AN OVERVIEW OF PYELONEPHRITIS DIAGNOSIS, AND MANAGEMENT APPROACH: A LITERATURE REVIEW

Muayad Mohammed Algrairy¹, Amani Mohammed H Al Zainaldeen², Khalid Ali Rofidi³, Nhlah Mohammed Nasser⁴, Hadeel Salim Rizvi⁵, Abdullah Aiad Own⁶, Ibrahim Ayed Alqahtani⁶, Rawan Fahad Alsubaie¹, Sara Adel Aljumaan⁷, Khalaf Mohammed Alkhalaf^3*, Edris Mohammad Alqannad³

ABSTRACT

Background: Pyelonephritis is a type of urinary tract infections (UTIs) that can cause severe systemic troublesome manifestations. Untreated cases of pyelonephritis can let the inflammation damage the renal pelvis and its parenchyma. Besides, untreated infections may lead to sepsis, which can increase the rate of mortality. Objective: To study the published literature and provide an adequate review of evaluating and managing pyelonephritis properly. Method: PubMed database was used for articles selection, and the following keys were used in the mesh ((“Pyelonephritis"[Mesh]) AND (“management” [Mesh]) OR (“evaluation"[Mesh])). Conclusion: There is a wide range of possibilities regarding the clinical course of pyelonephritis as it ranges from only mild symptoms to emphysematous pyelonephritis with a fulminant course. The diagnosis of pyelonephritis should depend on clinical findings as well as laboratory values. Imaging is also needed in order to properly treat the true nature of the disease. The mainstay of UTIs treatment is antibiotics. Choosing the proper antibiotic is a difficult challenge facing the physician. Hydration is also cardinal in managing UTIs especially when there is an association between dehydration and the condition.

Keywords: Pyelonephritis, Diagnosis, and Management

Introduction

Pyelonephritis is a type of UTIs that can be associated with serious outcomes [1]. In the United States, its incidence is 250,000 cases per year. Among females, 11.7 cases per 10,000 population are hospitalized due to pyelonephritis while the number of hospitalized cases per 10,000 populations among males is 2.4 cases [2].

It is also called upper UTI as it develops when the bacterial infection reaches the kidneys via the ureter or through the bloodstream [3, 4]. Pyelonephritis can lead to not only local symptoms but it can cause severe systemic troublesome manifestations such as fever, chills, nausea, and vomiting [1]. In cases of untreated pyelonephritis, the inflammation may damage the renal pelvis and its parenchyma. Besides, the untreated infection may lead to sepsis, which can increase the rate of mortality in such cases to 10-20% [5, 6]. In this article, we aim to review the literature that discussed pyelonephritis and to provide a summarized review explaining the proper evaluation and approaching cases of pyelonephritis.

Methods:

PubMed database was used for articles selection, and the following keys were used in the mesh ((“Pyelonephritis"[Mesh]) AND (“management” [Mesh]) OR (“evaluation"[Mesh])).

In regards to the inclusion criteria, the articles were selected based on the inclusion of one of the following topics: Pyelonephritis, evaluation, and management.

Exclusion criteria were all other articles, which did not have one of these topics as their primary endpoint.

Discussion:

Pyelonephritis can occur to healthy individuals without any functional nor structural anomalies present in the urinary tract [3, 4]. Pyelonephritis can present as an uncomplicated case or complicated. Uncomplicated cases present usually mild symptoms and can be treated as an outpatient. On the other hand, complicated pyelonephritis cases usually need hospitalization in order to avoid life-threatening complications such as sepsis, septic shock, and multiorgan failure [7].

Risk factors of complicated pyelonephritis include stones, obstruction, abnormal urinary tract, diabetes, pregnancy, and an immunocompromised state. There is a wide range of possibilities regarding the clinical course of pyelonephritis as it ranges from only mild symptoms to emphysematous pyelonephritis with a fulminant course [7, 8].

In pyelonephritis, Escherichia coli is the responsible bacteria for most cases. Klebsiella pneumoniae and enterococcus faecalis are other common causative agents [3, 9-11].

