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.

COVID-19

Limited benefit of nirmatrelvir-ritonavir in non-high-risk individuals with mild-to-moderate COVID-19 (May 2024)

Although nirmatrelvir-ritonavir reduces COVID-19-associated hospitalization and death in patients at high risk for severe disease, the benefit in lower-risk patients is uncertain. The EPIC-SR trial evaluated nirmatrelvir-ritonavir among 1200 outpatients who either had no risk factors for severe disease (and were unvaccinated or vaccinated) or had at least one risk factor but were vaccinated; median age was 42 years, and only 5 percent were 65 years old or older [1]. In the trial, nirmatrelvir-ritonavir did not reduce duration of symptoms, the risk of hospitalization from COVID-19, or all-cause mortality compared with placebo. We continue to suggest against treating patients who are not at high risk for severe disease. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Efficacy and rationale'.)

Pemivibart for prevention of COVID-19 in selected immunocompromised patients (April 2024)

Monoclonal antibodies have been used as adjunctive pre-exposure prophylaxis to reduce the risk of COVID-19 in individuals expected to have suboptimal response to vaccination, although emergence of variants that escape neutralization limit their utility. In March 2024 in the United States, the novel monoclonal antibody pemivibart received emergency use authorization (EUA) to prevent COVID-19 in individuals age 12 years or older (weighing at least 40 kg) who have moderate-to-severe immunocompromising conditions (table 1) [2]. Pemivibart is active against JN.1, the dominant SARS-CoV-2 variant. We suggest pemivibart in individuals at the highest risk for vaccine nonresponse (eg, those with hematologic malignancy or recent history of transplantation) as long as it remains active against the main circulating variants. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Limited role for monoclonal antibodies in selected patients'.)

Second dose of a 2023-2024 COVID-19 vaccine for individuals 65 years and older (April 2024)

In the United States, a single dose of an updated 2023-2024 formula COVID-19 vaccine is recommended for all immunocompetent adults and adolescents, regardless of prior vaccination history. In February 2024, the Centers for Disease Control and Prevention (CDC) updated its guidance to recommend a second dose (at least four months after the prior dose) for individuals 65 years and older [3]. Rates of COVID-19-associated hospitalization and death are higher in this age group than in any other, and the repeat dose is intended to improve protection by restoring the waning immune response; the 2023-2024 vaccine elicits response against currently circulating variants. Our recommendations are consistent with those of the CDC. (See "COVID-19: Vaccines", section on 'Adults 65 years and older'.)

Precautions for individuals with COVID-19 in the community (April 2024)

In March 2024, the United States Centers for Disease Control and Prevention updated guidance for precautions for people with COVID-19 in the community [4]. Such individuals should stay at home until their symptoms are improving and they have been afebrile for 24 hours without the use of antipyretics. They can subsequently resume normal activities but are encouraged to use other precautions (eg, masking, social distancing, good ventilation) for an additional five days to further reduce the risk of transmission to others. These measures are particularly important when around persons who are at increased risk for severe disease (eg, advanced age, immunocompromise, cardiopulmonary disease). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

Multisystem inflammatory syndrome in children incidence and severity (March 2024)

Although multisystem inflammatory syndrome in children (MIS-C) is increasingly rare as the overall COVID-19 burden declines, it continues to be associated with substantial morbidity. In 2023, 117 patients with MIS-C were reported to the Centers for Disease Control and Prevention, resulting in an estimated incidence of 0.11 cases per million person-months [5]. Of these patients, 50 percent required care in an intensive care unit, 34 percent experienced shock, and 27 percent experienced cardiac dysfunction; mortality was 2.6 percent (3 patients). More than 80 percent of patients were SARS-CoV2 vaccine eligible but had not been vaccinated; among 20 patients who had been vaccinated, 60 percent likely had waning immunity at the time of diagnosis. This study suggests that MIS-C severity remains high, but that SARS-CoV2 vaccination may provide some degree of protection. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis", section on 'Epidemiology'.)

Ensitrelvir for mild to moderate COVID-19 (March 2024)

Although nirmatrelvir-ritonavir reduces hospitalization and death from COVID-19,drug interactions preclude its use in some patients. Ensitrelvir is an oral protease inhibitor that prevents SARS-CoV-2 replication and has fewer drug interactions. In a randomized, double-blinded trial of over 1800 patients with mild to moderate COVID-19 (majority vaccinated) in Asia in early 2022, five days of ensitrelvir reduced time to symptom resolution by one day compared with placebo [6]. Since only two participants (one in each arm) had a COVID-19-related hospitalization within the 28-day study period, it is unknown whether the drug prevents hospitalizations or death from COVID-19. Ensitrelvir is approved for emergency use in Japan; it is undergoing US Food and Drug Administration approval process in the United States. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Therapies of limited or uncertain benefit'.)

