Infectious Disease Updates
May 1, 2025
By Carol A. Kemper, MD, FIDSA
Old Habits Die Hard, Especially with TB
Source: Nathavitharana RR, Pearl A, Biewer A, et al. Effects of respiratory isolation for tuberculosis to reduce community-based transmission: A systematic review. Clin Infect Dis. 2025;80:189-198.
A friend in public health once described aspects of tuberculosis (TB) management in the United States as a “first-world problem.” For years, the public health department’s (PHD) focus has been to minimize the risk of TB transmission to the lowest theoretical level — regardless of the public and private cost. In California, once a hospitalized patient with suspect or confirmed TB is initiated on TB treatment, a GOTCH (which peculiarly stands for Get Out of Tuberculosis Control Hospital) is submitted, by law, to the PHD, which requires a plan of care and approval from the local TB officer before the transfer or release of the patient. This ensures the “discharge of the patient in a safe and controlled manner” with a plan of follow-up. A hospital can face financial and reputational penalties for discharging a patient with active TB without clearance from the PHD. Hence, the PHD controls all the reins.
As a result, patients often wait in the hospital, hoping to be un-GOTCHed, while the PHD takes days, and sometimes weeks, to decide whether the patient is appropriate for discharge, requiring serial sputum assessments, a formal determination of the home environment, and arranging for medical assessment of any children in the home — and sometimes becoming distracted by other issues (e.g., whether that back pain described in a physician progress note on Tuesday [from spending too much time in bed] requires a computed tomography scan of the lumbar spine just in case they have spinal TB). Minimum requirements for de-isolation in the United States generally include two weeks of effective treatment and three consecutive negative daily smears. Thus, two recent patients with severe cavitary disease spent four months in isolation in our hospital, both becoming severely depressed to the point of incapacity, while they waited for negative smears. And a recent patient with extra-pulmonary nodal disease was kept in isolation in the hospital for five days of effective therapy despite three negative sputum smears and negative TB PCRs — just in case.
I once spent a week arguing with the then-TB official while a young woman with an abnormal chest X-ray was stuck in the hospital in isolation, unable to produce sputum for testing with repeated attempts at induction. The TB official insisted a bronchoscopy be performed to “prove” she was smear negative, which the patient declined. When has the absence of sputum not been an adequate marker of lack of infectivity?
For that matter, we allow family members to visit patients in airborne isolation wearing a simple surgical mask, with the idea being that their cumulative exposure to the patient prior to hospitalization outweighs whatever risk there may be in the hospital, while the patient is on treatment. But, at the same time, the patient is not allowed to go home with the same family member?
The basis for these de-isolation requirements was a 1976 consensus that “people with pulmonary TB are likely no longer infectious after > 2 weeks on treatment.” What was intended as guidance became dogma. Unfortunately, the clinical and laboratory evidence to support this consensus statement was slim.
These authors coordinated an eight-person review of the literature, examining six databases, identifying 3,691 articles, of which 17 examined the benefits of isolation for pulmonary TB. Only one article was a randomized controlled trial (RCT) (from Southern India in 1956-1957), while the others varied from descriptive to modeling studies. The 17 studies were performed in a variety of TB risk countries. The single RCT reviewed 693 close contacts of 193 culture- or smear-positive pulmonary TB patients, comparing the risk of TB in household contacts if patients were isolated (in a sanatorium) or allowed home with no precautions. Most of the patients had cavitary disease with a high organism burden. The risk of tuberculin skin test (TST) conversion at one year was similar for the two groups (~22% to 23%). At five years, TST conversion occurred in 45% vs. 39% of household contacts of those treated in a sanatorium vs. at home, respectively. Development of active TB in household contacts also was similar in both groups at one and five years.
Other studies provided little support for the benefit of isolation of patients with pulmonary TB. On the other hand, two studies described unnecessarily prolonged hospital stays for patients with TB. A descriptive study of 69 culture-positive TB patients in New York City found an average length of stay of 30 days, two-thirds of which was “longer than appropriate.” More than half were waiting for negative smear results despite clinical improvement or public health home assessments. Another descriptive study in Nigeria found an average length of hospital stay of 4.5 months for 98 patients with multidrug-resistant (MDR) TB.
Other studies demonstrated the significant downside and personal risks of prolonged isolation, including loss of income, loss of employment, social disconnection and ostracism, mood disorders, and severe depression. Financial ruin from isolation is especially likely for recent immigrants or persons already living paycheck to paycheck. I saw a patient in isolation break down in tears when his brother told him over the phone his truck had been towed away and repossessed. He had probably worked years for that truck — and it likely was instrumental to his ability to work. A smaller consideration is the enormous expense incurred by warehousing a patient with TB in a hospital isolation room for months. One 1999 study described how a pilot housing program in San Diego for seven homeless individuals with smear-positive TB saved $27,000 per patient compared to prolonged hospitalization (equivalent to $51,500 per patient today).