The diagnosis of pyelonephritis should depend on clinical findings as well as laboratory values. Clinically, patients of pyelonephritis may present with high-grade fever (more than 38.5 C), dysuria, increased frequency of micturition, flank pain, and costovertebral tenderness. The fever can be associated with rigors. In urinalysis, it is expected to find pus, bacteria, red blood cells, and white cell casts. Urine culture is usually positive [7].

Nevertheless, the clinical and laboratory findings alone cannot estimate the severity and clarify the extent of the condition. Therefore, imaging is also needed to treat properly the true nature of the disease [12]. However, the recent recommendations are against radiological imaging routine use in cases of uncomplicated pyelonephritis, especially in female patients [13]. In cases of suspected complicated pyelonephritis, cases with urinary tract anomalies, and immunocompromised patients, imaging is recommended, especially in male patients [14, 15]. It is also recommended when there is no improvement after 72 hours of antibiotic treatment initiation [7].

The recommended imaging modalities are ultrasound and computed tomography (CT). Ultrasound is useful and helpful but the main imaging tool is CT because CT can show highly specific findings [16]. Ultrasound is routinely used as a first-line tool to evaluate the urinary tract and to look for any positive findings. However, negative findings may appear in most clinically suspected cases of pyelonephritis. This is mostly because interstitial nephritis is not well defined on gray-scale images [16, 17]. However, ultrasound can detect a variety of positive findings in pyelonephritis cases such as congenital anomalies and renal parenchyma changes. Renal parenchyma changes include renal enlargement, edema, hemorrhages, hydronephrosis, and abscesses. Nevertheless, ultrasound is still considered limited regarding differentiating definitively between intraparenchymal gas (emphysematous changes) and calcification as well as accurately predicting the extension of perinephric infections [16, 18].

On the other hand, emphysematous change, parenchymal calcification, calculi, obstructions, and inflammatory masses can be detected and identified using a CT abdomen. CT abdomen with contrast is even more superior to MRI but in patients with contrast allergy, ultrasound and MRI are the alternatives.

In addition, the classification of emphysematous pyelonephritis is based on the findings from the CT scan. Emphysematous pyelonephritis is the presence of gas in the renal parenchyma, perinephric tissue, or collecting system. The classes of emphysematous pyelonephritis range from gas only in the collecting system to bilateral emphysematous pyelonephritis.

It is important to evaluate the potential cases properly to detect and avoid serious complications like systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. SIRS has criteria, which are relied on to define and diagnose. It should include ≥2 of the following findings: high temperature (more than 38.5 C) or hypothermia (less than 36 C), tachycardia, tachypnea, leukocytosis, or leukopenia.

SIRS can develop into sepsis if a clinical infection accompanied it. If the case was associated with hypoperfusion abnormalities like hypotension, oliguria, prerenal azotemia, or altered level of consciousness, it is considered severe sepsis. If the systolic blood pressure remained low (less than 90 mmHg) for at least 1 hour, the case should be diagnosed as septic shock. Without proper intervention, it may subsequently lead to multiple organ dysfunction syndromes (MODS). Therefore, adequate and early evaluation and management are crucial [19].

Management:

The mainstay of UTIs treatment is antibiotics [14]. Choosing the proper antibiotic is a challenge facing the physician. Choosing the antibiotic relies on the infection type, the level of complications, the nature of the condition, and the domestic patterns of antibiotics resistance. Escherichia coli has increased its resistance along with other pathogens throughout the years. This has led to many adjustments regarding UTI treatment in the guidelines [20]. Nevertheless, some uncomplicated cases of UTIs in females can improve without antibiotics in the first week [21].

As an alternative, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in UTIs cases has been studied in order to reduce the use of antibiotics but NSAIDs could not replace the antibiotics even in uncomplicated cases [22, 23].

As we mentioned earlier, antibiotic treatment should be chosen properly. Identification of the bacterial pathogen with a urine culture helps the approach and the choice of the antibiotics. However, there are recommended guidelines regarding the empirical treatment for outpatient management. Oral fluoroquinolones, such as ciprofloxacin (500 mg twice daily for 7 days) or levofloxacin (750 mg once daily for 5 days) are the recommended options when the known local rate of resistance to fluoroquinolone are <10%. If the local resistance fluoroquinolone rates are >10%, a single dose of intravenous ceftriaxone and one week of an oral fluoroquinolone is the preferred option. If susceptibilities are not known, a single dose of intravenous ceftriaxone and 1-2 weeks of trimethoprim/sulfamethoxazole (TMP-SMX) (160/800 mg twice daily) are recommended.

