Version May 2024
INTRODUCTION — Salmonellae are motile gram-negative bacilli that infect or colonize a broad range of mammalian hosts. They cause a number of clinical infections in humans, including:
●Gastroenteritis
●Enteric fever (systemic illness with fever and abdominal symptoms)
●Bacteremia and endovascular infection
●Focal metastatic infections such as osteomyelitis or abscess
●An asymptomatic chronic carrier state
Enteric fever is caused by Salmonella typhi and Salmonella paratyphi. The microbiology, epidemiology, clinical features, and treatment of these infections are discussed elsewhere. (See "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis" and "Enteric (typhoid and paratyphoid) fever: Treatment and prevention".)
Other Salmonella serotypes are collectively known as nontyphoidal salmonellae. Issues related to the epidemiology, clinical manifestations, diagnosis, and treatment of nontyphoidal Salmonella bacteremia and other invasive infections are reviewed here.
Issues related to nontyphoidal Salmonella gastrointestinal infection and asymptomatic carriage are discussed separately, as are general issues related to the microbiology, epidemiology, and pathogenesis of nontyphoidal salmonellae. (See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage" and "Nontyphoidal Salmonella: Microbiology and epidemiology" and "Pathogenesis of Salmonella gastroenteritis".)
EPIDEMIOLOGY
Incidence — Invasive infections due to nontyphoidal Salmonella occur globally; the burden varies by geographic location. Approximately 65 percent of cases worldwide occur among children <5 years of age.
Approximately 1 percent of enteric infections with nontyphoidal Salmonella result in bacteremia; however, the true rate of bacteremia is unknown since many enteric infections are not diagnosed microbiologically. In a systematic review that extrapolated the global incidence of invasive nontyphoidal Salmonella infections based on 35 studies, there were an estimated 535,000 cases in 2017 (7.5 cases per 100,000 people worldwide) [1]. The greatest burden was in sub-Saharan Africa, which accounted for 79 percent of all cases globally [1] and where nontyphoidal Salmonella bacteremia is a leading cause of bacteremia in adults and children [2-7]. According to one systematic review, nontyphoidal Salmonella causes 8 to 39 percent of cases of community-acquired bacteremia in sub-Saharan Africa [8]. In these areas, nontyphoidal Salmonella bacteremia may occur in epidemic waves (more common during and just after rainy seasons) and mortality may be very high.
Host risk factors — Patients at increased risk for nontyphoidal Salmonella bacteremia or associated complications include (table 1) [9-12]:
●Patients <12 months or >50 years of age
●Immunocompromised patients in the following categories:
•Patients with HIV infection, especially if poorly controlled
•Organ transplant recipients
•Patients receiving corticosteroids or other immunosuppressive agents
•Patients with cancer or lymphoproliferative disease with current or recent chemotherapy
•Patients with sickle cell disease or other hemoglobinopathies
•Patients with disorders of the reticuloendothelial system, including cirrhosis and chronic granulomatous disease
•Children with severe malarial anemia and malnutrition
●Patients with atherosclerosis or prosthetic heart valves
Alteration of the gastrointestinal tract (eg, by suppression of gastric acid, malnutrition, recent antibiotic use, or rotavirus infection) also predisposes patients to progression from enteric to systemic salmonellosis [13]. (See "Pathogenesis of Salmonella gastroenteritis".)
The importance of predisposing host risk factors was illustrated in a series of 55 Malaysian adults with nontyphoidal Salmonella bacteremia, in which over 90 percent of patients had an underlying medical illness; 65 percent were immunocompromised (most commonly due to HIV infection or malignancy) [2]. In a 2017 systematic review of global cases of invasive nontyphoidal Salmonella, 8 percent of cases were associated with HIV infection [1].
In sub-Saharan Africa, nontyphoidal Salmonella bacteremia most commonly occurs in patients with HIV infection, infants, and young children with severe malarial anemia and malnutrition [8]. The association with malaria may be related to increased intestinal permeability and bacterial translocation in the setting of malaria infection [14-16]. Relapsing bacteremia and higher mortality are observed in the setting of concurrent HIV infection.
