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What's new in infectious diseases

What's new in infectious diseases
Literature review current through: Jan 2024.
This topic last updated: Jan 29, 2024.

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.

COVID-19

Simnotrelvir-ritonavir for mild to moderate COVID-19 (January 2024)

Although nirmatrelvir-ritonavir reduces hospitalization and death from COVID-19, the many drug interactions make it difficult to use in some patients. Simnotrelvir-ritonavir is a similar protease inhibitor combination that inhibits viral replication but does not have as many drug interactions. In a randomized, double-blinded study of over 1000 patients with mild to moderate COVID-19 (majority fully vaccinated), 5 days of simnotrelvir-ritonavir reduced time to symptom resolution by 1.5 days [1]. Since no participant progressed to severe disease or died by day 29, it is unknown whether the drug prevents hospitalizations or death from COVID-19. Simnotrelvir-ritonavir has emergency use approval in China but is not yet approved for use in other countries. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Therapies of limited or uncertain benefit'.)

Convalescent plasma in mechanically ventilated patients with COVID-19 (November 2023)

Most randomized trials have not demonstrated a benefit for convalescent plasma in hospitalized patients with COVID-19, and we do not routinely use it in this setting. However, an open-label trial of 475 patients who were mechanically ventilated for severe COVID-19 did report a reduction in 28-day mortality with high-titer convalescent plasma compared with standard care (35 versus 45 percent) [2]. The inconsistency of this finding compared with the lack of effect in most other trials decreases confidence in the mortality benefit. Furthermore, the value of convalescent plasma against Omicron variants and in the context of contemporary management remains uncertain, as only a few patients in the trial had Omicron infection and most received only dexamethasone without other immunomodulatory agents. (See "COVID-19: Management in hospitalized adults", section on 'Limited role for antibody-based therapies (monoclonal antibodies and convalescent plasma)'.)

Lower survival among recipients of donor hearts from donors with active COVID-19 (November 2023)

It is unclear whether donor hearts from donors with active COVID-19 have similar survival when compared with those from donors without COVID-19. In a recent study of nearly 5900 patients who underwent heart transplantation, one-year survival was lower among recipients of hearts obtained from donors with active COVID-19 when compared with recipients of hearts from donors without COVID-19 (77 versus 91 percent) [3]. The cause of higher mortality was unclear, and despite adjustment for confounders, the difference in survival could be the result of unmeasured confounders or bias. The decision to accept a donor heart depends on each recipient's ongoing risk of waiting for transplantation and risks associated with the potential donor, including the donor's COVID-19 status at the time of donation. (See "Heart transplantation in adults: Donor selection and organ allocation", section on 'Donors with COVID-19'.)

Aerosol generation during noninvasive respiratory support modalities (October 2023)

Studies have reported conflicting data as to whether high levels of aerosols are generated when noninvasive ventilation (NIV) or high-flow nasal oxygen (HFNO) is used. In a 2023 systematic review including 12 studies in patients with respiratory infections and 15 studies in healthy volunteers, use of NIV or HFNO was not associated with increased generation of pathogen-laden aerosols compared with controls with unsupported normal or labored breathing, low-flow nasal oxygen, or oxygen or nonrebreather mask [4]. Inconsistency among studies may reflect differences in sampling and detection methodologies and operating room ventilation. Notably, the National Health Service in the United Kingdom has removed mask ventilation, intubation, and extubation from its list of aerosol-generating procedures. (See "Overview of infection control during anesthetic care", section on 'Considerations during aerosol-generating procedures'.)

Updated COVID-19 mRNA vaccine recommendations (September 2023)

The US Food and Drug Administration and Centers for Disease Control and Prevention have updated COVID-19 vaccine authorizations and recommendations [5,6]. Available COVID-19 vaccines have been updated to target Omicron variant XBB.1.5 (Moderna COVID-19 vaccine 2023-2024 formula, Pfizer COVID-19 vaccine 2023-2024 formula, and Novavax 2023-2024 formula); bivalent vaccines are no longer available. An updated 2023-2024 formula vaccine is recommended for all individuals aged six months and older. Immunocompetent individuals five years and older should receive one updated vaccine, regardless of prior vaccination history. For individuals who are four years or younger or have an immunocompromising condition (table 1), the number of recommended updated vaccines depends on their vaccination history. Our approach to COVID-19 vaccination is consistent with these recommendations. (See "COVID-19: Vaccines", section on 'Indications and vaccine selection' and "COVID-19: Vaccines", section on 'Benefits of vaccination'.)