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 [7]. 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'.)

ANTIMICROBIAL AGENTS

Caution with ciprofloxacin for chemoprophylaxis of meningococcal disease (March 2024)

Antimicrobial prophylaxis against meningococcal infection is warranted after high-risk exposure. According to the United States Centers for Disease Control and Prevention, ciprofloxacin should not be used for chemoprophylaxis when both of the following criteria are met over the prior 12-month period within the local catchment area: two or more cases of invasive meningococcal disease caused by ciprofloxacin-resistant strains have been reported, and ≥20 percent of all reported cases of invasive meningococcal disease are caused by ciprofloxacin-resistant strains [8]. Decisions on chemoprophylaxis should be made in conjunction with public health officials. (See "Treatment and prevention of meningococcal infection", section on 'Regimens'.)

Cefepime-taniborbactam, an investigational agent for difficult-to-treat infections (March 2024)

Taniborbactam is a novel beta-lactamase inhibitor that has broad activity against multidrug-resistant gram-negative bacilli when combined with cefepime. In a phase III randomized trial, cefepime-taniborbactam was superior to meropenem for treatment of complicated urinary tract infection, including acute pyelonephritis, with a combined clinical and microbiologic success rate of 71 versus 58 percent [9]. Both agents were effective against cefepime-resistant and extended-spectrum beta-lactamase-producing infections; carbapenem-resistant infections were not analyzed. These results suggest that cefepime-taniborbactam may be an option for infections due to difficult-to-treat pathogens if it becomes commercially available. (See "Combination beta-lactamase inhibitors, carbapenems, and monobactams", section on 'Beta-lactamase inhibitor combinations'.)

BACTERIAL INFECTIONS

Pivmecillinam for acute simple cystitis (May 2024)

In 2024, the US Food and Drug Administration approved a beta-lactam antibiotic, pivmecillinam, for treatment of acute simple cystitis in female adults [10]. Pivmecillinam is one of our preferred options for treatment of cystitis and has long been used in certain European countries because it is less likely than other agents to select for resistant isolates. It also retains activity against many extended-spectrum beta-lactamase-producing organisms. The recommended dose and formulation vary by region, and data do not clearly demonstrate better clinical outcomes with one versus the other. For empiric therapy, we would generally use 185 mg pivmecillinam base (equivalent to 200 mg pivmecillinam hydrochloride) orally three times daily for three to seven days, which is the dose recommended in the United States. (See "Acute simple cystitis in adult and adolescent females", section on 'First-line antimicrobial options'.)

Uncertain benefit of mass azithromycin in setting of seasonal malaria chemoprevention (March 2024)

Mass azithromycin distribution has been associated with a reduction in childhood mortality in sub-Saharan Africa in some studies; however, its benefit in the context of seasonal malaria chemoprevention is uncertain. In a randomized trial in Burkina Faso including more than 34,000 children, a single dose of azithromycin given twice yearly for three years resulted in lower mortality rates than placebo (8 versus 10 deaths per 1000 person-years), but the difference was not statistically significant [11]. All groups received monthly sulfadoxine-pyrimethamine and amodiaquine during high malaria transmission season. The study may have been underpowered to detect a clinically relevant difference; in addition, further evaluation of the antimicrobial resistance cost of mass azithromycin distribution is needed. (See "Trachoma", section on 'Wider impact of mass treatment'.)

Pyogenic liver abscess and colorectal cancer (February 2024)

Studies from Asia suggest that pyogenic liver abscess is associated with increased incidence of colorectal cancer, but studies outside Asia are scarce. In a 10-year retrospective study from 120 hospitals in the United States, the incidence of colorectal cancer among over 8000 patients with liver abscess was almost fourfold higher during the first six months after diagnosis of liver abscess compared with 23,000 matched controls without liver abscess [12]. The correlation was not observed among patients whose liver abscess was due to cholangitis or cholecystitis, and the type of organism causing the abscess did not correlate with the incidence of cancer. These findings support prompt screening for colorectal cancer in patients with pyogenic liver abscess, particularly in patients without an underlying hepatobiliary cause. (See "Pyogenic liver abscess", section on 'Association with colorectal cancer'.)

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 [13]. 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'.)

