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Prevention of infection in patients with impaired splenic function

Prevention of infection in patients with impaired splenic function
Literature review current through: Sep 2023.
This topic last updated: Sep 29, 2022.

INTRODUCTION — Patients with impaired splenic function are at risk for severe and overwhelming infections with encapsulated bacteria (eg, Streptococcus pneumoniae), bloodborne parasites, and other infections that the spleen plays an important role in controlling. Key measures for preventing such infections include patient and caregiver education, vaccination against encapsulated bacteria, influenza, coronavirus disease 2019 (COVID-19), and use of prophylactic antibiotics.

These preventive measures will be reviewed here. The role of the spleen in controlling infection, conditions leading to loss of splenic function, clinical manifestations of infection in asplenic and hyposplenic patients, and the evaluation and management of sepsis in these patients are discussed separately. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function" and "Splenomegaly and other splenic disorders in adults".)

DEFINITIONS — Both anatomic and functional asplenia and hyposplenism predispose to infection (table 1).

Asplenia refers to complete loss of function of the spleen and may be anatomic or functional. Anatomic asplenia is most often due to surgical splenectomy, performed for trauma or therapeutically (eg, for hemolytic anemias or immune thrombocytopenias) [1]. Functional asplenia refers to complete loss of function caused by medical conditions and occurs most frequently with sickle cell anemia [2]. Rarely, the spleen is congenitally absent.

Hyposplenism refers to partial loss of splenic function and is most often caused by medical disorders that lead to atrophy, infarction, engorgement, or infiltration of the spleen, such as thalassemias, chronic liver disease, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), immune disorders, or malignancies [2].

Hyposplenism is considered clinically significant (ie, warrants additional vaccination and/or antibiotic prophylaxis) in all patients with sickle cell disease, patients who have recurrent infections with encapsulated organisms (eg, S. pneumoniae, Haemophilus influenzae type b, or Neisseria meningitidis) in the absence of humoral deficiency, and/or patients who have Howell-Jolly bodies detectable on peripheral blood smear or other laboratory evidence of splenic dysfunction (eg, low number of circulating immunoglobulin [Ig]M memory B cells).

Additional details on the causes of impaired splenic function and the identification of patients at risk for infection are provided separately. (See "Splenomegaly and other splenic disorders in adults", section on 'Asplenia or hyposplenia' and "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Identifying patients at risk'.)

PATIENT EDUCATION — Educating patients with impaired splenic function as well as their families and/or caregivers on the lifelong increased risk of infection and strategies to minimize risk is critical to care. Patients with greater knowledge of their condition appear to have lower rates of severe and overwhelming infections compared with those who have lesser knowledge [3].

When counseling patients, we emphasize the following:

Increased risk for severe infection – We inform asplenic and hyposplenic patients that they have a small lifelong increased risk for severe or overwhelming infection with certain pathogens (table 2) [4,5]. Both the risk of infection and the associated mortality appear to be about two- or threefold higher than the general population. One analysis suggested the risk of overwhelming postsplenectomy sepsis to be 1.3/1000 years of patient observation [6]. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Identifying patients at risk' and "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Risk of severe infection'.)

Importance of vaccination – We emphasize the importance of receiving and staying up to date on all vaccinations, particularly those targeting pathogens associated with increased morbidity and mortality in patients with impaired splenic function (eg, S. pneumoniae, N. meningitidis, H. influenzae type b, and influenza virus) (table 3 and table 4). These vaccinations mitigate but do not eliminate the risk of infection with these pathogens because they do not target all serotypes and strains. (See 'Vaccinations' below.)

Use of antibiotic prophylaxis – Use of antibiotic prophylaxis, in addition to vaccination, further reduces the risk of infection and poor outcomes [7]. We discuss the risks and benefits of daily antibiotic prophylaxis with all patients and generally favor its use in asplenic and hyposplenic patients who are at highest risk of severe infection (eg, children <5 years old, immunocompromised patients, patients with a history of severe infections, and patients in the first year post-splenectomy). (See 'Daily antibiotic prophylaxis' below.)

We advise all patients to keep an emergency supply of antibiotics on hand to be used for the development of fever or other signs of systemic infection and to seek medical care immediately if these symptoms develop (table 5 and table 6). (See 'Emergency antibiotic supply' below.)

When to seek medical care – Because infections in patients with impaired splenic function can progress rapidly, we advise patients who develop fever (eg, temperature ≥101°F/38.3°C) or other signs of systemic infection (eg, chills, rigors, vomiting/diarrhea, headache) to present to the nearest emergency department immediately. Generally, patients with symptoms suggestive of viral upper respiratory illnesses (eg, rhinorrhea, nasal congestion) who lack fever do not need to seek immediate care and can be managed similarly to patients with normal splenic function. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Initial triage and management'.)

