What's new in infectious diseases

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ANTIMICROBIAL AGENTS

Aztreonam-avibactam for complicated intra-abdominal infections (March 2025)

The US Food and Drug Administration has approved aztreonam-avibactam to be used in combination with metronidazole for treatment of complicated intra-abdominal infections (cIAI) [1]. Approval was based primarily on a randomized trial of 422 patients with either cIAI or hospital-acquired pneumonia that found similar rates of clinical cure and all-cause mortality with aztreonam-avibactam (plus metronidazole for cIAI) compared with meropenem (with or without colistin) [2]. Aztreonam-avibactam may be particularly useful for infections due to carbapenem-resistant Enterobacterales spp that produce metallo-beta-lactamases. The combination drug was approved for use in Europe in 2024. (See "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Carbapenemase testing is positive'.)

BACTERIAL INFECTIONS

Trends of invasive group A Streptococcus infections in the United States (April 2025)

Since 1995, the United States Centers for Disease Control and Prevention (CDC) has tracked rates of invasive group A Streptococcus (GAS) infections, including toxic shock syndrome. In an analysis of data from 10 states from 2013 to 2022, overall incidence of invasive GAS infections increased from 3.6 to 8.2 cases per 100,000 persons [3]. The increase occurred predominantly in the adult population, and patients at highest risk included those over 64 years of age, American Indian or Alaskan Native individuals, residents of long-term care facilities, and people experiencing homelessness or who inject drugs. The percentage of isolates non-susceptible to both macrolides and clindamycin increased from 13 to 33 percent during the study period. Over 21,000 cases were identified, and 9 percent of patients died. This study highlights increasing rates of this severe infection and groups of individuals at the highest risk. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis", section on 'Incidence'.)

Doxycycline and hydroxychloroquine for Whipple's disease (April 2025)

Whipple's disease is a rare chronic infection; data informing the optimal management approach are limited. In a recent randomized trial that included 60 patients, rates of clinical remission were higher with oral doxycycline plus hydroxychloroquine for 12 months compared with intravenous ceftriaxone for two weeks followed by oral trimethoprim-sulfamethoxazole for 12 months (97 versus 81 percent), although the difference was not statistically significant [4]. The all-oral regimen was better tolerated. Despite limitations of the trial, we now prefer doxycycline plus hydroxychloroquine for classic Whipple's disease (joint and gastrointestinal involvement); we continue to use a regimen with an initial intravenous phase for infection involving the central nervous system or endocarditis. (See "Whipple's disease", section on 'Initial management'.)

Duration of antibiotics for gram-negative bacillary bacteremia (April 2025)

Although bacteremia had traditionally been treated with at least 14 days of antibiotics, mounting data indicate that shorter courses are often appropriate. In a randomized trial of over 3600 hospitalized patients with bloodstream infections (mostly due to gram-negative bacilli), 90-day mortality was similar in patients treated with 7 or 14 days of antibiotics (15 versus 16 percent) [5]. Patients with immunocompromising conditions, prosthetic heart valves or vascular grafts, a syndrome requiring prolonged therapy (eg, endocarditis), or Staphylococcus aureus bacteremia were excluded from the study. A recent meta-analysis reported similar findings [6]. These data support our approach to treat most patients with uncomplicated gram-negative bacillary bacteremia with seven days of antibiotics. (See "Gram-negative bacillary bacteremia in adults", section on 'Duration and route of therapy'.)

Gepotidacin for acute simple cystitis (April 2025)

In 2025, the US Food and Drug Administration approved gepotidacin, a novel antibiotic that retains activity against organisms resistant to fluoroquinolones and other antibiotic classes, for treatment of acute simple cystitis (uncomplicated urinary tract infection [UTI]) in adult females. In trials, gepotidacin resulted in combined clinical and microbiologic cure rates that were either similar to (51 versus 47 percent) or higher than (59 versus 43 percent) those with nitrofurantoin [7]. Diarrhea was common. Because of antimicrobial stewardship concerns, we reserve this agent for directed therapy of gram-negative pathogens that are resistant to other drug classes; it is not indicated for complicated UTI (including pyelonephritis). (See "Acute simple cystitis in female adults", section on 'Directed antimicrobial selection'.)

Outcomes associated with sepsis bundles (April 2025)

A "sepsis bundle" refers to a set of early interventions (eg, intravenous fluids, antibiotics, and laboratory tests) that improve the diagnosis, management, and survival of patients with sepsis; the time required to complete the "sepsis bundle" is widely used in hospitals as a pay-for-performance measure. A recent review analyzed 17 observational trials examining outcomes associated with compliance or implementation of a sepsis bundle [8]. Five studies demonstrated a mortality benefit from bundle compliance while seven did not. Only one study showed a mortality benefit from bundle implementation. High-quality data are needed to demonstrate a clear mortality benefit from sepsis bundles. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Early goal-directed therapy'.)

