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An Overview of Drug-Induced Nephropathies *
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Jean Paul Fillastre, Michel Godin
Methicillin-induced interstitial nephritis may be considered as the prototype of the clinical and pathological features associated with all drug-associated acute interstitial nephritis. The incidence of adverse renal reactions to methicillin is estimated between 1 to 2% of all patients taking the drug. Methicillin is now less prescribed and the number of cases of interstitial nephritis has decreased during the past few years. Patients developing this type of nephritis received normal doses of methicillin, and the appearance of renal symptoms ranges from 2 to 60 d. Characteristically, the fever appears after the initial fever caused by the original infection has subsided. Skin rash and eosinophilia associated with high fever are noted in approximately one third of all patients. Acute renal failure is nonoliguric in the majority of cases. The proteinuria is mild, microscopic hematuria is frequent, and gross hematuria is noted in about a third of the cases. In most of the patients examined, the urinary sediment shows eosinophiluria which ranged up to 30% of the urinary leukocytes in some observations.
Renal Pathophysiology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Herman S. Fernando, Mohamed Yehia Abdallah, Iqbal S. Shergill
The diagnosis of AKI secondary to AIN may be suggested by the urinalysis findings of sterile pyuria, white blood cell casts and eosinophiluria (using Hansel stain). The clinical presentation usually involves an abnormal urine sediment (described earlier), fever, a rising serum creatinine along with abnormal urinanalysis. While skin rash is seen in about 25% of cases, eosinophilia and eosinophiluria are present in more than 75% of cases except in AIN secondary to NSAIDs, where fever, rash and eosinophilia are typically absent. Proteinuria with most drugs is usually modest, with less than 0.5–1 g/day, while in the nephrotic range is frequently seen in selected cases on ampicillin, rifampin, ranitidine and interferon.
Methicillin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
An interstitial nephritis can be caused by large doses of methicillin (Baldwin et al., 1968; Woodroffe et al., 1974; Galpin et al., 1978). This is characterized by fever, rash, eosinophilia, hematuria, proteinuria, sterile pyuria, marked eosinophiluria, and renal insufficiency. Microscopic changes in the kidneys consist of patchy but usually heavy interstitial infiltrate with lymphocytes, plasma cells, and eosinophils—that is, interstitial changes without glomerular abnormalities. Cogan and Arieff (1978) reported a patient in whom methicillin-induced interstitial nephritis also resulted in functional impairment specific for the distal tubule. The patient developed dehydration due to a sodium-losing nephropathy, renal tubular acidosis, and hyperkalemia due to impaired ability to excrete potassium. Sometimes hematuria may be the sole manifestation of nephropathy, and in such cases it may be difficult to distinguish whether this is due to the drug or to the patient’s disease, such as staphylococcal septicemia (Gallagher and Wayne, 1971). Hematuria and dysuria may also result in some methicillin-treated patients because the drug occasionally causes a hemorrhagic cystitis, possibly by direct chemical irritation (Yow et al., 1976; Bracis et al., 1977; Godin et al., 1980). This complication is distinct from methicillin-induced interstitial nephritis, and its presence can be confirmed by cystoscopy. In methicillin cystitis, hematuria may disappear when a few doses of the drug are omitted, and therapy is resumed with a lower daily dose in association with an increase in fluid intake. As in the case of methicillin-induced interstitial nephritis, it is preferable to discontinue methicillin when this complication occurs.
Safety evaluation of current therapies for high-risk severely ill patients with carbapenem-resistant infections
Published in Expert Opinion on Drug Safety, 2022
Matteo Bassetti, Antonio Falletta, Giovanni Cenderello, Daniele R. Giacobbe, Antonio Vena
As for studies coming from real-life experiences, Munita et al [33] reported only 2 cases of AEs among their study population including 35 patients infected with carbapenem-resistant P. aeruginosa treated with ceftolozane-tazobactam (one patient developed self-limited diarrhea with a negative C. difficile molecular assay, and the other was found to have peripheral eosinophilia and eosinophiluria without acute kidney injury). Lower rates of AEs were observed by Bassetti et al, who reported only 3 patients experiencing drug-related AEs, among 101 patients treated with C/T [34]. In this study, AEs consisted of gastrointestinal symptoms (i.e. nausea, abdominal pain, and diarrhea), rash, and an asymptomatic increase in liver function test results. In this study, all except one patient experiencing AEs were treated with standard dosage of ceftolozane-tazobactam (1.5 g every 8 hours) and the time from starting study drug to AE onset varied widely from 5 days to 72 days. All episodes were considered as mild in severity. Nonetheless, ceftolozane-tazobactam was discontinued early in 2 out of 3 patients experiencing AEs [34].
Ceftolozane/tazobactam: place in therapy
Published in Expert Review of Anti-infective Therapy, 2018
Daniele Roberto Giacobbe, Matteo Bassetti, Francesco Giuseppe De Rosa, Valerio Del Bono, Paolo Antonio Grossi, Francesco Menichetti, Federico Pea, Gian Maria Rossolini, Mario Tumbarello, Pierluigi Viale, Claudio Viscoli
Regarding post-marketing safety evaluation, seven cases of medication error were reported to the FDA [79]. All cases were due to a wrong preparation of C/T in the pharmacy, leading to the administration of 50% more than was prescribed. However, no AEs were reported in all seven cases [79]. In a multicenter, retrospective study of 35 patients infected with carbapenem-resistant Pseudomonas aeruginosa and treated with C/T, dosage and length of therapy ranged from 375 to 3000 mg every 8 h and from 5 to 27 days, respectively [80]. Nine out of 20 patients with CrCL > 50 mL/min were given 3000 mg of C/T every 8 h. Two AEs were attributed to C/T: (i) self-limited diarrhea with a negative Clostridium difficile molecular test; (ii) peripheral eosinophilia with eosinophiluria, possibly due to interstitial nephritis. In the latter case, the eosinophil count normalized after C/T was stopped, and no renal damage was later found.