We also advise patients with impaired splenic function to seek immediate medical care for any animal bite. Dog bites, in particular, can transmit Capnocytophaga canimorsus, which can be rapidly progressive and fatal in patients with impaired splenic function. Additional precautions include avoiding tick bites in areas where babesiosis is endemic and seeing a health care provider prior to travel, particularly to areas where malaria is endemic. (See 'Travel planning' below and 'Animal exposures' below.)

Alert cards and bracelets – We generally advise patients to carry an alert card or wear an alert bracelet informing their health care providers of their condition and the increased risk for overwhelming infection [1]. Because asplenia and hyposplenism are often overlooked as immunocompromising conditions, informing all caregivers of their condition both verbally and by these alert mechanisms can help ensure that appropriate care is given [8].

Generally, we counsel patients in person and also provide patient handouts and links to online resources (see 'Information for patients' below). In certain regions, registries and services that provide ongoing education, vaccination reminders, alert cards, educational refrigerator magnets, smart phone applications, and other support are available [6,9,10]. The Spleen Australia registry also provides individual patient reports, which are shared with the patient and all health care providers. Use of such registries and services have been associated with increased adherence to preventive measures and reduced incidence of invasive infections with encapsulated bacteria [6,11]. The Spleen Australia registry has also been shown to be cost-effective [12]. However, enrollment is limited to local residents.

PRESPLENECTOMY CONSIDERATIONS — For patients undergoing complete or partial splenectomy, certain measures can help minimize the risk of infection postoperatively.

Timing of elective splenectomy — The timing of elective splenectomy is primarily dictated by the urgency of the underlying condition (eg, hemolytic anemia or hereditary spherocytosis). When splenectomy can be planned in advance, allowing sufficient time for receipt of important vaccinations and/or maturation of the immune system may help prevent postsplenectomy infections.

For children, we generally defer splenectomy until age 2 when antibody responses to polysaccharide bacterial antigen are functionally more developed. In the past, childhood splenectomy was often deferred until age 5 based on the high prevalence of invasive pneumococcal infections patients with asplenia [13,14]. However with widespread administration of the pneumococcal conjugate vaccine, the prevalence of pneumococcal infections has dropped substantially [15-18]. Concordantly, among children with sickle cell disease and hyposplenia under five years old, rates of invasive pneumococcal disease declined by over 90 percent with routine pneumococcal vaccine use [19]. With concurrent use of daily antibiotic prophylaxis, the risk of infection likely drops further [7]. Thus, in settings where pneumococcal vaccination is common, performing elective splenectomy after two years of age is reasonable when clinically indicated.

For all patients, preparing for splenectomy as early as possible in advance of the procedure is prudent in order to ensure that all routine vaccinations have been received and that the additional vaccine series recommended for asplenic patients can be begun. Starting vaccinations 10 to 12 weeks prior to splenectomy ensures that the primary pneumococcal vaccine series recommended for most adults and children with impaired splenic function can be completed prior to the procedure, maximizing protection against S. pneumoniae. (See 'Timing of vaccination' below and 'Vaccine schedules' below.)

Surgical approach — Because of the high mortality associated with sepsis in asplenic patients, measures that avoid splenectomy should be utilized when possible. As an example, performing splenic repair instead of splenectomy during exploratory laparotomy for intra-abdominal trauma or following inadvertent splenic injury during intra-abdominal procedures preserves functional splenic tissue and is believed to reduce the risk of infection. Similarly, splenic artery embolization may reduce the need to proceed with splenectomy among patients with closed abdominal trauma. (See "Surgical management of splenic injury in the adult trauma patient", section on 'Splenectomy versus salvage'.)

VACCINATIONS

Recommended vaccines — The most common vaccine-preventable causes of sepsis and severe infections in patients with impaired splenic function are S. pneumoniae (pneumococcus), H. influenzae type b, and N. meningitidis (meningococcus) [2,20,21].

For protection against these organisms, most patients with impaired splenic function require:

The 20-valent pneumococcal conjugate vaccine (PCV20) alone or a lesser valent pneumococcal conjugate vaccines (eg, 15-valent PCV [PCV15], 13-valent PCV [PCV13]) followed by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) ≥8 weeks later

The H. influenzae type b vaccine (Hib)

The quadrivalent meningococcal conjugate ACWY vaccine series (MenACWY)

The monovalent meningococcal serogroup B vaccine series (MenB-4C or MenB-FHbp)

The quadrivalent meningococcal vaccine requires revaccination (booster doses). Specific vaccine schedules vary with patient age and vaccine history, particularly among young children (table 3 and table 4). (See 'Vaccine schedules' below.)

