Index
It is a safe and widely used antibiotic.
Ceftriaxone is used to treat a wide variety of bacterial infections . It belongs to a class of drugs known as cephalosporin antibiotics. It works by stopping the growth of bacteria.
The use of ceftriaxone is not recommended in newborns with high levels of bilirubin in the blood or in premature babies due to the increased risk of side effects. Ask your doctor or pharmacist for details.
Ceftriaxone can also be used before dental procedures in people with certain heart conditions (such as artificial heart valves) to help prevent a serious infection of the heart (bacterial endocarditis).
Ceftriaxone is a third generation cephalosporin, a family of β-lactam ring that contains small molecules including penicillins, and shows bactericidal activity against a number of gram-positive and gram-negative bacteria.
Ceftriaxone inhibits bacterial cell wall synthesis by binding to proteins that bind to penicillin, eventually resulting in bacterial lysis, and has been approved by the Food and Drug Administration (FDA) for use. as a safe, broad-spectrum antibiotic for over 30 years.
Peak ceftriaxone concentrations in serum are obtained 2 to 3 hours after intramuscular administration in humans. It is eliminated unchanged in the urine, and in the feces through the bile, with a half-life of 6-9 hours.
After parenteral administration, the drug is widely distributed throughout the body including the brain, especially when the meninges are inflamed, and thus forms a mainstay of empirical therapy for the disease.
Cefotaxime, ceftriaxone, and cefoperazone have good in vitro activity against S. typhi and other salmonellae.
Although they have acceptable efficacy in the treatment of typhoid fever, they are less effective with a longer clinical response time than fluoroquinolones against susceptible strains. Only intravenous formulations are available.
Cefotaxime is given 1 gram three times a day (in children: 200 mg / kg a day in divided doses) for 14 days. Ceftriaxone, 2 grams / daily in adults, has the advantage of requiring only one daily dose.
The third-generation oral cephalosporins, cefixime, should not be used in typhoid or paratyphoid fever. Note that second-generation cephalosporins do not penetrate well intracellularly, are associated with a high recurrence rate, and are not appropriate for the treatment of typhoid fever either orally or intravenously.
Cefotaxime, ceftriaxone, and cefoperazone have good in vitro activity against S. typhi and other salmonellae.
Although they have acceptable efficacy in the treatment of typhoid fever, they are less effective with a longer clinical response time than fluoroquinolones against susceptible strains. Only intravenous formulations are available.
Cefotaxime is given 1 gram three times a day (in children: 200 mg / kg a day in divided doses) for 14 days. Ceftriaxone, 2 grams / daily in adults, has the advantage of requiring only one daily dose. The third-generation oral cephalosporins, cefixime, should not be used in typhoid or paratyphoid fever.
Note that second-generation cephalosporins do not penetrate well intracellularly, are associated with a high recurrence rate, and are not appropriate for the treatment of typhoid fever either orally or intravenously.
Side effects
Biliary tract
Ceftriaxone can cause bile sludge and cholelithiasis in children. Reports related to other cephalosporins, including cefotaxime, have been rare. Cefotaxime has already been implicated.
A 2-week-old girl developed fever, bloating, jaundice, and pale stools. Electrolyte and aspartate transaminase and alkaline phosphatase activities were normal, but gamma glutamyltransferase and bilirubin activity increased.
Ultrasound showed ascites, but the liver was normal and there was no intrahepatic or extrahepatic ductal ectasia or bile sludge. Aeromonas hydrophila and Klebsiella pneumoniae grew in blood cultures.
They gave him ampicillin and cefotaxime for 10 days and the jaundice disappeared. However, a week later, the jaundice and pale stools reappeared. There was mild hepatomegaly, and bilirubin and gamma-glutamyltransferase were elevated.
Ultrasound showed cholestasis, dilated intrahepatic and extrahepatic bile ducts with a lot of mud, and a large ball of mud in the gallbladder. They gave him ursodeoxycholic acid and his stools became pigmented after 2 days.
