Topic Discussion During Internal Medicine Rotation

1. 1
CCVss
 Acute complicated UTI
o Infection extending beyond the bladder
o Includes: pyelonephritis, unresolved simple UTI, men2
o Typically caused by a BORADER spectrum of bacteria
o Risk factors: Stones, catheters,3
immunocompromising
conditions, urologic abnormalities
Background and Terminology of Urinary Tract Infections (UTIs)
Anna Sandler
Urinary Tract Infections
PharmD Candidate, 2023
 Acute simple cystitis
o Infection confined to the bladder
o Exclusions: pregnancy, kidney transplant recipients, men
o Does not automatically exclude those with urologic abnormalities
or immunocompromised states1
o Epidemiology: More common in women (shorter urethra)
o Risk factors: Prior history, recent sexual intercourse, use of
spermicides, female gender, older or younger age
1. These states include neutropenia, diabetes mellitus, and advanced HIV infection.
2. In the absence of s/sx of an infection extending beyond the bladder, men can be treated with the acute simple cystitis
.approach. In general men have a lower risk of cystitis due to a longer urethra, a drier periurethral environment and
prostatic fluid that contains antibacterial substances.
3. Catheterization can compromise the bladder and promote an ideal environment for pathogens with the accumulation of
fibrinogen. The bacteria multiply, form biofilms, damage endothelium and ultimately spread to the kidneys.
UTIs
Uncomplicated Complicated
Pyelo
Prostatitis
Etiology and Pathophysiology
1. Adherence
2. Colonization
3. Migration to
bladder
4. Biofilm formation
and multiplication
5. Epithelial damage
6. Ascension to the
kidneys
 UTIs are one of the most common causes of sepsis (urosepsis), most common
infections in renal transplant patients, ~20% bacteremias originate from UTIs
Common culprits in uncomplicated UTIs:
1. Escherichia coli (GNR)
2. Klebsiella pneumoniae (GNR)
3. Staphylococcus saprophyticus (G+)
4. Enterococcus faecalis (G+)
5. Group B Streptococcus (G+)
6. Proteus mirabilis (GNR)
7. Pseudomonas aeruginosa (GNR)
Common culprits in complicated UTis:
1. Escherichia coli (GNR)
2. Klebsiella pneumoniae (GNR)
3. Enterococcus spp. (G+)
4. Candida spp.
5. Group B Streptococcus (G+)
6. Proteus mirabilis (GNR)
7. Pseudomonas aeruginosa (GNR)
The most
common
organisms are
gram negative
rods (GNRs)

2. 2
Directed antimicrobial
therapy
Diagnosis and Presentation
 Simple UTI:
o 1) Increased urinary frequency,
urgency, dysuria, hematuria
+ 2) suspicion of urinary source
 Urinalysis (UA)4
o Can begin empiric antibiotics if
meet these two criteria while
waiting for urine cultures (cx)
 Do not need urine cx unless resistant
organisms
Complicated UTI:
o Same s/sx as simple +
 Fever, chills, flank pain,
sepsis with suspected
urologic source, cystitis > 7
days, known antibiotic
(abx) resistance, acute
mental status changes
 High-risk groups: pediatrics,
pregnancy, renal failure
Treatment Principles
4. In women with typical acute simple cystitis symptoms, a UA is usually not necessary since pyuria is present in almost all women
who present with acute cystitis. However, a UA can be helpful in determining alternative diagnoses. Differentials can include
vaginitis, urethritis, and pelvic inflammatory disease.
Acute simple cystitis Complicated UTIs
Special Populations,
Asymptomatic Bacteriuria
PK/PD
properties
General themes:
 Understand complicated versus
uncomplicated infection
 Keep in mind risk of resistant
organisms and reserve specific
agents for them
 De-escalate and transition to oral
agents when appropriate