Adjunctive immunomodulators for severe COVID-19 (August 2023)

For patients hospitalized for COVID-19 who require high-flow oxygen or ventilatory support, we suggest adding baricitinib or tocilizumab to dexamethasone to further reduce mortality. Other immunomodulatory agents may also improve outcomes. In a randomized trial of patients with severe COVID-19, most of whom were on remdesivir and glucocorticoids, infliximab and abatacept each reduced 28-day mortality compared with placebo (10 and 11 versus 15 percent) but did not improve time to clinical improvement [7]. The trial did not detect a benefit with cenicriviroc. Despite their potential efficacy, we do not routinely use infliximab or abatacept for COVID-19, because they do not offer clear advantages over baricitinib or tocilizumab, which have more established benefit and, in the United States, are approved for this indication. (See "COVID-19: Management in hospitalized adults", section on 'Limited roles for alternative immunomodulators'.)

ANTIMICROBIAL AGENTS

Adverse effects with piperacillin-tazobactam versus cefepime (November 2023)

Observational data have raised concerns for nephrotoxicity with piperacillin-tazobactam (when given with vancomycin) and neurotoxicity with cefepime. In an open-label trial of over 2500 patients randomly assigned to piperacillin-tazobactam versus cefepime, the incidence of major kidney events was comparable between groups (9 versus 10 percent), including among the 1900 patients who also received vancomycin [8]. Median antibiotic use was three days. Although the incidence of neurotoxicity (primarily delirium) was higher with cefepime (21 versus 17 percent), imbalances in baseline delirium rates reduce confidence in that finding. These data reduce concern for nephrotoxicity with short-term coadministration of piperacillin-tazobactam and vancomycin (eg, for initial empiric therapy). For those who warrant prolonged therapy with vancomycin plus an antipseudomonal agent, we weigh the uncertain risks of nephrotoxicity and neurotoxicity when choosing between piperacillin-tazobactam and cefepime. (See "Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects", section on 'Renal reactions'.)

Sulbactam-durlobactam for Acinetobacter infections (November 2023)

Antibiotic options for infections due to Acinetobacter spp are limited due to high rates of resistance. The US Food and Drug Administration recently approved a new beta-lactam/beta-lactamase inhibitor antibiotic, sulbactam-durlobactam. In an international randomized trial of 125 patients with carbapenem-resistant Acinetobacter infection (mainly hospital-acquired or ventilator-associated pneumonia), sulbactam-durlobactam resulted in a trend toward lower all-cause mortality that was not statistically significant (19 versus 32 percent) and a higher clinical cure rate (62 versus 40 percent) compared with colistin [9]. We reserve this agent for patients with hospital-acquired pneumonia or bacteremia due to susceptible Acinetobacter baumannii complex isolates that are resistant to other first-line agents (ie, other beta-lactams, carbapenems, and fluoroquinolones). (See "Acinetobacter infection: Treatment and prevention", section on 'First-line antibiotics'.)

BACTERIAL INFECTIONS

Diagnostic "mini" bronchoalveolar lavage for ventilator-associated pneumonia (November 2023)

Bronchoscopic bronchoalveolar lavage (BAL) is the gold standard for the diagnosis of ventilator-associated pneumonia (VAP). Mini-BAL is less invasive than BAL and can be performed in ventilated patients by nurses and respiratory therapists with lower rates of complications. A meta-analysis of six studies in which patients underwent both mini- and bronchoscopic BAL (in succession) reported a sensitivity of mini-BAL for VAP that was 0.9 and a specificity that was 0.83 [10]. These results confirm the role of mini-BAL as a reasonable alternative to bronchoscopic BAL for the diagnosis of VAP. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section on 'Invasive respiratory sampling'.)

Polymicrobial sepsis from platelet transfusion (October 2023)

The risk of transfusion-transmitted bacterial infection is exceedingly low. However, a recent report documented seven cases of polymicrobial sepsis across six different states, three of which were fatal, from platelet transfusions [11]. An investigation determined the source to be the manufacturing facility of the apheresis platelet collection sets. This report highlights the importance of reporting suspected transfusion reactions to facilitate such investigations and the need for ongoing vigilance, despite the overall high and continuously improving safety of blood products. (See "Transfusion-transmitted bacterial infection", section on 'Microbiology'.)