In addition to these vaccinations, patients who have impaired splenic function should receive all routinely recommended age-appropriate vaccinations (figure 1A-D) and COVID-19 vaccination. Asplenia alone is not a contraindication for any vaccination, including live vaccines. However, immunocompromising conditions such as hematologic malignancies and HIV infection can co-occur with asplenia and can be contraindications. (See "Standard immunizations for nonpregnant adults" and "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Because influenza is associated with an increased risk of infection with S. pneumoniae, we emphasize the importance of annual vaccination against seasonal influenza virus to all patients ≥6 months old with impaired splenic function. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines".)

Antibody responses to vaccination appear to be sufficiently protective in most asplenic patients but may be lower than in healthy persons [22-25]. In order to optimize the immune response to vaccination, we vaccinate patients at least 2 weeks, and ideally 10 to 12 weeks, prior to splenectomy when possible. When vaccines cannot be given at least two weeks prior to splenectomy, we vaccinate two weeks following the procedure. For those with nonsurgical asplenia or hyposplenism, we vaccinate as soon as impaired splenic function is recognized. (See 'Timing of vaccination' below.)

Our approach to vaccinating patients with impaired splenic function is largely consistent with the Advisory Committee on Immunization Practices (ACIP) in the United States and with many international health authorities [1,26-29]. (See "Pneumococcal vaccination in children".)

Available vaccine formulations, their dosing schedules, and age-based recommendations also vary internationally. (See "Society guideline links: Immunizations in adults".)

Vaccine schedules

Adults — In addition to routine age-appropriate vaccinations and COVID-19 vaccination, adults who are undergoing splenectomy or who have functional or anatomic asplenia or hyposplenism should receive vaccinations against S. pneumoniae (pneumococcus), H. influenzae type b, and N. meningitidis (meningococcus) (table 3).

Pneumococcal vaccination – Two types of pneumococcal vaccines are available: PCV and PPSV. (See "Pneumococcal vaccination in adults", section on 'Vaccine types'.)

The PCV20 is preferred over other PCVs because it provide protection against 20 serotypes and does not require supplementation with a polysaccharide vaccine. When lesser valent conjugate vaccines are used (eg, PCV10, PCV13, PCV15), PPSV23 should be also be given [30]. The dosing schedule is as follows:

For adults with impaired splenic function who have not previously received a pneumococcal vaccine or whose vaccination history is unknown, we give one dose of PCV20. If PCV20 is not available, PCV15 can be used. If PCV15 is used, PPSV23 should be given ≥8 weeks after the PCV15 dose.

For those who have previously received a pneumococcal vaccine, the approach to vaccination varies based on the type of vaccine given:

-Adults who have already received both a PCV and PPSV23 vaccine require no further vaccination.

-Adults who have only received the PCV13 should receive the PPSV23 vaccine ≥8 weeks after receipt of PCV13.

-Adults who have only received the PPSV23 vaccine should receive PCV15 or PCV20 at least a year after PPSV23.

Pneumococcal vaccination is discussed in detail separately. (See "Pneumococcal vaccination in adults".)

H. influenzae type b vaccination – A single dose of Hib vaccine is recommended prior to splenectomy or for patients with asplenia or hyposplenism. Revaccination is not needed for Hib [31,32].

For adults who have not been previously vaccinated against Hib (or if vaccination status is unknown), we give a single dose of Hib. Because most adults are immune to Hib (regardless of vaccine status), some experts prefer to check a Hib antibody titer and vaccinate only if titers are low or undetectable.

For adults who have received one or more doses of Hib for other reasons (eg, concurrent immunocompromising condition), repeating this vaccination is not necessary.

Additional details on the prevention of Hib are discussed separately. (See "Prevention of Haemophilus influenzae type b infection".)

Meningococcal vaccination – There are two types of meningococcal vaccinations recommended for patients with impaired splenic function in the United States: a quadrivalent meningococcal conjugate vaccine that protects against meningococcal serotypes A, C, W, and Y (MenACWY; Menactra, Menveo, MenQuadfi) and a univalent serogroup B vaccine (MenB-4C [Bexsero] or MenB-FHbp [Trumenba]). Both vaccines are given as a primary series. (See "Meningococcal vaccination in children and adults".)

For most adults, we give two doses of a MenACWY vaccine ≥8 weeks apart (table 7) Menveo and MenQuadfi can be given at the same time as PCV13. However, Menactra must be given four weeks after PCV13 because Menactra may interfere with the protection conferred by pneumococcal conjugate vaccines. Revaccination is needed every five years.

In addition, we vaccinate adults against meningococcus serogroup B, either with Bexsero (two doses spaced at least one month apart) or Trumenba (three doses at 0, 1 to 2, and 6 months). Revaccination is also required for the serogroup B vaccine (table 7).

Seasonal influenza vaccination – We recommend that all asplenic or hyposplenic patients be vaccinated against seasonal influenza annually. Although live attenuated vaccines can be safely given to patients with impaired splenic function, the inactivated influenza vaccine is preferred over the live formulation because it is equally effective [31]. (See "Seasonal influenza vaccination in adults".)