3. 3
Acute simple cystitis
Low risk resistance
Nitrofurantoin
Trimethorpim-
sulfamethoxazole
Fosfomycin
Alternatives:
Oral beta lactams: Cefdinir,
Cefpodoxime,
Amoxicillin/Clavulanate
FLQs
High risk resistance
Nitrofurantoin
Fosfomycin
Treat based off cx
Empiric Treatment of Acute Simple Cystitis
 Depends on risk of infection with multidrug-resistant gram-negative organisms (MDROs)
o Prior urinary isolates
o Inpatient stays at health-care facilities
o Use of broad-spectrum agents
 Fluoroquinolones (FLQs)
 Third or fourth generation cephalosporins
o Obtain urine cx for high-risk patients and proceed to directed antimicrobial selection

4. 4
Drug MOA and coverage Dose and Duration Pearls
Nitrofurantoin Coverage: GNRs, Enterococci, S.
saprophyticus, Group B strep.
Inhibits bacterial enzymes
100 mg PO BID X 5-7
days (Macrobid)
50-100 mg Q6H X 5-
7 days
(Macrodantin)
Avoid in pyelo due to
poor concentration
outside the bladder
Admin. With food
Avoid if CrCl < 30
mL/min
Monitoring:
Pulmonary reaction,
LFTs, renal function
Fosfomycin Coverage: GNRs, (+ ESBLs!) Enterococci,
(+ VRE) S. saprophyticus
Inhibits bacterial enzymes
Cell wall synthesis inhibitor
3-gram powder
mixed in water X 1
dose
Typically reserved
due to coverage of
resistant organisms
Not renally dose
adjusted
ADRs: N/V, headache
Trimethoprim-
sulfamethoxazole
(TMP/SMX)
Coverage: MSSA, Strep spp. GNRs
TMP: Inhibits dihydrofolic acid reduction
SMP: Interferes with bacterial folic acid
synthesis
One double-
strength (DS) tablet
160/800 mg PO BID
X 3 days
Monitoring: CBC,
CMP, renal, function,
LFTs.
Amoxicillin-
clavulanate
Coverage: GNRs, anaerobes, strep spp.
enterococci
Beta lactam/beta lactamase inhibitor 
inhibit cell wall synthesis
500 mg PO BID X 5-7
days
Renal dosing based
on amoxicillin
component
ADRs: Diarrhea,
Monitoring;
Hypersensitivity
reactions
Cefdinir Coverage: GNRs, strep. spp.
Cell wall synthesis inhibitor, 3rd
gen
cephalosporin
300 mg PO BID X 5-7
days
Monitoring;
Thrombocytopenia,
hypersensitivity
reactions
Drug table: Acute Simple Cystitis
 Obtain urine cx from all and initiate empiric tx right away
 Empiric tx is dependent on:
o Severity of illness
o Risk factors for MDR
o Host factors (+/- urologic abnormalities, etc.)
o Prior susceptibilities and cultures, prior hx of extended-spectrum beta lactamase-
(ESBL) or carbapenemase (CRE)-producing organisms.
o Hx abx use
 Always keep in mind suspected culprits and resistant patterns
 Switch to appropriate oral regimen once sx improve and culture results return
Empiric Treatment of Complicated Cystitis
What organisms are we not
covering?
What organisms are not
covered by cephalosporins
?
Why is are CBC and CMP
panels required for
TMP/SMX?

5. 5
Drug MOA and Coverage Dose and Duration Pearls
Meropenem Coverage: PsA,
Anaerobes, GNRs
(+ESBLs) strep, MSSA,
Cell wall synthesis
inhibitor
1 g IV every eight hours
X 5-14 days
Renally dose adjusted
Has extended and
continuous infusion
methods
Monitoring:
Hypersensitivity, CNS
toxicity
Piperacillin/tazobactam Coverage: PsA
Anaerobes, GNRs, GNRs
(+ESBLs) strep, MSSA,
Beta lactam/beta
lactamase inhibitor
3.375 g IV every 6-8
hours X 5-14 days
Pay attention to
extended vs.
conventional infusion
methods and renal
function
Complicated Cystitis
Critical illness/sepsis
Anti-pseudomonal (PsA)
carbapenem (imi or
mero) +
vanco/dapto/linezolid
Reserved: fosfo,
cefideroocol, combos
Low risk MDROs
Ceftriaxone or
Piperacillin/Tazobactam
(Pip/tazo)
Alternatives: FLQs
High risk MDROs
Pip/tazo5
Cefepime
Imi or mero
Empiric Treatment of Complicated Cystitis
Drug Table: Complicated Cystitis
ESBLs are seen most
commonly in?
CREs are seen most
commonly in?

