ro13-9904 and Hemolysis

Guidelines for the treatment of Lyme arthritis were published by the Infectious Diseases Society of America in 2006 and recommended oral doxycycline for initial therapy. We report here the case of a young girl treated with intravenous ceftriaxone who subsequently developed drug-induced autoimmune hemolytic anemia and renal failure. Her severe sequelae highlight the importance of antimicrobial stewardship. We review here the goals of antimicrobial stewardship and several strategies for achieving them. In addition, we briefly discuss the rare adverse drug event experienced by our patient.

Topics: Acute Kidney Injury; Anemia, Hemolytic; Anti-Bacterial Agents; Blood Chemical Analysis; Blood Transfusion; Ceftriaxone; Child; Combined Modality Therapy; Female; Follow-Up Studies; Hemolysis; Humans; Kidney Cortex Necrosis; Kidney Function Tests; Lyme Disease; Methylprednisolone; Recovery of Function; Renal Dialysis; Risk Assessment; Severity of Illness Index; Treatment Outcome

The capacity of antibiotics to modulate bacterial virulence has raised concerns over the appropriateness of antibiotic therapies, including when dosing strategies fall below sub-therapeutic levels. In this work, we investigated the ability of antibiotics to influence virulence in Escherichia coli isolated from urinary tract infection (UTI).. Out of 120 isolates, 32.5% carried pap, 21.7% carried hlyA, and 17.5% carried cnf. The predominant B2 phylogroup was significantly associated with the quinolone-resistant isolates. A significant association was seen between the presence of hlyA hemolysin and susceptibility to ceftriaxone and ciprofloxacin (P < 0.05). Sub-inhibitory concentrations of both antibiotics reduced the levels of hlyA expression and hemolysis in isolates treated with antibiotics compared to untreated isolates (P < 0.05). Growth rate assay showed that the decrease in hlyA expression was not an effect of decreased growth rate.. Our study indicated the inhibitory effect of ciprofloxacin and ceftriaxone on the level of hemolysis, suggesting that the sub-inhibitory concentrations of these antibiotics may affect the outcome of infections. Further studies, including animal models may elucidate the outcome of virulence modulation by these antibiotics in UTI pathogenesis.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Hemolysis; Urinary Tract Infections; Virulence; Virulence Factors

We report the case of an 82-year old male patient admitted in our medical intensive care unit for diffuse skin lesions, 3 days after the onset of ceftriaxone for bilateral pneumonia without microbiological documentation. The patient concomitantly exhibited diffuse skin lesions compatible with livedo and neurological and haemodynamic failure. Biological analysis revealed acute haemolytic anaemia. Warming of patient, red blood-cells transfusion and high-doses corticosteroids were initiated and ceftriaxone was stopped. Despite these therapeutics, the patient exhibited multiple organ failure and died. The main suspected triggering factor of this acute and fatal haemolytic anaemia was ceftriaxone administration considering: (i) the delay between cephalosporin administration and symptoms; (ii) the worsening of livedo and acrocyanosis a few hours after meningeal ceftriaxone doses; and (iii) fatal evolution. Cephalosporin-induced autoimmune haemolytic anaemia is a rare and serious cause of livedo that should be suspected in patients exhibiting livedo and acute haemolytic anaemia within hours/days following cephalosporin administration.

Topics: Aged, 80 and over; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Ceftriaxone; Cephalosporins; Hemolysis; Humans; Male

The spread of antibiotic resistance among Gram-negative bacteria is a serious clinical threat, and infections with these organisms are a leading cause of mortality worldwide. Traditional novel drug development inevitably leads to the emergence of new resistant strains, rendering the new drugs ineffective. Therefore, reviving the therapeutic potentials of existing antibiotics represents an attractive novel strategy. Novicidin, a novel cationic antimicrobial peptide, is effective against Gram-negative bacteria. Here, we investigated novicidin as a possible antibiotic enhancer. The actions of novicidin in combination with rifampin, ceftriaxone, or ceftazidime were investigated against 94 antibiotic-resistant clinical Gram-negative isolates and 7 strains expressing New Delhi metallo-β-lactamase-1. Using the checkerboard method, novicidin combined with rifampin showed synergy with >70% of the strains, reducing the MICs significantly. The combination of novicidin with ceftriaxone or ceftazidime was synergistic against 89.7% of the ceftriaxone-resistant strains and 94.1% of the ceftazidime-resistant strains. Synergistic interactions were confirmed using time-kill studies with multiple strains. Furthermore, novicidin increased the postantibiotic effect when combined with rifampin or ceftriaxone. Membrane depolarization assays revealed that novicidin alters the cytoplasmic membrane potential of Gram-negative bacteria. In vitro toxicology tests showed novicidin to have low hemolytic activity and no detrimental effect on cell cultures. We demonstrated that novicidin strongly rejuvenates the therapeutic potencies of ceftriaxone or ceftazidime against resistant Gram-negative bacteria in vitro. In addition, novicidin boosted the activity of rifampin. This strategy can have major clinical implications in our fight against antibiotic-resistant bacterial infections.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Ceftazidime; Ceftriaxone; Cell Line; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterobacter; Erythrocytes; Escherichia coli; Fibroblasts; Hemolysis; Humans; Klebsiella pneumoniae; Membrane Potentials; Mice; Microbial Sensitivity Tests; Rifampin; Serratia