Procalcitonin and antibiotic duration in sepsis (April 2025)

While procalcitonin (PCT) has a clear role in determining antibiotic duration for patients with community-acquired pneumonia, its role in managing sepsis is less clear. A recent multicenter randomized trial of 2760 adults with sepsis, reported a reduction in antibiotic duration for patients in whom a daily PCT-guided protocol was implemented compared with standard care (9.8 versus 10.7 days) [9]. However, over half of study participants had lower respiratory tract infections which may have impacted the outcome. Based upon these and other cumulating data in patients with sepsis, we support measuring PCT to guide antibiotic duration. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial investigations'.)

Thymosin alpha 1 not beneficial in sepsis (February 2025)

Preliminary data suggest that thymosin-alpha 1, an agent that enhances the effect of T helper 1 cells, may be beneficial in patients with sepsis. However, a phase 3 randomized trial of subcutaneous thymosin alpha 1 for seven days in 552 patients with sepsis reported similar 28-day mortality when compared with 554 patients treated with placebo [10]. Other outcomes (including 90-day mortality, new onset infection rates, and microorganism clearance rates) were also similar. Although the drug may have been underdosed and the study underpowered to detect a mortality difference, these results are not encouraging for further trials of this agent in sepsis. (See "Investigational and ineffective pharmacologic therapies for sepsis", section on 'Immunostimulation'.)

Sulopenem etzadroxil-probenicid for acute simple cystitis (November 2024)

In 2024, the US Food and Drug Administration approved sulopenem etzadroxil-probenecid, an oral penem antibiotic that has activity against some extended-spectrum beta-lactamase (ESBL)-producing organisms, for treatment of acute simple cystitis (uncomplicated urinary tract infection [UTI]) in adult females. In trials, differences in the combined clinical and microbiologic cure rates were not statistically significant when comparing sulopenem etzadroxil-probenecid with amoxicillin-clavulanate (62 versus 55 percent) or ciprofloxacin (66 versus 68 percent) [11,12]. Because of antimicrobial stewardship concerns, we reserve this agent for gram-negative pathogens that are resistant to all other drug classes; it is not active against Pseudomonas and should not be used for complicated UTI (including pyelonephritis). (See "Acute simple cystitis in female adults", section on 'Directed antimicrobial selection'.)

High diagnostic uncertainty in community-acquired pneumonia (October 2024)

Because community-acquired pneumonia (CAP) is common and its symptoms overlap with many other cardiopulmonary disorders, it is both over- and underdiagnosed on presentation. In a recent study of over two million hospitalizations in the US Veterans Administration health system, 36 percent of over 215,000 patients with an initial emergency department (ED) diagnosis of pneumonia did not carry this diagnosis upon hospital discharge, and 33 percent of over 239,000 patients discharged with a diagnosis of pneumonia and positive initial chest imaging lacked an ED diagnosis [13]. These findings reinforce the importance of assessing patients initially diagnosed with CAP for alternative processes and being open to the possibility of CAP in patients initially diagnosed with other conditions. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'General approach'.)

HIV INFECTION

Updated IAS-USA guidelines for the treatment and prevention of HIV (February 2025)

In December of 2024, the International Antiviral Society-USA guideline panel released updated guidelines on the treatment and prevention of HIV [14]. They reaffirmed their preference for an initial regimen that includes dolutegravir or bictegravir combined with tenofovir-emtricitabine or lamivudine. Protease inhibitor-containing regimens are typically reserved for patients with suspected or confirmed resistance to integrase strand transfer inhibitors, such as those who acquire HIV while receiving cabotegravir as pre-exposure prophylaxis. Antiretroviral therapy (ART) should be initiated as soon as possible. When one of the preferred three drug regimens is used, ART can be started before the results of baseline testing return. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Approach for most patients'.)

Updated United States guidelines on perinatal HIV transmission (January 2025)

The United States Department of Health and Human Services has updated the perinatal HIV clinical guidelines [15]. They now categorize infants born to mothers with HIV into three risk stratification groups based on maternal HIV viral load during pregnancy, the most significant risk factor for transmission. The lowest-risk infants are born to mothers with sustained viral suppression (HIV RNA <50 copies/mL) since 20 weeks gestation. The highest-risk infants are born to mothers with a detectable HIV viral load within four weeks of delivery. All other infants fall into the middle-risk category. This risk stratification informs the antiretroviral regimen given to the infant to prevent HIV transmission, outlined in the table (table 1). Our approach to the management of infants exposed to HIV at birth is consistent with these updated guidelines. (See "Pediatric HIV infection: Management of infants born to mothers with HIV in resource-abundant settings", section on 'Approach to ARV drug management'.)

