Intern Emerg Med DOI 10.1007/s11739-015-1223-7
EM - ORIGINAL
Relevance of blood cultures in acute pyelonephritis in a single-center retrospective study Stanislas Ledochowski1 • Paul-Samuel Abraham1 • Xavier Jacob2 • Oana Dumitrescu3,4,5 • Ge´rard Lina3,4,5 • Alain Lepape1,4 • Vincent Piriou1,4 Florent Wallet1,4 • Arnaud Friggeri1,4,
•
Received: 26 June 2014 / Accepted: 5 August 2014 Ó SIMI 2015
Abstract Pyelonephritides are frequently encountered diagnosis in Emergency Departments. Urinalyses have a central place in the management of this situation but the usefulness of blood cultures is not clear. We conducted a single-center retrospective study of 24 months to study the microbiological relevance of blood cultures in pyelonephritis. We included patients with blood cultures (BC) and urine cultures (UC) drawn at the same time, if they were not exposed to antibiotics prior to these tests. Of our 264 patients, 39 (15 %) had no bacteriological documentation. There were 83 (31 %) bacteremic patients. Seven patients had contaminated or sterile UC with positive BC. Four patients had positive UC and BC with the latter allowing identification of a pathogen absent from the UC (n = 1) or identifying the main pathogen in three cases. A total of 11 patients theoretically benefited from BC representing 4.2 % of our population. Excluding one patient who was known to be infected with multi-drug resistant bacteria, all empirical antibiotics regimens were & Arnaud Friggeri [email protected] 1
Service d’Anesthe´sie-Re´animation Me´dicale et Chirurgicale, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, 69395 Lyon, Pierre-Be´nite, France
2
Service d’Accueil des Urgences, Centre Hospitalier LyonSud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, Lyon, Pierre-Be´nite, France
3
Laboratoire de Microbiologie, Centre de Biologie Sud, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, Lyon, Pierre-Be´nite, France
4
Universite´ Claude Bernard Lyon 1, 69007 Lyon, France
5
Inserm U1111 CIRI, Universite´ Claude Bernard Lyon I, 69007 Lyon, France
effective against the identified pathogens. We did not reveal any significant therapeutic impact of blood cultures in the management of pyelonephritis, when BC and UC are performed before any antimicrobials treatment. Keywords Pyelonephritis Blood cultures Bacteriology Costs and cost-analysis
Introduction Pathogen identification is a main concern in sepsis, with blood cultures (BC) being the most recommended technique [1]. However, when available and compared, other bacteriological samples than blood cultures, such as sputum or urine, have proved to be just as useful and even allow their questioning [2, 3]. For acute pyelonephritis, urine cultures (UC) have a central place in their management and the IDSA/ESCMID 2011 guidelines [4] do not precisely develop the role of BC. Recently, Spoorenberg et al. [5] argued that in real-life conditions with hard to obtain urine samples, blood cultures allow for more bacterial identification. Hence, to precisely evaluate the additional value of blood cultures compared to urine samples in acute pyelonephritis, we designed the present study to include only patients with confirmed pyelonephritis who had urine and blood cultures taken at the same time and whose samples were taken before any exposure to antibiotics.