Regarding oral cephalosporins, their efficacy is relatively low in comparison with other choices. Nevertheless, they should be used in limited cases such as when the susceptibilities are known and there are no other proper options. If an enterococcus infection is suspected, ampicillin can be used putting in mind its high rates of resistance for the typical gram-negative bacteria that are common in the UTIs [20].

Regarding inpatient management, one of the wide varieties of intravenous antibiotics can be the appropriate empiric choice as long as the choice was made depending on local resistance patterns and it is suitable for the patient [20]. There is no specific period when to switch to oral antibiotics but it is commonly accepted to choose the proper oral agent when the culture and the sensitivity of the bacteria become available [14].

Every antibiotic agent differs regarding the course duration and the efficacy may vary because of the different durations. Therefore, it is important to know the appropriate duration that should be used for the chosen antibiotic. The recommendations advise using the shortest effective duration possible in order to participate in decreasing the rate of antimicrobial resistance [24].

Regarding fluoroquinolones, the shortest recommended durations are 5 days for levofloxacin and 7 days for ciprofloxacin. TMP-SMX is recommended by the infectious diseases society of America (IDSA) to be used for 2 weeks [20]. However, studies have shown that 1 week of TMP-SMX has equivalent efficacy to a longer duration of the same agent and 1 week of ciprofloxacin [24, 25].

As we mentioned earlier, antibiotics are the mainstay of the treatment but there is a cardinal step in the management, which is hydration. Hydration is key especially when there is associated dehydration with the condition [26]. Pyelonephritis is expected to be associated with dehydration especially in children. If fever is present, the risk of dehydration increases because of fluid and calorie loss. Pyelonephritis can also decrease appetite and reduce fluid intake as well as induce vomiting that increases the level of dehydration [27, 28].

Therefore, hydration orally or intravenously is an important factor in the management process. Proper hydration can hasten the clearance of bacteria from the urinary system [29-31]. Moreover, intravenous fluids are recommended to optimize renal perfusion and urine excretion. Normal saline is the adequate choice as an immediate rehydration fluid in cases of pyelonephritis. For longer rehydration plans and maintenance, dextrose 5% normal saline and half normal saline are the preferred options. Nevertheless, iatrogenic hyponatremia should be avoided when intravenous fluids are administered. Therefore, solutions less than half normal saline are the recommended options to use in long rehydration plans [26].

The physician should always consider therapeutic failure and relapse as outcomes. Therapeutic failure is considered when the symptoms persist or even worsen after 5 days of proper management and relapse is the recurrence of the signs and symptoms of the same infection within the first month after completing the antibiotic course. Relapse sometimes can occur due to different bacterial pathogens causing a new infection. Therefore, proper reevaluation and repeated laboratory testing are recommended [19].

Conclusion:

There is a wide range of possibilities regarding the clinical course of pyelonephritis as it ranges from only mild symptoms to emphysematous pyelonephritis with a fulminant course. The diagnosis of pyelonephritis should depend on clinical findings as well as laboratory values. Imaging is also needed in order to treat properly the true nature of the disease.

The mainstay of UTIs treatment is antibiotics. Choosing the proper antibiotic is a difficult challenge facing the physician. Hydration is also cardinal in managing UTIs especially when there is an association between dehydration and the condition.