Lenacapavir for prevention of HIV (December 2024)

Antiretroviral pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy; however, available options are limited by adherence challenges and/or the risk of promoting resistance to first-line HIV regimens should infection occur. Lenacapavir, an HIV-1 capsid inhibitor, is a long-acting agent that had >96 percent efficacy for preventing HIV infection in two randomized, double-blind trials [16,17]. In both, lenacapavir was well tolerated and superior to oral regimens over at least 52 weeks of follow-up. In men and gender-diverse patients who have sex with men, new HIV infections occurred in 2 of 2179 versus 9 of 1086 persons receiving lenacapavir versus oral therapy, respectively. In cisgender women, new HIV infections occurred in 0 of 2134 versus 55 of 3204 persons. Although lenacapavir is not yet approved for use as PrEP in the United States, these data support its future role as an effective agent for HIV prevention. (See "HIV pre-exposure prophylaxis", section on 'Novel approaches to treatment'.)

Perinatal HIV transmission continues to occur in the United States (November 2024)

In the United States, when pregnant individuals with HIV and their infants receive all applicable perinatal transmission prevention interventions, perinatal HIV transmission rates can be reduced to less than 1 percent. However, cases of perinatal HIV transmission still occur, as outlined by a recently published case series of six children diagnosed with HIV due to perinatal transmission in 2022 [18]. Causes included delayed entry to prenatal care, discovery of HIV diagnosis during pregnancy rather than preconception, and delays in antiretroviral therapy (ART) initiation during pregnancy. Potential opportunities to reduce transmission include increasing pre-exposure prophylaxis (PrEP) utilization, routine HIV testing among individuals of childbearing age who are at high risk of HIV acquisition, and rapid start of ART for pregnant individuals with HIV. Additionally, once a mother is diagnosed with HIV, all biological children should be tested for HIV to avoid delayed identification. (See "Pediatric HIV infection: Epidemiology, clinical manifestations, and outcome", section on 'Resource-rich settings'.)

Kidney transplantation from donors with HIV (November 2024)

For persons with HIV and end-stage kidney disease who are candidates for kidney transplantation, there has been increased interest in the use of kidney donors with HIV given the limited supply of organs. In a report of nearly 200 persons with HIV undergoing kidney transplantation, the rates of overall patient survival and rejection at one and three years were similar with HIV-positive and HIV-negative donors [19]. Although the incidence of HIV breakthrough infection was higher among recipients of donors with HIV versus those without HIV, virologic control was regained in all cases. These findings are consistent with other studies and support the use of donor kidneys from persons with HIV in an effort to increase access to donor organs. (See "Kidney transplantation in patients with HIV", section on 'Donors with HIV'.)

IMMUNIZATIONS

Fractional dosing of yellow fever vaccine (April 2025)

Yellow fever vaccine supply is limited. The efficacy of one-fifth fractional dosing has been demonstrated in randomized trials; the minimum dose requirements for seroconversion remain unknown. In a trial including 480 adults with no history of yellow fever vaccination or infection in Uganda and Kenya, patients were randomly assigned to receive the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at standard dose (13,803 international units [IU]) or fractional doses (1000, 500, or 250 IU) [20]. Seroconversion rates within 28 days were similar with a vaccine dose as low as 500 IU compared with standard dosing. Follow-up to determine the durability of protection is needed, as is further study to evaluate other vaccine formulations. (See "Yellow fever: Treatment and prevention", section on 'Fractional vaccine dosing'.)

Revised dosing schedule for MenB-4C (Bexsero) (February 2025)

In December 2024, the US Centers for Disease Control published an updated dosing schedule for MenB-4C (Bexsero), one of two available meningococcal serogroup B vaccines [21]. Routine vaccination of healthy individuals now consists of two doses, separated by ≥6 months (table 2). Three doses (zero, one to two, and six months) should be administered to those at increased risk for serogroup B meningococcal disease and during an outbreak (table 3 and table 4). Previously MenB-4C was administered as two doses, separated by ≥1 month. This change was based on improved immunogenicity with the revised dosing schedule. MenB-4C is also available as part of a pentavalent vaccine (Penmenvy), which was approved for use in February 2025 [22]; updated recommendations on the use of this vaccine are pending. When administering serogroup B meningococcal vaccines, a single manufacturer's MenB products must be used for each dose of the primary series and all booster doses. Vaccine formulations are not interchangeable. (See "Meningococcal vaccination in children and adults", section on 'Vaccine schedules'.)

