Infectious Disease Compendium

Cystitis

Diagnosis

Pain, burning, frequency of urination with pyuria and bacteria in urine, in a normal female with classic symptoms, empiric therapy over the phone without cultures is reasonable. I have ruined more phones trying to stuff pills into the phone. There was one doofus who thinks homeopathic therapy can be sent over the phone; a whole new way to treat over the phone.

DO NOT TREAT ASYMPTOMATIC BACTIURIA. Stop. Really. And altered mental status in the eldery does count as a sypmtom. It does nothing and long term increases the rates of symptomatic disease. We have known this for years not but no one seems to pay attention (PubMed).

The following approaches have the same outcomes: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leukocytes and blood), or a positive result on midstream urine analysis (PubMed).

Pyelonephritis here.

If you have a patient with urosepsis, get blood cultures. About 7% of the time you will grow something other than the urine bug in the blood (PubMed).

Epidemiologic Risks

Manipulation of the urinary tract, sex, foley, stones (sex with one of the Rolling Stones who has a foley). Sadly, stone removal may not result in a decrease in infections (PubMed).

The true axis of evil is North Korea, Iran, and the Foley catheter, and so far this century more have died from the urinary catheters than have died from the other two combined.

Bladder prolapse, condom catheter use, diabetes, diaphragm use, functional or mental impairment, lack of circumcision, lack of urination after intercourse, neurogenic bladder, pregnancy, previous urinary tract infection, prostatic enlargement, renal transplantation, sexual intercourse, spermicidal contraceptive jellies, urethral catheterization, urinary tract obstruction including stones, urologic instrumentation or surgery.

Household dogs and cats can serve as a reservoir for pathogenic E. coli (PubMed). How do humans get it. Hate to tell you this, but dogs and cats lick their ass and you pet them or let them lick you. Food may also be a reservoir (PubMed).

And are antibiotics necessary in hip arthroplasty with asymptomatic bacteriuria? Spoiler alert: No (PubMed). Although asymptomatic bacteriuria is a risk for prosthetic joint infection, it is a marker since the organism in the joint is NOT in the one in the urine and treating the ASB does nothing (PubMed).

You do not even need to treat ASB in urologic cases (Pubmed)

And dogs can be trained to sniff and differentiate bacteria in urine (Pubmed). I am so glad I am not a dog.

Microbiology

Of interest, the urine and bladder may not be sterile as molecular techniques show the bladder may have an indigenous flora (PubMed) and confirmed by culture (PubMed): "Fifty-two of the 65 urine samples (80%) grew bacterial species using EQUC, while the majority of these (48/52 [92%]) were reported as no growth at 10(3) CFU/ml by the clinical microbiology laboratory using the standard urine culture protocol. Thirty-five different genera and 85 different species were identified by EQUC. The most prevalent genera isolated were Lactobacillus (15%), followed by Corynebacterium (14.2%), Streptococcus (11.9%), Actinomyces (6.9%), and Staphylococcus (6.9%). Other genera commonly isolated include Aerococcus, Gardnerella, Bifidobacterium, and Actinobaculum."

E. coli: young women in the childbearing years. They say the number two cause in this group is S. saprophyticus. This was not supported in a 2013 NEJM study comparing midstream to cath specimens where it was zero (PubMed) and note the colony count (I added the bold):

"The presence of Escherichia coli in midstream urine was highly predictive of bladder bacteriuria even at very low counts, with a positive predictive value of 102 colony-forming units (CFU) per milliliter of 93% (Spearman’s r=0.944). In contrast, in midstream urine, enterococci (in 10% of cultures) and group B streptococci (in 12% of cultures) were not predictive of bladder bacteriuria at any colony count (Spearman’s r=0.322 for enterococci and 0.272 for group B streptococci). Among 41 episodes in which enterococcus, group B streptococci, or both were found in midstream urine, E. coli grew from catheter urine cultures in 61%."

And 95% of women with symptoms but negative cultures still have E. coli by PCR (PubMed).

In the US, 25% of urine isolates are resistant to tmp/sulfa, 17% to ciprofloxacin (PubMed). And it will only get worse with time.

Enterococcus: elderly. Not the young. See above.

Actinobaculum: Hard to grow, suspect with a UTI that grows nothing but does not get better on treatment (PubMed).

