SEPSIS IN HIV PATIENT

Is there anything different?Miriam Haverkamp

May 2017

outline

◦ICU overall survival of HIV patients historical and current

◦ Sepsis – causes

◦Adrenal insufficiency – another diagnosis to not forget

Historical perspective

◦Before 1985

◦ 74% of ICU admissions for respiratory failure due to PCP, CMV, lymphoid

interstitial PNA, PCP and CMV together, 91% mortality for patients with

respiratory failure, overall ICU mortality 71%

◦ Now studies show HIV positive patients admitted to ICU have similar survival

rates as HIV negative patients at around 70%

Curently:

◦ Still respiratory failure is primary reason for admission to ICU

◦ Survival is the same HIV versus non HIV in UK and US based studies with over

75% ICU survival and around 70% overall hospital survival vs. non HIV patients

with 75% and 68%, respectively(15)

◦ This is in contrast to study in Brazil that showed a high mortality with HIV

positive patients ICU survival 56% and hospital survival 32% (8% intubated

patients, most AIDS associated diseases) (16)

ICU survival in Brazil of HIV + (16)

SEPSIS in HIV

◦ Unknown causes account for 40%, 18% gram negative rods

◦ In US Strep pneumo, E. coli, Staph. Aureus, Pseudomonas, Cryptococcus and

Salmonella are common causes (18)

◦ In a recent series in the US, 50% of HIV + patients with sepsis survived overall

versus 46% of non HIV patients

◦ APACHE II score underestimates mortality risk in HIV patients with CD4<200

admitted to ICU with sepsis or pneumonia (44% predicted, 61% observed)

(18)

◦ In Ethiopia recent study on 100 HIV positive patients with sepsis,

showed in bacteraemic patient with HIV Staph aureus 32%, CNS

(30%) (, Strep. Viridans (10%) , GNR (25%) no culture for TB done

(5)

◦ 1997 Uganda study, any febrile patient (>38 C axillary) enrolled

◦ 305 patients enrolled, 228/299 HIV positive, median age 30

◦ 24% overall positive blood cultures, 27% in HIV positive vs. 15% on

HIV negatives

◦ 28/64 had MTB isolated on BCX

◦With prior oral antimicrobial therapy blood culture positivity OR was

0.25

◦No predictor or MTB bacteremia was identified (8)

◦ In 1998 a study in Tanzania looked at causes of bacteremia in patients

presenting to A and E with axillary temp of 37.5 or above (7)

◦ 517 patients enrolled, 145 had positive BCX

◦ 10 patients had polymicrobial infection. 8 of those were HIV positive

◦ 23/145 had non-typhoid Salmonella isolated

◦ 61/145 (42%) had positive TB culture on blood stream, 1 MAC,60

MTB, 59/61 were HIV positive

◦Of TB positive patients: 38% had no pulmonary symptoms, no signs of

symptoms were predictive of MTB

◦ 27/60 (45%) died in hospital

◦ Study from Malawi in 1997 on all febrile patients with >37.5 C axillary

temperature enrolled

◦ 233 enrolled, median age 31, 173 (74%) HIV positive,

◦ Strep pneumo 34%, MTB 29% of all isolates, 1 MAC

◦People on antibiotics prior to admission were more likely to have

MTB+ BCX (RR 5.4)

◦ if pleural effusion, oral candidiasis, chronic fevers these predicted

MTB+ with 3 signs 59%, if 2 17%, if 1 4%, if none 0%

◦ 27/131 (21%) died during admission, HIV not associated with

mortality, BSI OR 3.5, altered MS OR 6.6(9)

◦ Study in Malawi from 2000 on patients with temp >37.4 C, or past 4

days hx of fever, or BP<100 or Pulse >120/min, 352 patients

enrolled

◦ 335 febrile on admission, 9 were in shock and febrile, 291 (81%) were

HIV+

◦ 69% had a cough, 32% had cough > 1 month, 62% had SOB, 12%

mortality

◦ 103 diagnosed with TB on admission

◦ 128 had positive BCX, 73 (21%) bacteremia, 59 (17%) TB + (57/59

MTB)

◦ 46 cases of non-typhoid Salmonella (if temp>39 OR 2.2, Temp >39

AND splenomegaly OR 8.4)(11)

◦ 2006 study on patients in Uganda admitted with severe sepsis

◦ 382 enrolled, 320 (84%) HIV positive, on ART 11%, median CD4 52. 57% had antimicrobials prior to admission