Children — Vaccine recommendations for children with impaired splenic function vary with patient age and vaccine history (table 4).

Children ≥2 years old

Pneumococcal vaccination – Two types of pneumococcal vaccination are recommended for children ≥2 years old with impaired splenic function in the United States: PCV (either PCV13 [Prevnar] or PCV15 [Vaxneuvance])and PPSV23 (Pneumovax) [1,28,31,33-35]. A conjugate PCV vaccine with enhanced coverage (PCV20) is available for adults. Its role in childhood immunization is being evaluated and these recommendations may be revised in the future. (See "Pneumococcal vaccination in children".)

For children ≥2 years old who are up to date on age-appropriate pneumococcal vaccinations (eg, have received the full four-dose series of PCV before age 2), we give a single dose of PPSV23.

We revaccinate with PPSV23 every five to seven years thereafter.

Because PCV13 first became available in 2010 in the United States, children born before 2010 may not have received a complete PCV13 series.

For children ≥2 to 5 who did not complete the PCV series, we give an additional one or two doses of PCV depending on the number of PCV doses previously received (table 8). Following receipt of the appropriate number of doses, we vaccinate with PPSV23 ≥8 weeks after the last PCV dose. We revaccinate with PPSV23 every five years thereafter.

For children ≥6 years old who have not completed the PCV series or never received PCV, we give one dose of PCV followed by PPSV23 ≥8 weeks later (table 9). We revaccinate with PPSV23 every five to seven years thereafter.

H. influenzae type b vaccination – Vaccination against Hib is recommended prior to splenectomy or for patients with established asplenia or hyposplenism.

For children who have completed the routinely recommended primary Hib vaccine series, additional vaccination is not needed.

For children ≥2 years who have not been vaccinated against Hib or who have not completed the full vaccine series or if vaccination status is unknown, we give one or two doses of Hib depending on the child's age and previous Hib vaccination history (table 10).

Revaccination is not needed for Hib. Additional detail on the prevention of Hib is discussed separately. (See "Prevention of Haemophilus influenzae type b infection", section on 'High risk of invasive Hib disease'.)

Meningococcal vaccination – Two types of meningococcal vaccinations are recommended for children with impaired splenic function: a quadrivalent meningococcal conjugate vaccine that protects against meningococcal serotypes A, C, W, and Y (MenACWY; Menactra, Menveo, or MenQuadfi) and a univalent serogroup B vaccine (MenB-4C [Bexsero] or MenB-FHbp [Trumenba]). (See "Meningococcal vaccination in children and adults".)

For children ≥2 years old who have not been vaccinated against N. meningitidis, we give a quadrivalent MenACWY vaccine. These vaccines are given as a two-dose series spaced at least eight weeks apart.

Menveo and MenQuadfi can be given at the same time as PCV13. By contrast, Menactra must be given four weeks after PCV13 because Menactra may interfere with the protection conferred by pneumococcal conjugate vaccines. Revaccination is required; revaccinations vary by age (table 7).

For children ≥10 years old, we also give one of the serogroup B vaccines, either Bexsero (two doses spaced at least one month apart) or Trumenba (three doses at 0, 1 to 2, and 6 months). Revaccination is also required for the serogroup B vaccine (table 7).

Seasonal influenza vaccination – We recommend that all asplenic or hyposplenic children ≥6 months old be vaccinated against seasonal influenza annually. Although live attenuated vaccines can be safely given to patients with impaired splenic function, the inactivated influenza vaccine is preferred over the live formulation because it is equally effective and available. Children over age 9 require only one influenza vaccination regardless of their vaccination history. Younger children (over six months of age) require two doses of influenza vaccine at least four weeks apart when they initiate seasonal influenza immunization, with annual single doses thereafter. (See "Seasonal influenza in children: Prevention with vaccines".)

Children <2 years old — For asplenic and hyposplenic children <2 years old, we give all vaccines that are routinely recommended for their age group following the same schedule as for children with normal splenic function (figure 1C). This includes the routinely recommended four-dose series of the pneumococcal conjugate vaccine (PCV13 or PCV15), the vaccine series targeting Hib, and the seasonal influenza vaccination (for those >6 months).

In addition, we give a single dose of the pneumococcal polysaccharide vaccine (PPSV23) once the child becomes two years old. As with all others, we revaccinate with PPSV23 every five to seven years thereafter.

We also give the quadrivalent meningococcal ACWY vaccine series. When vaccinating children <2 years old, we use Menveo. The number of doses and intervals between doses varies by age. Menactra and MenQuadfi (alternate formulations) are not recommended for use in children <2 years old with impaired splenic function. In the United States, the serogroup B meningococcal vaccine is recommended once the child becomes 10 (table 11).

Timing of vaccination — The optimal timing of vaccination varies with the cause of impaired splenic function, the urgency of splenectomy (when performed), and the need for concurrent immunosuppressive treatment.