However, among children with nontyphoidal bacteremia in resource-abundant
settings, most have associated gastroenteritis, have no underlying comorbid illness, and recover uneventfully [13,17,18]. In a series of 144 pediatric cases of nontyphoidal Salmonella bacteremia in Pittsburgh in the United States (median age 10.5 months), 82 percent of patients were previously healthy [17].
Risk by serotype — Salmonella enteritidis and S. typhimurium are the most commonly isolated nontyphoidal Salmonella serotypes overall and the most common causes of invasive infection.
Other serotypes have increased predisposition for invasive disease [19]; these include Salmonella enterica serotypes Dublin, Choleraesuis, Virchow, Infantis, Newport, and Heidelberg [20-22]. In addition, antibiotic-resistant strains of S. typhimurium are associated with a two- to threefold increase in the risk of bacteremia [23,24].
The microbiologic features of nontyphoidal Salmonella are discussed separately. (See "Nontyphoidal Salmonella: Microbiology and epidemiology", section on 'Microbiology'.)
Transmission — Nontyphoidal Salmonella are transmitted by the fecal-oral route; this includes transmission within households or between close contacts, outbreaks related to contaminated food and water, and transmission to humans from farm or pet animals. Eggs are a prime source for transmission of S. enteritidis; S. typhimurium has a broader range of food transmission sources.
Environmental reservoirs and host ranges of invasive strains remain poorly understood [19].
This issue is discussed further separately. (See "Nontyphoidal Salmonella: Microbiology and epidemiology", section on 'Modes of transmission'.)
CLINICAL FEATURES AND COMPLICATIONS — Bacteremia and other forms of extraintestinal infection are serious complications of Salmonella gastroenteritis. (See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage".)
Bacteremia — The clinical manifestations of nontyphoidal Salmonella bacteremia are nonspecific and may range from fever to sepsis.
In adults, the clinical presentation is variable and depends upon the Salmonella serotype as well as the host immune status and underlying comorbidities. "Occult" or "primary" bacteremia (defined as bacteremia not associated with an acute or recent episode of gastroenteritis) should raise clinical concern for an underlying immune defect or recrudescent infection from prior seeding of a vascular, osseous, or visceral focus. In immunocompromised hosts, even minimally symptomatic gastrointestinal illness can lead to deep infection.
In children, bacteremia is associated with gastrointestinal symptoms in 70 to 80 percent of cases [17,25]. In addition, respiratory symptoms occur among some children; in one case series including 229 children with invasive salmonellosis in Thailand, respiratory symptoms were observed in approximately 25 percent of patients [26].
Extraintestinal infection — Nontyphoidal Salmonella bacteremia can progress to development of infection at any site. The most clinically important forms are endovascular infection and central nervous system infection, since definitive debridement of these sites is not feasible in most cases. Other forms include endocarditis, musculoskeletal infection, visceral infection (involvement of the spleen, liver, heart, lung, or pleura), and urinary tract involvement [27].
Organisms are most commonly isolated from stool and blood, followed by urine. Positive urine cultures may occur as a result of hematogenous seeding in the setting of immune compromise, underlying urologic abnormality, or may reflect ascending spread of infection from the perineum to the urinary tract [28,29].
Suppurative secondary foci are more common in immunocompromised patients and patients <12 months or >50 years of age.
Endovascular infection — Endovascular infection is an uncommon but serious complication of nontyphoidal Salmonella bacteremia. The organisms have a propensity to home to existing atherosclerotic sites of large vessels in older adults. In one study from Taiwan, endovascular infection was linked to atherosclerosis in the absence of other clinical features or immunodeficiencies [30]. In small retrospective studies of adults >50 years of age with nontyphoidal Salmonella bacteremia, 7 to 10 percent of patients had endovascular infection, typically at the site of pre-existing vascular disease [31-33]. (See "Overview of infected (mycotic) arterial aneurysm".)
The abdominal aorta (especially infrarenal aorta) is the most frequent site of vascular infection. Other sites of involvement include the thoracic aorta and other central arterial sites [34]. Clinical manifestations of endovascular infection include subacute fever, abdominal pain, and back pain. In addition, patients with endovascular infection may present with relapsing or prolonged Salmonella bacteremia. Retrospective studies from Taiwan suggest that rapid "time to positivity" on automated blood culture systems (<10 hours) may portend a poor prognosis [35-37].
