Modalitas pilihan antibiotik pada demam tifoid bergantung pada sensitivitas organisme terhadap antibiotik. Namun saat ini terapi demam tifoid menjadi lebih sulit karena mulai berkembangnya strain Salmonella typhi yang resisten obat terutama di India dan negara Asia tenggara.
Dulu pilihan antibiotik utama sebagai terapi demam tifoid adalah chloramphenicol , ampisilin dan co-trimoxazole, namun saat ini telah banyak ditemukan strain MDR Salmonella typhi yang resistan terhadap obat-obatan tersebut. Saat ini antibiotik yang paling sering digunakan dan terbukti efektif sebagai pilihan terapi utama pada demam tifoid adalah golongan fluorokuinolon, kecuali terbukti strain yang dihadapi resistan terhadap fluorokuinolon.
Antibiotik fluorokuinolon yang paling efektif adalah c iprofloxacin dengan dosis mg per oral dua kali sehari selama hari. Selain fluorokuinolon, a moxicillin mg peroral 4 kali sehari selama 2 minggu, trimethoprim-sulfamethoxazole mg dua kali sehari selama 2 minggu dan chloramphenicol mg 4 kali sehari selama minggu dapat menjadi alternatif terapi pada pasien dewasa yang masih sensitif terhadap obat-obatan tersebut.
Pada pasien yang diketahui memiliki Multidrug-resistant MDR dan extremely drug-resistant XDR strains dari hasil kultur, pilihan terapi antibiotik utama pada kasus MDR adalah sefalosporin generasi ketiga seperti ceftriaxone, cefotaxime , dan cefixime 2g sekali sehari selama 2 minggu dan azithromycin. Selain itu fluorokuinolon seperti ciprofloxacin dapat menjadi alternatif terapi. Pasien dengan infeksi salmonella resistan obat strain XDR yang diketahui resistan terhadap sefalosforin generasi ketiga, pada kasus berat atau dengan komplikasi, antibiotik yang menjadi pilihan utama adalah golongan carbapenem seperti meropenem.
Bila pasien belum membaik dengan pemberian carbapenem, antibiotik dapat diberikan dalam bentuk kombinasi dua obat dengan azitromisin. Selain pemberian antibiotik, terapi simptomatik dan terapi yang bersifat suportif juga sangat penting bagi kesembuhan pasien demam tifoid.
Signs of metastatic complications appear. Dry cough due to pneumonia can also be present as well as neck rigidity due to meningitis, or rarely, chest pain due to myocarditis and pericarditis. Patients of endemic areas like India and Africa have more frequent neurologic manifestations like delirium, psychosis, insomnia, confusion, apathy, and in extremely rare cases, parkinsonism.
Other unusual presentations are severe epigastric pain radiating to the back due to pancreatitis, bone pain because of osteomyelitis, and abscesses, which can occur anywhere in the body. The approach to typhoid patients should be clinical.
Patients residing in areas with poor sanitation or impure drinking water or history of travel from endemic areas presenting with febrile illness for more than three days along with gastrointestinal manifestations pain, constipation, or diarrhea are highly suspicious.
Diagnosis in the first week is difficult, but a variety of laboratory studies assist in making the diagnosis. Blood culture: Blood culture remains the primary mechanism of confirmation of a typhoid fever diagnosis. It is widely available and the most commonly performed test, as it is not expensive or technically difficult. The efficacy of the blood culture is increased when high volume samples are taken.
Blood cultures done during secondary bacteremia i. Stool culture: Stool culture is less effective in the bacteremic phase of the disease. Stool culture is diagnostic in the second and third weeks. Chronic carriers intermittently pass pathogens in the fecal matter for a long time so, several samples should be taken. Additional metabolite biomarkers are under investigation. Bone marrow: Bone marrow culture is the gold standard for typhoid diagnosis. It is more sensitive than blood cultures due to the larger number of micro-organisms present in the bone marrow.
Widal test: The Widal test is a serological test for enteric fever, which detects antibodies against O surface and H flagellar antigens. An antibody titer of greater than and greater than for anti-H antigen and anti-O antigen respectively are considered as cut off levels to predict recent infection of typhoid fever in an endemic area. When the convalescent titer is four times greater than the acute titer, the study is considered positive.
