ro13-9904 and Renal-Insufficiency

Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events.. To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events.. In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel-Haenszel method, the Sidik-Jonkman estimator for τ. Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26-0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03-0.46], p = 0.0160) than AG.. Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE.

Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Drug Therapy, Combination; Endocarditis; Endocarditis, Bacterial; Enterococcus faecalis; Gentamicins; Gram-Positive Bacterial Infections; Heart Diseases; Humans; Renal Insufficiency

Drug induced immune hemolytic anemia (DIIHA) is a rare complication and often underdiagnosed. DIIHA is frequently associated with a bad outcome, including organ failure and even death. For the last decades, ceftriaxone has been one of the most common drugs causing DIIHA, and ceftriaxone-induced immune hemolytic anemia (IHA) has especially been reported to cause severe complications and fatal outcomes.. A 76-year-old male patient was treated with ceftriaxone for cholangitis. Short time after antibiotic exposure the patient was referred to intensive care unit due to cardiopulmonary instability. Hemolysis was observed on laboratory testing and the patient developed severe renal failure with a need for hemodialysis for 2 weeks. Medical history revealed that the patient had been previously exposed to ceftriaxone less than 3 weeks before with subsequent hemolytic reaction. Further causes for hemolytic anemia were excluded and drug-induced immune hemolytic (DIIHA) anemia to ceftriaxone could be confirmed.. The case demonstrates the severity of ceftriaxone-induced immune hemolytic anemia, a rare, but immediately life-threatening condition of a frequently used antibiotic in clinical practice. Early and correct diagnosis of DIIHA is crucial, as immediate withdrawal of the causative drug is essential for the patient prognosis. Thus, awareness for this complication must be raised among treating physicians.

Topics: Aged; Anemia, Hemolytic; Anti-Bacterial Agents; Ceftriaxone; Humans; Male; Renal Insufficiency

The aim of this systematic review is to review all human trials assessing the efficacy and safety of ampicillin and ceftriaxone for enterococcal endocarditis and to discuss the clinical implications of the findings.. MEDLINE (1946-), EMBASE (1974-), CENTRAL, Google Scholar, and the World Health Organization Clinical Trials Registry Platform were searched through January 2017 using the search terms ampicillin, penicillin, ceftriaxone, cephalosporin, enterococ*, and endocarditis. Unpublished studies were eligible for inclusion. Additional references were identified from literature citations.. Clinical trials in humans that reported on clinical efficacy or adverse outcomes with ceftriaxone and ampicillin therapy in patients with enterococcal endocarditis were included. Case reports, nonhuman, and non-English studies were excluded.. Four observational clinical studies were identified. One examined the effects of ceftriaxone and ampicillin alone, and 3 compared the therapy to the current standard of care, ampicillin and gentamicin. The studies had small sample sizes and were not adequately designed or powered to establish noninferiority or equivalence to the current standard of care. Rates of clinical cure with ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours were similar to those of ampicillin and gentamicin. Ampicillin and ceftriaxone therapy was well tolerated with low rates of renal failure (0%-33%).. The evidence to support the use of ampicillin and ceftriaxone for enterococcal endocarditis is not definitive. In the absence of compelling evidence, clinicians may consider ampicillin and ceftriaxone in patients with Enterococcus faecalis infection at high risk for nephrotoxicity or those with aminoglycoside-resistant pathogens.

Topics: Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Gentamicins; Humans; Renal Insufficiency

We report 2 cases of Shigella septicaemia in adult patients.. Two 57-year-old women presented with non-bloody diarrhoea and fever. The first patient was an inmate of a long-term care facility who was schizophrenic and the second patient was a diabetic who recently travelled to Medan, Indonesia. Both patients were febrile, hypotensive and dehydrated. The first patient was neutropenic, thrombocytopenic and had acute renal failure. Blood cultures yielded Shigella flexneri and stool cultures gave negative results for both patients.. Rehydration and intravenous ceftriaxone were instituted.. The patients' symptoms and hypotension resolved.. Appropriate antibiotics can decrease the severity and duration of Shigella septicaemia.

Topics: Ceftriaxone; Cephalosporins; Diarrhea; Female; Humans; Middle Aged; Neutropenia; Renal Insufficiency; Risk Factors; Sepsis; Shigella flexneri; Thrombocytopenia

The aim of this study was to determine the pharmacokinetic profile of the normal recommended dose of ceftriaxone in critically ill patients and to establish whether the current daily dosing recommendation maintains plasma concentrations adequate for antibacterial efficacy. Ceftriaxone at a recommended dose of 2 g iv was administered od to 12 critically ill patients with severe sepsis and normal serum creatinine concentrations. Blood samples were taken at pre-determined intervals over the first 24 h and on day 3 for measurement of ceftriaxone concentrations. There was wide variability in drug disposition, explained by the presence of variable renal function and identified by the measurement of creatinine clearance. In nine patients with normal renal function, there was a high level of creatinine clearance (mean +/- S.D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which resulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with normal subjects, ceftriaxone clearance was increased 100%, volume of distribution increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients correlates with renal clearance by glomerular filtration. The elimination half-life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal failure when compared with previously published data in non-critically ill patients with renal failure. We conclude that in critically ill patients with normal renal function, inadequate plasma concentrations may result following od bolus dosing of ceftriaxone. Drug accumulation may occur in critically ill patients with renal failure.