For patients with nonsurgical asplenia or hyposplenism (eg, impaired splenic function due to sickle cell disease or other medical condition), vaccine series should be started as soon as impaired splenic function is recognized.

For patients undergoing elective splenectomy, vaccinations should ideally be started approximately 10 to 12 weeks prior to surgery so that the recommended vaccine series can be completed at least 14 days prior to splenectomy. If all recommended vaccine series cannot be completed in this time period, vaccine series can be resumed 14 days after splenectomy for most patients.

For patients who will be receiving chemotherapy or other immunosuppressive treatment following splenectomy, vaccinations are usually resumed approximately three months after that treatment [31]. (See "Immunizations in adults with cancer", section on 'Timing of immunizations'.)

For patients undergoing emergency splenectomy, vaccine series should be started 14 days after splenectomy. If vaccinations were given prior to postoperative day 14, it is reasonable to repeat these vaccinations eight weeks after the initial doses were given.

Several small studies illustrate that patients probably develop adequate antibody responses to vaccination when vaccines are given approximately 14 days following the removal of the spleen [22,36,37]. In a small randomized trial, functional antibody responses appeared to be greatest in patients vaccinated at day 14 post-splenectomy when compared with those vaccinated at earlier time points [22]. Functional antibody responses on day 14 neared those of healthy controls but were not equivalent. In a subsequent small randomized trial, no significant difference in antibody responses to PPSV23 were detected between patients vaccinated at day 14 post-splenectomy versus those vaccinated at day 28 [37].

COVID-19 vaccination — All eligible individuals with impaired splenic function who lack contraindications should be vaccinated against severe acute respiratory coronavirus 2, the virus that causes COVID-19. While the efficacy of COVID-19 vaccination has not been directly studied in individuals with impaired splenic function, some attenuation of immune response is expected. Like other immunocompromised patients, patients with impaired splenic function should receive three doses of mRNA COVID-19 vaccines. The specific vaccine schedule is discussed separately (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

As with other vaccines, we generally try to vaccinate when the patient is most likely to mount a protective immune response (ie, at least two weeks before or two weeks after splenectomy or when the effect of immunosuppressive medications is at its nadir). However, during the pandemic, we weigh the likelihood of developing a protective immune response against the likelihood of COVID-19 acquisition (eg, local prevalence) when determining timing. (See 'Timing of vaccination' above.)

A trend toward increased risk of hospitalization and/or death among splenectomized patients with COVID-19 was observed in a population-based case control study in Denmark (adjusted odds ratio for combined endpoint 1.44, 95% CI 0.79-2.61) [38]. This risk was partly attributable to increased comorbidities among these patients, supporting the importance of COVID-19 immunization in this population.

There are no complications of COVID-19 vaccination that are directly related to splenectomy. However, the severity of immune thrombocytopenias (rare complications of vaccination) may be higher among splenectomized patients with a history of multiple prior therapies [39]. (See "COVID-19: Hypercoagulability" and "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)".)

ANTIBIOTIC PROPHYLAXIS — There are two main approaches to using antibiotics to prevent severe infections in asplenic and hyposplenic patients (table 5 and table 6):

Daily antibiotic prophylaxis

Empiric antibiotic treatment for fever or other signs of systemic infection

These approaches are complementary. We provide all asplenic or hyposplenic patients with an emergency supply of antibiotics to be used in case of fever or other signs and symptoms of infection, along with instruction to present to the nearest medical facility when such signs or symptoms occur. For selected patients, we prescribe daily antibiotic prophylaxis in addition to the emergency supply.

Daily antibiotic prophylaxis — We typically determine the need for daily prophylaxis and its duration on an individual patient basis. Factors that we consider in making this determination include patient age, immune status, history of infections with encapsulated organisms, potential antibiotic side effects, local prevalence of antibiotic-resistant organisms, and patient values and preferences. Generally, we favor providing daily antibiotic prophylaxis to asplenic or hyposplenic patients who are at higher risk for severe infections based on young age, concurrent immunocompromising conditions, or history of sepsis caused by encapsulated bacteria. Penicillin and amoxicillin are the preferred agents for daily prophylaxis. Cephalosporins, fluoroquinolones, and macrolides are alternatives to penicillins (table 5 and table 6). (See 'Antibiotic selection' below.)

For most children with anatomic or functional asplenia/hyposplenism, we provide daily antibiotic prophylaxis until age 5 and for at least one year following splenectomy.

For children and adults with concurrent immunocompromising conditions (eg, hematologic malignancy, hypogammaglobulinemia, solid organ transplantation, advanced liver disease, or HIV infection), we prescribe antibiotic prophylaxis until at least age 18 and often for as long as the patient is immunocompromised or for life.