FUNGAL INFECTIONS

Fusarium meningitis associated with epidural anesthesia (February 2024)

In early 2023, there was an outbreak of Fusarium spp meningitis in 33 immunocompetent patients who received epidural anesthesia at two clinics in Mexico. In a review of 13 cases, hospital admission was delayed by a median of 39 days after symptom onset [14]. Severe neurovascular complications, such as aneurysm, intracranial hemorrhage, stroke, and hydrocephalus, occurred despite initial improvement on antifungal therapy. Susceptibility testing was performed on one isolate and revealed resistance to all antifungals approved in the United States; however, it was susceptible to fosmanogepix, an investigational agent. Nine patients (69 percent) died from the infection; of the four survivors, three received compassionate-use fosmanogepix. Understanding the clinical features and management challenges of Fusarium meningitis are important to providing effective care should future outbreaks occur. (See "Clinical manifestations and diagnosis of Fusarium infection", section on 'Outbreaks of meningitis'.)

HIV INFECTION

Cabotegravir-rilpivirine for selected patients with detectable HIV (April 2024)

Cabotegravir-rilpivirine, a long-acting injectable antiretroviral regimen, is a treatment option for virologically suppressed patients with HIV switching therapy. The International Antiviral Society-USA guidelines now consider this regimen an option for selected patients with a detectable viral load who are at high risk for developing AIDS-related complications and are unable to take oral antiretroviral therapy as prescribed despite extensive adherence support [15]. In one report, such patients were able to achieve virologic suppression by a median of 33 days [16]. If cabotegravir-rilpivirine is being considered in this setting, patients must have virus that is susceptible to both agents and substantial adherence support. (See "Use of long-acting cabotegravir-rilpivirine in people with HIV", section on 'Considerations for persons with a detectable viral load'.)

Updates to the United States perinatal HIV clinical guidelines (February 2024)

The United States Department of Health and Human Services has released updates to the perinatal HIV clinical guidelines [17]. Ritonavir-boosted darunavir is now a preferred agent only for treatment-naïve pregnant individuals who have used cabotegravir-based pre-exposure prophylaxis, because of the concern for integrase inhibitor-resistant mutations; for other pregnant individuals, it is now an alternative rather than preferred agent. Additionally, bictegravir, which was previously not recommended for initial therapy in pregnant individuals, is now an alternative agent based on new pharmacokinetic data that support its use during pregnancy. Our approach to treating HIV during pregnancy is consistent with these updated guidelines. (See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings", section on 'Selecting the third drug'.)

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 [18]. 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; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 and older than 75 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

Impact of the RTS,S/AS01 malaria vaccine in national immunization programs (April 2024)

The RTS,S/ASO1 vaccine for prevention of malaria was incorporated into national immunization programs in Ghana, Kenya, and Malawi in 2019. A recent trial randomly assigned geographical clusters in these countries to receive early or delayed vaccination; three doses (months 0, 1, and 2) were administered to more than 490,000 children age five to nine months [19]. Early vaccination reduced all-cause mortality by 9 percent and rates of hospital admission for severe malaria by 32 percent. Evaluation is ongoing to assess the impact of a fourth (booster) dose administered at 24 months. Efforts to broaden malaria vaccine administration should be accelerated. (See "Malaria: Epidemiology, prevention, and control", section on 'RTS,S/ASO1 vaccine'.)

Immunogenicity and safety of novel oral polio vaccine type 2 (March 2024)

Important barriers to polio eradication are emergence of circulating oral poliovirus vaccine-derived polioviruses and reversion of those live attenuated viruses to a virulent phenotype. To address these issues, a novel type 2 oral polio vaccine (nOPV2) that is genetically stable was developed. In a randomized trial of 2345 infants and 600 children in The Gambia (all of whom had previously received a dose of inactivated poliovirus vaccine), seroconversion rates with two nOPV2 doses were 93 to 95 percent, similar to those achieved with bivalent oral polio vaccine [20]. The study showed no safety concerns for nOPV2, with a similar rate of adverse events among both groups. These findings support the licensure and World Health Organization approval of nOPV2. (See "Poliovirus vaccination", section on 'Monovalent OPVs and nOPV2'.)

Investigational single-dose dengue virus vaccine (March 2024)

Two dengue virus vaccines are commercially available, CYD-TDV (Dengvaxia) and TAK-003 (Qdenga); both require multiple doses. In a phase III randomized trial of another vaccine (TV003/Butantan-DV), vaccine efficacy of a single dose was 80 percent with minimal serious adverse effects [21]. The vaccine was effective regardless of baseline dengue serostatus. These results show promise for a single-dose vaccine that is suitable for use in children and adults without regard to prior dengue immunity. It is not yet commercially available. (See "Dengue virus infection: Prevention and treatment", section on 'Investigational vaccines'.)