Subsequent ultrasound showed a reduction of sludge in the biliary tree and gallbladder. At 6 months there was a complete resolution.
Urinary tract
Shortly after the introduction of ceftriaxone it became clear that it can cause pseudolithiasis or gallbladder sludge in many patients, especially children, and reports continue to appear.
One patient had biliary pseudolithiasis and kidney stones . Since then, at least seven other cases have been reported, six in children and one in adults.
All had some form of kidney damage with either anuria, an increase in serum creatinine, or a dilated collection system on imaging.
One required extracorporeal shock wave lithotripsy and one required nephrostomy. Now another case has been reported.
A 14-year-old boy with severe sinusitis complicated by an epidural abscess was administered intravenous ceftriaxone 4 grams / day and metronidazole. On day 8 he developed abdominal cramps and vomiting. His serum creatinine had increased from 70 to 420 μmol / L.
His urine output dropped and he had anuria for 24 hours. A CT scan of the abdomen showed high-density material in her gallbladder and in the collecting system of both kidneys and through both ureters.
Ceftriaxone was withdrawn. On day 9, bilateral urethral stents were placed at the time of cystoscopy and protein toothpaste-like material was found in both ureters.
After another 3 weeks, a CT scan showed complete resolution of the biliary pseudolithiasis and material in the ureters, and serum creatinine had returned to 60 μmol / L.
Taking all the reports together, it is easy to accept the authors’ suggestion that nephrolithiasis secondary to ceftriaxone is generally more severe than biliary complications, as intervention is often necessary to relieve renal obstruction.
In patients receiving ceftriaxone, any deficiency in kidney function should be taken as a warning sign.
Cardiovascular Cardiac Asystole
Cardiovascular asystole has been attributed to ceftriaxone.
A 55-year-old man was given 1 gram intravenous ceftriaxone for a urinary tract infection and 1 minute after the infusion, he had cardiac arrest requiring cardiopulmonary resuscitation and tracheal intubation.
He was discharged after a 10-day hospital stay with no further sequelae. Although there have been some cases of anaphylaxis to ceftriaxone after the first exposure, as in this case, this is the first known report of asystole.
Hematologic hemolytic anemia
Autoimmune hematologic hemolytic anemia has been attributed to ceftriaxone. An 11-year-old girl developed autoimmune hemolytic anemia and kidney failure requiring dialysis while taking ceftriaxone for Lyme arthritis.
After 1 week she began to have fever, chills, and worsening knee pain after ceftriaxone infusions, and 1 week later she developed vomiting, abdominal pain, and anorexia.
His hemoglobin was 6.9 g / dl, erythrocytes (which were IgG-negative and complement component 3-positive) were normocytic without schistocytes, blood urea nitrogen was 18 mmol / l (50 mg / dl), creatinine 415 μmol / l (4.7 mg / dl), and there was proteinuria.
A kidney biopsy showed pigment-induced acute tubular necrosis with hemoglobin-like casts, consistent with intravascular hemolysis. Ceftriaxone was withdrawal.
She was treated with hemodialysis, red blood cells and glucocorticoids and after 2 weeks her kidney function and anemia had improved. Doxycycline for 28 days resolved the knee arthritis.
Anticeftriaxone antibodies may have been responsible for the hemolysis associated with ceftriaxone in two other cases.
A 2-year-old boy with sickle cell anemia received ceftriaxone for an acute chest syndrome and after the third infusion he became insensitive and hypotensive (BP 69/30 mmHg) and required endotracheal intubation.
He was acidotic (venous pH 6.9) and anemic (hematocrit <0.10), with gross hematuria, requiring 1 unit of compressed red blood cells. He made a full recovery after 3 days.
A 10-year-old girl with sickle cell anemia received ceftriaxone for suspected bacteremia. Within 20 minutes he developed a tachycardia (160 / minute), was incontinent in his bowel and bladder, and developed acute changes in his mental state.