2025 immunization schedules for adults in the United States (February 2025)

The United States Centers for Disease Control and Prevention (CDC) has published the 2025 immunization schedule for adults (figure 1 and figure 2) [23]. Persons 65 years of age or older are now recommended to receive two or more doses of a 2024-2025 COVID-19 vaccine. Pneumococcal vaccine is now recommended for all adults 50 years or older, and the newest conjugate vaccine (PCV21) is now included in the recommendations. Respiratory syncytial virus (RSV) vaccine has a stronger recommendation for persons 75 years or older. Our approach to immunization is largely consistent with these recommendations. (See "Standard immunizations for nonpregnant adults", section on 'Immunization schedule for nonpregnant adults'.)

Egg allergy no longer a concern for any vaccines (February 2025)

Some vaccines contain trace amounts of egg protein (table 5), but none contain enough to cause reactions in egg-allergic patients. For the last several years, it has been recommended that patients not be asked about egg allergy prior to receiving influenza vaccine. More recently, data have accumulated to show that egg allergy is similarly not a concern for administration of the yellow fever vaccine. In the largest study to date, 171 children with egg allergy, including 24 percent with a history of anaphylaxis, underwent skin testing with the yellow fever vaccine and then received it regardless of skin test results, with no allergic reactions [24]. Thus, we no longer inquire about egg allergy prior to the administration of any vaccine. Vaccine providers should remain prepared to treat rare allergic reactions that may occur after any vaccine, but no special precautions are necessary for recipients with egg allergy. (See "Allergic reactions to vaccines", section on 'Hen's egg'.)

Respiratory syncytial virus vaccination in pregnancy and risk of preterm birth (January 2025)

Respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants. Maternal vaccination with the inactivated nonadjuvanted recombinant RSV vaccine (RSVPreF; Abrysvo) can reduce this risk. While randomized trials have established the vaccine's safety and efficacy, a trend toward an increased risk of preterm birth was observed. Now, the final analysis of a randomized trial including more than 7000 pregnant individuals worldwide reported that preterm birth rates were similar for those vaccinated with RSVPreF versus placebo (5.7 versus 4.7 percent), with most of the preterm births occurring at ≥34 weeks of gestation [25]. These data are consistent with other studies and further support our practice of vaccinating eligible pregnant individuals with the RSVPreF vaccine. (See "Immunizations during pregnancy", section on 'Strategies for prevention'.)

HepB-CpG for hepatitis B vaccine nonresponders with HIV (January 2025)

Persons with HIV are less likely to develop a protective serologic response to conventional hepatitis B vaccines (eg, Engerix-B or Recombivax HB) compared with those without HIV; nonresponders to the initial series should be reimmunized. In a randomized trial of patients on antiretroviral therapy who did not respond to HBV vaccination, revaccination with two or three doses of HepB-CpG (Heplisav) led to greater seroprotection than three doses of the conventional hepatitis B vaccine (93 and 99 versus 81 percent, respectively) [26]. Seroprotective responses were also achieved more rapidly with HepB-CpG. Thus, for nonresponders to an initial hepatitis B vaccine series, we recommend repeat vaccination with HepB-CpG rather than conventional hepatitis B vaccines. However, if HepB-CpG is not available, the vaccine series should be repeated using a double dose of a conventional hepatitis B vaccine. (See "Prevention of hepatitis B virus infection in adults with HIV", section on 'Initial approach for most patients'.)

RSV vaccination and Guillain-Barré syndrome (January 2025)

In January of 2025, the US Food and Drug Administration issued a warning about Guillain-Barré syndrome (GBS) in persons receiving either of the glycoprotein subunit RSV vaccines [27]. In analyses of observational data from persons ≥65 years, there were an estimated seven excess cases of GBS per million doses of the adjuvanted vaccine (Arexvy) and nine excess cases of GBS per million doses of the bivalent vaccine (Abrysvo). By contrast, RSV disease in adults ≥65 years causes 60,000 to 160,000 hospitalizations and 6000 to 10,000 deaths annually. This information is important for patients considering RSV vaccination, with decisions tailored to individualized risk assessment for severe RSV disease (table 6). (See "Respiratory syncytial virus infection in adults", section on 'Risk of Guillain Barré'.)

Recombinant hepatitis B vaccine (Heplisav-B) during pregnancy. (December 2024)

Hepatitis B vaccination may be warranted during pregnancy for selected patients (eg, those at high risk of acquiring hepatitis B virus). In December 2024, the Advisory Committee on Immunization Practices endorsed the US Food and Drug Administration approval of the adjuvanted recombinant vaccine (Heplisav-B) for use in pregnancy [28]. In an unpublished observational study that included 75 pregnant patients who received the adjuvanted recombinant vaccine during the 28 days before conception or during pregnancy, no major birth defects were identified nor was there an increased rate of pregnancy loss. This approval expands the list of hepatitis B vaccines that are approved for use during pregnancy. (See "Immunizations during pregnancy", section on 'Hepatitis B'.)