Topics: Adolescent; Adult; Aged; Ceftriaxone; Cephalosporins; Critical Illness; Female; Half-Life; Humans; Kidney; Male; Middle Aged; Pneumonia; Renal Insufficiency; Sepsis

PTA of protein-unbound ceftriaxone may be compromised in critically ill patients with community-acquired pneumonia (CAP) with augmented renal clearance (ARC). We aimed to determine an optimized ceftriaxone dosage regimen based on the probability of developing ARC on the next day (PARC,d+1; www.arcpredictor.com).. Thirty-three patients enrolled in a prospective cohort study were admitted to the ICU with severe CAP and treated with ceftriaxone 2 g once daily. Patients contributed 259 total ceftriaxone concentrations, collected during 1 or 2 days (±7 samples/day). Unbound fractions of ceftriaxone were determined in all peak and trough samples (n = 76). Population pharmacokinetic modelling and simulation were performed using NONMEM7.4. Target attainment was defined as an unbound ceftriaxone concentration >4 mg/L throughout the dosing interval.. A two-compartment population pharmacokinetic model described the data well. The maximal protein-bound ceftriaxone concentration decreased with lower serum albumin. Ceftriaxone clearance increased with body weight and PARC,d+1 determined on the previous day. A high PARC,d+1 was identified as a clinically relevant predictor for underexposure on the next day (area under the receiver operating characteristics curve 0.77). Body weight had a weak predictive value and was therefore considered clinically irrelevant. Serum albumin had no predictive value. An optimal PARC,d+1 threshold of 5.7% was identified (sensitivity 73%, specificity 69%). Stratified once- or twice-daily 2 g dosing when below or above the 5.7% PARC,d+1 cut-off, respectively, was predicted to result in 81% PTA compared with 47% PTA under population-level once-daily 2 g dosing.. Critically ill patients with CAP with a high PARC,d+1 may benefit from twice-daily 2 g ceftriaxone dosing for achieving adequate exposure on the next day.

Topics: Anti-Bacterial Agents; Body Weight; Ceftriaxone; Critical Illness; Humans; Pneumonia; Probability; Prospective Studies; Renal Insufficiency; Serum Albumin

Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated. The aim of this study was to investigate the cumulative incidence of CTRX-associated BPL in adults and to assess if renal dysfunction is a risk factor.. We retrospectively analyzed the medical records of 478 patients treated with CTRX to assess the incidence and risk factors of CTRX-associated BPL. We examined age, sex, body weight, dosage, and duration of CTRX therapy, and the concentrations of serum creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum calcium in all the patients. The cumulative incidence of BPL was calculated using a competing risk model. The multivariate analysis of each variable for the development of BPL was assessed by a Cox proportional hazards model.. A total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The cumulative incidence of BPL in patients with renal dysfunction was significantly higher than that in patients with normal kidney function (4.1 vs. 0.6%, p = 0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045) and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk factors of CTRX-associated BPL, which was confirmed using multivariate analysis (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65, 95% CI 1.03-21.1, p = 0.046).. Renal dysfunction is an independent risk factor of CTRX-associated BPL in adults.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Biliary Tract Diseases; Ceftriaxone; Female; Humans; Incidence; Japan; Male; Middle Aged; Renal Insufficiency; Retrospective Studies; Risk Factors

Topics: Aged; Anti-Bacterial Agents; Ceftriaxone; Critical Illness; Dose-Response Relationship, Drug; Hemofiltration; Humans; Liver Failure; Male; Renal Insufficiency

The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4-6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997-2006 and 49% in 2007-2011; p 0.03). The use of A+C increased over time: 1997-2001, 4/18 (22%); 2002-2006, 5/16 (31%); 2007-2011, 30/35 (86%) (p <0.001). Renal failure developed in 65% of the A+G group and in 34% of the A+C group (p 0.014). Thirteen patients (43%) in the A+G group had to discontinue treatment, whereas only one patient (3%) treated with A+C had to discontinue treatment (p <0.001). Only development of heart failure and previous chronic renal failure were independently associated with 1-year mortality, while the individual antibiotic regimen (A+C vs. A+G) did not affect outcome (OR, 0.7; 95% CI, 0.2-2.2; p 0.549). Our study shows that the prevalence of HLAR EFIE has increased significantly in recent years and that alternative treatment with A+C is safer than A+G, with similar clinical outcomes, although the sample size is too small to draw firm conclusions. Randomized controlled studies are needed to confirm these results.