References

1. Lee DG, Jeon SH, Lee CH, Lee SJ, Kim JI, Chang SG. Acute pyelonephritis: clinical characteristics and the role of the surgical treatment. Journal of Korean medical science. 2009 Apr 1;24(2):296-30 https://doi.org/10.3346/jkms.2009.24.2.296.
2. Bergeron MG. Treatment of pyelonephritis in adults. The Medical clinics of North America. 1995 May 1;79(3):619-49. https://doi.org/10.1016/s0025-7125(16)30060-8.
3. Kang CI, Kim J, Park DW, Kim BN, Ha U, Lee SJ, Yeo JK, Min SK, Lee H, Wie SH. Clinical practice guidelines for the antibiotic treatment of community-acquired urinary tract infections. Infection & chemotherapy. 2018 Mar 1;50(1):67-100. https://doi.org/10.3947/ic.2018.50.1.67.
4. Hooton TM. Uncomplicated urinary tract infection. New England Journal of Medicine. 2012 Mar 15;366(11):1028-37. https://doi.org/10.1056/nejmcp1104429.
5. Roberts FJ, Greere IW, Coldman A. A three-year study of positive blood cultures, with emphasis on prognosis. Reviews of infectious diseases. 1991 Jan 1;13(1):34-46. https://doi.org/10.1093/clinids/13.1.34.
6. Ispahani P, Pearson NJ, Greenwood D. An analysis of community and hospital-acquired bacteraemia in a large teaching hospital in the United Kingdom. QJM: An International Journal of Medicine. 1987 May 1;63(2):427-40. https://doi.org/10.1093/oxfordjournals.qjmed.a068113.
7. Venkatesh L, Hanumegowda RK. Acute pyelonephritis-correlation of clinical parameter with radiological imaging abnormalities. Journal of Clinical and Diagnostic Research: Jcdr. 2017 Jun;11(6):TC15. https://doi.org/10.7860/jcdr/2017/272410033.
8. Stunell H, Buckley O, Feeney J, Geoghegan T, Browne RF, Torreggiani WC. Imaging of acute pyelonephritis in the adult. European radiology. 2007 Jul 1;17(7):1820- https://doi.org/10.1007/s00330-006-0366-3.
9. Scholes D, Hooton TM, Roberts PL, Gupta K, Stapleton AE, Stamm WE. Risk factors associated with acute pyelonephritis in healthy women. Annals of internal medicine. 2005 Jan 4;142(1):20-7. https://doi.org/10.7326/0003-4819-142-1-200501040-00008.
10. Efstathiou SP, Pefanis AV, Tsioulos DI, Zacharos ID, Tsiakou AG, Mitromaras AG, Mastorantonakis SE, Kanavaki SN, Mountokalakis TD. Acute pyelonephritis in adults: prediction of mortality and failure of treatment. Archives of internal medicine. 2003 May 26;163(10):1206-12. https://doi.org/1001/archinte.163.10.1206.
11. Farrell D, Morrissey I, De Rubeis D, Robbins M, Felmingham DA. A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection. Journal of infection. 2003 Feb 1;46(2):94-100.https://doi.org/10.1053/jinf.2002.1091.
12. Talner LB, Davidson AJ, Lebowitz RL, Dalla Palma L, Goldman SM. Acute pyelonephritis: can we agree on terminology?. Radiology. 1994 Aug;192(2):297-305. https://doi.org/10.1148/radiology.192.2.8029384.
13. Nikolaidis P, Dogra VS, Goldfarb S, Gore JL, Harvin HJ, Heilbrun ME, Heller MT, Khatri G, Purysko AS, Savage SJ, Smith AD. ACR appropriateness criteria® acute pyelonephritis. Journal of the American College of Radiology. 2018 Nov 1;15(11):S232-9.https://doi.org/10.1016/j.jacr.2018.09.011.
14. Kolman KB. Cystitis and pyelonephritis: diagnosis, treatment, and prevention. Primary Care: Clinics in Office Practice. 2019 Jun 1;46(2):191-202. https://doi.org/10.1016/j.pop.2019.01.001.
15. Solomon CG. Acute Pyelonephritis in Adults. New England Journal of Medicine, 2018; 378(11): 1069–69. https://doi.org/10.1056/nejmx180009.
16. Craig WD, Wagner BJ, Travis MD. Pyelonephritis: radiologic-pathologic review. Radiographics. 2008 Jan;28(1):255-76. https://doi.org/10.1148/rg.281075171.