Ceftobiprole for treatment of Staphylococcus aureus bacteremia (October 2023)

Antibiotic options for treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. In a randomized trial including 387 patients with S. aureus bacteremia (75 percent methicillin-susceptible), ceftobiprole and daptomycin resulted in similar rates of treatment success, defined as the combination of survival, symptom improvement, S. aureus bloodstream clearance, absence of new bacteremia-related complications, and no use of other potentially effective antibiotics (70 versus 69 percent), and serious adverse events (19 versus 23 percent) [12]. The most common sources of bacteremia were soft tissue infection and osteoarticular infection; the median treatment duration was 21 days. The trial was not powered for subgroup evaluation; further evaluation of ceftobiprole in patients with MRSA bacteremia, specifically, is needed. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia", section on 'Agents warranting further study'.)

Revised Duke criteria for diagnosis of infective endocarditis (August 2023)

The Duke criteria for diagnosis of infective endocarditis (IE) have been revised to reflect changes in the epidemiology of IE, as well as new imaging and diagnostic tools [13]. The 2023 Duke-International Society for Cardiovascular Infectious Disease criteria classify Enterococcus faecalis as a typical cause of IE regardless of acquisition site (eg, community or healthcare associated) or presence of a primary extracardiac focus; previously E. faecalis was included as a major criterion only if community acquired and in the absence of a primary focus. The criteria also incorporate advances in microbiologic diagnostic testing, such as tissue polymerase chain reaction (such as amplicon or metagenomic sequencing and in situ hybridization). Advances in imaging include improved understanding of the diagnostic utility of cardiac computed tomography (CT) and fluorodeoxyglucose positron emission tomography with CT for detection of IE. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Basis for Duke criteria revision'.)

FUNGAL INFECTIONS

Rezafungin for invasive candidiasis (August 2023)

Echinocandins are the treatment of choice for initial treatment of invasive candidiasis. A new echinocandin, rezafungin, has been approved by the US Food and Drug Administration and is now available for adults 18 years or older with candidemia or invasive candidiasis who have limited alternative options [14]. Approval was based on two randomized trials that found no difference in overall mortality, clinical cure, or mycological eradication with rezafungin compared with caspofungin [15,16]. Of note, the trials excluded children, patients with severe liver disease, and patients with endocarditis, osteomyelitis, prosthetic joint infection, central nervous system infection, or eye infection. Rezafungin is unique in that it is administered as a once-weekly infusion, which is practical for outpatient echinocandin therapy; however, we continue to favor the other echinocandins for initial inpatient management and oral azole therapy for step-down therapy. (See "Management of candidemia and invasive candidiasis in adults", section on 'Non-neutropenic patients'.)

HIV INFECTION

Statins for primary prevention of cardiovascular disease in persons with HIV (September 2023)

HIV infection is associated with an excess risk of cardiovascular disease. A randomized trial evaluated the efficacy of lipid-lowering therapy with pitavastatin for primary prevention in over 7700 persons with HIV ≥40 years of age receiving antiretroviral therapy who had a 10-year atherosclerotic cardiovascular disease (ASCVD) risk score <15 percent [17]. Pitavastatin reduced the relative risk of major cardiovascular events (eg, myocardial infarction, stroke) by 35 percent compared with placebo; the trial was stopped early for this apparent benefit. Based on these data, we now advise statins in all persons ≥40 years of age with an ASCVD score ≥5 percent, particularly if the score is ≥7.5 percent; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 years of age, our approach is the same as in persons without HIV. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Indications for statins'.)

IMMUNIZATIONS

2024 immunization schedule for adults (January 2024)

The United States Centers for Disease Control and Prevention has published the 2024 immunization schedule for adults (figure 1 and figure 2) [18]. Respiratory syncytial virus (RSV) vaccine is a new addition to the schedule; it is recommended for pregnant people 32 to 36 weeks' gestation during RSV season and is an option for adults ≥60 years of age. Mpox vaccine has also been added and is recommended for adults of all ages who are at risk for infection. Other changes include updates to COVID-19, polio, and meningococcal vaccine recommendations. Our approach to immunization is largely consistent with these updated recommendations. (See "Standard immunizations for nonpregnant adults", section on 'Immunization schedule for nonpregnant adults'.)