His hemoglobin concentration was 4 g / l. After administration of two units of packed red blood cells, his mental status and tachycardia improved.
The chest radiograph showed a new infiltrate in the right lower lobe and pleural effusion, and required hemodialysis for acute renal failure with hemoglobinuria.
She had evidence of disseminated intravascular coagulation and was intubated to worsen hypoxic respiratory failure. His condition decreased despite plasmapheresis. Support was withdrawn and he died on the third day.
Both patients had received ceftriaxone in the previous two weeks, and anti-ceftriaxone antibodies were found in both. The proposed mechanism was sensitization by repeated exposure to ceftriaxone.
Ceftriaxone binds to red blood cell membranes and can cause the formation of antibodies that recognize and attack drug-membrane complexes and activate complement, resulting in hemolysis.
From November 1987 to December 2010, the American Red Cross research laboratory evaluated samples from 79 patients suspected of having drug-induced hemolytic anemia caused by ceftriaxone.
There were antibodies against ceftriaxone in sera from 25 of the 79 patients (32%). The authors reported that in the United States, ceftriaxone appears to be the second most common drug for causing drug-induced hemolytic anemia.
Mucosal infections in adolescents and adults
A single dose of ceftriaxone 250 mg cures> 99% of uncomplicated anorectal and urogenital infections and 99% of pharyngeal infections. Gonococci are eradicated from the urine, urethra, and semen of symptomatic men within 24 hours of therapy.
Azithromycin administered orally as a single dose, or doxycycline orally twice daily for 7 days, should also be administered routinely to treat C. trachomatis.
If ceftriaxone is not available, oral cefixime or other single-dose injectable cephalosporin regimens (intramuscular ceftizoxime 500 mg, intramuscular 2 g cefoxitin administered with oral probenecid 1 g, or intramuscular cefotaxime 500 mg) may be used to treat infection. uncomplicated anorectal and urogenital.
Although oral therapy avoids the cost and hassle of injections and decreases the risk of accidental needle stick injuries for medical personnel who may be treating a population at high risk for HIV infection.
The recommended oral dose of 400 mg of cefixime does not provide as high or as sustained a bactericidal level as that provided by the 250 mg intramuscular dose of ceftriaxone.
In published clinical trials, cefixime 400 mg orally cured 98% of uncomplicated anorectal and urogenital infections, but only 92% of pharyngeal infections.
None of the other injectable cephalosporins offers any advantage over ceftriaxone for urogenital infection, and efficacy for pharyngeal infection is less certain.
Gonococcal conjunctivitis should be treated with a single dose of 1 gram ceftriaxone intramuscularly; saline flush (one time) should be considered. Presumptive treatment should also be given for concurrent C. trachomatis infection.
Hypersensitivity
A 7-year-old boy received ceftriaxone for a respiratory infection. Shortly after an outpatient injection, he developed a fever, a maculopapular rash, ocular congestion, and tachypnea.
Measles was in the differential but was ruled out and ceftriaxone was then continued. The rash got worse and he developed itching. He started taking corticosteroids and the antibiotics were changed to azithromycin.
Before receiving ceftriaxone, the patient did not react to a test dose or skin test and did not have eosinophilia during treatment. However, reactions may be delayed and therefore a test dose may not show an immediate reaction.
Similarly, skin tests are not highly sensitive. Patients should always be closely monitored for reactions while on any antimicrobial.
Acute generalized exanthematous pustulosis
A 70-year-old woman was given intravenous ceftriaxone 1 g / day for acute pyelonephritis and after 4 days she became confused, hypotensive (90/50 mmHg), tachycardic (120 / minute), and febrile (38.9 ° C).
He also developed erythematous pustules on his abdomen, back, legs, and oral mucosa. He had had a drug rash six months earlier. There was a leukocytosis (35 × 109 / L, with 94% neutrophils and 2.9% eosinophils).