◦ 90/380 died (23.7%), 15 on day one, 42 within first 3 days, 70 within 7 days, another 55 (22.3%) died after d/c within 30 days

◦ Only 12% received >1500ml in first 6 hours, median 500ml in first 6 hours

◦ In GNR bactermia receiving at least 1 liter of fluids versus <1000ml decreased mortality from 66 to 20%

◦ 84% patients only received anti-microbials

◦ Bacteraemic patients had 33% mortality versus 21.4%

◦ TB cultures were done on 245 patients, 55 were positive for MTB

◦ If MTB positive mortality was 44% versus 22.3 (OR 1.97) (10)

◦ Study in Zambia (2014) in early goal directed therapy based on clinical signs

◦ Enrollment: infection suspected, SIRS and one or more organ dysfunction

◦ Intervention: 2 liters over 1 hour, then if JVP<3 another 2 liters over next 4 hours, if MAP <65 after 2 liters Dopamine was started

◦ 80% HIV positive patients median CD4 49, intervention group received 2.8l versus 1.6 in the first 6 hours

◦ Most patients received abx withing 1 hour of arrival in A and E,

◦ 62% mortality (no difference between groups)

◦ 26/109 had positive BCX showing: Staphylococcus (7), Streptococcus (3), Salmonella (3)

◦ 31/82 HIV positive patients had BCX positive for TB, if CD4<75 47.8% had positive TB culture

◦ 2 had malaria, 4 cryptococcal meningitis

◦ If RR>40 then intervention group had 100% mortality (8/8) versus 70% (7/10) in non-intervention group (6)

◦ Substudy analysis of two studies on sepsis in Malawi, first one is

previous study plus a subsequent sepsis treatment study

◦Enrollment of only HIV positive patients, between 2012 and 2013,

201 patients enrolled

◦Median age 32, Median CD4 52, 109 not on ART, those on ART

median time was 3.5 months, 92% had weight loss, 74% reported

previous fever, cough 69%

◦ 27 patients had sputum of which 11 were positive for AFB, 105 Chest

xray of which 72 had CXR TB findings, CXR did not correlate with

MTB positivity

◦ 70 had MTB detected on BCX, 33 had aerobic bacteria detected, 8

had MTB PLUS another bacteria identified (12)

Salmonella - bacteremia

◦ In Africa 227 cases per 100 000, worldwide 49 per 100 000

◦ Case fatality rate is 19% in Africa in meta-analysis

◦ Grows readily in blood culture

◦ Can affect lungs, GI tract, CNS (<1 and HIV + adults), bones, joints, pleura and

muscles

◦ Tx: Third generation Cephalosporin, FQ, Ampicillin, Cotrim, if resistance

suspected Carbapenems

◦ Treatment should be 14 days if no complications such as abscess or endovascular infection

◦ May need 4 to 6 weeks of treatment, if lower CD4 need longer tx

◦ Possibility of recurrent infection

Salmonella (13,14)

Specific Bugs - Histoplasmosis◦ Infection: soil contaminated from bats or bird droppings, caves

◦ Presentation:

◦ Usually CD4<150/mcl

◦ Fever, weight loss, cough (50%), night sweat, fatigue, LAD at times hepatosplenomegaly, can progress to sepsis

◦ limited pulmonary disease in CD4>150

◦ Diagnosis: Histoplasmosis Ag in Urine (97% sensitive)

◦ Treatment: Initially Amphotericin B (induction 14days) and once response Itraconazole

◦ Survival reported between 55 and 65%

◦ Recent review of patient with invasive fungal disease in North America

◦ 100% of patients with disseminated Histoplasmosis had CD4<50

◦ Majority had Blood stream infection (20/27), lung, abdomen, CNS, skin

◦ Patient were treated with Amphotericin B vs. itraconazole vx. Fluconazole

◦ Survival at 90 days was 84%(1)

Adrenal Insufficiency (AI)

◦ AI rates are reported to be high in HIV positive patients

◦ Symptoms: occur if 80% of adrenals are necrotic: Weight loss, fever, nausea, diarrhea

hypotension

Study in Nigeria on healthy HIV patients detected 38% AI prevalence, if

<18mcg/dl used as cut off then even 83%(3)

Study in SA used 14.5 mcg/dl and found 27% AI (4)

◦ Study on HIV patients in ICU with sepsis found between 7 and 75% adrenal insufficiency

depending on definition used – no studies on steroid treatment benefit

◦ Study in Uganda on patients with signs of severe illness showed 21% adrenal

insufficiency, no worse outcomes(2)

Questions?

