Pulmonary OI Flashcards
When is immediate empirical PCP therapy not indicated?
If CD4<200 effort should be made to confirm a specific diagnosis
Predictive factors for PCP
90% of cases if CD4 <200 or <14%
Not on ART
Not adherent to prophylaxis
Oral candidiasis
OHL
Weight loss
Recurrent bacterial pneumonia
Previous PCP
High plasma HIV VL
Presentation of PCP
Exertional dyspnoea progressing over several weeks
Malaise
Dry cough
Inability to take a deep breath
Fever
Physical exam findings in PCP
Tachyonoea
Normal breath sounds of end exp crackles (less common)
What should be considered if HIV positive individual has spontaneous or infection induced pneumothorax?
PCP
CXR findings in PCP
Perihilar haze, interstitial infiltrates sparing apices and costophrenic angles, pneumatoceles, pneumothoraces
Normal in up to 39%
How to diagnose PCP?
Microbiological investigations required to confirm
Induced sputum if available send 50-90%
If not, negative or inconclusive assess for BAL sensitivity >90%
Open lung biopsy more sensitive but reserved for occasional patient with negative initial tests and no improvement
When should lung biopsy be considered in PCP?
Occasional patients with negative initial test and not improving on empirical treatment
Can spontaneously expectorated sputum be used in PCP diagnosis?
No, not an adequate alveolar sample
How is pneumocystis jirovercii diagnosed from samples?
Can’t be cultured in vitro
Visualisation of organism using silver stains or immunoflourescent stains
NAAT increased sensitivity but decreased specificity compared to stains
How long after starting PCP therapy can adequate pulmonary samples for PCP be gained?
7-10 days
Criteria for mild PCP
Dyspnoea on exertion +/- cough and sweats
PaO2 > 11
Sats at rest on air >96
Normal or minor perihilar shadowing on CXR
Criteria for moderate PCR
Dyspnoea on minimal exertion and occasionally at rest, cough and fever +/- sweats
PaO2 8.1-11.0
Sats 91-96
Cxr - diffuse interstitial shadowing
Criteria for severe PCP
Dyspnoea and tachypnoea at rest, fever and cough
PaO2 <8
Sats <91
Cxr - extensive interstitial shadowing with or without diffuse alveolar shadowing
Treatment categories for PCP
Mod-severe - PaO2 <9.3
Mild >9.3
How effective is septrin for PCP?
70% in more severe cases
90% in mild disease
Treatment for moderate/severe PCP
PaO2 <9.3
Septrin 120mg/kg/day for 3/7
Reduce to 90mg/kg/day for 18/7
IV preferred for severe disease
Reducing dose reduces risks of adverse effects
Treatment for mild PCP
Either oral septrin 1920mg TDS or 90mg/kg/day tds
Or IV regime as per severe (120mg/kg/day 3/7 and 90/mg/kg/day 18/7)
Use of prednisone in PCP
PaO2 <9.3 or sats <92 reducing course
Day 1-5 40mg BD
6-10 40mg OD
11-21 20mg OD
If unable to take orally methylpred at 75% of dose
Start within 72hrs of anti PCP tx
Resistance to Sulphamethoxazole
DHPS mutations associated with long term septrin prophylaxis
Decreasing now we have ARVs and therefore less use of prophylaxis
Salvage treatment for severe PCP
Failure occurs after at least 5/7
Occurs in up to 1/3
Severe - clindamycin 600-900mg qds/tds iv or 300-450mg qds/tds PO and primaquine 15-30mg od PO or pentamidine 4mg/kg od iv for 21/7
Clindamycin less toxicity than pentamidine
Mild-mod - if septrin not tolerated trimethoprim 20mg/kg/day and dapsone 109mg OD PO for 21/7 or atovaquone liquid 750mg BD for 21/7
What to do in mild-mod disease if septrin not tolerated
trimethoprim 20mg/kg/day and dapsone 109mg OD PO for 21/7 or atovaquone liquid 750mg BD for 21/7
When should G6PD levels be checked in context of PCP?
Before or as soon after starting tx with dapsone, primaquine, High dose sulphamethoxazole
Treatment shouldn’t be delayed while awaiting result.
Who is at risk of G6PD deficiency?
Classified by level of RBC enzyme activity
Common in patients of African origin
Also some Mediterranean populations, Sephardic Jews, certain Chinese population
Which drugs trigger harmony saus in G6PD deficient patients?
Oxidant drugs - dapsone, primaquine, high level sulphamethoxazole
Options for deteriorating PCP patient?