For children or adults with history of sepsis or other severe infections caused by encapsulated organisms (eg, S. pneumoniae), we often provide lifelong prophylaxis.

For adults, we provide daily antibiotic prophylaxis for at least one year following splenectomy.

For other asplenic and hyposplenic patients >5 years old, we do not routinely prescribe daily antibiotic prophylaxis in the absence of the high-risk features outlined above.

When making the decision to start or stop daily antibiotic prophylaxis, we generally discuss the risk and benefits of antibiotic prophylaxis with each patient and/or their families. While the benefits of preventing severe infection are evident, the disadvantages of long-term antibiotic use are not insignificant. These include the potential for hypersensitivity reactions or other adverse events, alteration of the microbiome, the emergence of drug-resistant pathogens, difficulty with adherence [40], and incomplete protection in regions where antibiotic-resistant S. pneumoniae is high. Patients in whom daily prophylaxis is not being used or being discontinued should have well-established medical care, understand the warning signs as well as the management of possible asplenic sepsis, and be aware that their risk for severe infection is lifelong.

Our approach is based on clinical trial data demonstrating reduced rates of invasive pneumococcal disease in children with functional and anatomic asplenia who receive daily antibiotic prophylaxis [41-43], knowledge of the relative prevalence of infection with encapsulated organisms in adults and children, and risk factors for poor outcomes (eg, immunocompromise and personal history of sepsis). (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Risk of severe infection'.)

In a meta-analysis of two randomized trials evaluating 457 children with sickle cell disease and functional hyposplenism, daily penicillin prophylaxis was associated with a threefold reduction (3 versus 9 percent) in the incidence of pneumococcal infection when compared with placebo (odds ratio [OR] 0.37, 95% CI 0.16-0.86) [43]. The larger of these two trials was performed in children <5 years old and was terminated early following the occurrence of 13 cases of pneumococcal sepsis (three fatal) in the placebo group and two in the penicillin group, corresponding to an 84 percent risk reduction with penicillin prophylaxis [42]. Large reductions in incidence of pneumococcal disease and associated mortality have also been observed among splenectomized children receiving antibiotic prophylaxis compared with those who did not receive prophylaxis [41]. Because these studies were performed in an era when pneumococcal vaccine use was not yet widespread and penicillin resistance among S. pneumoniae was extremely low, the magnitude of risk reduction observed in these studies may not be as large today.

The optimal duration of antibiotic prophylaxis has not been determined. Our decision to stop antibiotic prophylaxis at age 5 for most children is derived from a randomized trial that showed a similar risk of invasive pneumococcal disease in patients who stopped antibiotic prophylaxis at age 5 when compared with those who continued antibiotic prophylaxis beyond age 5 [44]. In an analysis of 400 children with sickle cell disease and functional asplenia, followed for a mean 3.2 years, invasive pneumococcal disease occurred in 2 percent of patients receiving prophylaxis beyond age 5 compared with 4 percent in patients who stopped prophylaxis at age 5 (OR 0.99, 95% CI 0.14-7.10) [43,44]. No deaths occurred during the study period and all participants received pneumococcal vaccination.

Because data supporting best practice are limited, recommendations among authorities vary. As examples, the 2017 Spleen Australia guidelines recommend daily antibiotic prophylaxis for asplenic and hyposplenic children until age 5, at least three years of antibiotic prophylaxis following splenectomy in both adults and children, and lifelong prophylaxis for immunocompromised patients and/or those with a history of sepsis [1]. The 2011 British guidelines recommend daily antibiotic prophylaxis for high-risk groups, which include asplenic and hyposplenic children (up to age 16), adults >50 years old, immunocompromised patients, and/or those with a history of sepsis [45]. Individualized decision-making is recommended for patients without high-risk features. By contrast, other experts suggest that for patients >5 years of age who lack high-risk features, one to two years of daily prophylaxis following splenectomy is sufficient due to the overall decline in incidence of pneumococcal disease [20].

Antibiotic selection — Penicillin and amoxicillin are the preferred agents for daily prophylaxis. Cephalosporins, fluoroquinolones, and macrolides are alternatives to penicillins (table 5 and table 6).

For most adults and children who require daily prophylaxis, we use oral penicillin V or oral amoxicillin.

For adults and children with hypersensitivity reactions to penicillin, we use a cephalosporin (eg, cephalexin) when possible. Generally, patients who have mild non-IgE-mediated reactions to penicillin can tolerate cephalosporins. Because many patients with other types of hypersensitivity reactions to penicillin can also tolerate cephalosporins, we often refer these patients to an allergist to determine if a cephalosporin can be safely used before starting prophylaxis.

For adults who cannot use cephalosporins, we use a fluoroquinolone (eg, levofloxacin) or a macrolide (eg, azithromycin or erythromycin). For children who cannot use cephalosporins, we use a macrolide (eg, azithromycin).