Endemic areas will require higher titers to make the diagnosis and are still limited in that they may represent prior infection. The Widal test is not reliable due to its common false-negative and false-positive results, poor agreement with blood culture, and poor performance. This testing is also cost-prohibitive in many low resource settings. Miscellaneous: Urine cultures and duodenal content culture via string capsule are not regularly performed, but may identify Salmonella typhi.
Liver function testing may show a pattern of viral hepatitis, and though nonspecific C-reactive protein may be elevated. When obtained, cerebrospinal fluid studies may reveal mild pleocytosis less than 35cells , though most are unremarkable. Antibiotic therapy is the mainstay of treatment. The treatment has been complicated by multidrug resistance strains developed in many endemic areas, especially in India and south-east Asia.
The modality of treatment depends upon the severity of the disease, duration, dissemination, and complications. Antibiotic therapy : Prompt administration of the relevant antibiotic therapy protects from severe complications of typhoid fever.
Initial drug therapy of choice depends upon the susceptibility of the strains. In most areas, fluoroquinolones are the most effective drug of choice.
In severe conditions that necessitate prompt treatment, fluoroquinolones can be administered empirically on clinical suspicion before the result of the diagnostic culture test.
Ciprofloxacin mg orally twice daily for days is the most effective fluoroquinolone. Amoxicillin mg orally 4 times daily for about 2 weeks , trimethoprim-sulfamethoxazole mg twice daily for 2 weeks , and outside of the United States, chloramphenicol mg 4 times daily for weeks are all alternative treatments for adults in fully susceptible cases, but they are increasingly met with resistance. Uncomplicated cases can be managed at home with oral antibiotics and antipyretics. Patients with significant complications, including vomiting, diarrhea, and abdominal distension, should be hospitalized.
Additional supportive therapy and parenteral antibiotics such as third-generation cephalosporins guided by culture sensitivities should be continued until 5 days after recovery. The intracellular nature of bacteria safeguards against the extracellular antibiotics. The addition of azithromycin and cefixime lowers the rate of failure and reduces the duration of hospitalization.
Vaccination prophylaxis: Typhoid burden has been reduced since the invention of Salmonella typhi vaccination. The vaccine is recommended for those traveling to areas with risk of exposure. In the United States, there are two types of licensed, unconjugated vaccines. It should be given 2 weeks or more before travel, and a booster should be provided every two years.
A live attenuated oral vaccine Ty21a strain of serotype Typhi enhances immunity by stimulating the production of endogenous antibodies. It is indicated for those over 6 years old traveling to endemic areas or coming into close contact with chronic carriers or infected patients. It is done with a regimen of 4 capsules taken every other day with strict guidelines regarding the temperature of liquids used to ingest the capsule and ingestion on an empty stomach.
It should be completed at least 1 week before exposure, and a booster is indicated every 5 years. As it is a live vaccine, the oral vaccine is not appropriate for pregnant patients or those with immunocompromised status. Though not licensed for this indication, the oral Ty21a vaccine may offer some protection against Salmonella paratyphi B. Miscellaneous treatment: Symptomatic and supportive care is essential. Maintaining adequate hydration during diarrhea, as well as appropriate ventilation and oxygenation for pulmonary complications, should be provided along with analgesics and antipyretics as supportive care for metastatic complications.
Corticosteroids have been suggested for severe cases with encephalitis. Surgery: When gallstones accompany a carrier state, cholecystectomy can be curative.
Prevention through sanitation : Epidemiological data reveals that typhoid is more prevalent in low and middle-income countries, in areas with poor drinking water, and lack of sanitation. Safe drinking water, sanitation, and avoidance of overcrowding contribute remarkably to the reduction in the number of cases.
Typhoid fever has non-specific manifestations. It may resemble multiple infectious diseases with similar clinical presentations. So a wide differential diagnosis must be considered. Diseases with symptoms including diarrhea, dysentery, abdominal distension, fever, splenomegaly, and shock, should trigger consideration in the correct clinical context. Dengue fever: Dengue is a hemorrhagic fever with non-specific symptoms like fever, headache, myalgia, shock, which may be confused with typhoid fever.
Malaria: Malaria has non-specific clinical features such as fever, headache, myalgia, diarrhea, nausea, vomiting, and anemia. The involvement of multiple organs may make it difficult to differentiate it from typhoid clinically, but unlike typhoid, jaundice is common in malaria.