References

◦ 1. Marik PE, Kiminyo K, Zaloga GP. Adrenal insufficiency in critically ill patients with human immunodeficiency virus. CritCare Med. 2002;30(6):1267-73.

◦ 2. Meya DB, Katabira E, Otim M, Ronald A, Colebunders R, Njama D, et al. Functional adrenal insufficiency among critically ill patients with human immunodeficiency virus in a resource-limited setting. Afr Health Sci. 2007;7(2):101-7.

◦ 3. Odeniyi IA, Fasanmade OA, Ajala MO, Ohwovoriole AE. CD4 count as a predictor of adrenocortical insufficiency in persons with human immunodeficiency virus infection: How useful? Indian J Endocrinol Metab. 2013;17(6):1012-7.

◦ 4. Ekpebegh CO, Ogbera AO, Longo-Mbenza B, Blanco-Blanco E, Awotedu A, Oluboyo P. Basal cortisol levels and correlates of hypoadrenalism in patients with human immunodeficiency virus infection. Med Princ Pract. 2011;20(6):525-9.

◦ 5. Alebachew G, Teka B, Endris M, Shiferaw Y, Tessema B. Etiologic Agents of Bacterial Sepsis and Their Antibiotic Susceptibility Patterns among Patients Living with Human Immunodeficiency Virus at Gondar University Teaching Hospital, Northwest Ethiopia. Biomed Res Int. 2016;2016:5371875.

◦ 6. Andrews B, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Bernard GR. Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia. Crit Care Med. 2014;42(11):2315-24.

◦ 7. Archibald LK, den Dulk MO, Pallangyo KJ, Reller LB. Fatal Mycobacterium tuberculosis bloodstream infections in febrile hospitalized adults in Dar es Salaam, Tanzania. Clin Infect Dis. 1998;26(2):290-6.

◦ 8. Ssali FN, Kamya MR, Wabwire-Mangen F, Kasasa S, Joloba M, Williams D, et al. A prospective study of community-acquired bloodstream infections among febrile adults admitted to Mulago Hospital in Kampala, Uganda. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;19(5):484-9.

◦ 9. Archibald LK, McDonald LC, Nwanyanwu O, Kazembe P, Dobbie H, Tokars J, et al. A hospital-based prevalence survey of bloodstream infections in febrile patients in Malawi: implications for diagnosis and therapy. J Infect Dis. 2000;181(4):1414-20.

◦ 10. Jacob ST, Moore CC, Banura P, Pinkerton R, Meya D, Opendi P, et al. Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population. PLoS One. 2009;4(11):e7782.

◦ 11. Peters RP, Zijlstra EE, Schijffelen MJ, Walsh AL, Joaki G, Kumwenda JJ, et al. A prospective study of bloodstream infections as cause of fever in Malawi: clinical predictors and implications for management. Trop Med Int Health. 2004;9(8):928-34.

◦ 12. Muchemwa L, Shabir L, Andrews B, Bwalya M. High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia. Int J STD AIDS. 2017;28(6):584-93.

◦ 13. Moir S, Fauci AS. Immunology. Salmonella susceptibility. Science. 2010;328(5977):439-40.

◦ 14. MacLennan CA, Gilchrist JJ, Gordon MA, Cunningham AF, Cobbold M, Goodall M, et al. Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults. Science. 2010;328(5977):508-12.

◦ 15. Adlakha A, Pavlou M, Walker DA, Copas AJ, Dufty N, Batson S, et al. Survival of HIV-infected patients admitted to the intensive care unit in the era of highly active antiretroviral therapy. Int J STD AIDS. 2011;22(9):498-504.

◦ 16. Amancio FF, Lambertucci JR, Cota GF, Antunes CM. Predictors of the short- and long-term survival of HIV-infected patients admitted to a Brazilian intensive care unit. Int J STD AIDS. 2012;23(10):692-7.

◦ 17. Dickson SJ, Batson S, Copas AJ, Edwards SG, Singer M, Miller RF. Survival of HIV-infected patients in the intensive care unit in the era of highly active antiretroviral therapy. Thorax. 2007;62(11):964-8.

◦ 18. Coquet I, Pavie J, Palmer P, Barbier F, Legriel S, Mayaux J, et al. Survival trends in critically ill HIV-infected patients in the highly active antiretroviral therapy era. Crit Care. 2010;14(3):R107.