Lower age cutoff for pneumococcal vaccine indications (November 2024)

In October 2024, the United States Advisory Committee (ACIP) extended pneumococcal vaccination recommendations to include all adults ≥50 years of age, regardless of risk factors (table 7) [29]. Previously, the age threshold was ≥65 years for healthy adults and ≥19 years for those at risk for pneumococcal infection or severe complications from pneumococcal infection. This decision is based on knowledge that the incidence of pneumococcal disease starts to increase at age 50 (table 8) and the predicted reduction in invasive pneumococcal disease cases in certain underrepresented ethnic/racial groups within the United States. We agree with the new guidelines from the ACIP and now suggest pneumococcal vaccination beginning at age 50 for all adults. (See "Pneumococcal vaccination in adults", section on 'Indications for vaccination'.)

RSV vaccine effective in mild to moderately immunocompromised individuals (October 2024)

The respiratory syncytial virus (RSV) vaccine is recommended for immunocompromised individuals aged 60 and above, although the data on the efficacy of the RSV vaccine in this population is limited. In an electronic health records-based observational study that included over 10,000 predominantly mild to moderately immunocompromised individuals ≥60 years old (46 percent of whom had a malignancy), the adjusted RSV vaccine effectiveness against respiratory virus-associated hospitalizations in the first year of follow-up was 73 percent [30]. This study provides preliminary evidence of vaccine efficacy in this patient population and supports vaccination against RSV in immunocompromised individuals aged 60 and above. (See "Immunizations in adults with cancer", section on 'Respiratory syncytial virus (RSV)'.)

Electronic letters to improve influenza vaccination rates (October 2024)

Electronic letters have been proposed to improve annual influenza vaccination rates. In a study including more than 300,000 Danish patients aged 18 to 64 years with chronic diseases, influenza vaccination rates were higher among those randomly assigned to receive one of six letters that included a behavioral nudge compared with those who received no letter (40 versus 28 percent) [31]. The largest effect sizes were observed with a repeat letter sent 10 days after the initial letter (42 percent) and a letter emphasizing potential cardiovascular benefits of vaccination (40 percent). Electronic letters are scalable, cost-effective, and may have beneficial public health implications. (See "Seasonal influenza vaccination in adults", section on 'Improving vaccination rates'.)

INFECTION CONTROL

Nursing homes as sources of spread of multidrug-resistant microorganisms (April 2025)

Nursing homes are thought to be a major reservoir of multidrug-resistant microorganisms. In a nursing home in Chicago, shot-gun metagenomic sequencing of skin swabs from 42 residents revealed widespread sharing of specific strains of Candida auris and multidrug-resistant bacteria among residents [32]. Comparing the strains to publicly available databases of genomic sequences from other locations revealed geographic spread throughout metropolitan Chicago and to patients and healthcare facilities in other states as far away as New Hampshire and Massachusetts. These findings highlight the efficiency of nursing homes as sources of spread across broad geographic regions and the importance of infection prevention measures to minimize person-to-person spread and skin colonization. (See "Outbreaks in long-term care facilities: Detection and management", section on 'Candida auris'.)

Uncertain role of systemic antibiotics to prevent ventilator-associated pneumonia (December 2024)

Ventilator-associated pneumonia (VAP) is a significant cause of mortality in patients in the intensive care unit (ICU). In a recent randomized trial of patients with moderate or severe traumatic brain injury (TBI) or acute stroke, ceftriaxone 2 g intravenously (IV) within 12 hours of intubation reduced 7-day VAP rates (14 versus 32 percent) and 28-day mortality rates (15 versus 25 percent) compared with placebo without excess adverse effects [33]. However, in a subsequent meta-analysis including that trial and six others with over 800 patients with acute brain injury (stroke, TBI, or post-cardiac arrest), a short course of peri-intubation IV antibiotics reduced the incidence of VAP, but significant differences in the number of ventilator-free days, ICU length of stay, or in-hospital mortality were not detected [34]. Given the uncertainty around these effects, practice among UpToDate contributors vary; some do not routinely use systemic antibiotics for prevention of VAP in the ICU because of concern for promoting antibiotic resistance, whereas others suggest a single peri-intubation dose of ceftriaxone to prevent VAP in selected populations at high risk (eg, patients with acute TBI). (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Prevention' and "Management of acute moderate and severe traumatic brain injury", section on 'Mechanical ventilation'.)

