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Nontyphoidal
Salmonella bacteremia. Bacteremia por Salmonela no tifoidea
Literature
review current through: Jan
2013. | This topic last updated: ene 2, 2013.
INTRODUCTION — Nontyphoidal salmonellae are an important bacterial cause
of diarrheal disease. The epidemiology and pathophysiology of nontyphoidal
strains differ from typhoidal strains
Issues related to the epidemiology, clinical microbiology, clinical
manifestations, and treatment of nontyphoidal Salmonella bacteremia will be
reviewed here. Nontyphoidal Salmonella gastrointestinal disease and typhoid
fever are discussed in detail separately.
EPIDEMIOLOGY
Incidence — Bacteremia and other forms of extraintestinal Salmonella
infection are serious complications that may not be suspected in the setting of
mild primary infection. It is estimated that perhaps 1 percent of enteric infections
with nontyphoidal Salmonella result in bacteremia, but the true rate of
bacteremia is unknown, as many primary enteric infections are mild or not
microbiologically diagnosed.
Risk factors — Factors affecting the incidence of bacteremia include Salmonella
serotype, geographic location, time of year, and host factors. Host risk
factors for nontyphoidal Salmonella bacteremia include extremes of age and
chronic or immunosuppressing conditions, including malignancy, rheumatological
disease, TNF blockade (eg, agents such as etanercept or infliximab),
transplantation, HIV infection, and congenital immune defects [2-5]. Other predisposing comorbidities include liver
disease, hemoglobinopathies (especially sickle cell disease), schistosomiasis,
and chronic granulomatous disease. Alteration of the GI tract also predisposes
to progression from enteric to systemic salmonellosis (eg, by suppression of
gastric acid, malnutrition, recent antibiotic use, or rotavirus infection)
In a series of 55 Malaysian adults with nontyphoidal Salmonella
bacteremia, over 90 percent of patients had an underlying medical illness; 65
percent had severe immunosuppression, most commonly HIV infection or malignancy
[7]. In sub-Saharan Africa nontyphoidal Salmonella
bacteremia is a leading cause of bacteremia in adults and children [7-12]. Such infections may
occur in epidemic waves and mortality may be very high (12 to 30 percent).
Relapsing bacteremia and higher mortality are observed in the setting of
concurrent HIV infection.
Children with nontyphoidal bacteremia in developed settings usually have
associated gastroenteritis, do not typically have underlying comorbid illness,
and most recover uneventfully [6,13,14]. In a series of 144
pediatric cases of nontyphoidal Salmonella bacteremia in Pittsburgh (median age
10.5 months), 82 percent of patients were previously healthy [13].
MICROBIOLOGY
AND DIAGNOSIS — Blood cultures
should be drawn in patients with Salmonella gastroenteritis ill enough to
require hospitalization. Nontyphoidal Salmonella are vigorous organisms that
grow readily in aerobic and anaerobic blood culture bottles.
Serotype distribution varies greatly by location and over time. S.
enteritidis and S. typhimurium are the most commonly isolated pathogenic
serotypes; therefore, they are also most frequently isolated from the blood.
Some less frequently isolated serotypes can be more invasive than others and
are more likely to cause bacteremia (including S. enterica serotypes Dublin,
Cholerasuis, Virchow, Infantis, Newport, and Heidelberg) [1,15]. A "primary
bacteremia" (ie, a positive blood culture in the absence of recent or current
gastrointestinal symptoms of Salmonella infection) may be an initial signal of
unappreciated immunological dysfunction. HIV infection should be considered;
recurrent Salmonella infection was a relatively frequent AIDS-defining
infection in the US in the pre-HAART era. Other more frequently encountered
co-morbidities include malignancy, diabetes, and rheumatologic illness.
Therapeutic immunosuppression with steroids and other immunomodulatory drugs is
increasingly common.
CLINICAL
MANIFESTATIONS
Extraintestinal
focal infection — Nontyphoidal
salmonellae bacteremia can progress to development of infection at any site,
including the urinary tract, lung, pleura, heart, long bones, joints, muscle,
and central nervous system. After stool and blood, urinary isolates are
encountered most frequently; these may reflect urologic abnormalities,
bacteremia in the setting of chronic medical illness, and/or retrograde spread
of infection [16,17].
Salmonella meningitis is a rare complication that typically occurs in
neonates and children ≤1 year; for this reason, any form of nontyphoidal
salmonellosis in infants should prompt immediate and attentive management [18,19]. Mortality is high and
survivors may not have complete neurological recovery.
Endovascular
infection — Endovascular infection is an uncommon
but serious complication of nontyphoidal Salmonella bacteremia. Initially noted
in the 1970s, subsequent population-based studies have noted that approximately
10 to 20 percent of adults over 50 years of age with documented nontyphoidal
Salmonella bloodstream infections have a suppurative endovascular focus of
infection [20,21]. The organisms are
presumed to home to existing atherosclerotic sites in large vessels in older
adults; this is the rationale for a more aggressive approach to treatment of
Salmonella gastroenteritis in older individuals.
Endovascular infection was specifically linked to atherosclerosis in one
Taiwanese study, in the absence of other clinical features or
immunodeficiencies [22]. The abdominal aorta (especially infrarenal) is
the most frequent site of vascular infection, though involvement of the
thoracic aorta, other central arterial sites and endocarditis occur as well.