6. 6
Drug MOA and Coverage Dose and Duration Pearls
Ceftriaxone Coverage: GNRs, strep,
3rd
generation
cephalosporin
1 g IV once daily X 5-14
days
Not renally dose adjusted
Monitoring:
Hypersensitivity reactions
Cefepime Coverage: PsA
Anaerobes, GNRs, GNRs
strep spp.,
4th
generation
cephalosporin
2 g IV every 12 hours X
5-14 days
Avoid if patients have
risk-factors for ESBL-
producing organisms
Monitoring:
Thrombocytopenia,
hypersensitivity reactions
Vancomycin Coverage: Gram
positive organisms
only: MRSA, strep. Spp.,
enterococci,
Follow institutional
dosing protocols
Monitoring: Renal function
Linezolid Coverage: Gram
positive organisms
only: MRSA, strep. Spp.,
enterococci (+ VRE)
Bacterial protein
synthesis inhibitor
600 mg IV every 12
hours X 7-10 days
ADRs: Diarrhea, decreased
white blood cell count,
increased serum lipase,
anemia,
thrombocytopenia,
peripheral/optical
neuropathy
Not renally dose adjusted
Ciprofloxacin Coverage: Atypicals,
strep spp. Enterococci,
GNRs, PsA
DNA gyrase inhibitor
breakage of DNA
400 mg IV every 12
hours X 5-7 days
Monitoring: QTc, drug-
drug interactions,
neuropathy, tendon
rupture, CBC, LFTs and
renal function, glucose
Avoid in those with a hx of
myasthenia gravis
Ceftazidime-avibactam
(Avycaz)
Coverage: PsA
Anaerobes, GNRs, GNRs
(+ESBLs) strep,
carbapenem- resistant
enterobacterales
(CREs)
2.5 g Every 8 hours X 5-
14 days
Monitoring: anaphylaxis
after first dose, renal
function
Cefiderocol (Fetroja) Coverage: GNRs, PsA,
CREs,
2 g IV every 8 hours X 5-
14 days
Monitoring: LFTs, CMP,
neurotoxicity
Renally dose adjusted,

7. 7
Bacteria Agents Notes
GNRs Levofloxacin 750 mg PO once
daily
Ciprofloxacin 500 mg PO BID or
1000 mg ER PO once daily
TMP-SMX One DS tab PO BID
Oral beta lactams may be less
effective but may be
appropriate alternatives
Enterococcus Amoxicillin 500 mg PO every 8
hours or 875 mg BID
PsA Simple cystitis: Fosfomycin,
ciprofloxacin
Complicated: Ciprofloxacin
Duration in acute simple: 3-5
days
Pyelonephritis duration: 2-3
weeks
Staphylococcus TMP-SMX One DS tab PO BID S. aureus is an uncommon
isolate but when present,
blood cultures should be sent
to r/o bacteremia
Directed antimicrobial therapy
 Acute simple cystitis:
o Often times only treated empirically unless there is risk of resistance
 Complicated UTIs
o Often times, broad-spectrum regimens can be replaced with narrow-spectrum agents
 Always try to tailor to susceptibility results