Endocarditis — Endocarditis is a relatively rare complication of nontyphoidal Salmonella bacteremia; it usually occurs in patients with underlying valve disease or prosthetic valves [38,39].
Clinical manifestations of endocarditis are described separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)
Musculoskeletal infection
●Osteomyelitis – Salmonellae may seed and persist within osseous abnormalities. Salmonella osteomyelitis occurs more commonly in children (especially those with hemoglobinopathies) and typically involves the epiphyses of long bones [40]; in adults, the axial skeleton is more typically involved [41,42]. Numerous case reports describe Salmonella osteomyelitis mimicking malignancy, highlighting the need for operative cultures in unusual cases.
●Septic arthritis – Septic arthritis may occur in native or prosthetic joints [43]. Salmonella musculoskeletal infection may be complicated and difficult to eradicate, particularly in the setting of orthopedic prostheses.
●Reactive arthritis – Postinfectious reactive arthritis can occur after salmonellosis (as well as after Campylobacter, Shigella, and Yersinia gastrointestinal infection); the incidence and relative risk of each varies significantly across studies [44,45].
Visceral infection — Deep infection of virtually every body site has been reported due to bacteremic seeding, local extension, or failed clearance of organisms within the lymphatic and reticuloendothelial system, including the lymph nodes, liver, and spleen. Other described sites of involvement include the pleural space, neck, ovaries, epidural sites, and many others.
These complications are more likely in patients with immune defects or anatomical abnormalities but may occur in healthy individuals without predisposing conditions.
Central nervous system infection
●Meningitis – Salmonella meningitis is a rare complication that typically occurs in neonates and children ≤12 months of age; for this reason, any form of nontyphoidal salmonellosis in infants should prompt immediate and attentive management [46,47]. Manifestations include fever and lethargy; complications include hydrocephalus and ventriculitis [48].
In settings with high HIV prevalence, nontyphoidal Salmonella meningitis has also been described in adults. In one review of 278 cases of nontyphoidal Salmonella meningitis in South Africa, there were bimodal peaks at <5 and >15 years of age; 46 percent of patients had HIV infection [49]. Headache and signs of meningeal irritation are more common among adults.
Mortality is high (65 percent among patients >15 years old in the large series above), and survivors may not have complete neurological recovery.
●Brain abscess – Salmonella brain abscess may occur as a complication of meningitis or rarely after neurosurgical procedures [50].
Relapse — Among immunocompromised patients, if bacteremia occurs at an immunological nadir, infection may become established within the reticuloendothelial system. Relapse may occur even after an asymptomatic interval and in the absence of a known focus of infection (such as osteomyelitis or an abnormal biliary or urinary tract) [51].
The risk of relapse varies by host characteristics:
●In one United States study including 82 patients with malignancy (of whom 55 had hematologic malignancy) and nontyphoidal Salmonella infection, relapse occurred in 6 percent of cases [52]. All relapses occurred in patients treated with less than 10 days of antibacterial therapy; mortality at 30 days was 8 percent.
●In a United States study including 51 otherwise healthy children with nontyphoidal bacteremia, there was no difference in outcome between those treated with a short duration of antibiotic therapy (<7 days; median 4 days) versus a longer duration (>7 days; median 9 days) [53].
EVALUATION AND DIAGNOSIS
Clinical suspicion — Nontyphoidal Salmonella bacteremia should be suspected in patients with gastrointestinal symptoms (recent or current) and systemic febrile illness in the setting of risk factors outlined in the table (table 1).
Obtaining cultures — The diagnosis of nontyphoidal Salmonella bacteremia is established by blood culture. Nontyphoidal Salmonella grow readily in aerobic and anaerobic blood culture bottles. (See "Nontyphoidal Salmonella: Microbiology and epidemiology", section on 'Microbiology'.)
Blood cultures should be obtained in patients with clinical suspicion for nontyphoidal Salmonella bacteremia as outlined above (see 'Clinical suspicion' above). Isolation of Salmonella from urine culture should also prompt collection of blood cultures.