Efficacy of recombinant influenza vaccine in adults <65 years of age (January 2024)

Data suggest that the recombinant influenza vaccine is more effective than standard-dose inactivated influenza vaccine in preventing influenza among adults ≥65 years of age; the relative efficacy of recombinant vaccine in adults <65 years is uncertain. In a study during the 2018–2019 and 2019–2020 influenza seasons, clinical facilities of a large health care system were randomly assigned to administer either the recombinant vaccine or a standard-dose inactivated influenza vaccines and alternated the vaccine administered each week [19]. Among adults aged 50 to 64 years, receipt of the recombinant vaccine was associated with a lower rate of influenza (2.00 versus 2.34 cases per 1000); the relative vaccine effectiveness was 15.3 percent. Pending further data, we continue to administer any inactivated influenza vaccine for adults aged 50 to 64 years. (See "Seasonal influenza vaccination in adults", section on 'Alternatives to egg-based inactivated influenza vaccines'.)

Respiratory syncytial virus vaccination in pregnancy (April 2023, Modified October 2023)

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants. In October 2023, the United States Centers for Disease Control and Prevention, along with guidelines from other expert groups, endorsed RSV vaccination of pregnant individuals to reduce severe RSV infections in their infants [20-23]. Nirsevimab, a monoclonal antibody that can be given to infants postnatally to reduce the risk of severe RSV, has also been recently approved and endorsed by expert guidance panels. In settings where nirsevimab is not available, we suggest vaccination of pregnant individuals between 32 0/6 and 36 6/7 weeks of gestation in September through January (in the northern hemisphere) with inactivated nonadjuvanted recombinant RSV vaccine (RSVPreF; Abrysvo). In settings where both maternal vaccination and nirsevimab are available, the optimal preventive strategy remains uncertain, and, in most cases, it will not be possible to use both. For such patients, both options should be discussed and shared decision-making undertaken. (See "Immunizations during pregnancy", section on 'Choosing the optimal strategy'.)

ACIP recommendations for 2023-24 seasonal influenza vaccination (September 2023)

The Advisory Committee on Immunization Practices (ACIP) issued new recommendations for seasonal influenza vaccination in August 2023 (table 2) [24]. The antigenic composition has been updated. In addition, the ACIP now states that egg allergy alone no longer necessitates additional safety measures for influenza vaccination, including with egg-based vaccines, beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg. All vaccines should be administered in settings where personnel and equipment needed for prompt recognition and treatment of acute hypersensitivity reactions are available. This is consistent with our previous guidance. (See "Seasonal influenza vaccination in adults", section on 'Antigenic composition'.)

INFECTION CONTROL

Emerging microbiologic colonization in mechanically ventilated patients (January 2024)

Mechanically ventilated patients act as reservoirs for hospital-acquired pathogens, including Staphylococcus, Pseudomonas, and Aspergillus species. However, a recent surveillance study of 51 acute care and long-term health care facilities reported the emergence of two additional species in mechanically ventilated patients, Acinetobacter baumannii (31 percent of patients, and one-half were carbapenem-resistant) and Candida auris (7 percent, and one-third were newly identified) [25]. Clinicians should be aware of emerging microbiologic species in their local facility so that appropriate surveillance can be conducted and antimicrobial therapy initiated, if indicated. (See "Clinical and physiologic complications of mechanical ventilation: Overview", section on 'Aspiration and ventilator-associated pneumonia and microbial colonization'.)

Taurolidine catheter locks for the prevention of hemodialysis catheter-related bloodstream infections (December 2023)

Catheter-related bloodstream infections (CRBSIs) are an important cause of morbidity and mortality in patients on hemodialysis. In a randomized trial of nearly 800 patients on maintenance hemodialysis via a tunneled central venous catheter, a catheter lock solution containing taurolidine, an antimicrobial agent, plus heparin reduced the incidence of CRBSI compared with a heparin control lock solution (2 versus 8 percent) over a mean of 200 days [26]. No trial participants used chlorhexidine-coated catheter caps, which are commonly used to reduce the risk of CRBSI. Based on these results, taurolidine lock solutions are a reasonable alternative to chlorhexidine-coated catheter caps to help prevent CRBSIs in select patients. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention", section on 'Methods we use'.)

