Treatment of chronic urinary tract infections with gentamicin

Lindberg, Anna‐Lena; Bucht, H; Kallings, L. O.

doi:10.1136/jcp.20.5.760

Cited by 6 publications

(6 citation statements)

References 6 publications

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“…The main finding of our trial is that in small children the serum level obtained with a certain dose varies very much, as has earlier been report ed in many papers concerned with adult patients [3,6,7,8], A relatively high dose is necessary to obtain a therapeutic serum level (this is con firmed by at least two other authors [4,9], and it seems as if a minimum of 3 mg/kg daily was necessary. However, the serum levels should by de termined, and the dose corrected accordingly.…”

Section: Discussionsupporting

confidence: 62%

Gentamicin in the Treatment of Infections in Early Childhood

Elfving¹,

Pettay²,

Renkonen³

1969

Chemotherapy

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Section: Discussionsupporting

confidence: 62%

Gentamicin in the Treatment of Infections in Early Childhood

Elfving¹,

Pettay²,

Renkonen³

1969

Chemotherapy

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“…Importantly, urinary gentamicin concentrations were previously found to be in the range 100-1200 mM in humans, whereas plasma gentamicin concentrations were 10-20 mM. [59][60][61][62] In dogs, gentamicin concentrations have been measured at 75-733 mM in urine and 20 mM in plasma. 63,64 Peak concentrations in rat after gentamicin administration were measured at 20-42 mM in plasma and when the bolus was followed by an infusion it could reach 147 mM in plasma.…”

Section: Discussionmentioning

confidence: 99%

“…70 In these in vitro studies, this occurs at a 10-fold higher concentration than observed in human plasma after gentamicin infusion. [59][60][61][62] Furthermore, gentamicin does not appear to change PTH release after acute and chronic administration in rats. 68 Reports on PTH in patients receiving gentamicin are scarce, but hypocalcemia is not typically observed after gentamicin administration, in contrast to what would be expected if gentamicin had a strong effect on the CaSR, acting to reduce PTH secretion in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…, 18 Accordingly, patch clamp experiments showed that gentamicin reduces rabbit and human TRPV5 activity in a dose-dependent manner in vitro . Importantly, urinary gentamicin concentrations were previously found to be in the range 100–1200 µ M in humans, whereas plasma gentamicin concentrations were 10–20 µ M 59 – 62 In dogs, gentamicin concentrations have been measured at 75–733 µ M in urine and 20 µ M in plasma 63 …”

Section: Discussionmentioning

confidence: 99%

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Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor–Claudin-14 Pathway

Megen

Beggs

et al. 2022

JASN

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Background Treatment with the aminoglycoside antibiotic gentamicin can be associated with severe adverse effects, including renal calcium wasting. The underlying mechanism is unknown but it has been proposed to involve activation of the Ca2+-sensing receptor (CaSR) in the thick ascending limb, which would increase expression of claudin-14 (CLDN14) and limit Ca2+ reabsorption. However, no direct evidence for this hypothesis has been presented. Methods We studied the effect of gentamicin in vivo using mouse models with impaired Ca2+ reabsorption in the proximal tubule and the thick ascending limb. We used a Cldn14 promoter luciferase-reporter assay to study CaSR activation and investigated the effect of gentamicin on activity of the distal nephron Ca2+ channel transient potential receptor vanilloid 5 (TPRV5), as determined by patch-clamp in HEK293 cells. Results Gentamicin increased urinary Ca2+ excretion in wild-type mice following acute and chronic administration. This calciuretic effect was unaltered in mice with genetic CaSR overactivation and was present in furosemide-treated animals, whereas the calciuretic effect in Cldn14-/-mice and mice with impaired proximal tubular Ca2+ reabsorption (claudin-2 [CLDN2]-deficient Cldn2-/- mice) was equivalent to that of wild-type mice. In vitro, gentamicin failed to activate the CaSR. In contrast, patch-clamp analysis revealed that gentamicin strongly inhibited rabbit and human TRPV5 activity and that chronic gentamicin administration downregulated distal nephron Ca2+ transporters. Conclusions Gentamicin does not cause hypercalciuria via activation of the CaSR-CLDN14 pathway or by interfering with proximal tubular CLDN2-dependent Ca2+ reabsorption. Instead, gentamicin blocks distal Ca2+ reabsorption by direct inhibition of the Ca2+ channel TRPV5. These findings offer new insights into calcium wasting in patients treated with gentamicin.