Laboratory testing should rule out malaria in cases of fever in or after travel to endemic areas. Amebiasis: Amebiasis is caused by Entamoeba histolytica ingested in water or uncooked food.
Etiological factors such as impure drinking water and lack of sanitation should increase suspicion for amebiasis, similar to typhoid fever. Abdominal manifestations of amebiasis such as dysentery and liver abscess are common and may be difficult to distinguish from typhoid fever on a clinical basis alone.
Leptospirosis: It is one of the most common zoonotic diseases. It presents with fever and jaundice as well as features like myalgias, headaches, and conjunctival suffusion. Organisms spread throughout the body after brief bacteremia. Less common symptoms include cough, diarrhea, meningitis, acute kidney injury, hemorrhages, and macular rash. Q fever: Q fever Coxiella burnetii infection is a worldwide disease that presents with non-specific symptoms of fever that may include headache, chills, maculopapular rash, pneumonia, and osteomyelitis.
Those in direct contact with cattle, sheep, and goats, such as ranchers and veterinarians, may be at higher risk of contracting Q fever. Tularemia: It is primarily a zoonotic disease prevalent in the northern hemisphere caused by a highly infectious gram-negative bacillus, Francisella tularensis. Though clinical features like hepatosplenomegaly, diarrhea vomiting, and pneumonia may be seen in typhoid fever, it is distinguished by skin ulceration with regional lymphadenopathy that is characteristic of tularemia.
Melioidosis is most likely to present in patients with chronic diseases such as diabetes, renal and liver disease, thalassemia, chronic lung disease, and cancer. Pneumonia is the most common feature though other common features include hepatosplenomegaly, diarrhea, and skin abscesses, and ulcerations. Giardiasis: Giardia is a small intestine infection by the parasite Giardia lamblia. It is characterized by diarrhea, malaise abdominal cramps, and weight loss, but fever is typically absent or not prominent.
It occurs worldwide and is common in the tropics transmitted by the waterborne, foodborne, and fecal-oral routes. Bacterial gastroenteritis: A variety of other bacteria cause gastroenteritis with common clinical manifestations. These include Staphylococcus, Bacillus cereus, Clostridium perfringens, Campylobacter, Escherichia coli, Clostridium difficile, Vibrio cholerae , and bacillary dysentery shigellosis. Rickettsial infection: Rickettsia fever is characterized by fever with a rash caused by rickettsiae, a gram-negative bacteria.
A skin lesion is prominent long with multi-systems manifestations. Toxoplasmosis: Toxoplasma gondii is an intracellular parasite causing toxoplasmosis. Enlarged spleen, lymphadenopathy, fever, malaise, sore throat, headache are the usual signs which may be self-limited or may even go unnoticed in immunocompetent individuals. Tuberculosis: Tuberculosis TB is a common disease in developing countries. Fever associated with night sweats and weight loss is the characteristic feature that often leads to the diagnosis.
Osteomyelitis in typhoid mimics Pott disease of the spine in TB. Brucellosis: Is an enzootic infection, similar to salmonella, in that it is also an intracellular organism that invades the reticuloendothelial system.
Brucellosis spreads to humans typically from eating raw and unpasteurized dairy products or through contact with infected animals. Brucellosis presents with undulating fevers, fatigue, and arthralgias.
Typhoid fever produces a major burden of mortality and morbidity worldwide, yet the problem is most prominent in south Asia and African countries. Now, mortality is low despite the high frequency of episodes with complications. As the primary site of Salmonella invasion is the gastrointestinal GI tract, gut complications are not surprising.
Gastrointestinal irritation results in diarrhea, and Payer patch hypertrophy causes obstruction of lumen and constipation. In severe cases, necrosis of Payer patches leads to ulceration and bleeding.
Sequelae of ulceration are eventually perforation of the terminal ileum. Diarrhea is usually non-bloody and loose.
However, large-volume watery stools, bloody stools, and symptoms of dysentery may occur. The temperature may drop falsely at a normal or subnormal level due to intestinal hemorrhage. While seeding can occur in nearly every organ system, it is uncommon to see complications outside of the GI tract. Widespread dissemination of bacteria causes multiorgan failure due to septicemia.
Intraabdominal infections lead to hepatic and splenic abscesses. Pneumonia is less common. Other pulmonary complications include lung abscesses, empyemas, and bronchopleural fistula formation, though the majority of cases occur in patients with lung cancer, glucocorticoid use, and other structural lung diseases.