MYCOBACTERIAL INFECTIONS

Limited effect of digital adherence technologies on tuberculosis treatment outcomes (April 2025)

Incomplete adherence to treatment for tuberculosis (TB) disease remains a major obstacle to TB control. Four cluster-randomized trials evaluated two digital adherence technology tools among more than 20,000 individuals with drug-susceptible TB in the Philippines, South Africa, Tanzania, and Ukraine: use of a 'smart' pillbox with reminders and tracking or use of medication labels requiring patients to send a text upon taking a dose [35]. The studies detected no difference in poor treatment outcomes (defined as documented treatment failure, prolonged treatment interruption, switch to a regimen for multidrug-resistant tuberculosis, or death during treatment) with these adherence tools compared with standard care. Their potential benefit for other important outcomes (such as loss to follow-up, relapse) warrants further investigation. (See "Adherence to tuberculosis treatment", section on 'Digital reminders'.)

Updated guidelines for treatment of tuberculosis (February 2025)

New guidelines for treating tuberculosis (TB) have been issued by the American Thoracic Society, US Centers for Disease Control, European Respiratory Society, and Infectious Disease Society of America [36]. For drug-susceptible TB in patients ≥12 years of age who meet all conditions, the guidelines conditionally recommend a rifapentine-moxifloxacin-based regimen (rifapentine, moxifloxacin, isoniazid, and pyrazinamide for four months); we suggest a traditional regimen given the need for special monitoring in some patients on the shortened regimen. For patients age 3 months to 16 years with nonsevere, smear-negative, presumed drug-susceptible disease, we agree with the guidelines, which favor a shortened four-month regimen (isoniazid, rifampin, and pyrazinamide, with or without ethambutol). For patients ≥14 years of age with rifampin-resistant TB, we agree with the new guidelines, which favor bedaquiline, pretomanid, and linezolid, with or without moxifloxacin for six months (BPaL[M]). (See "Tuberculosis disease in children: Treatment and prevention", section on 'Regimen selection'.)

Oral regimens for treatment of multidrug-resistant tuberculosis (February 2025)

Shorter, all-oral regimens to treat multidrug-resistant TB (MDR-TB) are under investigation. A randomized trial including 699 patients ≥15 years with MDR-TB in 7 countries compared five nine-month regimens of combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx), moxifloxacin (M), clofazimine (C), and pyrazinamide (Z): BCLLfxZ, BLMZ, BDLLfxZ, DCMZ, and DCLLfxZ with standard therapy (longer, individualized regimen) [37]. The primary endpoint was favorable outcome at week 73 (two negative sputum cultures or favorable bacteriologic, clinical, and radiologic evolution). Three regimens (BCLLfxZ, BLMZ, and BDLLfxZ) were noninferior in both modified intention-to-treat and per-protocol populations. Hepatotoxicity occurred in 12 percent of participants overall and in 7 percent of the standard therapy group. We continue to suggest B, pretomanid, and L (with or without M) for treating most patients with MDR-TB. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Other bedaquiline-based regimens'.)

Levofloxacin following exposure to multidrug-resistant tuberculosis (January 2025)

The optimal approach to preventive treatment for contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is uncertain. Two recent randomized trials compared daily levofloxacin with placebo for six months following MDR-TB exposure in 2041 adult patients in Vietnam [38] and 453 pediatric patients in South Africa [39]. In a meta-analysis of those trials, levofloxacin reduced the incidence of TB at 54-week follow-up by 60 percent (8 versus 21 cases) [40]. Musculoskeletal events of any grade occurred more frequently in the levofloxacin group but not among children <10 years of age. Based on these findings, for contacts of patients with MDR-TB that is susceptible to fluoroquinolones, we treat with levofloxacin daily for six months. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV infection", section on 'Drug-resistant tuberculosis infection (TBI)'.)

Bedaquiline for mulitbacillary leprosy (January 2025)

Because of severe adverse effects associated with current multidrug treatment regimens for leprosy, there is interest in evaluating other agents. In an open-label, proof-of-concept study, nine patients with previously untreated multibacillary leprosy in Brazil were treated with bedaquiline for eight weeks followed by standard multidrug therapy [41]. After four weeks, skin biopsy specimens were negative for M. leprae growth and had undetectable polymerase chain reaction for M. leprae. After eight weeks, all patients had improvement in the appearance of skin lesions. No serious adverse events were observed during bedaquiline treatment. These findings should prompt further investigation of bedaquiline for treatment of leprosy; combination therapy will remain important to avoid development of resistance. (See "Leprosy: Treatment and prevention", section on 'Outside the United States'.)