Durability of typhoid conjugate vaccine effect (February 2024)

Typhoid conjugate vaccines (TCVs) are preferred over other vaccine formulations for prevention of typhoid fever in endemic areas, given favorable efficacy and safety; however, data on the durability of protection beyond two years are sparse. In a trial including more than 28,000 children (9 months to 12 years) in Malawi randomly assigned to receive TCV with Vi polysaccharide conjugated to tetanus toxoid (Vi-TT) or meningococcal vaccine as an active control, fewer cases of typhoid fever were observed over four-year follow-up among those who received Vi-TT (24 versus 110 cases); overall vaccine efficacy was 78.3 percent [22]. These findings support current guidance for typhoid vaccination in endemic areas and help inform decisions regarding the need for and timing of revaccination. (See "Enteric (typhoid and paratyphoid) fever: Treatment and prevention", section on 'Licensed vaccines'.)

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) [23]. 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 [24]. 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 'Efficacy of alternatives to egg-based IIVs'.)

INFECTION CONTROL

Skin preparation prior to fracture repair (March 2024)

The optimal preparation of contaminated or dirty wounds and whether any skin preparation can influence surgical site infection (SSI) independent of other factors (eg, prophylactic systemic antibiotics) are unknown. In a multiple-period, cluster-randomized, crossover trial comparing skin preparation with iodine povacrylex in alcohol versus chlorhexidine gluconate in alcohol in 1700 open fracture repairs, the incidence of superficial or deep SSI was similar for both approaches [25]. Based on these findings, which are consistent with those from a previous trial, either chlorhexidine- or iodine-based skin preparations can be used prior to surgery for open, traumatic lower extremity wounds. (See "Surgical management of severe lower extremity injury", section on 'Limb preparation and skin antisepsis'.

Universal decolonization in nursing homes for infection control (February 2024)

Routine decolonization of patients prevents healthcare-associated infections in certain hospital settings (eg, intensive care units), but its value in long-term care facilities has not been thoroughly evaluated. In an 18-month randomized trial of 28 nursing homes in the United States, universal decolonization with chlorhexidine bathing and intranasal povidone iodine reduced infection-related hospitalization rates by 30 percent compared with usual bathing protocols [26]. Colonization with multidrug-resistant organisms also decreased in the decolonization group. However, potential sources of bias in the study (eg, audits and staff training that only occurred in the decolonization arm) reduce confidence in these findings, and lack of resources in nursing homes may impede implementation. (See "Principles of infection prevention and control in long-term care facilities", section on 'Bundled interventions'.)

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) [27]. 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 [28]. 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'.)

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 [29]. 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'.)

MYCOBACTERIAL INFECTIONS

Demographic disparities in tuberculosis incidence among US-born individuals (April 2024)

In the United States (US), the incidence of tuberculosis (TB) is increased among certain populations. A study including national TB registry data for 2011 to 2021 among US-born individuals found that, compared with individuals who identify as White, TB incidence rate ratios were 4.4 to 14.2 times higher among individuals who self-identified as American Indian/Alaska Native, Asian, Black, or Hispanic [30]. Genotyping data suggested an important role of recent transmission in the observed disparities, supporting the need for timely identification and prevention of ongoing chains of transmission. These findings warrant targeted efforts by TB prevention and control programs. (See "Epidemiology of tuberculosis", section on 'In the United States'.)

Electronic medication monitoring for tuberculosis treatment adherence (February 2024)

Use of electronic medication monitoring has been proposed to improve tuberculosis (TB) treatment adherence. In a randomized trial including 278 patients with TB disease in Tibet, TB cure occurred more frequently among those who used an electronic medication monitor (including reminders, recorded box-opening data transmitted to health care providers, and a smartphone app to communicate with providers) compared with usual care plus a deactivated electronic medication monitor (94 versus 73 percent) [31]. Poor adherence (missing ≥20 percent of planned medication doses in a month) occurred more frequently with usual care. These findings suggest that electronic medication monitoring may be helpful for improving TB treatment adherence in resource-limited settings. (See "Adherence to tuberculosis treatment", section on 'Electronic medication monitoring'.)

PARASITIC INFECTIONS

Monoclonal antibodies for malaria prevention (May 2024)

Monoclonal antibodies targeting Plasmodium falciparum sporozoites are a novel approach to malaria prevention. In a phase 2 randomized trial including 225 children 6 to 10 years of age in Mali, subcutaneous administration of the monoclonal antibody L9LS reduced the frequency of P. falciparum infection (detected on blood smear performed at least every 2 weeks for 24 weeks) compared with placebo (40 and 48 percent with a 300 mg and 150 mg dose, respectively, versus 81 percent) [32]. Compared with placebo, the efficacy of the 300 mg L9LS dose against P. falciparum infection was 70 percent. Further study of monoclonal antibodies, including geographic and age-dependent variation in efficacy, is needed. (See "Malaria: Epidemiology, prevention, and control", section on 'Monoclonal antibodies'.)

