Salmonella gastroenteritis is typically self-limiting, and antibiotics should not be used in most cases. For patients meeting specific criteria for antibiotic use, the goal of therapy is to resolve the infection and lower the rate of more severe disease or extraintestinal complications.
Supportive treatment
Fluid replacement
All patients with gastroenteritis should be assessed for volume depletion and electrolyte imbalances.[83]Szajewska H, Dziechciarz P. Gastrointestinal infections in the pediatric population. Curr Opin Gastroenterol. 2010 Jan;26(1):36-44.
http://www.ncbi.nlm.nih.gov/pubmed/19887936?tool=bestpractice.com
Most individuals with acute diarrhea or gastroenteritis are able to maintain fluid and salt balances through the consumption of water, juices, sports drinks, soups, and saltine crackers.[67]Riddle MS, DuPont HL, Connor BA. ACG Clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 May;111(5):602-22.
http://www.ncbi.nlm.nih.gov/pubmed/27068718?tool=bestpractice.com
Reduced osmolarity oral rehydration solution (ORS) is recommended for mild to moderate dehydration:[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Infants, children, and adults with mild to moderate dehydration should receive ORS until clinical dehydration is corrected.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Once the patient is rehydrated, maintenance fluids should be administered. Replace ongoing losses in stools from infants, children, and adults with ORS, until diarrhea and vomiting are resolved.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Nasogastric administration of ORS may be considered in infants, children, and adults with moderate dehydration, who cannot tolerate oral intake, or in children with normal mental status who are too weak or who refuse to drink adequately.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Severe dehydration
Intravenous fluids, such as lactated Ringer and normal saline solution, should be administered when there is severe dehydration, shock, or altered mental status and failure of ORS therapy or ileus.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
The use of balanced crystalloid solutions may be associated with slightly shorter duration of hospitalization in children, compared with normal saline.[84]Florez ID, Sierra J, Pérez-Gaxiola G. Balanced crystalloid solutions versus 0.9% saline for treating acute diarrhoea and severe dehydration in children. Cochrane Database Syst Rev. 2023 May 17;5(5):CD013640.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013640.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/37196992?tool=bestpractice.com
[
]
How do balanced crystalloid solutions compare with 0.9% saline for treating acute diarrhea and severe dehydration in children?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.4409/fullShow me the answer Intravenous rehydration should be continued until pulse, perfusion, and mental status normalize, and the patient awakens, has no risk factors for aspiration, and has no evidence of ileus.
Antidiarrheal/antiemetic treatment
Treatment with an antidiarrheal and/or an antiemetic is not a substitute for fluid and electrolyte therapy.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
It can be considered once the patient is adequately hydrated.
Loperamide, an antidiarrheal agent, may be given to immunocompetent adults with acute watery diarrhea, but should be avoided in suspected or proven cases where toxic megacolon may result in inflammatory diarrhea, or diarrhea with fever. Loperamide should not be given to children <18 years of age with acute diarrhea.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Bismuth subsalicylate, another antidiarrheal, can be given to adults to control rates of passage of stool, and may help patients function better during bouts of mild to moderate illness.[67]Riddle MS, DuPont HL, Connor BA. ACG Clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 May;111(5):602-22.
http://www.ncbi.nlm.nih.gov/pubmed/27068718?tool=bestpractice.com
Ondansetron, an antiemetic, may be given to facilitate tolerance of oral rehydration in children >4 years of age, and in adolescents with acute gastroenteritis associated with vomiting.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
[
]
Is there randomized controlled trial evidence to support the use of antiemetics for reducing vomiting in children and adolescents with acute gastroenteritis?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.403/fullShow me the answer
Probiotics
Probiotics may be offered to reduce the symptom severity and duration in immunocompetent adults and children with infectious or antimicrobial-associated diarrhea.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Zinc
Oral zinc supplementation reduces the duration of diarrhea in children 6 months to 5 years of age who reside in countries with a high prevalence of zinc deficiency, or who have signs of malnutrition.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Medical treatments
As most cases of gastroenteritis are self-limited in nature, antibiotics are not recommended as the initial treatment.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
[67]Riddle MS, DuPont HL, Connor BA. ACG Clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 May;111(5):602-22.