Early ITU review
CPAP early if hypoxic but not hypercapnic
Mechanical ventilation if needed for those who deteriorate early in tx or have good premorbid state
Who should have PCP prophylaxis?
All HIV patients with CD4 <200 or <14%, or oral candidiasis, or previous aids defining illness
What drug is used for PCP prophylaxis?
Septrin (TMP-SMX)
Other drugs would work for PCP but septrin provides additional protection against other infections
960 or 480mg OD (similar efficacy, lower dose less side effects, lower rate drug toxicity now lifespan living with HIV longer)
What should be done for patients who cannot tolerate cotrimoxazole?
Often can still tolerate lower dose as prophylaxis
Desensitisation frequently used
Treating through rash or stopping and restaring equally effective
When can cotrimoxazole desensitisation be carried out?
2 weeks after a non severe grade 3 or less reaction
Rarely causes serious reactions
Who would not be a candidate for septrin desensitisation?
Individuals with grade 4 reaction to previous septrin or other sulpha drugs
Cotrimoxazole desensitisation regime
Start with 80mg SMX 16mg trimethoprim day 1
Increase by 80/16 each day
Day 5 single dose 480mg tablet
Day 6 onwards 960mg
Things to look out for if taking septrin
Tired, bruising, bleeding, evidence of infection (bone marrow suppression)
Nausea and vomitting - should settle
Allergic reaction - mild to severe - rash, itching, dizziness- if severe also CP, SOB
Sunlight sensitivity wear suncream and hat
Monitoring for those on septrin
Regular FBC, LFT, UE
Who cannot have septrin?
People on other drugs that interfere with folate processing eg methotrexate
Can increase effect of warfarin
When should ART be started after PCP?
IRIS reported but infrequent
Some clinicians treat immediately, some prefer to see a clinical response to PCP TX (4-7 days)
When should PCP prophylaxis be stopped?
CD4 >200 for more than 3/12 - in practice this is usually checked when VL persistently undetectable
Restart if drops back below 200
When might you stop PCP prophylaxis with cd4 <200
If between 100-200 and sustained suppressed VL with maximal adherence to ARVs
Not enough evidence to formally recommend this but may be stopped if issues re treatment toxicity or interaction with other medications
Risk factors for HIV related bacterial pneumonia
Declining CD4, IVDU, smoking
Treatment for CAP
Same as for HIV negative population
Sputum sample for mc&s helpful
Treatment of CAP in HIV patients?
Non severe - amoxicillin (alternative po clari, po doxy)
Mod-severe - amox and clari or doxy. OR iv coamoxiclav or 2nd/3rd gen cephalosporin with Clari or doxy (alternative levo/moxi - anti pneumococcal activity)
Severe - iv coamox or 3rd gen cephalosporin and IV macrolide (alternative IV levo/moxi)
How does pulmonary cryptococcus present?
Disseminated disease more common
Fever, cough, SOBOE, pleuritic CP
What would be seen on CXR if pulmonary cryptococcus?
Solitary nodules, interstitial infiltrates, cavities, intratjoracic lymphadenopathy or pleural effusion
Infiltrates more common with advance immunosuppression
How is c.neoformans diagnosed in lungs?
induced sputum, BAL or pleural fluid - giemsa stain, Indian ink (encapsulated yeast), fluorescence microscopy
CrAg in BAL sensitivity 100%, spec 98%
Yeast can be cultured from BAL or biopsy using blood agar or fungal media
What other investigations are needed in pulmonary cryptococcosis?
CSF to r/o meningitis
What is the treatment for pulmonary cryptococcosis?
Usually same as CNS infection - liposomal amphotericin B (ambisome) 4mg/kg/day
Criteria for treating pulmonary cryptococcosis with fluconazole only?
CSF negative
No evidence of dissemination
Radiological infiltrates focal
No hypoxia
400mg OD 10/52 200mg OD after this
Risk factors for invasive aspergillosis?
Rare in HIV without other risk factors - neutropenia, transplant, glucocorticoid steroid use
Symptoms of IA?
Fever, cough, dyspnoea, insidious onset
Chest pain may occur
Haemoptysis rare
What is tracheobro chorus?
Syndrome in HIV+ individuals caused by IA.
Rare.
Ulcerative or nodular lesions in airway.
Fever, cough, dyspnoea, wheeze, stridor.