In all cases, we take the local prevalence of antibiotic resistance of S. pneumoniae into account when weighing the benefits and risks of using daily prophylaxis and selecting an antibiotic. In areas where resistance rates are high, the benefit of daily prophylaxis is lower. When the prevalence of penicillin/beta-lactam resistance exceeds 30 percent, we favor fluoroquinolone use for adults. However, this is an uncommon scenario, and fluoroquinolones are associated with significant adverse effects (eg, QT prolongation, tendinopathies, and potential for adverse drug-drug interactions). We thus weigh risks and benefits carefully and individually in this situation.

Emergency antibiotic supply — We provide all asplenic and hyposplenic patients with an emergency supply of antibiotics to be used in case of fever or other signs and symptoms of systemic infection (eg, chills, rigors, headache, vomiting, or diarrhea) (table 5 and table 6). The emergency supply should be kept on hand in the home, at work, and ideally with the patient at all times for immediate use when needed. Both patients and providers should be diligent in ensuring that the emergency antibiotic supply does not expire.

For most adults and children, we usually prescribe amoxicillin-clavulanate. Cefdinir is an alternative.

For adults who cannot use beta-lactams due to allergy or other intolerance, we prescribe an extended-spectrum fluoroquinolone such as levofloxacin or moxifloxacin.

For children who are unable to use beta-lactams, we use levofloxacin.

For adults or children who are taking daily antibiotic prophylaxis, we generally select an antibiotic with a broader spectrum of activity and/or from a different antibiotic class than the antibiotic used for daily prophylaxis.

We advise patients to take a single dose of their prescribed emergency antibiotic (if on hand) and present to the nearest emergency department immediately if fever or other signs and symptoms of infection develop. Infections in patients with impaired splenic function can become fulminant and/or fatal within hours of symptom onset. Prompt management, including early appropriate antibiotic use, can improve outcomes. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Evaluation and management'.)

Prophylaxis for procedures — We generally provide antibiotic prophylaxis for asplenic patients or hyposplenic patients undergoing procedures that involve the paranasal sinuses or respiratory tract (eg, endoscopic sinus surgery, bronchoscopy). Although there is no direct evidence supporting this practice, encapsulated organisms (eg, S. pneumoniae and/or H. influenzae type b) can colonize or infect these sites, and bacteremia complicating these procedures in patients with impaired splenic function can be fatal [46].

For adults, we use amoxicillin 2 g orally 30 to 60 minutes prior to the procedure.

For children >3 months of age and <40 kg, we use amoxicillin 50 mg/kg one hour before the procedure (maximum dose 2 g).

Alternatives to amoxicillin include cephalosporins (eg, cephalexin) for patients without contraindications, clindamycin, and macrolides such as azithromycin or erythromycin. Levofloxacin and moxifloxacin are additional alternatives for adults.

Because most other procedures, including dentistry, do not carry a substantially increased risk of infection with encapsulated bacteria, we do not provide antibiotic prophylaxis in addition to what is routinely recommended. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults" and "Antibiotic prophylaxis for gastrointestinal endoscopic procedures" and "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

OTHER CONSIDERATIONS

Travel planning — Patients with asplenia or hyposplenism who are planning to travel abroad should visit a travel clinic or health care provider, ideally 4 to 12 weeks prior to travel. (See "Travel advice".)

A pretravel clinic visit is particularly important for patients travelling to areas where malaria is endemic (eg, most tropical regions, especially sub-Saharan Africa). The spleen is important for the control of malaria, and patients with impaired splenic function should be educated on the importance of malaria prophylaxis and mosquito avoidance. (See "Prevention of malaria infection in travelers".)

Outbreaks of meningococcal disease also occur with some frequency in certain regions of the world (eg, sub-Saharan Africa and Saudi Arabia during the Hajj). Because patients with impaired splenic function are at increased risk for severe and overwhelming infection with meningococcus, this risk should be reviewed before travel, and additional meningococcal vaccines should be administered when indicated. (See "Immunizations for travel" and "Meningococcal vaccination in children and adults".)

All patients should be reminded of the need to carry an emergency supply of antibiotics with them while traveling and to have a medical alert card or device for the benefit of emergency care providers. (See 'Emergency antibiotic supply' above.)

Animal exposures — Patients with asplenia or hyposplenism who are bitten by an animal should seek immediate medical care. Dog bites, in particular, are associated with C. canimorsus infection, which can lead to fulminant sepsis in patients with impaired splenic function. Care for animal bites in asplenic patients should include thorough irrigation of any wounds and the administration of an antibiotic regimen that includes treatment for Capnocytophaga species. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Unusual exposures' and "Capnocytophaga".)