For patients with imaging or other findings suggestive of a mycotic aneurysm who are already receiving systemic antibiotics (which may reduce the yield of blood cultures), stool culture may be diagnostically useful.
Evaluation for extraintestinal complications
●Physical examination – Patients with nontyphoidal Salmonella bacteremia should have a careful physical examination for possible extraintestinal metastatic foci of infection. A pulsatile abdominal mass should raise concern for aortic aneurysm. A cardiac murmur should raise concern for endocarditis. Bone or joint pain should prompt consideration of osseous infection, especially in patients with chronic granulomatous disease or sickle cell disease. (See 'Extraintestinal infection' above.)
●Imaging – Decisions regarding whether to pursue radiographic evaluation should be guided by clinical circumstances and physical examination findings. We have a lower threshold for radiographic imaging in patients >50 years of age, patients with recurrent or prolonged bacteremia, patients with underlying immune compromise or known atherosclerotic disease, and patients with implanted prosthetic material (such as a prosthetic heart valve or prosthetic joint).
In the setting of suspected endovascular infection, radiographic evaluation should consist of computed tomography (CT) or magnetic resonance imaging (MRI), preferably with contrast angiographic analysis. (See "Overview of infected (mycotic) arterial aneurysm", section on 'Diagnosis'.)
Echocardiography is warranted for patients with prosthetic valves as well as for patients with native valves in the context of underlying valve disease and/or new cardiac murmur. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Cardiac imaging' and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis", section on 'Cardiac imaging'.)
Evaluation for underlying comorbidities — In patients with "primary bacteremia" (ie, a positive blood culture in the absence of recent or current gastrointestinal symptoms of Salmonella infection), this finding may reflect an underlying immunocompromising condition (such as HIV infection, liver disease, or malignancy). In such cases, further evaluation is warranted, guided by individual clinical circumstances.
MANAGEMENT — Infectious diseases consultation is advisable for management of patients with known or suspected nontyphoidal Salmonella bacteremia.
Bacteremia
Initial antibiotic therapy
Indications — Initial antibiotic therapy is warranted for patients with nontyphoidal Salmonella bacteremia pending susceptibility results. (See 'Clinical suspicion' above.)
In such cases, prompt initiation of antibiotic therapy is likely of greater clinical importance than the possibility of prolonging fecal carriage. (See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage", section on 'Asymptomatic carriage'.)
Selection — Given the increasing prevalence of antimicrobial resistance, local antibiotic resistance patterns must be taken into account when choosing empiric therapy. Antibiotic therapy should be tailored to susceptibility data once available. (See "Nontyphoidal Salmonella: Microbiology and epidemiology", section on 'Antimicrobial resistance'.)
●Preferred agents – Preferred antibiotic agents for treatment of nontyphoidal Salmonella bacteremia include a third-generation cephalosporin or fluoroquinolone, given the high tissue and intracellular concentrations of these agents. Antibiotic dosing is summarized in the table (table 2).
For patients with suspected endovascular infection (eg, patients with bacteremia in the setting of a prosthetic heart valve), initial empiric treatment with both a third-generation cephalosporin as well as a fluoroquinolone is reasonable (given the potential morbidity of such infections), pending susceptibility data.
The US Food and Drug Administration (FDA) has issued warnings about adverse effects associated with fluoroquinolones [54]; the benefits of fluoroquinolones may outweigh these risks in treatment of Salmonella infections and should be considered carefully. In children, fluoroquinolones are frequently avoided [55]; however, treatment of serious Salmonella infection is a reasonable indication for their use, especially if other agents are not readily available [56]. (See "Fluoroquinolones".)
●Alternative agents – Alternative agents for treatment of nontyphoidal Salmonella bacteremia include trimethoprim-sulfamethoxazole or ampicillin. Azithromycin is another possible alternative agent, although microbiology laboratory capabilities for susceptibility testing are varied and evolving; in rare cases, azithromycin may be useful for treatment of select patients with nontyphoidal Salmonella infection. Antibiotic dosing is summarized in the table (table 2).