http://www.ncbi.nlm.nih.gov/pubmed/27068718?tool=bestpractice.com
However, although antibiotics do not shorten the duration of symptoms in uncomplicated and self-limited cases of gastroenteritis, they may be beneficial in severe or complicated infections and in patients at increased risk of complications, including immunocompromised hosts.[85]Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD001167.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001167.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/23152205?tool=bestpractice.com
[86]Khoshoo V, Raj P, Srivastava R, et al. Salmonella typhimurium-associated severe protracted diarrhea in infants and young children. J Pediatr Gastroenterol Nutr. 1990 Jan;10(1):33-6.
https://journals.lww.com/jpgn/abstract/1990/01000/salmonella_typhimurium_associated_severe.6.aspx
http://www.ncbi.nlm.nih.gov/pubmed/2182815?tool=bestpractice.com
[87]Gendrel D, Raymond J, Legall MA, et al. Use of pefloxacin after failure of initial antibiotic treatment in children with severe salmonellosis. Eur J Clin Microbiol Infect Dis. 1993 Mar;12(3):209-11.
http://www.ncbi.nlm.nih.gov/pubmed/8389706?tool=bestpractice.com
[88]Mori N, Szvalb AD, Adachi JA, et al. Clinical presentation and outcomes of non-typhoidal Salmonella infections in patients with cancer. BMC Infect Dis. 2021 Sep 29;21(1):1021.
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06710-7
http://www.ncbi.nlm.nih.gov/pubmed/34587893?tool=bestpractice.com
Empiric antibiotic treatment is not recommended for patients who are immunocompetent who have bloody diarrhea while waiting for the results of investigations.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
The use of antibiotics does not significantly shorten the length of illness or decrease symptoms in typical cases.[85]Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD001167.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001167.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/23152205?tool=bestpractice.com
[89]Carlstedt G, Dahl P, Niklasson PM, et al. Norfloxacin treatment of salmonellosis does not shorten the carrier stage. Scand J Infect Dis. 1990 Jul 8;22(5):553-6.
http://www.ncbi.nlm.nih.gov/pubmed/2259863?tool=bestpractice.com
[90]Bassily S, Hyams KC, el-Masry NA, et al. Short-course norfloxacin and trimethoprim-sulfamethoxazole treatment of shigellosis and salmonellosis in Egypt. Am J Trop Med Hyg. 1994 Aug;51(2):219-23.
http://www.ncbi.nlm.nih.gov/pubmed/8074256?tool=bestpractice.com
[91]Guarino A, Ashkenazi S, Gendrel D, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr. 2014 Jul;59(1):132-52.
http://www.ncbi.nlm.nih.gov/pubmed/24739189?tool=bestpractice.com
[92]Gendrel D, Cohen R; European Society for Pediatric Infectious Diseases, European Society for Gastroenterology, Hepatology and Nutrition. Bacterial diarrheas and antibiotics: European recommendations. Arch Pediatr. 2008 Oct;15 Suppl 2:S93-6. [in French]
http://www.ncbi.nlm.nih.gov/pubmed/19000862?tool=bestpractice.com
Furthermore, antibiotics may cause adverse effects, prolong the carriage of Salmonella, and increase the risk of relapse.[85]Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD001167.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001167.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/23152205?tool=bestpractice.com
Treatment of an undifferentiated diarrheal illness (e.g., Shiga toxin-producing Escherichia coli) with an antibiotic may have adverse consequences, such as a potentially increased risk of hemolytic uremic syndrome.[93]Tarr PI, Freedman SB. Why antibiotics should not be used to treat Shiga toxin-producing Escherichia coli infections. Curr Opin Gastroenterol. 2022 Jan 1;38(1):30-8.