Myocarditis and nephritis are the consequences of toxic phenomena. Patients with HLA-B27 antigens have a higher likelihood of reactive arthritis. Previously damaged organs, such as infarcts and aortic aneurysms, are the most frequent sites of the metastatic abscess. Complications are increased by prolonged duration of disease prior to hospitalization, long duration of hospitalization, techniques of antibiotic therapy, and immune compromise in debilitated patients with chronic diseases such as cancer, TB, and HIV.
Patients that are inadequately treated for typhoid continue to excrete bacteria and are considered chronic carriers. The bacteria in the chronic stage of typhoid colonizes the gallbladder, and if not treated, can be linked to gallbladder cancer. Travelers must continue to practice good hygiene and take care to avoid exposure. Additional typhoid Vi conjugate vaccines have been approved in India and may become available soon with better efficacy. Typhoid fever is a global public health problem.
Community health education about the mode of transmission, association with living standards, sanitation, prevention, signs and symptoms, the importance of early treatment, will not only reduce the prevalence of disease but also lower the healthcare workload. Counseling of patients about treatment modality and side effects is an important part of patient education. Despite public health efforts, typhoid fever is still a significant cause of morbidity and mortality worldwide.
Intersectoral coordination by other non-medical organizations and authorities in sanitation management, public healthcare awareness, and nutritional programs boost both the control and prevention of disease.
Travelers to endemic areas should be advised to seek vaccination and to practice good food hygiene. A concerning trend is the emergence of extremely drug-resistant Salmonella typhi. Clinicians must encourage early care to establish the diagnosis and the correct antibiotic treatment that focuses on the appropriate choice of drug with adequate dosing and treatment duration to ensure patients face minimal complications.
In times of outbreaks in endemic areas, coordinated public health campaigns swiftly administering vaccine and addressing sanitation concerns can decrease the burden of typhoid fever illness. Rose spots on the chest of a patient with typhoid fever due to the bacterium Salmonella typhi. Symptoms of typhoid fever may include a sustained fever as high as to F 39 to 40 C , weakness, stomach pains, headache, loss of appetite. In some cases, more Contributed by Charles N.
This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. National Center for Biotechnology Information , U. StatPearls [Internet]. Search term. Continuing Education Activity Typhoid fever is an enteric fever characterized by systemic illness along with abdominal pain and fever in a "step-ladder" pattern. Introduction Typhoid fever is also called enteric fever. Etiology The main causative agent of typhoid fever is Salmonella typhi and Salmonella paratyphi , both are members of the Enterobacteriaceae family.
Epidemiology While the United States reports only about culture-confirmed cases of typhoid fever and fewer than paratyphi A cases each year since , enteric fever remains an important cause of illness worldwide.
Pathophysiology The pathogenesis of typhoid fever depends upon a number of factors, including infectious species, virulence, host's immunity, and infectious dose. History and Physical Clinical presentations of both Salmonella typhoid and Salmonella paratyphoid are similar, though arthralgia is more common with typhoid.
Evaluation The approach to typhoid patients should be clinical. Differential Diagnosis Typhoid fever has non-specific manifestations. Prognosis Typhoid fever produces a major burden of mortality and morbidity worldwide, yet the problem is most prominent in south Asia and African countries.
Complications As the primary site of Salmonella invasion is the gastrointestinal GI tract, gut complications are not surprising. Enhancing Healthcare Team Outcomes Despite public health efforts, typhoid fever is still a significant cause of morbidity and mortality worldwide.
Review Questions Access free multiple choice questions on this topic. Comment on this article. Figure Rose spots on the chest of a patient with typhoid fever due to the bacterium Salmonella typhi. References 1.
Typhoid fever. N Engl J Med. A genomic overview of the population structure of Salmonella. PLoS Genet. PLoS One. Front Vet Sci. Pathogenesis of typhoid fever.
Indian J Pediatr. Chiodini J. Travel Med Infect Dis. An epidemic with remarkably few clinical signs and symptoms. Arch Intern Med. Chronic urinary carrier state due to Salmonella Typhi causing urinary tract infection in an immunocompetent healthy woman. Trop Doct. Epidemiology of typhoid carriers among blood donors and patients with biliary, gastrointestinal and other related diseases.
Microbiol Immunol.
0コメント