Topics: Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Cohort Studies; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis; Enterococcus faecalis; Female; Gentamicins; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Spain; Survival Analysis; Treatment Outcome; Withholding Treatment

Topics: Anti-Bacterial Agents; Ascites; Ascitic Fluid; Brain Diseases; Ceftriaxone; Diagnosis, Differential; Humans; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Middle Aged; Paracentesis; Percussion; Postoperative Complications; Renal Insufficiency; Risk Factors; Serum Albumin

Renal glycosuria is defined as the excretion of glucose in urine in a normoglycemic state. It results from renal tubular dysfunction or immaturity of tubular function in the newborn. Etiologically, renal glycosuria is of 3 types-benign renal glycosuria, glycosuria with diabetes mellitus (including gestational diabetes) and tubular defects (Fanconi syndrome). Prognosis of benign renal glycosuria is excellent and reversible. Acute interstitial nephritis (AIN) is one of the main causes of acute renal failure and may often result in tubular dysfunction. In this study, the authors report the occurrence of AIN with acute renal failure that contributed to reversible renal glycosuria. The glycosuria observed in the patient of this study was an isolated tubular defect, with no phosphaturia, aminoaciduria or bicarbonaturia. Such a presentation is very rare in adults and has not been previously reported. These findings confirm that AIN with acute renal failure can cause an isolated tubular defect with benign reversible glycosuria in an adult.

Topics: Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Female; Glycosuria, Renal; Humans; Middle Aged; Naproxen; Nephritis, Interstitial; Renal Insufficiency; Treatment Outcome

Concomitant leptospirosis and scrub typhus is rare. The spectrum of clinical severity for both scrub typhus and leptospirosis ranges from mild to fatal. Acute pancreatitis and cholecystitis are infrequent complications in adult patients with either leptospirosis or scrub typhus. We report a case of leptospirosis and scrub typhus coinfection in a 41-year-old man presenting with acute acalculous cholecystitis, pancreatitis and acute renal failure. Abdominal computed tomography revealed edematous change of the gallbladder without intrahepatic or pancreatic lesions. The patient was successfully treated with doxycycline and ceftriaxone, and supportive management.

Topics: Acalculous Cholecystitis; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Ceftriaxone; Cholecystitis, Acute; Doxycycline; Drug Therapy, Combination; Humans; Leptospira interrogans; Leptospirosis; Military Personnel; Orientia tsutsugamushi; Pancreatitis; Renal Insufficiency; Scrub Typhus; Tomography, X-Ray Computed

Nonconvulsive status epilepticus is an unusual complication of cephalosporin therapy, with only a few isolated cases reported.. We reviewed the clinical and electroencephalographic (EEG) characteristics of 10 patients with renal failure in whom developed alteration of consciousness without convulsions associated with continuous epileptiform EEG activity while being treated with cephalosporins.. Nonconvulsive status epilepticus developed in 5 men and 5 women, with a mean (+/- SD) age of 69 +/- 14 years, while receiving intravenous cephalosporins (ceftriaxone, 2 patients; ceftazidime, 2; and cefepime, 6). All patients had renal failure; 1 also had hepatic failure. Patients presented with progressive disorientation or agitation, sometimes associated with mild facial or limb myoclonus, that had begun 1 to 10 days (mean, 5 +/- 2 days) after starting cephalosporin treatment. The EEG showed continuous or intermittent bursts of generalized, high-voltage, 1 to 2 Hz sharp wave activity or sharp and slow wave activity that resembled, but could be differentiated from, the triphasic waves seen in metabolic encephalopathies. Intravenous clonazepam suppressed the epileptiform activity completely in 5 patients and partially in the other 5. Cephalosporins were withdrawn, and antiepileptic therapy was started for all patients. All patients improved, 2 in less than 24 hours and the remainder within 2 to 7 days.. Cephalosporins can cause nonconvulsive status epilepticus in patients with renal failure. The clinical picture is difficult to differentiate from a that of metabolic encephalopathy unless an EEG is obtained. Physicians should be aware of this potentially dangerous complication.

Topics: Adult; Aged; Aged, 80 and over; Brain; Cefepime; Ceftazidime; Ceftriaxone; Cephalosporins; Electroencephalography; Female; Humans; Infusions, Intravenous; Male; Meningitis, Bacterial; Middle Aged; Osteomyelitis; Renal Insufficiency; Respiratory Tract Infections; Status Epilepticus