Intermittent preventive treatment against malaria in pregnant women with HIV infection (February 2024)

Pregnant women with HIV infection in malaria-endemic areas are prescribed daily co-trimoxazole (known as trimethoprim-sulfamethoxazole in many areas) to protect against malaria and opportunistic infection. Given emergence of Plasmodium falciparum resistance to antifolate drugs, adding monthly intermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) may confer greater protection against malaria. In a randomized trial including 904 pregnant women with HIV infection in Malawi and western Kenya, daily co-trimoxazole plus monthly IPT-DP reduced the risk of clinical malaria infection during pregnancy compared with daily co-trimoxazole plus placebo (2.3 versus 8.2 percent) [33]. Based on these findings, for pregnant women with HIV infection in areas with moderate to high malaria transmission and high background rate of antifolate drug resistance, we suggest adding monthly IPT-DP to daily co-trimoxazole prophylaxis. (See "Malaria in pregnancy: Prevention and treatment", section on 'Patients with HIV infection'.)

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) [34]. 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'.)

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) [35]. 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

Hepatitis C virus antiviral treatment for patients with opioid use disorder (May 2024)

Despite concerns about adherence to antiviral therapy among individuals with opioid use disorder, hepatitis C virus (HCV) treatment can be highly successful in this population, particularly in nontraditional care settings. In a cluster-randomized trial that included 600 individuals with chronic HCV infection who were engaged in an opioid treatment program, provision of antiviral therapy through the program, directed by an HCV specialist over telemedicine, increased rates of antiviral initiation (92 versus 40 percent) and sustained virologic response (85 versus 30 percent) compared with traditional referral to a specialist clinic for treatment [36]. These data highlight the impact of reducing barriers to care for individuals with opioid use disorder and support our recommendation to treat all patients for chronic HCV, regardless of active drug use. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'Active drug use'.)

OTHER INFECTIOUS DISEASES

Maternal sepsis risk with membrane rupture before 23 weeks of gestation (April 2024)

Chorioamnionitis can be a cause or a consequence of preterm prelabor rupture of membranes (PPROM), especially before 24 weeks of gestation. Development of maternal sepsis is a major concern in these pregnancies. In a prospective study of 364 patients with PPROM between 16 weeks 0 days and 22 weeks 6 days, maternal sepsis developed in 10 percent of patients with singleton pregnancies who chose to undergo pregnancy termination soon after diagnosis of PPROM and in 13 percent of those who initially chose to continue the pregnancy [37]. Two patients died. These findings underscore the importance of close maternal monitoring, early diagnosis of chorioamnionitis, timely fetal extraction, and appropriate antibiotic treatment in patients with PPROM. (See "Prelabor rupture of membranes before and at the limit of viability", section on 'Maternal sepsis and death'.)

Antibiotic prophylaxis prior to ERCP for biliary obstruction (February 2024)

For patients with biliary obstruction undergoing endoscopic retrograde cholangiopancreatography (ERCP), the benefit of antibiotic prophylaxis in all versus selected patients is uncertain. In a randomized trial including 378 patients with biliary obstruction undergoing ERCP, antibiotic prophylaxis resulted in lower risk of cholangitis compared with no prophylaxis (2 versus 6 percent) [38]. Based on these and older data, we reserve antibiotic prophylaxis for patients who are at risk for incomplete biliary drainage with ERCP and await further data before administering antibiotic prophylaxis to all patients with biliary obstruction. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic retrograde cholangiopancreatography (ERCP)'.)

Duration of antibiotic therapy following appendectomy for perforated appendicitis (February 2024)

The duration of antibiotic therapy following appendectomy for perforated appendicitis is debated. In a trial of 104 patients with complicated appendicitis (defined as gangrenous or perforated) who received 24 hours of intravenous or oral amoxicillin-clavulanate, the 30-day complication rate was not different (15 percent in both groups) [39]. Because the study population was dominated by patients with gangrenous appendicitis (75 percent) and 67 percent of organ/space infections occurred in patients with perforated appendicitis, these findings may not be generalizable to the latter group. Thus, until further data are available, we continue to suggest two to four days of intravenous antibiotics after appendectomy for those with perforated appendicitis, based on data from previous trials. (See "Management of acute appendicitis in adults", section on 'Antibiotics for perforated appendicitis'.)

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 [40]. 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'.)