PARASITIC INFECTIONS

Trajectory of global malaria burden between 2000 and 2022 (March 2025)

Tracking malaria prevalence is important for guiding control efforts. In a study using data from 2000 to 2022, a plateau in malaria prevalence within sub-Saharan Africa was observed, with no improvement since 2015 [42]. In 2022 there were an estimated 234.8 million cases of Plasmodium falciparum malaria, the most since 2004. The plateau occurred in more densely populated areas; sparser areas had a trajectory of modest improvement. Outside Africa, an outbreak in Pakistan after flooding in 2022 contributed to a global total of 12.4 million cases of P. vivax malaria. The study did not reflect the impact of new malaria vaccines implemented since 2022. These findings demonstrate the heterogeneity of malaria and highlight the importance of tailoring control interventions to individual geographic locations. (See "Malaria: Epidemiology, prevention, and elimination", section on 'Geographic distribution'.)

Spatial insect repellant for malaria prevention (January 2025)

Spatial insect repellent products are designed to release active ingredient into the air to disrupt human contact with mosquitoes and are a potential strategy for malaria prevention. A cluster-randomized trial in Kenya evaluated the efficacy of a transfluthrin-based spatial repellent for prevention of malaria infection following mass distribution of insecticide-treated nets (ITNs) [43]. At 24-month follow-up, spatial repellents reduced the hazard rates of first-time malaria infection and overall new infections (by 33 and 30 percent, respectively). Further study is needed to understand the efficacy of spatial repellents in the absence of ITN use, as well as the benefit of spatial repellant for reducing the risk of other mosquito-borne infections. (See "Malaria: Epidemiology, prevention, and elimination", section on 'Other vector control tools'.)

Role of malaria rapid diagnostic tests in sub-Saharan Africa (November 2024)

It is uncertain how malaria rapid diagnostic test (RDT) availability affects management and outcomes for children with febrile illness in endemic areas. In a study including more than 1.3 million children <5 years of age with 250,000 episodes of febrile illness in sub-Saharan Africa, each additional malaria RDT distributed per child was associated with an increase in blood testing, antimalarial use, antibiotic use, and symptomatic treatment (3.5, 1.5, 0.4 and 0.4 percentage points, respectively), and, in areas with high malaria prevalence, a reduction in mortality (0.34 deaths per 1000 child-years) [44]. The study was limited in its ability to control for confounders, including that RDT distribution may reflect access to better care, better access to antimalarials, and/or better adherence to management guidelines. The findings reflect the importance of implementing RDT use in the context of a broader approach to management of febrile illness. (See "Laboratory tools for diagnosis of malaria", section on 'In endemic areas'.)

SEXUALLY TRANSMITTED DISEASES

New reports of Trichophyton mentagrophytes genotype VII infection in the United States (November 2024)

Trichophyton mentagrophytes genotype VII infection, an emerging dermatophyte infection that can spread through sexual contact, has been primarily documented in reports from Europe. A new report adds four patients to a single preceding report of this infection in the United States, including three patients with no recent international travel [45]. Clinical findings may include pruritic, scaly, annular patches or plaques, or inflamed papules in sites such as the trunk, groin, genitals, or face. Definitive diagnosis requires DNA sequencing; extended courses of oral antifungal therapy may be necessary for resolution. This report supports increased awareness of T. mentagrophytes genotype VII infection in the United States. (See "Dermatophyte (tinea) infections", section on 'Tinea genitalis'.)

VIRAL INFECTIONS, NON-HIV

Mpox in Central and East Africa (March 2025)

Mpox is an increasing cause of morbidity and mortality in Central and East Africa. In one report, the annual incidence in the Democratic Republic of the Congo (DRC) increased between 2010 to 2023 from approximately 3 to 11 cases per 100,000 people [46]. From January to August 2024, 21,786 laboratory-confirmed mpox cases leading to 607 deaths were reported from 12 African countries [47]. Although the vast majority of these cases were in the DRC, cases were also reported in neighboring countries, including the previously nonendemic countries of Burundi, Rwanda, and Uganda. These findings support ongoing efforts (public health measures, vaccination) to reduce the continued spread of mpox. (See "Epidemiology, clinical manifestations, and diagnosis of mpox (formerly monkeypox)", section on 'Outbreak in Central and East Africa starting in 2023'.)