Topics: Administration, Intravenous; Anemia, Hemolytic; Ceftriaxone; Child, Preschool; Contraindications; Croup; Dexamethasone; Drug-Related Side Effects and Adverse Reactions; Erythrocytes; Female; Hemolysis; Humans; Immunosuppression Therapy; Parainfluenza Virus 2, Human; Steroids

The aim of the present study was to utilize chitosan (CS) nanoparticles for the intracellular delivery of the poorly cell-penetrating antibiotic, ceftriaxone sodium (CTX). In vitro characterization of (CTX-CS) nanoparticles was conducted leading to an optimized formula that was assessed for its biocompatibility to blood (hemolysis test) and cells (MTT assay). Progressively, confocal laser scanning microscopy (CLSM), cellular uptake (microfluorimetry), and antibacterial activity of the nanoparticles were investigated in two cell lines: Caco-2 and macrophages J774.2 pre-infected with Salmonella typhimurium. Results showed that the optimized formula had size 210 nm, positive zeta potential (+30 mV) and appreciable entrapment efficiency for CTX (45%) and included a biphasic release pattern. The nanoparticles were biocompatible and were internalized by cells as verified by CLSM whereas microfluorimetry indicated substantial cellular uptake. Moreover, the CTX-chitosan nanoparticles showed a significant reduction in the count of intracellular S. typhimurium in Caco-2 and macrophages J774.2. This reduction was significantly higher than that obtained in case of placebo nanoparticles, CTX, and CTX-chitosan solutions and might be attributed to enhanced endocytic uptake of the nanoaprticles and antibacterial effect of the chitosan polymer. In conclusion, the results provide evidence for the potential use of chitosan nanoparticles to enhance the intracellular delivery and antibacterial effect of CTX in enterocytes and macrophages.

Topics: Animals; Anti-Bacterial Agents; Biological Transport; Caco-2 Cells; Ceftriaxone; Cell Survival; Chemistry, Pharmaceutical; Chitosan; Cytophotometry; Dose-Response Relationship, Drug; Drug Carriers; Hemolysis; Humans; Inhibitory Concentration 50; Intestinal Mucosa; Macrophages; Mice; Microscopy, Confocal; Nanoparticles; Nanotechnology; Particle Size; Permeability; Salmonella typhimurium; Solubility; Technology, Pharmaceutical

Topics: Anemia; Bartonella bacilliformis; Bartonella Infections; Ceftriaxone; Ciprofloxacin; Fever; Hemolysis; Humans; Male; Middle Aged; Peru; Treatment Outcome

Ceftriaxone-induced immune haemolytic anemia is rare but severe complication of this type of antibiotics. In this article, we present a 43-year old patient who suffered from ceftriaxone-induced haemolysis complicated with acute portal vein thrombosis. After successful salvage and transfusion, we underwent thrombolysis via superior mesenteric artery route. Totally recanaliztion achieved. Repeated CT venography showed portal vein still patent with 6 months oral anti coagulation treatment.

Topics: Adult; Ceftriaxone; Female; Hemolysis; Humans; Portal Vein; Venous Thrombosis

Ceftriaxone is a commonly administered antibiotic, and hemolytic crisis is a dangerous potential adverse event. We describe 2 children with sickle cell disease who developed severe hemolytic crisis after ceftriaxone administration. Both subsequently demonstrated the presence of anticeftriaxone antibodies that may have been responsible for the massive hemolysis.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Female; Hemolysis; Humans; Male; Severity of Illness Index

Ceftriaxone-induced hemolytic anemia is a rare and often fatal phenomenon. We report here the case of a 6-year-old female with sickle cell disease who survived a brisk and profound hemolytic reaction, resulting in hemoglobin of 0.4 g/dL, after ceftriaxone infusion. Ongoing hemolysis was abrogated with aggressive supportive care, but the patient suffered extensive neurologic sequelae as a result of the event. Serologic testing confirmed the presence of ceftriaxone antibodies.