She was switched to meropenem and teicoplanin and the lesions greatly improved within 48 hours. Blood cultures and pustule cultures were sterile. A biopsy showed neutrophils and eosinophils.
The authors attributed the generalized acute exanthematic pustulosis (SGAP) to ceftriaxone, and it should be noted that it did not have a reaction similar to meropenem and improved without glucocorticoids.
Drug interactions
Ceftriaxone has been attributed an interaction with warfarin. A 67-year-old American Indian woman had a large increase in the international normalized ratio after receiving warfarin and ceftriaxone.
She had been taking warfarin for a prior mitral valve replacement, and 4 days after receiving a single 1g intramuscular dose of ceftriaxone her international normalized ratio increased to 11 from 3.0 the week before.
The next dose of warfarin was withheld and vitamin K 5 mg was administered orally. The next day, his international normalized index was 3.4.
His international normalized ratio was stable for the next 4 weeks, but then he received another intramuscular injection of ceftriaxone followed by cefuroxime and phenazopyridine for a urinary tract infection, and 4 days later his international normalized ratio was 17.
She did not report changes in diet or other medications at any time. Antibiotics that have an N-methylthiotetrazine side chain are believed to increase the international normalized ratio, but ceftriaxone does not have this side chain.
The authors suggested that potential mechanisms for this interaction included the displacement of warfarin from albumin and the hypoprothrombotic effects of the sulfhydryl group of ceftriaxone.
An additional partial mechanism for the effect of ceftriaxone on clotting could be the fact that vitamin K is synthesized by gut bacteria, and disrupting the gut microbiome could reduce the amount of circulating vitamin K, although there is also a considerable contribution of the diet.
A 5-month-old boy received ceftriaxone (dose and duration unknown) for a urinary tract infection and developed diarrhea and bleeding, even though he was receiving vitamin K supplements and breastfeeding at home.
Prothrombin time and activated partial thromboplastin time (APTT) were elevated.
Ceftriaxone was withdrawn and vitamin K 3 mg was administered intravenously. Prothrombin time and activated partial thromboplastin time normalized 24 hours later. The authors concluded that this effect suggested a vitamin K deficiency secondary to ceftriaxone.
Standard therapies
Treatment measures should include avoiding sexual intercourse until the course of therapy is completed. If avoidance is not followed, condoms should be used until the condition is cured. All sexual partners need evaluation and treatment.
The standard treatment for gonococcal urethritis is an intramuscular dose of 125 mg of ceftriaxone. Alternative therapies for gonococcal urethritis include ciprofloxacin, ofloxacin, cefixime, and spectinomycin. Each is administered only once in the appropriate dose.
All patients receiving alternative therapy should be treated with 200 mg doxycycline for two days to treat coexisting chlamydial infection.
The standard treatment for noonococcal urethritis is a dose of 1g of oral azithromycin or 100 mg of oral doxycycline on offer for seven days. Alternative therapies for the noonococcal form include erythromycin or ofloxacin.
Management
Ceftriaxone (2 grams once a day intravenously) or penicillin (3-4 mU intravenously every 3-4 hours) for 2-4 weeks treats encephalitis.
Examine cerebrospinal fluid towards the end of the treatment course for 2 to 4 weeks to assess the need for continued treatment and again 6 months after the conclusion of therapy.
Intrathecal antibody production can persist for years after successful treatment, and alone does not indicate active disease. However, patients in whom cerebrospinal fluid pleocytosis fails to resolve within 6 months should be removed.
Treatment of peripheral or cranial nerve involvement without cerebrospinal fluid abnormalities is done with oral agents, either doxycycline, 100 mg twice daily for 14-21 days, or amoxicillin, 500 mg every 8 hours for 10-21 days. days.
An effective vaccine against Lyme disease is available and can be used for children living in endemic areas.
A subcommittee of the American Academy of Neurology concluded in 2007 that some evidence supports the use of penicillin, ceftriaxone, cefotaxime, and doxycycline in both adults and children with neuroborreliosis.