An updated Canadian Thoracic Society de-isolation guideline concludes that isolation of patients with pulmonary TB after initiation of appropriate treatment probably has little impact on reducing community and household transmission but has significant deleterious personal and public impact. It will be hard for TB controllers in the United States to loosen the reins — but it is time their decisions were based on scientific evidence and the collective benefit of the patients, their families, and the community. At the least, public health authorities should be prepared to provide timely assessments and plans.
Paxlovid: Is It Still Worth the Cost?
Source: Faust JS, Meyerowitz-Katz G. Is Paxlovid still worth it? Clin Infect Dis. 2024;79:111-114.
Paxlovid is one of the most effective antivirals developed during the COVID-19 years, demonstrating significant reductions in hospitalization and death in higher-risk persons, as well as the time to viral elimination. However, it does not shorten the duration of symptoms, and there is little evidence that Paxlovid reduces the risk of developing long COVID symptoms. In a University of California San Francisco study of vaccinated, non-hospitalized, non-pregnant patients recruited in 2022, long COVID symptoms occurred at 5.4 months in 16% of those who received Paxlovid and in 14% of those who were untreated (P = NS).1 Of those receiving Paxlovid, 21% developed rebound symptoms, although this also was not associated with the development of long COVID symptoms.
Earlier data in support of Paxlovid found statistically significant — and meaningful — reductions in hospitalization and mortality. In the EPIC-HR study published in 2022, the risk of hospitalization and death by day 28 in unvaccinated persons receiving placebo vs. Paxlovid was 6.45% vs. 0.72%, respectively.2 None of the patients who received Paxlovid died, compared with 7/285 patients (2.4%) receiving placebo.
But those unvaccinated patients were recruited in ~2021, and the risk of severe outcomes has since improved, either because of improved population immunity (from vaccination and/or prior infection) or attenuation of newer viral strains. Current Centers for Disease Control and Prevention (CDC) data in March 2025 indicate the rate of hospitalization from COVID is only 2 per 100,000 population and the percent of all deaths in the United States from COVID is 0.8%. Among 130,263 Department of Veterans Affairs patients with COVID-19 between September 2023 and October 2024, the risk of hospitalization and death with newer strains was substantially lower (2.0% vs. 0.03%, respectively) than historical figures.3 The majority of these patients were vaccinated, including two-thirds who had received booster vaccination, although less than one-third received antiviral therapy for their COVID infection.
With this kind of information in mind, is Paxlovid still worth taking? These authors performed a cost-effective analysis. If the EPIC-HR data were used, the cost to prevent one hospitalization in an unvaccinated adult would be US $9,636. As the cost of Paxlovid increases, and the risk of hospitalization and death decreases, this cost-benefit analysis shifts considerably. Using more current figures, the cost to prevent one hospitalization jumps to $232,000 to $278,000. The cost may be as high as $450,000 to prevent one hospitalization in an adult < 65 years of age at lower risk of hospitalization. Among individuals with three or more doses of messenger ribonucleic acid (mRNA) vaccine, the estimated cost may be as high as $485,000 to prevent one hospitalization.
The authors estimate that if all eligible persons in the United States received Paxlovid, and one-fourth of the population developed COVID twice in the next year, the annual cost would be US $28.7 billion. At present, only a fraction of those eligible for Paxlovid seem to be taking it — and the cost has increased to an estimated US $1,390 per course, and availability may be a concern. Last week, I personally experienced one major pharmacy was “out” at three different stores in St. Paul, MN; a prescriber insisted a serum creatinine be obtained before the drug was dispensed, which entailed a separate trip to an urgent care for a blood test at night. And unfortunately, as of December 2025, the federal government will no longer cover the cost of the drug for those receiving Medicare, Medicaid, or those who are uninsured, which pretty much guarantees that only those with insurance will have access to the drug. It seems the best approach is to continue to encourage the use of Paxlovid for those at highest risk for complications — including those without insurance.
Carol A. Kemper, MD, FIDSA, is Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation.
References
1. Durstendfeld MS, Peluso MJ, Lin F, et al. Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent long COVID symptoms in an observational cohort study. J Med Virol. 2024;96:e29333.
2. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386:1397-1408.
3. Choi T, Xie Y, Al-Aly Z, et al. Rates of hospitalization and death due to COVID-19 in US veterans with SARS-CoV-2 infection in the XBB-, JN.1-, and KP-predominant eras. Open Forum Infect Dis. 2025;12:ofaf115.
Old Habits Die Hard, Especially with TB; Paxlovid: Is It Still Worth the Cost?
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