Management of the Critically Ill AIDS Patient

Presented by: Dr. Jaime Moran

Summarized by: Dr. Yonatan Yohannes

Reviewed by: Dr. Ian deSouza, Dr. Wendy Chan

A guy walks into a bar and orders a drink. He syncopizes before taking his first sip. I know what you’re thinking and the answer is no, he didn’t pre-game (i.e. pre-drink/use drugs). He’s 56 years old with a PMH HIV, CHF (EF 45-50%), HTN, dyslipidemia and was recently admitted for pneumonia. On the same admission, he was found to be HIV positive with a CD4 count of 4. Bronchoalveolar lavage was positive for PCP. He was treated with trimethoprim/sulfamethoxazole and steroids during his 4 week hospital course and was started on highly-active antiretroviral therapy prior to discharge.

On arrival to your hospital, he is afebrile with HR 86, BP 63/47, RR 18, SaO2 97% on room air. He appears weak with diffuse rales on the right side and is slightly confused. ECG is normal sinus rhythm. Significant labs show pH 7.26, lactate 1.4, Cr 6.01. CT head is normal and CXR shows a large opacification of the right hemithorax. The patient is given a total of 5 liters of IV fluid and antibiotics for healthcare-associated pneumonia and PCP (vancomycin, piperacillin/tazobactam, ciprofloxacin, and trimethoprim/sulfamethoxazole). He remains hypotensive. A norepinephrine drip is initiated for septic shock, followed by epinephrine drip for refractory hypotension. The patient is then admitted to the intensive care unit with a diagnosis of septic shock secondary to health-care associated pneumonia and acute renal failure.

What are the most common reasons for admission?

The two most common causes of hospital admissions worldwide in people living with HIV are AIDS-related illnesses and bacterial infections. These also represent the top two causes of mortality worldwide, in all geographic regions and in all age groups.

• For the AIDS-related illnesses, the pulmonary system is involved 67% of the time and tuberculosis is the most common diagnosis, responsible for 18% of hospital admissions.
• Pneumonia leads all other diagnoses in the bacterial infections group, causing 15% of hospital admissions, followed by isolated bacteremia and diarrhea causing 11% and 9% of hospital admissions respectively.

Antibiotics in patients predisposed to resistant pathogens

Traditionally, the antibiotic choice for hospital-acquired pneumonia (HAP), healthcare-associated pneumonia (HCAP), or ventilator-associated pneumonia (VAP) of late-onset or with risk factors for multi-drug resistant (MDR) pathogens included coverage for MRSA (with vancomycin or linezolid) AND double-coverage for P. aeruginosa (antipseudomonal cephalosporin/carbapenem/beta-lactam plus antipseudomonal fluoroquinolone or aminoglycoside).

*Chart adapted from the American Thoracic Society and Infectious Disease Society of America Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-associated, and Healthcare-associated Pneumonia, 2004.

Recent studies have challenged this recommendation due to concerns over the risk vs benefit profile of added aminoglycoside therapy.  A Cochrane review in 2014 compared trials that treated hospitalized patients with severe infections with beta-lactam monotherapy vs beta-lactam plus an aminoglycoside and found no advantage of combination therapy, however combination therapy was associated with increased risk of renal injury. Limitations of this review include an underpowered P. aeruginosa subgroup analysis, limited number of trials comparing the same beta-lactam in both arms, and many of the trials did not include data on all-cause deaths.

According to Kumar, et al. there may be a survival benefit in combination therapy specifically in patients with septic shock at high risk of a MDR pathogen. The reasons include:

• Increased likelihood of efficacy of the regimen against the culprit pathogen
• Generation of an additive/synergistic antimicrobial effect
• Preventing the emergence of a resistant superinfection

In summary, it appears that MRSA coverage plus single-agent antipseudomonal coverage is sufficient antimicrobial therapy in the case of sepsis due to HAP/HCAP/VAP. In the case of septic shock with a high risk of MDR organism, consider double-coverage for P. aeruginosa, however current data is insufficient to determine if there truly is a survival benefit. (Sigh) If there were only a prospective, randomized controlled-trial…

Effects of HIV/AIDS on chronic diseases

As the life expectancy in patients with HIV/AIDS continues to improve, they are more likely to come to the emergency department for non-HIV/AIDS related illness. They have an increased risk of diabetes, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and venous thromboembolism (VTE). Therefore, it’s very important to approach our HIV/AIDS patients with a wide differential, just as we would any other patient.

Coronary Artery Disease

Coronary artery disease (CAD) is the 3^rd most common cause of death in patients with HIV. The effects of HIV/AIDS on the cardiovascular system include accelerated atherogenesis, procoagulant effects of the virus, and metabolic dysregulation due to HAART. The mean age of the first episode of acute coronary syndrome is 48 years, significantly younger than in the non-HIV population.

HIV & COPD

HIV has been shown to cause accelerated obstructive lung disease. There are several proposed mechanisms including:

• Increased prevalence of high-risk behaviors (i.e. tobacco smoking)
• Increased susceptibility to pulmonary infections and colonization
• Aberrant inflammatory responses
• Increased apoptosis
• Effects of antiretroviral therapy

Venous Thromboembolism

The overall incidence of VTE, about 1% in this population, has been similar across several different studies. This is a rate roughly 10 times greater in HIV/AIDS patients than in the non-HIV population of the same age. This is due to increased traditional risk factors such as age, recent hospitalization, and central venous catheter use, however having a CD4 count of < 500 has also been found to be an independent risk factor associated with VTE.

References

Ford N, Shubber Z, Meinties G, et al. Causes of hospital admission among people living with HIV worldwise: a systematic review and meta-analysis. Lancet HIV. 2015. Oct;2(10):e438-44.

American Thoracic Society. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005. Feb 15;171(4):388-416.

Kumar A, Zarychanski R, Light B, et al. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med. 2010. Sep;38(9):1773-85.

Vardakas KZ, Tansarli GS, Bliziotis IA, Falagas ME. B-lactam plus aminoglycoside or fluoroquinolone combination versus B-lactam monotherapy for Pseudomonas aeruginosa infections: A meta-analysis. Int J Antimicrob Agents. 2013. Apr;41(4):301-10.

Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev. 2014. Jan 7;1.

Boccara F, Lang S, Meuleman C, et al. HIV and coronary heart disease: time for a better understanding. J Am Coll Cardiol. 2013. Feb 5;61(5):511-23.

Fanari Z, Hammami S, Hammami MB, et al. Acute coronary syndrome in HIV naïve patient with low CD4 count and no other significant risk factors: case report and literature review. Open J Clin Med Case Rep. 2015;1(2):1009.

Morris A, George MP, Crothers K, et al. HIV and chronic obstructive pulmonary disease: Is it worse and why? Proc Am Thorac Soc. 2011. Jun 1;8(3):320-325.

Ahonkhai AA, Gebo KA, Streiff MB, Moore RD, Segal JB. Venous thromboembolism in patients with HIV/AIDS: a case-control study. J Acquir Immune Defic Syndr. 2008. Jul 1;48(3):310-4.

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