No benefit to routinely adding vancomycin for prophylaxis before joint replacement (November 2023)

For preoperative antibiotic prophylaxis in patients undergoing joint replacement, vancomycin is sometimes added to cefazolin to empirically cover methicillin-resistant staphylococci. In a randomized trial of over 4000 patients undergoing joint replacement, the rate of surgical site infection was similar following prophylaxis with cefazolin plus vancomycin compared with cefazolin plus placebo (4.5 versus 3.5 percent) [27]. There were no differences in rates of infection due to methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis. We use cefazolin alone for prophylaxis in patients undergoing joint replacement who are not known to have MRSA colonization or infection. (See "Prevention of prosthetic joint and other types of orthopedic hardware infection", section on 'Antimicrobial prophylaxis'.)

Nasal decolonization in intensive care units (November 2023)

To reduce hospital-acquired infections, many hospitals provide nasal decolonization with either mupirocin or an iodophor to all patients in intensive care units (ICUs). In a cluster-randomized trial in over 130 hospitals that used universal nasal mupirocin and daily chlorhexidine bathing for ICU patients, switching to nasal iodophor was associated with a higher rate of Staphylococcus aureus growth on clinical cultures than continuing with mupirocin [28]. There was no difference in the rate of bloodstream infection from any pathogen. For hospitals that elect to use nasal decolonization in the ICU, we suggest mupirocin rather than iodophors. This practice may be particularly beneficial in ICUs with high rates of S. aureus infections, including methicillin-resistant strains. (See "Nosocomial infections in the intensive care unit: Epidemiology and prevention", section on 'Patient bathing plus decolonization'.)

Uncertain role for inhaled antibiotics in prevention of ventilator-associated pneumonia (November 2023)

Whether inhaled antibiotics are effective in preventing ventilator-associated pneumonia (VAP) is unclear. In a randomized trial of 850 patients on mechanical ventilation for 72 to 96 hours, daily inhaled amikacin for the next 3 days reduced the 28-day incidence of VAP compared with placebo (15 versus 22 percent) but did not reduce the number of days on mechanical ventilation, days of antibiotic utilization, or mortality [29]. While promising, the lack of benefit for patient-important outcomes reduces our confidence in the preventive value of inhaled antibiotics, and thus we have not adopted this practice in our intensive care units. (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Inhaled antibiotics'.)

MYCOBACTERIAL INFECTIONS

Role of glucocorticoids for tuberculous meningitis in patients with HIV (October 2023)

Glucocorticoids are an adjunctive therapy for tuberculous (TB) meningitis; however, data for patients with HIV infection are limited. In a randomized trial including 520 adults with TB meningitis and HIV in Vietnam and Indonesia (approximately one-half with CD4 cell count ≤50/microL), mortality over 12-month follow-up was comparable when a dexamethasone taper or placebo was added to antituberculous therapy (44 versus 49 percent) [30]. The incidence of immune reconstitution inflammatory syndrome during the first six months and the number of patients with adverse events were similar. We continue to suggest adjunctive glucocorticoid therapy for patients with HIV and TB meningitis; while available data do not clearly demonstrate improved survival, it may confer a small reduction in mortality with no increased risk of significant adverse effects. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Glucocorticoids'.)

Nutritional supplementation for prevention of tuberculosis (September 2023)

Malnutrition is an important risk factor for tuberculosis (TB) disease; the optimal approach to nutritional supplementation for TB prevention is uncertain. In a cluster-randomized trial in Jharkhand, India, over 10,000 household contacts of patients with pulmonary TB were randomly assigned to receive nutritional intervention (a food basket comprising 750 kcal per day [including 23 g of protein] plus micronutrients) or not [31]. During two-year follow-up, fewer cases of TB, most diagnosed via sputum smear, were observed in the intervention group (1.7 versus 2.1 percent); there were no adverse effects. Those who referred participants for TB evaluation were unblinded to randomization assignment. These findings are important for policy decisions regarding nutritional supplementation as a tool for TB prevention. (See "Prevention of tuberculosis: BCG immunization and nutritional supplementation", section on 'Nutritional supplementation'.)