Subacute fever and abdominal and back pain are the typical presenting symptoms;
a pulsatile mass is a late and ominous finding.
The diagnostic approach should consist of CT or MRI (preferably with
contrast angiographic analysis) when an aortic or vascular focus is possible or
suspected. Medical therapy alone is inadequate; surgery is required [23]. Experienced vascular surgeons should be
consulted. Because of the morbidity of extra-anatomic bypass, most experts
perform in-situ debridement and grafting despite the risk of leak and relapsed
infection. There are a variety of specific surgical approaches and grafts,
depending on the site involved, intraoperative findings, and degree of
debridement deemed necessary and achieved. Small surgical series of 23 and 24
patients have demonstrated a 60 to 100 percent survival rate, respectively [14,24].
Antibiotics are an essential component of therapy, but the duration of
therapy is debated. (See 'Treatment' below.)
TREATMENT — Extraintestinal nontyphoidal Salmonella infections
generally require surgical drainage or debridement and prolonged antimicrobial
therapy.
Antibiotic
selection — Fluoroquinolones are a reasonable
empiric antibiotic choice for treatment of nontyphoidal Salmonella bacteremia (ciprofloxacin 400 mg
intravenously twice daily or levofloxacin 500 to
750 mg intravenously once daily). Fluoroquinolones have excellent intracellular
penetration and oral bioavailability, allowing transition to oral therapy with
clinical improvement.
Fluoroquinolones are frequently avoided in children because of cartilage
abnormalities observed in developing animals, although data suggest that
fluoroquinolones may be used in children over short courses [25]. Treatment of serious Salmonella infections is a
reasonable indication for use of fluoroquinolones in children, especially if
other agents are not readily available [26]. Third generation cephalosporins are a reasonable
alternative to fluoroquinolones (eg, ceftriaxone 1 to 2 g
intravenously once daily or cefotaxime 2 g
intravenously every eight hours).
Reduced susceptibility and frank resistance to fluoroquinolones and
third generation cephalosporins is increasing [27,28]. Resistance has been
reported frequently in Asia and history of travel to this region should be
considered in clinical management [29]. Antibiotics must be tailored to susceptibility
data once available. Nalidixic acid disc resistance testing should be
performed if possible; resistance to nalidixic acid indicates relative
resistance to fluoroquinolones and should prompt use of an alternative drug.
Other reasonable antibiotic alternatives include trimethoprim-sulfamethoxazole (8 to 10 mg/kg/day of the trimethoprim component
divided three times per day) and ampicillin (2 g IV
every 4 hours).
For management of infections due to highly resistant organisms,
infectious disease consultation is advisable. Carbapenems are appropriate
agents for treatment of infection due to highly resistant organisms; resistance
to carbapenems has rarely been noted in case reports [30-32]. Azithromycin is
another possible alternative in exceptional cases, although there are no
standard NCCLS antimicrobial susceptibility break points reported for
salmonellae.
Duration of
therapy
Bacteremia — The optimal duration of antimicrobial therapy for
nontyphoidal Salmonella bacteremia in the absence of extraintestinal focal
infection depends upon the immune status of the host. A 14 day course of
antimicrobial therapy for otherwise healthy individuals is likely appropriate.
Patients with Salmonella gastroenteritis hospitalized with the suspicion of
bacteremia should have blood cultures drawn and empiric treatment initiated
while awaiting culture results. In such circumstances, prompt initiation of
antibiotic therapy is of greater clinical importance than the possibility of
prolonging fecal carriage, especially in older patients.
Longer courses of antimicrobial therapy (4 to 6 weeks) are warranted for
patients with significant immunosuppression for whom recurrence or relapse is
likely (eg, such as in the setting of HIV/AIDS, solid organ transplant, or bone
marrow transplant) [8,33,34]. If infection and/or
bacteremia occurs at an immunological nadir in these patients, the infection
may become established within the immunologically compromised
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 system) [24].
A period of suppressive therapy may also be appropriate for patients
with significant immunosuppression, especially if relapse of bacteremia is
documented after an initial successful treatment.
Extraintestinal
focal infections and endovascular infection — In general, complete debridement and drainage of soft tissue
or visceral foci of infection should be followed by a minimum of 3 weeks of
antimicrobial therapy if there are no clinical complications. Extraintestinal
foci are virtually always seeded by bacteremic spread, so the issues discussed
in the preceding section apply.
Longer courses of therapy (6 to 12 weeks) may be advisable depending
upon the site, adequacy of surgical debridement achieved, presence of any
prosthetic material (vascular grafts, joints, screws, plates, valves or other
hardware), presence or absence remaining fluid collections or devitalized
tissue, immunological status, and age of the patient. Duration of therapy
should be commensurate with standard courses for the site of infection at a
minimum; for example, a brain abscess, endocarditis, or osseous infection
should be treated for at least 6 to 8 weeks if Salmonella are present.
Salmonella are hardy organisms that adapt to stressful environments and
may be difficult to eradicate, especially if devitalized tissue or prosthetic
material is present. Chronic suppressive therapy may be appropriate for
patients with infection of prosthetic joints, heart valves, or vascular grafts
where the potential consequences of relapsed infection may be dire. Reasonable
suppressive regimens (depending on the sensitivity of the organism)
include trimethoprim-sulfamethoxazole (one DS tablet once daily), levofloxacin (500 mg
once daily) or ciprofloxacin (750 mg
once daily). Consultation with infectious disease expertise is recommended.
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