For highly resistant organisms, ertapenem, imipenem, and meropenem may be used, with expert consultation.
Susceptibility testing for first- and second-generation cephalosporins is generally not reported by most laboratories, and these agents are not recommended for treatment of salmonellosis.
Directed antibiotic therapy
●Susceptibility testing – Once susceptibility data are available, antibiotics should be tailored to the microbiology data and clinical circumstances.
For determination of fluoroquinolone susceptibility in cases of invasive salmonellosis, direct testing should be performed [57]. Previously, nalidixic acid disc resistance screening was used as a marker for relative resistance to fluoroquinolones; however, this approach does not detect all mechanisms of fluoroquinolone resistance.
●Antibiotic selection
•Susceptible isolates – The options for directed antimicrobial therapy (including preferred and alternative agents) are the same as for empiric therapy (table 2). (See 'Selection' above.)
There are no comparative trials of antimicrobial agents for treatment of nontyphoidal Salmonella bacteremia. The choice of agent should be guided by the clinical presentation, patient age, presence or absence of suppurative foci (and, if present, feasibility of debridement), and adverse drug effects.
•Drug-resistant isolates – For treatment of infection due to highly resistant organisms, carbapenems (eg, meropenem 1 g intravenously (IV) every eight hours for adults; 20 mg/kg IV every eight hours [maximum 1000 mg/dose] for children) may be used [58,59]; carbapenem resistance has only rarely been noted in case reports [60,61]. In such cases, consultation with an expert in infectious diseases is advised.
Treatment duration and suppressive therapy — For patients with nontyphoidal Salmonella bacteremia in the absence of extraintestinal focal infection, the duration of antimicrobial therapy should be guided by the host immune status.
●Immunocompetent patients – For otherwise healthy individuals with bacteremia complicating acute gastroenteritis, a 10- to 14-day course of antimicrobial therapy is reasonable. For patients >12 months and <50 years of age with no comorbidities, shorter courses may be acceptable; however, rare cases of focal infection or relapse can occur even in these groups, and clinical studies regarding treatment of salmonellosis are limited to retrospective data [62,63]. Immunocompetent patients who have improved on IV therapy, are not believed to be at high risk for focal infections, have susceptible organisms, and can be followed closely as outpatients may complete treatment with highly bioavailable oral antibiotic therapy (eg, a fluoroquinolone).
●Immunocompromised patients – For immunocompromised patients (table 1), we treat for four to six weeks, given higher risk of recurrence or relapse [3,64,65].
Following initial treatment, we administer oral suppressive therapy, especially if relapse has already occurred after an initial course of treatment:
•The choice of suppressive therapy should be guided by antimicrobial susceptibility data; options include levofloxacin (500 mg once daily), ciprofloxacin (750 mg once daily), or trimethoprim-sulfamethoxazole (one double-strength tablet once daily). Consultation with infectious disease experts is recommended.
•The optimal duration of suppressive therapy is uncertain and should be determined in conjunction with infectious diseases consultation; considerations include patient age, life expectancy, site of infection, consequences of relapse, and adverse drug effects.
Extraintestinal infection — Management of extraintestinal nontyphoidal Salmonella infection consists of surgical consultation regarding debridement in conjunction with prolonged antimicrobial therapy.
Surgical debridement
●Endovascular infection – Experienced vascular surgeons should be consulted for management of patients with endovascular nontyphoidal Salmonella infection [66,67]. Medical therapy alone is inadequate; surgery is required.
The surgical approach should be determined based on anatomic site, radiographic findings, intraoperative findings, and degree of debridement necessary and possible. Most experts perform in-situ debridement and grafting (despite the risk of leak and relapsed infection) given the morbidity of extra-anatomic bypass. For patients who are too frail to undergo open surgical repair, endovascular aneurysm repair may be a reasonable alternative [68-70].
Infectious and mechanical complications may occur, including relapse [69].
●Other forms of extraintestinal infection – Patients with visceral infection warrant debridement; the approach should be guided by the anatomic site of involvement.