Patients with asplenia or hyposplenism should also be advised to avoid tick bites, particularly in areas where babesiosis is endemic (eg, coastal New England and the Upper Midwest United States). Like malaria, babesiosis is a bloodborne parasite that the spleen plays an important role in controlling. Because early symptoms of babesiosis are nonspecific and the disease is relatively uncommon, delays in diagnosis are not infrequent. Enhancing patient and provider knowledge of this infection may increase recognition and promote prompt therapy (see "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'Unusual exposures' and "Babesiosis: Treatment and prevention"). Pasteurella multocida has been very rarely reported as a cause of overwhelming sepsis in patients with asplenia or hyposplenism following cat bites.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Infections in asplenic patients".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Splenectomy (The Basics)")

Beyond the Basics topic (see "Patient education: Preventing infection in people with impaired spleen function (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Risk of severe and overwhelming infection – Patients with impaired splenic function are at risk for severe and overwhelming infection with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis), bloodborne parasites, and other infections that the spleen plays an important role in controlling. (See 'Introduction' above.)

Importance of patient education – Patient education is a key component of care and has been associated with decreased rates of severe infections in patients with impaired splenic function. When counseling patients, we emphasize the increased risk of infection, that this risk is lifelong, and strategies to minimize this risk (ie, vaccination, use of prophylactic antibiotics, and instructions on when to seek medical care). (See 'Patient education' above and 'Information for patients' above.)

Vaccinations indicated for patients with impaired splenic function – We advise all patients with impaired splenic function to receive vaccinations against S. pneumoniae (pneumococcus), H. influenzae type b, and N. meningitidis (meningococcus). Vaccine schedules vary based on patient age and vaccine history, particularly among young children (table 3 and table 4). (See 'Vaccinations' above and 'Vaccine schedules' above.)

Other routinely indicated vaccinations – In addition to these vaccinations, patients with impaired splenic function should receive all routinely recommended age-appropriate vaccinations including COVID-19 vaccination. Because influenza is associated with an increased risk of pneumococcal pneumonia, we emphasize the importance of annual vaccination against seasonal influenza virus to all patients with impaired splenic function. (See 'Vaccinations' above and 'Vaccine schedules' above.)

Timing of vaccination – For patients undergoing splenectomy, vaccine administration series should be completed ≥14 days prior to the procedure when feasible. When vaccines cannot be given in this time frame, they should be given 14 days after splenectomy. For patients with nonsurgical asplenia or hyposplenism (eg, impaired splenic function due to sickle cell disease), vaccine series should be started as soon as impaired splenic function is recognized. (See 'Timing of vaccination' above.)

Antibiotic prophylaxis – In addition to vaccination, use of prophylactic antibiotics further reduces the risk of severe infections in patients with impaired splenic function. (See 'Antibiotic prophylaxis' above.)

Emergency antibiotic supply – We provide all asplenic and hyposplenic patients with an emergency supply of antibiotics to be used in case of fever or other signs and symptoms of systemic infection (eg, chills, rigors, headache, vomiting, or diarrhea) along with instruction to present to the nearest emergency department for additional care when such symptoms arise (table 5 and table 6). (See 'Emergency antibiotic supply' above.)

Risks and benefits of daily antibiotic prophylaxis – We discuss the risks and benefits of daily antibiotic prophylaxis with all patients and generally favor its use in asplenic and hyposplenic patients who are at highest risk of severe infection. Penicillin and amoxicillin are the preferred agents for daily prophylaxis. Cephalosporins, fluoroquinolones, and macrolides are alternatives to penicillins (table 5 and table 6). (See 'Daily antibiotic prophylaxis' above and 'Antibiotic selection' above.)

For most children with anatomic or functional asplenia, we suggest daily antibiotic prophylaxis until age 5 and for at least one year following splenectomy (Grade 2B).

For children and adults with concurrent immunocompromising conditions (eg, hematologic malignancy, hypogammaglobulinemia, solid organ transplantation, advanced liver disease, or HIV infection), we suggest antibiotic prophylaxis until at least age 18 and often for as long as the patient is immunocompromised or for life (Grade 2C).

For children or adults with history of sepsis or other severe infections caused by an encapsulated organism (eg, S. pneumoniae), we suggest lifelong prophylaxis (Grade 2C).

For adults undergoing splenectomy, we provide daily antibiotic prophylaxis for at least one year following the procedure (Grade 2C).

For most other asplenic or hyposplenic patients >5 years old, we do not routinely prescribe daily antibiotic prophylaxis in the absence of the features outlined above.

Animal bites – We also advise patients with impaired splenic function to seek immediate medical care for any animal bite. Dog bites, in particular, can transmit Capnocytophaga canimorsus, which can be rapidly progressive and fatal in patients with impaired splenic function. (See 'Animal exposures' above.)

Other precautions – Additional precautions include avoiding tick bites in areas where babesiosis is endemic and seeing a health care provider prior to travel, particularly to areas where malaria is endemic. (See 'Other considerations' above and 'Travel planning' above.)

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References

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