http://www.ncbi.nlm.nih.gov/pubmed/34871193?tool=bestpractice.com
Patients at risk of developing severe disease
For patients with severe illness, or who are at high risk of developing more severe disease i.e., bacteremia, or other forms of extraintestinal salmonellosis, a short course of oral antibiotics should be considered. These patient groups include:[43]Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis. 2001 Jan 15;32(2):263-9.
https://cid.oxfordjournals.org/content/32/2/263.full.pdf+html
http://www.ncbi.nlm.nih.gov/pubmed/11170916?tool=bestpractice.com
[44]Pegues DA, Miller SI. Salmonella species, including Salmonella Typhi. In: Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010:2887-903.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
[94]Gilbert DN, Chambers HF, Eliopoulos GM, et al. The Sanford guide to antimicrobial therapy, 47th ed. Sperryville, VA: Antimicrobial Therapy, Inc.; 2017.[95]Benenson S, Raveh D, Schlesinger Y, et al. The risk of vascular infection in adult patients with nontyphi Salmonella bacteremia. Am J Med. 2001 Jan;110(1):60-3.
http://www.ncbi.nlm.nih.gov/pubmed/11152867?tool=bestpractice.com
[96]Gordon MA, Banda HT, Gondwe M, et al. Non-typhoidal salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence. AIDS. 2002 Aug 16;16(12):1633-41.
http://www.ncbi.nlm.nih.gov/pubmed/12172085?tool=bestpractice.com
infants <3 months of age with suspicion of a bacterial etiology
adults over 50 years, to reduce the risk of seeding preexisting atherosclerotic lesions with bacteremia
HIV-infected patients
people who have recently traveled internationally with body temperatures ≥101.3°F (38.5°C) and/or signs of sepsis
patients with vascular abnormalities, such as prosthetic valves or grafts
patients with prosthetic joints
immunocompromised people with severe illness and bloody diarrhea.
Antibiotics recommended to treat adults include a fluoroquinolone (e.g., ciprofloxacin) or azithromycin, depending on the local susceptibility patterns and travel history.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
[67]Riddle MS, DuPont HL, Connor BA. ACG Clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 May;111(5):602-22.
http://www.ncbi.nlm.nih.gov/pubmed/27068718?tool=bestpractice.com
Resistance to fluoroquinolones has been described in some locations; therefore patients without an appropriate clinical response to a fluoroquinolone should be considered for alternative antibiotic therapy based on susceptibility results.[97]Nakaya H, Yasuhara A, Yoshimura K, et al. Life-threatening infantile diarrhea from fluoroquinolone-resistant Salmonella enterica typhimurium with mutations in both gyrA and parC. Emerg Infect Dis. 2003 Feb;9(2):255-7.
http://www.ncbi.nlm.nih.gov/pubmed/12604000?tool=bestpractice.com
[98]Whichard JM, Gay K, Stevenson JE, et al. Human Salmonella and concurrent decreased susceptibility to quinolones and extended-spectrum cephalosporins. Emerg Infect Dis. 2007 Nov;13(11):1681-8.
http://www.ncbi.nlm.nih.gov/pubmed/18217551?tool=bestpractice.com
In 2012, the Clinical Laboratory Standards Institute (CLSI) adjusted the fluoroquinolone breakpoints for Salmonella in recognition of reports of suboptimal treatment responses in infections caused by strains with modest reductions in in vitro susceptibility.[99]Humphries RM, Fang FC, Aarestrup FM, et al. In vitro susceptibility testing of fluoroquinolone activity against Salmonella: recent changes to CLSI standards. Clin Infect Dis. 2012 Oct;55(8):1107-13.
