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July '25 Infectious Diseases Update

Posted by Doug Black, PharmD., Ann Lloyd, PharmD. on Jul 8th 2025

Article of the Month (Editors' Choice)

Switching from TMP-SMX to Atovaquone Does Not Resolve Hyperkalemia─and May Increase Infection Risk

By Brian S. Schwartz, MD

  • Trimethoprim-sulfamethoxazole (TMP-SMX)* is the first-line agent for Pneumocystis jirovecii pneumonia (PJP) prophylaxis* in solid organ transplant recipients, including those who have undergone orthotopic heart transplantation (OHT). However, TMP-SMX is known to cause hyperkalemia, due in part to trimethoprim's amiloride-like effect on renal potassium excretion (particularly at higher doses). As a result, patients receiving TMP-SMX prophylaxis who develop hyperkalemia are often transitioned to atovaquone* (ATQ). ATQ is considered a second-line prophylactic agent with a narrower antimicrobial spectrum and higher cost.
  • It turns out that for patients with hyperkalemia receiving TMP-SMX prophylaxis, switching to ATQ may not resolve the hyperkalemia and may increase the risk for infection. A single-center retrospective study (Transpl Infect Dis 2025;0:e70043 (online ahead of print)) evaluated whether switching from TMP-SMX to ATQ after OHT improves hyperkalemia without compromising infection protection. Among 321 OHT patients, 76% were switched to ATQ, primarily due to hyperkalemia. However, 80% of those transitioned to ATQ continued to experience hyperkalemia, compared to 42% who remained on TMP-SMX (p<0.0001). Severe hyperkalemia also occurred more frequently in the ATQ group, and patients were more likely to require interventions such as potassium-binding resins.
  • Infections were more common in patients receiving ATQ prophylaxis. The incidence of infections, including PJP, nocardiosis, and UTIs, was more common in the ATQ group (52% vs. 27%, p<0.001), with five nocardiosis and two PJP episodes occurring exclusively in ATQ-treated patients. However, Poisson regression analysis adjusting for follow-up time found no statistically significant difference in infection rates between groups (incidence rate ratio: 1.32; 95% CI: 0.93-1.86; p=0.119), although the numerical trend favored TMP-SMX.
  • Notably, even in a subset of patients without chronic kidney disease, those switched to ATQ had significantly more recurrent and severe hyperkalemia (80% vs. 39%; p<0.0001) reinforcing that comorbidities like diabetes and age, rather than TMP-SMX alone, contribute meaningfully to potassium dysregulation.
  • An accompanying editorial (Transpl Infect Dis 2025;0:e70062 (online ahead of print)) argues for a more nuanced approach. TMP-SMX has activity beyond PJP─including against Nocardia and Listeria─and may reduce other infection risks. Second-line agents like ATQ are often less effective and have their own drawbacks (e.g., cost, taste). The high recurrence of hyperkalemia despite TMP-SMX discontinuation challenges the reflex switch to ATQ and calls into question its routine use.
  • Taken together, these findings suggest that TMP-SMX discontinuation in response to hyperkalemia may be premature. Alternative strategies─such as adjusting concurrent nephrotoxic or potassium-sparing drugs─should be considered before abandoning TMP-SMX prophylaxis, particularly in high-risk transplant patients.

Recent Drug Approvals

  • mNEXSPIKE (COVID-19 Vaccine, mRNA, Moderna) 2024-25 formulation was FDA-approved in May. It is indicated for use in individuals who have been previously vaccinated with any COVID-19 vaccine and are (1) ≥65 years of age, or (2) 12-64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19. It has a reduced dose of 10 µg compared to 50 µg in Spikevax to increase tolerability. It has not been presented to ACIP. Commercial plans so far are unstated.
  • Yeztugo (lenacapavir*) for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing ≥35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test beforehand. The dosing schedule consists of initiation (927 mg sc x1, 600 mg po q24h x2) followed by continuation (927 mg sc every six months).

COVID Guidelines for 2025-26 Winter

  • FDA has given an initial indication that 2025-26 COVID-19 vaccines will be approved only for those age ≥65 years and people age ≥6 months with one or more underlying medical conditions that put them at high risk for severe illness.
    • Final guidance for Fall 2025 is pending official FDA and CDC/ACIP action.
    • The ACIP meeting in June 2025 did not consider COVID recommendations at all.
    • Guide content will be updated as available.
  • Currently posted CDC routine immunization schedules now state:
    • Shared clinical decision-making regarding COVID-19 vaccinations for all children and adolescents aged 6 months through 17 years, including those who are moderately or severely immunocompromised. CDC data clearly show, however, that COVID-19-related hospitalizations are continuing to occur among children <5 years with high rates of hospitalization among those <6 months.
    • Pregnancy is now shaded gray (indicating "no guidance"). The data, however, have not changed. The COVID-19 vaccine is safe during pregnancy, and vaccination protects pregnant patients who are at higher risk of severe COVID-19 and provides protection for infants in the first 3-4 months of life.
    • No changes in the ongoing 2024-25 recommendations for adults.