PARASITIC INFECTIONS

Primaquine to prevent vivax parasitemia after acute falciparum malaria (November 2023)

Acute falciparum malaria may reactivate dormant vivax malaria hypnozoites in people living in coendemic areas; antirelapse therapy to eradicate the hypnozoites may reduce the risk of vivax parasitemia following falciparum infection. In a randomized trial including more than 490 patients who were treated with artemisinin combination therapy (ACT) for uncomplicated falciparum monoinfection and had normal glucose-6-phosphate dehydrogenase (G6PD) activity, antirelapse therapy with primaquine reduced the rate of vivax parasitemia at day 63 compared with standard care (2.5 versus 11 percent) [32]. There were no serious adverse events related to primaquine. The overall benefit of antirelapse therapy may depend on several factors, including the ACT regimen used and availability of G6PD screening. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children", section on 'Recurrent infection'.)

R21/Matrix-M vaccine to prevent malaria in children (November 2023)

In October 2023, the World Health Organization (WHO) approved the R21/Matrix-M vaccine for prevention of malaria in children [33]. In a placebo-controlled randomized trial of 4800 children (age 5 to 36 months) in four African countries, 12-month efficacy of a three-dose vaccine series against clinical malaria was 75 percent at sites with seasonal transmission and 68 percent at sites with year-round transmission; these data are under peer review prior to publication [34]. The vaccine was well tolerated. Injection site pain and fever were the most frequent adverse events. Together with the RTS,S/AS01 vaccine (recommended by the WHO in 2021), this approval is expected to facilitate sufficient vaccine supply to benefit all children living in areas where malaria is a public health risk. (See "Malaria: Epidemiology, prevention, and control", section on 'R21/Matrix-M vaccine'.)

Drug-resistant malaria parasites that may evade rapid diagnostic tests (October 2023)

In Eritrea, Plasmodium falciparum parasites have emerged that are artemisinin-resistant and may elude detection by some rapid diagnostic tests (RDTs). In a study including 841 patients with uncomplicated malaria treated with artemisinin combination therapy between 2016 and 2019, the rate of clinical artemisinin resistance increased from 0.4 to 4.2 percent during the study period [35]. Resistance was associated with a kelch13 gene mutation, which in turn was associated with a deletion in hrp2 (which encodes a histidine-rich protein that is an RDT target). The expansion of parasites harboring these mutations could compromise malaria control by delaying diagnosis, as well as by rendering treatment less effective. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children", section on 'Sub-Saharan Africa'.)

Malaria drug resistance in Uganda (September 2023)

Artemisinin-based combination therapy is a cornerstone of antimalarial treatment; however, resistance is emerging. In a surveillance study including more than 6500 blood samples collected from patients with uncomplicated malaria in Uganda between 2016 and 2022, the prevalence of parasites with resistance markers reached more than 20 percent by 2022 in 11 of 16 districts [36]. Mutations in the A675V or C469Y allele of the kelch13 gene (a principal mediator of partial artemisinin resistance in Plasmodium falciparum) reached a combined prevalence of 10 to 54 percent across much of northern Uganda. Possible reasons for these observations include discontinuation of effective malaria control, low level of malaria immunity due to low burden of disease, and use of artemisinin monotherapy. Maintenance of effective malaria control interventions and preemptive action in countering drug resistance are needed. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children", section on 'Scope'.)

SEXUALLY TRANSMITTED DISEASES

Doxycycline PEP not effective among cisgender women (January 2024)

Among men who have sex with men (MSM) and transgender women, data suggest that a dose of doxycycline for post-exposure prophylaxis (PEP) following condomless sex can reduce the risk of bacterial sexually transmitted infections (STIs). In contrast, data do not show a clear benefit of doxycycline PEP for cisgender women. In a trial of 450 cisgender women in Kenya who were taking pre-exposure prophylaxis for HIV, the incidence of bacterial STIs over 12 months was similar between those who were randomly assigned to use doxycycline PEP after condomless sex and not (25 versus 29 cases per 100 person years) [37]. Testing for doxycycline levels in hair specimens suggested that adherence was likely suboptimal, which may have contributed to the discrepant findings between cisgender women and other populations. Pending further data, doxycycline PEP should not be used among cisgender women. (See "Prevention of sexually transmitted infections", section on 'Doxycycline post-exposure prophylaxis for selected individuals'.)