P. aeruginosa: chronic foley, neurogenic bladder.

S. aureus: S. aureus in the urine presumptively comes by way of bloodstream and increases mortality 3x (Ref) (PubMed). So look around for an endovascular source: lines etc, although it can occur after instrumentation.

Candida: catheters.

Empiric Therapy

First do NOT treat asymptomatic bacteriuria in young women with recurrent urinary tract infections. They will have an increase in symptomatic disease, probably because the bacteria are protective (PubMed).

Actually, do NOT treat any asymptomatic bacteriuria outside of pregnant women. That includes catheter associated (PubMed).

Prior cultures predict current culture and sensitivities. "In areas of high fluoroquinolone resistance, ciprofloxacin can be used empirically when prior urine culture results indicate a ciprofloxacin-susceptible organism and there has been no history of intervening fluoroquinolone use (PubMed)."

And most of the time acute cystits is a self limited disease, if not we would never have made it out of the preantibiotic era.  2/3 at least will get better with just ibuprofen, but they will have more symptoms and more pyelonephritis (PubMed).

With resistance increasing, penicillins of all kinds can no longer be used. If there is >20% resistance in your community, don’t use that drug.

- In the female in her childbearing years with uncomplicated cystitis (NEJM):

Primary options

Nitrofurantoin macrocrystals, 100 mg twice daily for 5 days (with meals).

TMP/Sulfa, 160 mg and 800 mg twice daily for 3 days.

Fosfomycin trometamol (Monurol), 3-g. Useful for resistant organsims (PubMed).

Pivmecillinam, 400 mg twice daily for 3 to 7 days.

For ESBL producing organisms, cefmetazole po was no worse than carbapenems (PubMed).

And consider cyloserine for resistant E. coli. Yes, it's a TB drug, but it is effective against gram negative rods (PubMed).

Second-line therapy

Quinolone: Ciprofloxacin, 250 mg twice daily for 3 day; levofloxacin, 250 mg or 500 mg once daily for 3 days.

Beta-lactams (e.g., amoxicillin–clavulanate, cefdinir, cefaclor, and cefpodoxime– proxetil) for 3 to 7 days; Ciprofloxacin is superior to cefpodoxime (PubMed).

In febrile UTI, 7 days is fine for females; males need 14(PubMed).

- In the elderly with recurrent UTI, intravaginal estrogens can prevent disease.

- Hospitalized patients should receive either a third generation cephalosporin OR a quinolone; aminoglycosides are reasonable as well. You have to know your local antibiotic susceptibility patterns to make a reasonable decision. Yeah, what a shock. You have to know some microbiology.

Candida? Probably not a cause of fever and symptoms although it may represent a marker/risk for disseminated disease, especially in the ICU. Treat? Probably a waste of time if the foley is left in and self-limited if removed. was equally efficacious in achieving overall cure, and resulted in greater clearance of candiduria compared to fluconazole.Amphotericin bladder is equal fluconazole for the treatment of candiduria and may be preferred over fluconazole in patients with renal dysfunction (Pubmed) although not pleasant for the patient.

- Chronic Foley, urinary diversions, and suprapubic catheters present a particular problem, esp in the quad. Is the multiply resistant organism in the urine a pathogen? Or part of the normal flora? Got me. You have to make a clinical decision based on symptoms. As a rule these patients should be treated for 14 days, and remember the convenience of once daily im aminoglycosides in these patients; they will not feel the injection if they are paraparetic. Otherwise, see a specific organism for optimal antibiotic therapy.

In trauma ICU patients 5 days was sufficient for foley associated UTI's (PubMed).

In spinal injury patients, 5 days of rx with a catheter change is as good as 10 days without (PubMed).

Prevention: usually doesn't work, UTI associated with a new sexual partner benefits from a single dose of antibiotics after intercourse. Cranberry juice almost certainly is not effective (PubMed). Lactobacillus was equal to TMP/Sulfa for prevention post-menopausal women in a study that, since it had no placebo group, is suspect (PubMed).

Drinking 12 cups of water a day halves the recurrance rate and doubles the duration between infections (PubMed)compared to drinking 6 cups of water a day.