Measles Immunity in Older Travelers

  • According to CDC, no revisions to current ACIP guidance are needed.
    • Persons born before 1957 are presumed to have innate immunity given the high prevalence of measles when they were young.
    • In general (unless there is a specific reason, e.g., a history of immunosuppression), CDC does not recommend checking MMR titers prior to travel in this age group.
    • There isn't any evidence of substantial waning immunity in this age group.
      • Overall, people >60 years of age represent a very small fraction of measles cases reported to CDC, with <1% of cases this year in persons born before 1957.
      • Although not directly applicable to this age group, CDC has current national serosurveillance data that show 95% measles seropositivity among persons age 6-59 tested without significant decline from the last study about 10 years before.

New or Updated Practice Guidelines

Antimicrobial Stewardship: Antibiotic Prescribing at Hospital Discharge

  • A quasi-experimental pilot study described the use of a prospective audit and feedback intervention to improve the appropriateness of antibiotic prescribing at discharge.
  • The antimicrobial stewardship (AMS) team was notified of discharges and documented notes in the electronic health record if either the duration or choice of antibiotic was inappropriate based on local treatment guidelines. The appropriateness of antibiotic prescriptions increased from 50% preintervention to 83% postintervention (p <0.001), and the number of prescription days from discharge decreased by 1 day (5 vs. 4 days, p<0.001). 
  • Additional observations included that prescribers followed fixed longer durations of therapy, preset order durations, and continued antibiotic therapy when no further antibiotics were needed.
  • AMS teams can use the findings from this study to expand prospective audit and feedback interventions at the time of discharge. Antimicrob Steward Healthc Epidemiol. 2025;5(1):e147.

Antimicrobial Shortages (US)

  • Recent shortages:
    • None
  • Recently resolved shortages:
    • Fluconazole injection (1 July 2025) NEW
    • Nystatin oral suspension (21 June 2024) NEW
  • Antimicrobial drugs or vaccines in continued reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons: 
    • Antibacterial drugs:
      • Aminoglycosides:
        • Gentamicin injection (22 Feb 2021)
      • Bacitracin ophthalmic ointment 500 units/gm (12 Sep 2024)
      • Cephalosporins:
        • Cefazolin injection (4 Jun 2018)
        • Cefdinir 300 mg capsules (29 Jun 2023)
        • Cefdinir 125 mg/5 mL, 250 mg/5 mL oral suspension (29 Jun 2023)
        • Cefotaxime injection (10 Jun 2015)
          • FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Provepharm Life Solutions and its distributor Direct Success.
      • Chloramphenicol injection (9 Oct 2023)
      • Fluoroquinolones:
        • Ciprofloxacin injection (13 Jan 2023)
        • Levofloxacin injection in D5W (29 May 2024)
        • Levofloxacin oral solution, 25 mg/mL (15 Sep 2023)
        • Moxifloxacin 400 mg tablets (6 Dec 2023)
      • Glycopeptides, glycolipopeptides, lipopeptides:
        • Vancomycin injection (1 Jun 2015)
      • Lincosamides
        • Clindamycin phosphate injection (25 Jun 2015)
      • Macrolides, azalides:
        • Azithromycin oral suspension, 1 gm packets (20 Nov 2024)
        • Erythromycin lactobionate injection (23 Apr 2025)
      • Neomycin and Polymyxin B sulfates GU irrigant (25 Jun 2023)
      • Nitrofurantoin oral suspension (5 Jun 2018)
      • Nitroimidazoles:
        • Metronidazole injection (20 Oct 2021)
      • Oxazolidinones:
        • Linezolid injection (16 Oct 2024)
      • Penicillins:
        • Amoxicillin, all oral formulations (18 Oct 2022)
        • Amoxicillin-clavulanate, all oral formulations (17 Nov 2022)
        • Dicloxacillin 250 mg, 500 mg capsules (18 Aug 2021)
        • Penicillin G benzathine injection (1 Feb 2023) Availability update
        • Penicillin G benzathine/Penicillin G procaine (31 Mar 2023) Availability update
        • Penicillin VK oral solution 250 mg/5 mL (17 May 2023)
        • Penicillin VK 250 mg, 500 mg tablets (17 May 2023)
      • Rifaximin 200 mg tablets (11 Apr 2024)
    • Antifungal drugs: 
      • Amphotericin B Lipid Complex (5 Aug 2022)
      • Ibrexafungerp 150 mg tablets (3 Dec 2024)
    • Antimycobacterial drugs: 
      • Rifapentine 150 mg tablets (25 Feb 2025)
    • Antiparasitic drugs:
      • Mefloquine 250 mg tablets (14 May 2024)
      • Nitazoxanide oral susp 100 mg/5 mL (15 Feb 2024)
    • Antiviral drugs: 
      • Oseltamivir 30 mg, 45 mg, 75 mg capsules (1 Nov 2022)
      • Oseltamivir powder for oral suspension (1 Nov 2022)
      • Peginterferon alfa-2a (Pegasys) (8 Jan 2025)
      • Ribavirin for inhalation solution (23 May 2023)
  • Antimicrobial drugs recently discontinued: 
    • Bezlotoxumab injection (31 Jan 2025, by Merck)
    • Posaconazole oral susp 40 mg/mL (Dec 2023, by Merck)
    • Sulfacetamide 10%/Prednisolone acetate 0.2% oph ointment (Aug 2023 by Allergan, sole supplier)
    • Penicillin G procaine 600,000 units/mL IM injection (Jun 2023)
    • Ritonavir oral solution 80 mg/mL (Jan 2023)
  • For more information including estimated resupply dates, see ASHP Drug Shortages website.
  • Data shown are current as of 6 July 2025.
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