Ring vaccination for prevention of Ebola virus disease (February 2025)

A ring vaccination strategy using the single-dose recombinant vesicular stomatitis virus-Zaire Ebola vaccine (rVSV-ZEBOV; sold as Ervebo) should be employed in the setting of an Ebola virus disease outbreak to prevent ongoing transmission; this involves vaccinating close contacts of patients with Ebola virus disease, as well as close contacts of those contacts. A prospective observational study followed nearly 200,000 persons ring-vaccinated during the 2018 Ebola virus disease outbreak in the Democratic Republic of the Congo [48]. Approximately 430 patients were diagnosed with Ebola virus disease, and almost all cases developed within the first nine days after vaccination, before optimal protection was achieved. The rVSV-ZEBOV vaccine does not provide protection against Sudan virus disease. A study employing ring vaccination with an experimental vaccine has been initiated in Uganda as part of the response to the 2025 outbreak of Sudan virus disease [49]. (See "Treatment and prevention of Ebola and Sudan virus disease", section on 'Outbreak setting'.)

Advanced respiratory support in COVID-19 (January 2025)

In patients with COVID-19 who need advanced respiratory support, choosing between high-flow oxygen delivered via nasal cannulae (HFNC) and noninvasive ventilatory (NIV) support is challenging. In a recent trial of 1800 patients with acute respiratory failure from COVID-19 randomized to HFNC versus NIV, similar rates of endotracheal intubation (approximately 30 percent) and death (12 percent) were reported at the end of one week [50]. Subgroup analyses were not helpful in modality selection. In patients with COVID-19 who need advanced respiratory support, we use the patient's comorbidities and the tolerability of the device to help choose between NIV and HFNC. (See "COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation)", section on 'Choosing oxygen via high-flow nasal cannulae versus noninvasive ventilation'.)

Highly pathogenic avian influenza A(H5N1) virus infection in humans (January 2025)

Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. In a report of 46 human cases in 2024 from the United States, infections were generally mild and self-limited [51]. Notable exposures included poultry (20 patients) and dairy cows (25 patients); one patient had no defined exposure. Most patients (93 percent) presented with conjunctivitis; 49 percent presented with fever, and 36 percent presented with mild respiratory symptoms; all recovered. No evidence of human-to-human transmission was identified. Among patients with occupational exposure, the use of personal protective equipment was not universal, suggesting additional strategies are needed to reduce exposure risk. (See "Avian influenza: Clinical manifestations and diagnosis", section on 'Signs and symptoms'.)

Lithium aspartate ineffective for neurocognitive effects of long COVID (November 2024)

Anecdotal reports have suggested a benefit from low-dose lithium in patients with neurocognitive symptoms due to long COVID. However, in a placebo-controlled randomized trial in 52 patients with at least four weeks of neurocognitive symptoms following COVID-19 infection, three weeks of lithium aspartate (10 to 15 mg daily) failed to improve fatigue or cognitive dysfunction scores [52]. Limitations included small sample size and possible under-dosing. While low-dose lithium does not appear to benefit patients with long COVID-associated neurocognitive symptoms, further exploratory studies may be warranted. (See "COVID-19: Management of adults with persistent symptoms following acute illness ("long COVID")", section on 'Investigational therapies'.)

OTHER INFECTIOUS DISEASES

Population-based study of scrub typhus in India (March 2025)

Scrub typhus is endemic across Asia, but its precise epidemiology is uncertain. In a two-year surveillance study of over 30,000 individuals in rural India, 328 cases of scrub typhus, or 6 cases per 1000 person-years, were diagnosed [53]. Most were mild or asymptomatic. Hospitalization was required in 71 cases (22 percent), 29 cases (9 percent) were severe (ie, had organ dysfunction or an adverse pregnancy outcome), and the case-fatality rate was 1.5 percent. Seropositivity did not prevent new infection but may have prevented severe disease. This study adds important information about the epidemiology, immunology, and spectrum of illness of this neglected infection. (See "Scrub typhus", section on 'Epidemiology'.)

Treatment of Helicobacter pylori infection in adults (November 2024)

Over half of individuals in the United States with Helicobacter pylori infection continue to receive clarithromycin-based treatment regimens, despite rising rates of H. pylori resistance to clarithromycin and declining rates of treatment success with these regimens [54]. Recent guidelines from the American College of Gastroenterology reinforce the importance of using non-clarithromycin-based regimens for the initial and salvage treatment of H. pylori infection [55]. Preferred regimens for the empiric management of H. pylori infection in treatment-naïve adults include optimized bismuth quadruple therapy, rifabutin triple therapy, and vonoprazan-amoxicillin dual therapy. The guidelines also emphasize testing to confirm H. pylori eradication after treatment and discuss the role of antimicrobial susceptibility testing in H. pylori management. Based on available evidence, we suggest optimized bismuth quadruple therapy as the preferred regimen for H. pylori infection in treatment-naïve adults. (See "Treatment of Helicobacter pylori infection in adults".)