VIRAL INFECTIONS, NON-HIV

Testing for hepatitis C virus infection in infants with perinatal exposure (November 2023)

Perinatally acquired hepatitis C virus (HCV) infection in the United States has increased sharply since 2010. New guidance from the Centers for Disease Control and Prevention recommends early testing for infants with perinatal exposure to HCV (algorithm 1) [38]:

● Test for HCV RNA during early infancy after two months of age, and ideally before six months of age.

● After 18 months of age, test any infant who has not previously been tested by measuring anti-HCV antibodies, with reflexive testing for HCV RNA.

A negative HCV RNA result at any time point after two months of age virtually excludes HCV infection and further testing is not required. Children with a positive HCV RNA test before three years of age should have repeat testing for HCV RNA before initiating antiviral therapy to determine whether they have spontaneously cleared the infection. This new guidance is consistent with our previous recommendations for early testing for infants with perinatal exposure to HCV. (See "Hepatitis C virus infection in children", section on 'How to test'.)

Valacyclovir for prevention of congenital cytomegalovirus infection (October 2023)

Emerging evidence suggests that maternal administration of valacyclovir for primary cytomegalovirus (CMV) infection substantially reduces the risk of congenital CMV infection, especially if begun prior to 14 weeks of gestation and within 8 weeks of the maternal infection. In a 2023 individual patient data meta-analysis (one randomized trial, two observational studies), maternal valacyclovir administration upon diagnosis of periconception or first-trimester primary CMV infection was associated with a 66 percent reduction in congenital CMV (11 versus 25 percent) [39]. We suggest high-dose oral valacyclovir (8g per day) for patients with a primary CMV infection in early pregnancy after a comprehensive discussion of the potential benefits and risks (eg, 2 percent risk of reversible maternal kidney failure). (See "Cytomegalovirus infection in pregnancy", section on 'Antiviral medication'.)

Thrombocytopenia and thrombosis syndrome with adenovirus infection (August 2023)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, autoantibody-mediated syndrome of thrombocytopenia and thrombosis (central venous thrombosis is common) that can occur after vaccination with an adenoviral-vectored COVID-19 vaccine. The clinical syndrome is similar to heparin-induced thrombocytopenia. A new report describes two individuals with a similar syndrome and VITT-like autoantibodies following documented adenovirus infection [40]. Neither patient had COVID-19 and neither received a COVID-19 vaccine. This finding suggests that a component of the adenoviral sequence may provide the source of the neoantigen. The inflammatory response to infection could provide the "second hit" that causes the syndrome. (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'Mechanisms/triggers of antibody formation'.)

OTHER INFECTIOUS DISEASES

Guidelines for fever management in critically ill patients (November 2023)

Updated guidelines on the management of fever in the intensive care unit have been recently published by the Society for Critical Care Medicine and the Infectious Diseases Society of America [41]. Differences with the previous guidelines include an emphasis on the use of core methods when feasible (eg, pulmonary artery catheter, bladder, esophageal) and oral or rectal measurement when not feasible. Also promoted was the use of bedside imaging (eg, ultrasonography) in the evaluation process and biomarkers to facilitate duration of antimicrobial therapy. We agree with the recommendations, most of which were based upon weak evidence. (See "Fever in the intensive care unit", section on 'Temperature measurement'.)

Negative pressure wound therapy for contaminated surgical wounds (November 2023)

Prophylactic negative pressure wound therapy (NPWT) is used on clean surgical wounds, but it may also be useful for contaminated surgical wounds. In a randomized trial that compared NPWT with standard wound care in 69 patients who underwent surgery for gastrointestinal perforation and had fascial closure, NPWT reduced rates of surgical site infection (18 versus 61 percent) and fascial dehiscence (9 versus 48 percent), increased the rate of delayed primary skin closure (91 versus 48 percent), and decreased median time to wound healing (19 versus 26 days) [42]. The results of this small trial are encouraging, and, in the absence of contraindications, we use NPWT over intact fascia to expedite closure of contaminated surgical wounds. (See "Negative pressure wound therapy", section on 'Prophylactic use'.)

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Topic 8358 Version 12473.0

References

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