Chronic Pyelonephritis is a particular pattern of kidney scarring that occurs after repeated episodes of pyelonephritis. This is a problem for people with architectural GU abnormalities, like vesicoureteral reflux (VUR) or prostate problems. If you were to look at the kidneys, you would see that the renal cortices are scarred and the calyces have blunted. Scarring at the upper and lower poles is characteristic of VUR. If you looked at the kidneys under a microscope, you would see atrophic tubules full of protein-rich material. It would be reminiscent of the colloid bubbles inside of thyroid follicles (take my word for it), hence the damage is described as “thyroidization.” The symptoms are pretty similar to regular pyelonephritis. 

If a case of pyelonephritis does NOT improve with appropriate antibiotics, then you should consider (a) a kidney abscess or (b) an infected struvite kidney stone. Kidney Abscesses are relatively rare, but they can form during an episode of pyelonephritis. The abscess walls block the antibiotic molecules. I’ll talk about struvite stones more on the kidney stone page. 

UTI Specific Drugs

Nitrofurantoin (Macrobid) is a peculiar antibiotic. It’s the only FDA approved agent in the “urinary antiseptic” class. It has only one indication: cystitis. That’s because Nitrofurantoin is inactive while circulating through your bloodstream. It only becomes activated once it reaches the urine. Once activated, bacteria gobble it up and use their flavoproteins to unwittingly transform the drug into a free radical explosion. The free radicals obliterate the bacteria completely, damaging the ribosomes, DNA, proteins, cell wall, etc. It has very low rates of antibiotic resistance. And it’s pretty cheap! But there’s a downside to Nitrofurantoin, and it’s a big one. Nitrofurantoin cannot treat pyelonephritis, because like Donald Trump, it requires a golden shower (submersion in urine) to get turned on (activated). If you have even the slightest suspicion that the UTI you’re treating may involve the kidney, then you should avoid Nitro like the plague. Now let’s talk about side effects. The first is pretty intuitive once you know about the free-radical-explosion mechanism -- it’s an oxidizing drug, so it can precipitate a G6PD flare! Taking Nitrofurantoin can also cause pulmonary fibrosis, although this is rather rare. Finally, Nitrofurantoin is potentially teratogenic during the first trimester (it should also be avoided right before delivery out of concern for a G6PD flare in mom or baby).

Fosfomycin is a new addition to the UTI scene. It works by inhibiting the enzyme enolpyruvate transferase, which blocks an early step in bacterial cell synthesis. The reason that it’s somewhat popular is that it can be taken as a single dose! It is currently only approved for treating cystitis. Pretty low yield.