For other forms of extraintestinal infection (including endocarditis, musculoskeletal infection, and central nervous system infection), the approach to surgical intervention is discussed separately. (See "Surgery for left-sided native valve infective endocarditis" and "Surgery for prosthetic valve endocarditis" and "Septic arthritis in adults", section on 'Joint drainage' and "Prosthetic joint infection: Treatment", section on 'Surgical management' and "Hematogenous osteomyelitis in children: Management", section on 'Indications for surgery' and "Vertebral osteomyelitis and discitis in adults", section on 'Surgery' and "Treatment and prognosis of bacterial brain abscess", section on 'Surgery'.)
Antibiotic therapy
Initial management — The approach to antibiotic therapy should be guided by the site of infection:
●Endovascular infection, endocarditis, musculoskeletal infection, or central nervous system infection – For patients with involvement of these sites, we administer antimicrobial therapy for at least six to eight weeks following surgical debridement. The approach to antibiotic selection is as discussed above for treatment of bacteremia (table 2). (See 'Bacteremia' above.)
●Visceral infection
•Immunocompetent patients – For immunocompetent patients with visceral infection who undergo complete surgical debridement in the absence of complications, we administer antimicrobial therapy for at least three weeks postoperatively. The approach to antibiotic selection is the same as discussed above for treatment of bacteremia (table 2). (See 'Bacteremia' above.)
If complete debridement is not feasible, the duration of treatment should be tailored to individual circumstances, guided by follow-up imaging.
•Immunocompromised patients – For immunocompromised patients (see 'Clinical suspicion' above), we administer antimicrobial therapy for at least six to eight weeks, given higher risk of recurrence or relapse [3,64,65].
Suppressive therapy — For patients with extraintestinal infection in the settings outlined below, we administer oral suppressive therapy following completion of initial antibiotic therapy:
●Immunocompromised patients
●Patients with indwelling hardware or devices (such as vascular grafts, prosthetic heart valves, or orthopedic hardware), given the challenge of eradicating Salmonella infection and the potentially severe consequences of relapsed infection.
The choice of suppressive therapy should be guided by antimicrobial susceptibility data, in conjunction with infectious diseases consultation. Options include levofloxacin (500 mg once daily), ciprofloxacin (750 mg once daily), or trimethoprim-sulfamethoxazole (one double-strength tablet once daily).
The optimal duration of suppressive therapy is uncertain and should be determined in conjunction with infectious disease consultation; considerations include patient age, life expectancy, site of infection, consequences of relapse, and adverse drug effects.
OUTCOMES — The prognosis of nontyphoidal Salmonella bacteremia is highly variable and depends on host immunity as well as the presence or absence of suppurative foci of infection. Acute bacteremia complicating gastroenteritis in immunocompetent patients between 12 months and 50 years of age usually resolves promptly with appropriate antibiotic therapy. Among infants with nontyphoidal Salmonella meningitis, mortality may be ≥50 percent; among adults, complications are rare [48].
For patients with endovascular infection, small surgical series of up to 26 patients have demonstrated a 60 to 100 percent survival rate [18,51,67]. In a study in Sweden including 19 patients with infected aortic aneurysm due to nontyphoidal Salmonella infection who underwent vascular surgery, two-year survival was 74 percent (compared with 62 percent patients with S. aureus as the etiologic pathogen) [71].
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: Acute diarrhea in adults" and "Society guideline links: Acute diarrhea in children".)
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 e-mail 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 topics (see "Patient education: Salmonella infection (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Salmonellae are motile gram-negative bacilli that cause a broad range of clinical infection in humans.
•Host risk factors – Patients at increased risk for nontyphoidal Salmonella bacteremia are summarized in the table (table 1).
•Transmission – Nontyphoidal Salmonella are transmitted by the fecal-oral route; this includes transmission within households or between close contacts, outbreaks related to contaminated food and water, and transmission to humans from farm or pet animals. (See 'Transmission' above.)
●Clinical manifestations
•Bacteremia – In adults, the clinical presentation is variable and depends upon the Salmonella serotype as well as the host immune status and underlying comorbidities. In children, bacteremia is associated with gastrointestinal symptoms in 70 to 80 percent of cases. (See 'Bacteremia' above.)