https://academic.oup.com/cid/article/55/8/1107/340237
http://www.ncbi.nlm.nih.gov/pubmed/22752519?tool=bestpractice.com
A UK study suggested that foreign travel is associated with having a fluoroquinolone-resistant strain.[100]Al-Mashhadani M, Hewson R, Vivancos R, et al. Foreign travel and decreased ciprofloxacin susceptibility in Salmonella enterica infections. Emerg Infect Dis. 2011 Jan;17(1):123-5.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204643/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/21192872?tool=bestpractice.com
Fluoroquinolones are associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[101]Food and Drug Administration. FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. Aug 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-updates-warnings-oral-and-injectable-fluoroquinolone-antibiotics
[102]European Medicines Agency. Quinolone- and fluoroquinolone-containing medicinal products. November 2018 [internet publication].
https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products
The Food and Drug Administration has also issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[103]US Food & Drug Administraton. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. 10 July 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-reinforces-safety-information-about-serious-low-blood-sugar-levels-and-mental-health-side
[104]Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. December 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics
Alternative antibiotic therapy
A third-generation cephalosporin or azithromycin is recommended specifically for infants <3 months of age, depending on local susceptibility patterns and travel history.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Treatment of children is complicated, given both increasing resistance among Salmonella isolates and potential toxicity of fluoroquinolone antibiotics in pediatric patients.[98]Whichard JM, Gay K, Stevenson JE, et al. Human Salmonella and concurrent decreased susceptibility to quinolones and extended-spectrum cephalosporins. Emerg Infect Dis. 2007 Nov;13(11):1681-8.
http://www.ncbi.nlm.nih.gov/pubmed/18217551?tool=bestpractice.com
[105]Sjölund-Karlsson M, Rickert R, Matar C, et al. Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States. Foodborne Pathog Dis. 2010 Dec;7(12):1503-9.
http://www.ncbi.nlm.nih.gov/pubmed/20704496?tool=bestpractice.com
[106]Wadula J, von Gottberg A, Kilner D, et al. Nosocomial outbreak of extended-spectrum beta-lactamase-producing Salmonella isangi in pediatric wards. Pediatr Infect Dis J. 2006 Sep;25(9):843-4.
http://www.ncbi.nlm.nih.gov/pubmed/16940846?tool=bestpractice.com
[107]Usha G, Chunderika M, Prashini M, et al. Characterization of extended-spectrum beta-lactamases in Salmonella spp. at a tertiary hospital in Durban, South Africa. Diagn Microbiol Infect Dis. 2008 Sep;62(1):86-91.
http://www.ncbi.nlm.nih.gov/pubmed/18513912?tool=bestpractice.com
[108]Lunguya O, Lejon V, Phoba MF, et al. Antimicrobial resistance in invasive non-typhoid Salmonella from the Democratic Republic of the Congo: emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases. PLoS Negl Trop Dis. 2013 Mar;7(3):e2103.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597487
http://www.ncbi.nlm.nih.gov/pubmed/23516651?tool=bestpractice.com
A study of ciprofloxacin for the treatment of typhoid fever suggested that it may be used safely for Salmonella infections.[109]White NJ, Dung NM, Vinh H, et al. Fluoroquinolone antibiotics in children with multidrug resistant typhoid. Lancet. 1996 Aug 24;348(9026):547.
http://www.ncbi.nlm.nih.gov/pubmed/8757168?tool=bestpractice.com
Ciprofloxacin is generally not recommended in the pediatric population due to the potential risk of arthropathy, but there are reports of successful and safe use in this patient population for certain indications.[110]Adefurin A, Sammons H, Jacqz-Aigrain, et al. Ciprofloxacin safety in paediatrics: a systematic review. Arch Dis Child. 2011 Sep;96(9):874-80.