Topics: Anemia, Hemolytic; Anemia, Sickle Cell; Anti-Bacterial Agents; Antibodies; Brain Ischemia; Ceftriaxone; Child; Female; Hemolysis; Humans

Drug-induced haemolytic anaemia can be life threatening. We report a case of ceftriaxone-induced severe haemolytic anaemia in a previously healthy 68-year-old woman. The patient had a positive direct antiglobulin test (anti-C3d positive, anti-immunoglobulin G negative). Serological tests showed ceftriaxone-specific antibodies. The patient recovered after cessation of the drug. This complication may cause milder anaemia and thus be poorly recognized.

Topics: Aged; Anemia, Hemolytic; Anti-Bacterial Agents; Antibodies; Ceftriaxone; Endocarditis, Bacterial; Female; Follow-Up Studies; Hemolysis; Humans; Injections, Intravenous

Ceftriaxone can be associated with catastrophic immune hemolysis in pediatric patients, particularly those with underlying diseases such as sickle cell disease and human immunodeficiency virus infection. We designed a study to screen for ceftriaxone-induced RBC antibodies in these 2 pediatric populations. The prevalence of anticeftriaxone antibody was 12.5% (8 of 64). Two of these 8 patients with the antibody experienced hemolysis; 1 case was fatal.

Topics: Adult; Anemia, Sickle Cell; Autoantibodies; Ceftriaxone; Erythrocytes; Hemolysis; HIV Infections; Humans; Infant; Infant, Newborn

A case of native valve endocarditis caused by Enterococcus durans in a patient with transposition of the great vessels is reported. The patient was treated initially with gentamicin and ceftriaxone; after isolation of enterococci, ceftriaxone was switched to ampicillin. The only virulence factors established in the strain were haemolytic activity and biofilm formation.

Topics: Adult; Ampicillin; Biofilms; Ceftriaxone; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus; Gentamicins; Gram-Positive Bacterial Infections; Hemolysis; Humans; Male; Microbial Sensitivity Tests; Transposition of Great Vessels; Virulence

Topics: Adult; Anemia, Hemolytic, Autoimmune; Anti-Bacterial Agents; Ceftriaxone; Child; Hemolysis; Humans

A 14-year-old girl with perinatally acquired human immunodeficiency virus infection had fatal intravascular hemolysis after intravenous administration of ceftriaxone. Laboratory studies confirmed the presence of an antibody against ceftriaxone in the serum and on the patient's red blood cells. No evidence of sepsis, glucose-6-phosphate dehydrogenase deficiency or anaphylaxis was found.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anemia, Hemolytic; Antibodies; Ceftriaxone; Cephalosporins; Fatal Outcome; Female; Hemolysis; HIV Infections; Humans

Topics: Acute Disease; Ceftriaxone; Child, Preschool; Fatal Outcome; Female; Hemolysis; Humans

A 2-year-old boy with sickle cell anemia had a massive, fatal hemolytic reaction after administration of an intravenous dose of ceftriaxone. Laboratory studies demonstrated the presence of an IgM antibody against ceftriaxone, binding to and destroying the patient's erythrocytes by an immune complex mechanism. This rare complication should be considered in the differential diagnosis when hemoglobinuria develops in a child after administration of ceftriaxone or a similar agent.

Topics: Anemia, Hemolytic, Autoimmune; Anemia, Sickle Cell; Ceftriaxone; Child, Preschool; Fatal Outcome; Hemoglobinuria; Hemolysis; Humans; Immunoglobulin M; Male

After receiving ceftriaxone intravenously, a boy with leukemia died suddenly of massive hemolysis. The diagnosis was made retrospectively only after a similar case of sudden fatal immune hemolysis after intravenous administration of ceftriaxone was reported.

Topics: Ceftriaxone; Child, Preschool; Death, Sudden, Cardiac; Fatal Outcome; Hemolysis; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Anemia, Hemolytic; Ceftriaxone; Cephalosporins; Child; Fatal Outcome; Hemolysis; HIV-1; Humans; Infusions, Intravenous; Male