17. June CH, Browning MD, Smith LP, Wenzel DJ, Pyatt RS, Checchio LM, Amis ES. Ultrasonography and computed tomography in severe urinary tract infection. Archives of internal medicine. 1985 May 1;145(5):841-5. https://doi.org/10.1001/archinte.1985.00360050089016.
18. Rigsby CM, Rosenfield AT, Glickman MG, Hodson J. Hemorrhagic focal bacterial nephritis: findings on gray-scale sonography and CT. American Journal of Roentgenology. 1986 Jun 1;146(6):1173-7. https://doi.org/10.2214/ajr.146.6.1173.
19. Umesha L, Shivaprasad SM, Rajiv EN, Kumar MS, Leelavathy V, Sreedhara CG, Niranjan MR. Acute pyelonephritis: A single-center experience. Indian Journal of Nephrology. 2018 Nov;28(6):454. https://doi.org/10.4103/ijn.ijn_219_16.
20. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE. 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 Mar 1;52(5):e103- https://doi.org/10.1093/cid/ciq257.
21. Knottnerus BJ, Geerlings SE, van Charante EP, ter Riet G. Women with symptoms of uncomplicated urinary tract infection are often willing to delay antibiotic treatment: a prospective cohort study. BMC family practice. 2013 Dec 1;14(1):71. https://doi.org/10.1186/1471-2296-14-71.
22. Gágyor I, Bleidorn J, Kochen MM, Schmiemann G, Wegscheider K, Hummers-Pradier E. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. bmj. 2015 Dec 23;351:h6544. https://doi.org/10.1136/bmj.h6544.
23. Vik I, Bollestad M, Grude N, Bærheim A, Damsgaard E, Neumark T, Bjerrum L, Cordoba G, Olsen IC, Lindbæk M. Ibuprofen versus pivmecillinam for uncomplicated urinary tract infection in women—A double-blind, randomized non-inferiority trial. PLoS medicine. 2018 May 15;15(5):e1002569. https://doi.org/10.1371/journal.pmed.1002569.
24. Eliakim-Raz N, Yahav D, Paul M, Leibovici L. Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection—7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. Journal of Antimicrobial Chemotherapy. 2013 Oct 1;68(10):2183-91. https://doi.org/10.1093/jac/dkt177.
25. Fox MT, Melia MT, Same RG, Conley AT, Tamma PD. A seven-day course of TMP-SMX may be as effective as a seven-day course of ciprofloxacin for the treatment of pyelonephritis. The American journal of medicine. 2017 Jul 1;130(7):842-5. https://doi.org/10.1016/j.amjmed.2017.01.0
26. Chishti AS, Maul EC, Nazario RJ, Bennett JS, Kiessling SG. A guideline for the inpatient care of children with pyelonephritis. Annals of Saudi Medicine. 2010 Sep;30(5):341-9. https://doi.org/10.4103/0256-4947.68549.
27. Berg U. Renal function in acute febrile urinary tract infection in children: pathophysiologic aspects on the reduced concentrating capacity. Kidney International. 1981 Dec 1;20(6):753-8. https://doi.org/10.1038/ki.1981.207.
28. Åbyholm G, Monn E. Intranasal DDAVP-test in the study of renal concentrating capacity in children with recurrent urinary tract infections. European journal of pediatrics. 1979 Sep 1;130(3):149-54. https://doi.org/10.1007/bf00455260.
29. Alzahrani MI, Alzahrani MI, Alsolami EA, Al Sulami AH, Abdulrahman A, Alhejaili MA, Alahmdi YM, Alharbi FS, Assery AA, Ahmed Z. Evaluative Role of Family Physician in Diagnosis and Management of Gout in Primary Health Care Centers: A Simple Literature Review. Archives of Pharmacy Practice. 2019 Jul 1;1:126.
30. Hanawi SA, Saat NZ, Zulkafly M, Hazlenah H, Taibukahn NH, Yoganathan D, Abdul Rahim NN, Mohd Bashid NA, Abdul Aziz FA, Low FJ. Impact of a Healthy Lifestyle on the Psychological Well-being of University Students. International Journal of Pharmaceutical Research & Allied Sciences. 2020 Apr 1;9(2).
31. Algahtani FD. Healthy Lifestyle among Ha'il University Students, Saudi Arabia. Int. J. Pharm. Res. Allied sci. 2020;9(1):160-7.