http://adc.bmj.com/content/96/9/874.long
http://www.ncbi.nlm.nih.gov/pubmed/21785119?tool=bestpractice.com
Studies (both in vitro and in vivo) have suggested that carbapenems and tigecycline may be active against nontyphoidal strains, but further research is needed before these are recommended in clinical practice.[111]Tang HJ, Ko WC, Chen CC, et al. In vitro and in vivo intracellular killing effects of tigecycline against clinical nontyphoid Salmonella isolates using ceftriaxone as a comparator. Antimicrob Agents Chemother. 2011 Jun;55(6):2755-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101431/pdf/zac2755.pdf
http://www.ncbi.nlm.nih.gov/pubmed/21402846?tool=bestpractice.com
[112]Tang HJ, Chen CC, Zhang CC, et al. Use of Carbapenems against clinical, nontyphoid Salmonella isolates: results from in vitro and in vivo animal studies. Antimicrob Agents Chemother. 2012 Jun;56(6):2916-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370812/pdf/zac2916.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22470122?tool=bestpractice.com
Clinical experience with tigecycline in Salmonella infections is very limited.[113]Tang HJ, Chen CC, Ko WC. Tigecycline therapy for bacteremia and aortitis caused by Salmonella enterica serotype choleraesuis: a case report. J Microbiol Immunol Infect. 2016 Feb;49(1):131-3.
https://www.sciencedirect.com/science/article/pii/S168411821200028X?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/22503800?tool=bestpractice.com
Clinical experience with carbapenems is also limited, and failures with meropenem have been reported.[114]Kleine CE, Schlabe S, Hischebeth GTR, et al. Successful therapy of a multidrug-resistant extended-spectrum β-lactamase-producing and fluoroquinolone-resistant Salmonella enterica subspecies enterica serovar typhi infection using combination therapy of meropenem and fosfomycin. Clin Infect Dis. 2017 Oct 30;65(10):1754-6.
https://academic.oup.com/cid/article/65/10/1754/4037508
http://www.ncbi.nlm.nih.gov/pubmed/29020162?tool=bestpractice.com
[115]Blumentrath CG, Müller G, Teichmann D, et al. Relapse of typhoid fever following delayed response to meropenem: a case report and review of previously published cases indicating limited clinical efficacy of meropenem for the treatment of typhoid fever. Ger Med Sci. 2019 Jan 7;17:Doc01.
https://www.egms.de/static/en/journals/gms/2019-17/000267.shtml
http://www.ncbi.nlm.nih.gov/pubmed/30837820?tool=bestpractice.com
Ertapenem may be preferred due to its ability to kill intracellular Salmonella.[112]Tang HJ, Chen CC, Zhang CC, et al. Use of Carbapenems against clinical, nontyphoid Salmonella isolates: results from in vitro and in vivo animal studies. Antimicrob Agents Chemother. 2012 Jun;56(6):2916-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370812/pdf/zac2916.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22470122?tool=bestpractice.com
Treatment failure
Patients not responding to antibiotic therapy should be assessed for the possibility of a drug-resistant Salmonella strain.
Resistance has been associated with a greater risk of complicated disease and mortality.[59]Talbot EA, Gagnon ER, Greenblatt J. Common ground for the control of multi-drug resistant Salmonella in ground beef. Clin Infect Dis. 2006 May 15;42(10):1455-62.
https://cid.oxfordjournals.org/content/42/10/1455.full.pdf+html
http://www.ncbi.nlm.nih.gov/pubmed/16619160?tool=bestpractice.com
Antimicrobial susceptibility testing should therefore be performed on every clinical isolate. Antimicrobial therapy should be altered during clinical failures and be based on susceptibility results.[65]Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017 Nov 29;65(12):1963-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848254
http://www.ncbi.nlm.nih.gov/pubmed/29194529?tool=bestpractice.com
Chronic carrier state
A chronic carrier state is defined as positive stool or urine culture for Salmonella at 12 months or more following the acute illness.[31]Corrado ML, DuPont HL, Cooperstock M, et al. Evaluation of new anti-infective drugs for the treatment of chronic carriage of Salmonella. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis. 1992 Nov;15 Suppl 1:S259-62.
http://www.ncbi.nlm.nih.gov/pubmed/1477240?tool=bestpractice.com
Chronic carriage of nontyphoidal Salmonella occurs in 0.5% of cases (compared with 3% of those with S Typhi).[32]Crum-Cianflone NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep. 2008 Aug;10(4):424-31.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753534
http://www.ncbi.nlm.nih.gov/pubmed/18627657?tool=bestpractice.com
Certain groups are at higher risk for chronic carriage, including infants, women, patients with gallstones or kidney stones, and patients coinfected with Schistosoma haematobium.