Investigations to diagnose aspergillosis
CT chest
Sputum sample
BAL
Fungal stains such as KOH and grocott-gomori methenamine silver stains on all sputum or bal samples from HIV + individuals with pulmonary syndromes
Fungal cultures
What is the galactomann test?
Used to detect cell wall component if aspergillosis
Commonly used in haematology patients
Few data to support use in HIV patients and false pos may occur
Confirmation of invasive aspergillosis diagnosis
Either -
Clinical syndrome associated with a biopsy specimen developing aspergillus by culture or histopathology
OR consistent clinical plus radiological appearance with positive microbiology from sputum or BAL
How is invasive aspergillosis treated?
Voriconazole - no specific studies in HIV positive population due to declining incidence of IA with HAART
6mg/kg/bd for 48hr, 4mg/kg bd 7 days, 200mg BD to complete 12/53
Alternative treatments for voriconazole for IA?
Voriconazole superior to amphotericin B deoxycholate - improved response rates, decreased side effects - however did not compare to ambisome
Ambisome 3mg/kg OD IV main alternative to voriconazole
Caspofungin 70mg loading 50mg od iv thereafter alternative if can’t have V or ambisome - preferred agent if significant renal or hepatic disease
Posaconazole an oral alternative
After 4-6 weeks if clinical and radiological improvement to switch to oral itraconazole/voriconazole to complete 12/52
Is there a risk of aspergillus IRIS with HAART?
Case reports exist of individuals who developed chronic necrotising pulmonary aspergillosis as an IRS following HAART
CMV lifecycle?
Infects and establishes latency
Reactivation of latent virus common in those with advanced immunosuppression and does not cause end organ disease although CMV may be detected in blood/urine/BAL
Typical presentation of pulmonary CMV
Dry non productive cough and exertional dyspnoea with fever
Marked hypoxaemia
Radiological findings with pulmonary CMV infection
Bilateral interstitial infiltrates or ground glass attenuation but unilateral alveolar consolidations, bilateral nodular opacities, pleural effusions, rarely cavities, hilar adenopathy may occur
How is CMV pneumonia required?
CMV may be shedded in respiratory secretions without there being CMV pneumonitis therefore culture, PCR or antigen from BAL or biopsy do not distinguish so should be interpreted with caution.
Negative culture result excludes CMV pneumonia.
Diagnosis requires pulmonary biopsy plus compatible clinical syndrome.
What is seen on pulmonary biopsy in CMV pneumonia?
Intranuclear or intracytopladnic viral inclusions, positive immunostaining for CMV antigens or detection of CMV via molecular techniques
Who should receive treatment for CMV pneumonitis?
Cases with compatible clinical syndrome, positive microbiology for CMV in BAL or biopsy AND positive histology on biopsy without an alternative cause of respiratory disease.
In coinfection treat other pathogen first and add CMV tx if no response
What is the treatment for CMV pneumonitis?
Ganciclovir 5mg/kg bd iv 21 days
Alternatives - foscarnet 90mg/kg bd iv or cidofovir 5mg/kg per week iv for those who can’t tolerate ganciclovir although data limited in hiv+ population
Valganciclovir 900mg BD PO alternative for those able to tolerate oral/switching from IV
When would we use prophylaxis against CMV?
900mg od or BD valganciclovir
Only for select individuals where CD4<50 persistently and not likely to improve with HAART, persistent cmv detection or viraemia, no evidence of CMV end organ disease
Treatment for influenza A virus?
Oseltamivir 75mg bd 5/7
If CD4 > 200 only give if there is fever and within first 48hr of fever
If CD4 <200 can be given if afebrile or greater than 48hrs
Alternative agent to Oseltamivir for flu A
Inhaled zanamivir 10mg (2 puffs) BD
Should HIV patients be given prophylaxis if a contact of Flu A?
No specific HIV data
If very immunosuppressed (CD4 <200), not received vaccine or unlikely to have responded, exposed within last 48hrs - Oseltamivir 75mg OD 10/7
If more significantly immunosuppressed 10mg OF inhaled zanamivir may be considered
Treatment treatment for PCP in pregnancy)?
Septrin treatment of choice
Alternatives -
Clindamycin with primaquine (primaquine can cause haemolysis)
Dapsone (may cause haemolysis) with trimethoprim
Atovaquone
PCP prophylaxis in pregnancy
Emphasis put on CD4 percentage because false reduction of absolute CD4 cell counts particularly in 3rd trimester
Septrin preferred but concerns about trimethoprim in first trimester - could have alternative during this period eg OD dapsone, neb pentamidine