•Extraintestinal infection – The most clinically important forms of extraintestinal infection are endovascular infection and central nervous system infection since definitive debridement of these sites is not feasible in most cases. Other forms include endocarditis, musculoskeletal infection, and visceral infection (involvement of the spleen, liver, heart, lung, or pleura). (See 'Extraintestinal infection' above.)
•Relapse – Among immunocompromised patients, if bacteremia occurs at an immunological nadir, infection may become established within the reticuloendothelial system. Relapse may occur even after an asymptomatic interval and in the absence of a known focus of infection. (See 'Relapse' above.)
●Evaluation and diagnosis
•Clinical suspicion and obtaining cultures – Nontyphoidal Salmonella bacteremia should be suspected in patients with gastrointestinal symptoms (recent or current) and systemic febrile illness in patients with risk factors (table 1). In such patients, blood cultures should be obtained to establish a microbiologic diagnosis. (See 'Clinical suspicion' above and 'Obtaining cultures' above.)
•Evaluation for extraintestinal complications – Patients with nontyphoidal Salmonella bacteremia should have a careful physical examination for possible extraintestinal metastatic foci of infection. Decisions regarding whether to pursue radiographic evaluation should be guided by clinical circumstances. We have a lower threshold for radiographic imaging in patients >50 years of age, patients with recurrent or prolonged bacteremia, patients with underlying immune compromise or known atherosclerotic disease, and patients with implanted prosthetic material (such as a prosthetic heart valve or prosthetic joint). (See 'Evaluation for extraintestinal complications' above.)
●Initial antibiotic therapy
•Bacteremia
-Antibiotic selection – For patients with nontyphoidal Salmonella bacteremia, we suggest initial treatment with either a third-generation cephalosporin or fluoroquinolone (Grade 2C), given the high tissue and intracellular concentrations of these agents.
For patients with suspected endovascular infection (eg, patients with bacteremia in the setting of a prosthetic heart valve), we suggest initial empiric treatment with both a third-generation cephalosporin as well as a fluoroquinolone (Grade 2C), given the potential morbidity of such infections.
Antibiotic dosing is summarized in the table (table 2). Antibiotic selection should be guided by local resistance patterns and tailored to susceptibility data when available. (See 'Selection' above.)
-Duration – For otherwise healthy individuals with bacteremia complicating acute gastroenteritis, a 10- to 14-day course of antimicrobial therapy is reasonable. For immunocompromised patients, we treat for four to six weeks, given higher risk of recurrence or relapse. (See 'Treatment duration and suppressive therapy' above.)
•Extraintestinal infection – Management of extraintestinal nontyphoidal Salmonella infection consists of surgical debridement in conjunction with prolonged antimicrobial therapy. (See 'Extraintestinal infection' above.)
The approach to antibiotic selection is the same as for treatment of bacteremia (table 2).
The duration of antibiotic therapy should be guided by the site of infection (see 'Initial management' above):
-Endovascular infection, endocarditis, musculoskeletal infection, or central nervous system infection – For patients with involvement of these sites, we administer antimicrobial therapy for at least six to eight weeks following surgical debridement.
-Visceral infection – For immunocompetent patients with visceral infection who undergo complete surgical debridement in the absence of complications, we administer antimicrobial therapy for at least three weeks postoperatively.
For immunocompromised patients, we administer antimicrobial therapy for at least six to eight weeks, given higher risk of recurrence or relapse.
●Suppressive therapy – For patients in the following categories, we suggest oral suppressive therapy following completion of initial antibiotic therapy (Grade 2C) (see 'Suppressive therapy' above):
•Immunocompromised patients, especially if relapse has already occurred after an initial course of treatment.
•Patients with indwelling hardware or devices (such as vascular grafts, prosthetic heart valves, or orthopedic hardware), given the challenge of eradicating Salmonella infection and the potentially severe consequences of relapsed infection.
The choice of suppressive therapy should be guided by antimicrobial susceptibility data. The duration of suppressive therapy is uncertain; considerations include patient age, life expectancy, site of infection, consequences of relapse, and adverse drug effects. Decisions regarding suppressive therapy should be made conjunction with infectious diseases expertise.
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