How about preventing catheter infections in the hospital? There is a 'bundle' of techniques that if applied will decrease the number of catheter related UTI's. Your best bet is not put them in (I am DNF. Do not foley) and take them out asap. A dose of antibiotics at catheter removal may decrease subsequent UTI's but it is it worth the cost and driving resistance (PubMed)?

Maybe D-Mannose, 2 grams a day, for prevention of recurrent disease (PubMed). There is one study, and given that most of the medical literature is false I am less that sanguine as to its validity.

Pearls

- Children and adult males with cystitis should be evaluated: children for reflux and sexual abuse, men for anatomical reasons. Women if they get more than 3 cases in a year not associated with a new sexual partner.

- removing stones will decrease recurrent infections by only 50% (PubMed).

- prophylaxis only really works in patients who get a UTI after intercourse. A single tablet immediately after intercourse, will prevent infection. The rest of the time all you are doing is breeding resistance.

- prophylaxis with a single dose of antibiotics may work after pulling a catheter, but like all such studies one does not know how good basic foley care is (probably not so good) and the antibiotics are a surrogate for sloppy care (PubMed). Or maybe the catheter is the moral equivalent of sex. Ouch.

- treat bacteruria without pyuria pregnant women and maybe patients with recent Foley. In the bedridden elderly probably ignore it: it is a marker of their illness.

- treating asymptomatic bacteruria in the diabetic female will lead to decreased infections, but they will get rapidly recolonized with new strains (PubMed).

- in a study out of Mexico 100 mg a day of vitamin C more than halved the UTI rates in pregnant women (PubMed).

- it is impossible to know if the bacteruria in a quad or chronically catheterized patient is the cause of infection; you usually have to make a clinical decision. Don't call me, I do not know any better than you do.

- if a child has a UTI, think abuse.

- in the elderly with recurrent UTI, intravaginal estrogens can prevent disease.

- cranberry juice? Nope. It is certainly not effective (PubMed) (PubMed). Its use should be limited to Cosmopolitans.

- in a phase two trial, intravaginal Lactobacillus decreased recurrence rates by half (PubMed). Probiotics are somewhat helpful in preventing recurrent disease in postmenopausal women, but not as good as antibiotics (PubMed). Lactobacillus was equal to TMP/Sulfa for prevention in post-menopausal women in a study that, since it had no placebo group, is flawed and the results suspect (PubMed).

- screening for asymptomatic bacteriuria should be limited to pregnant females (PubMed). Diabetics with asymptomatic bacteriuria need not be treated (PubMed).

- Asymptomatic white cells in the urine is not a risk for infection and is not a reason to postpone surgery (PubMed).

- And are antibiotics necessary in hip arthroplasty with asymptomatic bacteriuria? Spoiler alert: No (PubMed). Nor for open heart (PubMed).

Rants

I think Candida cystitis is rarely a cause of fever in and of itself, however it may well be a marker in you patient for disseminated candidiasis.

Chronic nitrofurantoin is stupid stupid stupid, it can lead to pulmonary fibrosis and retroperitoneal fibrosis.

The true axis of evil is Iran, North Korea and the Foley Catheter, and until the first two lob a nuke at use, more have died from the third in this century. People leave it in FOREVER, if you do not need it, remove it. I bet you have a half dozen patients on your in patient service right now who have a foley and do not need it. Yes you do, you just don't know it. What a maroon.

From me (RDCT).The guidelines say

In patients with spinal cord injury, increased spasticity, autonomic dysreflexia, or sense of unease are also compatible with CA-UTI (A-III).

Both of these reccomendations are A-III

A is Good evidence and III is the source of the evidence:

evidence of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.

In other words, III is likely worthess biased garbage. If there is one thing I have learned in by time at SBM, A and III do not belong together. Ever. It is "in my experience" hidden in Roman numerals.

The expert committee is from 1992. 35 years ago. It would be safe there is little from that era concerning UTI’s that holds true today. Just what the 1992 report based its opinion on I cannot say; after 35 years it is still behind a paywall.

As best I can tell there is not a lick of real data to support increased spasticity, autonomic dysreflexia, or sense of unease as indicative of a UTI. But we have trained patients and health care workers alike to say it is so.

And when you think about how much money is spent on this problem, mostly breeding bacterial resistance, you would think there would at least at least some hard evidence to guide us. Nope.