Prolonged carriage may be treated with long-term antibiotic therapy, and surgery should be considered in the case of concurrent gallstones.[32]Crum-Cianflone NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep. 2008 Aug;10(4):424-31.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753534
http://www.ncbi.nlm.nih.gov/pubmed/18627657?tool=bestpractice.com
Antibiotics
Long-term rather than short-term antibiotics should be used. Despite appropriate antibiotic use, therapy may eradicate carriage in only 80% of cases.[116]Freerksen E, Rosenfield M, Freerksen R, et al. Treatment of chronic Salmonella carriers. Chemotherapy. 1977;23(3):192-210.
http://www.ncbi.nlm.nih.gov/pubmed/319963?tool=bestpractice.com
The type of antibiotic therapy is similar to that used for S Typhi: amoxicillin, trimethoprim/sulfamethoxazole, or ciprofloxacin.[44]Pegues DA, Miller SI. Salmonella species, including Salmonella Typhi. In: Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010:2887-903.[116]Freerksen E, Rosenfield M, Freerksen R, et al. Treatment of chronic Salmonella carriers. Chemotherapy. 1977;23(3):192-210.
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[117]Ferreccio C, Morris JG Jr, Valdivieso C, et al. Efficacy of ciprofloxacin in the treatment of chronic typhoid carriers. J Infect Dis. 1988 Jun;157(6):1235-9.
http://www.ncbi.nlm.nih.gov/pubmed/3373023?tool=bestpractice.com
[118]DuPont HL. Quinolones in Salmonella typhi infection. Drugs. 1993;45 Suppl 3:119-24.
http://www.ncbi.nlm.nih.gov/pubmed/7689442?tool=bestpractice.com
The latter 2 antibiotics have superior penetration capabilities and may be the preferred agents.[119]Diridl G, Pichler H, Wolf D. Treatment of chronic salmonella carriers with ciprofloxacin. Eur J Clin Microbiol. 1986 Apr;5(2):260-1.
http://www.ncbi.nlm.nih.gov/pubmed/2941298?tool=bestpractice.com
[120]Clementi KJ. Trimethoprim-sulfamethoxazole in the treatment of carriers of Salmonella. J Infect Dis. 1973 Nov;128:Suppl:738-42.
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Many providers opt for a fluoroquinolone given the possibility of resistance to other agents and the shorter treatment duration.[121]Rodriguez-Noriega E, Andrade-Villanueva J, Amaya-Tapia G. Quinolones in the treatment of Salmonella carriers. Rev Infect Dis. Jul-Aug 1989;11 Suppl 5:S1179-87.
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The choice of the antibiotic should ultimately be based on sensitivity testing of the colonizing isolate.
Praziquantel
Patients with coexisting S haematobium infection should be treated with praziquantel before antibiotic therapy.[32]Crum-Cianflone NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep. 2008 Aug;10(4):424-31.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753534
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Surgery
Carriage of Salmonella may persist in the setting of concurrent gallstones.[32]Crum-Cianflone NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep. 2008 Aug;10(4):424-31.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753534
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Cholecystectomy is recommended, especially if chronic carrier state persists despite antibiotic therapy.[122]Dinbar A, Altmann G, Tulcinsky DB. The treatment of chronic biliary salmonella carriers. Am J Med. 1969 Aug;47(2):236-42.
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