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“…It has been noted by previous workers that gentamicin-resistant strains are unlikely to emerge during gentamicin treatment (Bulger et al 1963, Jackson 1967, Lindberg et al 1967). This has been related to the failure of extra chromosomal resistance to appear with gentamicin, in contrast with other aminoglycosides.…”

Section: Discussionmentioning

confidence: 97%

Treatment of Persistent Urinary Tract Infections with Gentamicin

Lorber

Formby

1968

Develop Med Child Neuro

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SUMMARY Gentamicin, an aminoglycoside antibiotic drug, has been used in the treatment of 20 children with gross chronic urinary tract infection, resulting from neurogenic bladder. In 17 cases hydronephrosis was present and the renal function was much reduced in all, as shown by creatinine clearance tests, blood urea levels and radiological data. Infection was due to Proteus, Ps. pyocyanea or E. coli in the large majority of cases. Treatment with intramuscular dosage of 2 mg. (first 6 cases) or 4 mg./kg. daily (subsequent cases) led to clearing of the infection in 18. Failure in the others was due to insufficient gentamicin level in the urine related to the M.I.C. required for the organisms concerned. Relapse within one month occurred in 5 and fresh infection occurred in 5 children. In only 3 instances were gentamicin‐resistant strains encountered. Gentamicin was of value in the treatment in these highly selected, difficult cases. RÉSUMÉ La gentamycine, antibiotique à base d'un aminoglucoside, a été utilisé dans le traitement de l'infection chronique des voies urinaires consécuties à des troubles nerveux de la vessie chez 20 enfants. Dans 17 cas, il y avait une hydronéphrose et la fonction rénale était très altérée dans tous les cas, comme le montraient les tests d'élimination de la créatinine, les taux d'urée sanguine et sle données urographiques. L'infection était dûe au Proteus, au pyocyanique ou a E. coli dans la grande majorite des cas. Le traitement par voie intramusculaire à dose de 2 mg. (dans les 6 premiers cas) ou 4 mg. par kilo et par jour (dans les autres cas) a permis d'obtenir la disparition de l'infection chez 18 malades. L'insuccès dans les deux cas restants était liéà un taux insuffisant de gentamycine dans l'urine par rapport à la concentration requise en ce qui concernait les germes présents. 5 malades ont présentés une rechute durant le premier mois et une nouvelle infection a été observée chez 5 autres enfants. Des souches résistantes à la gentamycine n'ont été recontrées que dans 3 cas. La gentamycine a done une grande valure thérapeutique dans ces cas sévèrement sélectionnés et difficiles. ZUSAMMENFASSUNG Gentamicin, ein Aminoglycozid‐Antibiotikum, wurde bei der Behandlung von 20 Kindern verwendet, die an einer schweren chronischen Harnwegsinfektion infolge neurogener Blasentörung litten. In 17 Fällen bestand eine hydronéphrose, die Nierenfunktion war in alien Fällen eingeschränkt, kenntlich an der Kreatininclearance, den Blutharnstoffwerten und an radiologischen Untersuchungsbefunden. Die Infektion wurde bei der Mehrzahl der Fälle von Proteus, Pyocyaneus oder Colibakterien verursacht. Die Behandlung mit intramuskulären Dosen von 2 mg (die ersten 6 Fälle) oder 4 mg pro kg täglich (restliche Fälle) führten zur Beseitigung der Infektion in 18 Fällen. Der Mißerfolg in den übrigen Fällen war bedingt durch einen ungenügenden Gentamicinspiegel im Urin. Ein Rezidiv trat innerhalb des ersten Monates bei 5 Fällen auf, 5 Kinder machten eine neuer‐liche Infektion durch. Nur in 3 Fällen wurden gentamici...

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Treatment of chronic urinary tract infections with gentamicin

Cited by 6 publications

References 6 publications

Gentamicin in the Treatment of Infections in Early Childhood

Gentamicin in the Treatment of Infections in Early Childhood

Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor–Claudin-14 Pathway

Treatment of Persistent Urinary Tract Infections with Gentamicin

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