8. 8
•Mainly gram negative organisms (E. coli, PsA, Enterobacter, Klebsiella)
•Simple or complex
•Prophylaxis:TMP/SMX (alternatives: atovaquone, nitrofurantoin, cephalexin) six months-one year post-
transplant
•Simple: Oral agents (cipro, nitro,cefdinir, amoxicillin-clavulanate) X 10-14 days or 5-7 days if > 6
months post-transplant
•Complicated: Cover PsA (Pip/Tazo 4.5 g IV every six hours, Meropenem, vancomycin + cefepime) X
?14-21 days
Kidney Transplant Recipients5
•Lack of treatment benefits in most
•Special populations: Pregnancy, Renal Transplant recipients, Planned urologic interventions
•Pregnancy: Beta-lactams, nitro, fosfo, TMP/SMX6 X 5-7 days
Asymptomatic Bacteruria
•Acute Empiric: Cover gram-negative organisms: Oral- TMP/SMX or FLQ; IV-FLQ +/- AMG or beta-lactam
treated up to 4 weeks
•Consider N. gonorrhoeae and C. trachomatis coverage in select populations7
•Chronic empiric: FLQ 8 > TMP/SMX, macrolide, doxycycline or oral beta-lactams X 4-6 weeks
(TMP/SMX > 6 weeks), fosfo
Acute and Chronic Prostatatitis
•Education: Increased fluid intake, frequent voiding, contraception modification
•Continous prophylaxis for recurrent simple cystitis in females: Nitro, TMP/SMX with lower doses <
treatment
Reccurent UTIs and Education
Special Populations and Asymptomatic Bacteriuria
5. Kidney transplant recipients are susceptible to UTIs due to absence of a sphincter between the transplanted ureter and the
native bladder. Ureteral stents that are placed during transplantation serve as reservoirs for bacteria, placing patients at higher
risks of recurrent UTIs. The highest risk of developing a UTI is believed to be within the first month after transplant.
6. Avoid during first trimester and at term but only appropriate during these periods when the alternatives cannot be used.
7. Men < 35 y/o who are sexually active and men >35 who engage in high-risk sexual behavior.
8. FLQs have better penetration into prostatic fluid; the prostatic fluid has a low pH, resulting in higher concentrations of drugs
with alkaline pKas.
Do not use
prophylactic
agents for tx!

9. 9
1. Harris PNA, Tambyah PA, Lye DC, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-
Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and
Ceftriaxone Resistance: A Randomized Clinical Trial. JAMA. 2018;320(10):984.
doi:10.1001/jama.2018.12163
2. Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the
Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the
Infectious Diseases Society of America and the European Society for Microbiology and Infectious
Diseases. Clinical Infectious Diseases. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257
3. Bono MJ, Leslie SW, Reygaert WC, Doerr C. Urinary Tract Infection (Nursing). In: StatPearls.
StatPearls Publishing; 2022. Accessed September 4, 2022.
http://www.ncbi.nlm.nih.gov/books/NBK568701/
4. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology,
mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269-284.
doi:10.1038/nrmicro3432
UpToDate Links:
1. https://www.uptodate.com/contents/acute-complicated-urinary-tract-infection-including-
pyelonephritis-in-
adults?search=complicated%20cystitis%20treatment&source=search_result&selectedTitle=1~15
0&usage_type=default&display_rank=1#H2417976538
2. https://www.uptodate.com/contents/acute-simple-cystitis-in-
women?search=urinary%20tract%20infection%20&source=search_result&selectedTitle=5~150&
usage_type=default#H88979215
3. https://www.uptodate.com/contents/image?imageKey=ID%2F98083&topicKey=ID%2F8065&se
arch=asymptomatic%20bacteriuria%20pregnancy&source=see_link
4. https://www.uptodate.com/contents/urinary-tract-infection-in-kidney-transplant-
recipients?search=complicated%20uti%20&source=search_result&selectedTitle=9~113&usage_
type=default#H1473408516
5. https://www.uptodate.com/contents/acute-bacterial-
prostatitis?search=prostatitis%20treatment&source=search_result&selectedTitle=1~99&usage_
type=default&display_rank=1#H29437530
Picture Links:
1. https://www.niddk.nih.gov/health-information/diagnostic-tests/urinary-tract-imaging
2. https://www.labtestsguide.com/urine-culture
3. https://todayhealth24.com/the-main-causes-of-kidney-infection-and-treatment.html
4. https://infectionsinsurgery.org/core-elements-of-antibiotic-stewardship/
5. https://www.nhsbt.nhs.uk/organ-transplantation/kidney/at-the-transplant-centre/kidney-
transplant-surgery/
References

10. 10
Appendix
Common pathogens in complicated and uncomplicated UTIs
Ureteral stent placed during kidney transplantation

11. 11
Spectrum of beta-lactam resistance