal or diffuse lung infiltrates

• Tissue diagnosis required if chemotherapy is considered



Pulmonary Case

• Angula was admitted for evaluation• WBC was 2700• Sputum gram stain and AFB stains: no

organisms• CXR: diffuse interstitial infiltrates• Did not improve on empiric penicllin and

gentamicin• Received cotrimoxazole desensitization

and responded to 21 day courseUnit 7: Respiratory Conditions, Slide 48


CXR Patterns

Focal Infiltrates Diffuse Infiltrates

BacterialAtypicalMTB

PCPMTBFungalViral

Hilar Nodes Cavities

MTB, MOTTFungalLymphoma

MTB, MOTTBacterialFungal

Nodules/Masses Normal

MTBFungalKS, Lymphoma

PCPMTB

Slide 49


Key Points

1. First assess for respiratory distress

2. Treat empirically if signs/symptoms NOT severe

3. If not responding get AFB sputum exams

4. If severe or not responding get chest x-ray and sputums

5. Although TB is the most common opportunistic infection, consider other treatable conditions as well


Documents

Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions