What if it’s not just cystitis? Disposition of pyelonephritis…

Authors: Diksha Mishra, MD (New York Presbyterian Hospital Weill Cornell-Columbia Irving Medical Centers) and Mark Curato, MD (New York Presbyterian Hospital Weill Cornell Medical Center) // Reviewed by: Tim Montrief, MD (@EMinMiami); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 68-year-old male, with no past medical history, presents with two days of dysuria, increased urinary frequency, left flank pain, and subjective fevers. He has no trouble urinating. He is febrile, tachycardic, and normotensive. His physical examination reveals suprapubic and left flank tenderness. He is otherwise well-appearing. His BUN, creatinine, lactate, and electrolytes are normal, and his leukocyte count is 16,000 u/L. His urinalysis reveals nitrites, white blood cells, and bacteria.

The diagnosis of pyelonephritis is made, and attention turns to the patient’s disposition.

Disposition:

Traditionally, the teaching has been to hospitalize all patients diagnosed with acute pyelonephritis.¹ Recent literature, including multiple randomized control trials, has suggested otherwise and supports outpatient therapy with oral antibiotics for low-risk immunocompetent individuals.^2–7 For example, in a study done by Ward et al. in emergency department observation units, 44 females with suspected pyelonephritis and positive urine cultures (but otherwise no comorbidities, no one above the age of 55, and no concern for sepsis/systemic illness) were given two doses of intravenous trimethoprim- sulfamethoxazole and then discharged on an oral trimethoprim-sulfamethoxazole regimen. 7 were lost to follow-up but the rest did well despite initially presenting with fever and/or nausea.⁸

Many studies have also suggested that some moderately ill patients may be able to be discharged from the emergency department after a period of observation. In a retrospective study done in the municipal teaching hospital of Denver’s emergency department observation unit by Scott et al., 63 of 87 moderately ill patients with acute pyelonephritis (72% of studied patients) received two IV doses of ampicillin and went home on amoxicillin or trimethoprim- sulfamethoxazole with success while 24 (28% of studied patients) were later hospitalized. Moderately ill was being defined by febrile temperatures, heart rates greater than 90, and a white blood cell count (WBC) of greater than 10,000 per microliters of blood. The authors concluded that with initial admission to an emergency department observation unit, most patients had good outcomes.⁹

A different study suggests that perhaps a period of observation isn’t even necessary at all. A retrospective chart review performed by Safrin et al. showed that the majority of immuno- competent women could potentially be treated as outpatients. Safrin’s group reviewed the records of 94 non-hospitalized and 100 hospitalized adult female pyelonephritis patients with similar characteristics and clinical comorbidities at San Francisco General Hospital with follow-up obtained on 67 non-hospitalized and 76 hospitalized patients. 90% of the non-hospitalized follow-up group, despite the presence of 8 patients older than age 50, 3 patients with a history of renal calculi, 13 patients with a temperature higher than ~38.9°C, and 11 patients with a peripheral WBC of more than 15,000/per microliters of blood, had a successful response to oral trimethoprim-sulfamethoxazole or ampicillin. The success rate for both outpatient and inpatient treatment were similar. The study concluded that the majority of healthy females, despite fevers or high WBCs, could be managed with outpatient antibiotics and close 24-48 hour follow-up.¹⁰

Most remarkably, in a 2007 Cochrane review of fifteen randomized control trials involving 1743 patients receiving oral vs intravenous vs “switch” therapy (intravenous dosing in the emergency department and then discharged on oral antibiotics) for the treatment of acute pyelonephritis, the evidence suggests that oral antibiotic therapy is not inferior to intravenous or switch therapy.¹¹ As a result, it is fairly well suggested in the literature that most pyelonephritis patients with mild to moderate illness could potentially be managed outpatient with oral antibiotics +/- possible observation in the emergency department.

The issue that arises then is how we define pyelonephritis in terms of mild and moderate illness. A study done at the University of Virginia Health Sciences Center by Pinson et al. looked at 28 hospitalized and 83 non-hospitalized pyelonephritis patients to see which were most likely to be kept inpatient. The team showed that patients being admitted were more likely to be older (odds ratio [OR] = 1.07), with diabetes (OR = 10.57), genitourinary tract abnormalities (OR = l0.53), vomiting (OR = 12.17), and/or temperatures greater than 38 degrees Celsius (OR = 8.12).¹² Studies done by Choi et al. and Chung et al. showed a similar distribution of patients. In the observational cohort study done by Choi et al. in 18 different hospitals in South Korea, the outpatient treatment group was younger, had fewer comorbidities, and were more likely to have milder infection. They stated these patients could be safely treated with oral medications.¹³ Out of the 68 hospitalized pyelonephritis patients the Chung study looked at, 57% of the patients had impaired renal function and 37% were diabetic; 75% of the patients demonstrated radiological evidence of urinary tract obstruction and required subsequent drainage procedures.¹⁴

Not only is it useful to look at the characteristics of pyelonephritis patients who have been admitted, but, more importantly, to also investigate what factors play into determining if a patient is at a higher risk for treatment failure and need of hospitalization. A study done by Efstathiou et al. specifically showed that factors associated with death among hospitalized male and female patients with pyelonephritis included age > 65 years, septic shock, and bedridden status. The patients they looked at, especially the females, tended to be bed-ridden and debilitated at baseline. Prolonged hospitalization was noted among male patients and female patients with diabetes mellitus, long-term urinary catheterization, and change in initial antimicrobial therapy.¹⁵

 In a study done by Pertel et al. that looked at five hundred and twenty-two patients, a mix of men and women, to identify risk factors for the failure of treatment for acute pyelonephritis, the multivariate analysis found that hospitalization at baseline (OR 30.3 (6.8–142.9), P < 0.001), the presence of a resistant infecting organism (OR 8.7 (3.5–21.7), P < 0.001), diabetes mellitus (OR 8.3 (2.3–30.3), P = 0.001), and a history of kidney stones (OR 7.2 (1.9–27.8), P = 0.004) were significant predictors of treatment failure.¹⁶

A study done by Foxman et al. sought to look at in-hospital mortality and the relation of hospitalization to length of hospital stay, race, and hospital location. The odds of dying in the hospital were 27% higher among males than females hospitalized for acute pyelonephritis (OR 1.30, 95% CI: 0.99, 1.62)). The odds of dying in the hospital also grew with increasing age, number of procedures and diagnoses, and having a major diagnostic category other than “Disorders of the kidney and urinary tract.”  Mortality was decreased for those living in zip codes with higher median incomes (mean OR 0.7, 95% CI: 0.4-1.15).¹⁷

There has also been some research done on special populations and pyelonephritis. For instance, in pregnancy, pyelonephritis has been strongly related to both medical and obstetrical adverse outcomes. In a retrospective study done in Southern California’s Kaiser Healthcare system looking at 543,430 pregnant women, out of which 2894 patients were diagnosed with pyelonephritis, the rate of preterm birth in these patients with pyelonephritis was 10.3% vs 7.9% in females without pyelonephritis (OR 1.3, 95% CI 1.2-1.5). Rates of anemia, sepsis, and respiratory distress were other complications that were also shown to be elevated in patients with pyelonephritis.¹⁸ In a prospective study done at Parkland Hospital in Dallas, 32,282 pregnant women, of which 440 were diagnosed with acute pyelonephritis, showed complications including anemia (23 %), bacteremia (17 %), and respiratory insufficiency (7 %).¹⁹ The studies related to pyelonephritis in those with kidney transplants are not as clear in regards to adverse outcomes, but do show possible increased chances of renal failure, graft rejection, and patient mortality.^20–22

Despite limited and sometimes conflicting data, especially on outcomes for male, kidney transplant, diabetic, and immunocompromised patients, the above studies help to guide appropriate disposition for patients diagnosed with pyelonephritis. Below are listed guidelines, but remember to take the entire clinical picture into consideration when determining disposition.

Discharge home from the ED

• Indicated for mild to moderately ill patients who are able to tolerate oral intake; not persistently tachycardic, hypotensive, or tachypneic; have stable coexisting medical comorbidities, a reliable psychosocial situation, an appropriate oral antimicrobial regimen, and can obtain outpatient follow-up.²³

Prolonged observation in the ED or observation unit

• Indicated for moderately ill patients who are initially unable to tolerate oral intake, require intravenous hydration, have transiently abnormal vital signs, or initially appear ill.²³

Admission to the Hospital

• While the majority of patients with pyelonephritis can be discharged from the emergency department, admission should be considered in the following instances:
  • Unstable vital signs, e.g. persistent tachycardia, hypotension, tachypnea, or signs of septic shock
  • Resistance to oral antibiotics or complicated antibiogram with history of repeat infections
  • Inability to take oral medications regardless of medical interventions
  • Refractory pain
  • Psychosocial issues hindering self-care
  • Pregnancy
  • Immunocompromised state
  • Infected transplanted graft
  • Repeat presentation to the emergency department with worsening condition
  • Imaging demonstrating obstructing urolithiasis, abscess, cyst, or abnormal genitourinary tract anatomy

Take Home Points:

• A diagnosis of pyelonephritis is made through a combination of vital signs, clinical presentation, physical exam, and urinalysis. It is essential to take the entire clinical picture into account when deciding on a disposition for a patient
• Discharge home with oral antibiotics is an appropriate disposition plan for the majority of mild to moderately ill acute pyelonephritis patients who are able to tolerate oral intake and are not persistently tachycardic, hypotensive, or tachypneic. They should also have stable coexisting medical comorbidities, a reliable psychosocial situation, an appropriate oral antimicrobial regimen, and access to outpatient follow-up.
• It is important that, regardless of disposition decision, all of your patients have appropriate follow-up to assess for improvement in symptoms

Further Reading:

• emDocs: Pyelonephritis
• EMRAP: Pyelonephritis Treatment in an Obs Unit
• EMRAP: Pyelo Inpt Vs Outpt
• First10em0 UTIs

References:

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2. Sabbaj J, Hoagland VL, Shih WJ. Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections. Antimicrob Agents Chemother. 1985; 27:297-301
3. Karachalios GN. Randomized comparative study of amoxicillin-clavulanic acid and co-trimoxazole in the treatment of acute urinary tract infections in adults. Antimicrob Agents Chemother. 1985; 28: 693-694
4. Stamm WE, McKevitt M, Counts GW. Acute renal infection in women:Treatment with trimethoprim-sulfamethoxazole or ampicillin for two or six weeks; a randomized trial. Ann Intern Med. 1987; 106: 341-345
5. Dobrovits G, Reicher. Treatment of acute pyelonephritis using two dosage regimens of amoxicillin. Curr Ther Res. 1990; 47:1043-1048
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9. Scott M. Management of Acute Pyelonephritis in an Emergency Department Observation Unit.  Annals of Emergency Medicine. 1991; 20: 253-257
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13. Choi H, Chung J, Won O. Outpatient treatment in women with acute pyelonephritis after visiting emergency department. Korean J Intern Med 2017; 32:369-373
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20. Pelle G, Vimont S. Acute Pyelonephritis Represents a Risk Factor Impairing Long‐Term Kidney Graft Function. American Journal of Transplantation. 2007; 7: 899-907
21. Ariza-Heredia, EJ et al. Impact of Urinary Tract Infection on Allograft Function After Kidney Transplantation. Clin Transplant. 2014; 28(6):683-90
22. Chuang, P. Parikh, CR. Langone, A. Urinary Tract Infection After Renal Transplantation: A Retrospective Review at Two US Transplant Centers. Clin Transplant. 2005;19(2):230-5
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