Method We conducted a single-center teaching-hospital retrospective study for 24 months (June 2011–June 2013) to evaluate the clinical utility of blood cultures in acute
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pyelonephritis. Clinical utility was determined by a BC identifying a pathogen not present in UC, whether because these were sterile or contaminated, or if it was a supplemental pathogen only present in the BC. If that was the case, the patient was added to the ‘‘Additional information’’ group. We included adult patients admitted to our Emergency Department (ED), whether they were managed as in-patients or out-patients. The final diagnosis was retrieved through a diagnosis-based search through our ED program (Cristal-NetÒ AlmaÒ, Saint Martin d’He`res, France.), double-checked by the encoded diagnosis in case of in-patient management and hand-checked by comparing to the clinical findings and all available documents. UC and BC were both taken at the ED, at the same time, and before any antibiotic (ABx) exposure, including the time between the blood and urine sampling. BC and UC were referred to as ‘‘positive’’ when a bacterial pathogen was discovered and considered as being qualitatively and quantitatively (more than 10,000 colony forming units per milliliter) pathogenic by the microbiologist and reported with a susceptibility pattern. A contaminated culture was labeled by the microbiologist if the BC revealed only coagulasenegative staphylococci (excluding Staphylococcus saprophyticus) or if the UC revealed more than three bacterial pathogens. A ‘‘sterile’’ culture was defined when no proof of bacterial culture was found. Laboratory practices concerning collection of BC are based on a closed system through the sampling bottles BacT/ ALERTÒ FN Plus (bioMe´rieuxÒ, Marcy l’Etoile, France) and culture system BACT ALERTÒ 3D (BioMe´rieuxÒ Marcy l’Etoile, France) that is used in our labs. Our practices consist of a single sample of series of four blood culture bottles (two aerobic and anaerobic bottles). Urinary cultures are exclusively aerobic and incubated at 36° C on URIÒ 4 or URISELECT4Ò mediums (Bio-RadÒ, Hercules, USA) to allow bacterial count and identification. Processing is automated for BC, but is manual for UC. The local Ethics Committee exempted our study from their approval.
Results For the study period, we initially analyzed 553 patients with acute pyelonephritis, 264 of whom had both urine cultures (UC) and blood cultures (BC) drawn and were not exposed to antibiotics (ABx) (Fig. 1).
189 (72 %) were hospitalized. An emergent urinary diversion was performed in 14 (5 %) of them and 8 (3 %) were in septic shock or were admitted to an ICU. Comparison of findings from BC and UC Only 83 patients (31 %) were bacteremic while 219 patients had a positive UC. Forty-five patients (17 %) had sterile or contaminated UC. In that group of patients, seven had positive BC allowing a definitive bacterial identification. In the group of patients with positive UC (n = 219), 76 patients had positive BC. Seventy-two patients had concordant bacteriological results between their UC and BC. Only four patients with positive UC and BC had additional information provided by the BC. In one case the BC allowed the identification of a pathogen absent from the UC, while in three cases it allowed the identification of the main pathogen (UC with more than one pathogen at 100,000 colony forming units per milliliter of urine and BC identifying only one pathogen). Thirty-eight patients (15 %) had, in fine, no bacteriological documentation: 22 had both, sterile UC and BC, 15 had a contaminated UC and sterile BC, and one had a contaminated UC and BC. A total of 11/264 patients theoretically benefited from BC representing 4.2 % of those patients with both microbiological samples analyzed but less than 2 % of all pyelonephritis treated at our ED during the study period (Table 2). Microbiological findings Overall, 239 bacterial strains were isolated in the 264 patients. Fourteen pyelonephritides (5 %) were polymicrobial. Gram-negative bacilli (GNB) accounted for 92 % of all identified germs with Escherichia coli (74 %) being the dominant pathogen, followed by Klebsiella spp. (8 %) and Proteus spp. (4 %). As for the gram-positive cocci, Enterococcus faecalis was the main pathogen, representing 6 % of all identifications. For the GNB, 47 % of them had a preserved sensitivity to amoxicillin. Regarding their resistance profiles, 35 % of all GNB-strains were resistant to amoxicillin, with a preserved sensitivity to amoxicillin–clavulanate. Ten percent were resistant to 3rd generation cephalosporins (3GC). Quinolone resistance accounted for 9 % of GNB-strains. A single community labeled E. coli with an extended-spectrum b-lactamase (ESBL) was identified, representing less than 0.5 % of all E. coli strains.
Clinical findings Treatment modalities and ABx regimens Women accounted for 189 (60 %) of our patients, their clinical characteristics are summarized in Table 1. Outpatient treatment was performed in 75 (28 %) patients and
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The initial antibiotic treatment was in line with the IDSA/ ESCMID 2011 guidelines In the case of a guideline-based
Intern Emerg Med
Pyelonephris N= 553
Excluded N = 288 (Anbiocs prior to admission N= 94 Missing either Urine or Blood Cultures or both N= 194)
Pyelonephris with Urine and Blood Cultures
Sterile Urine Cultures N = 23
Contaminated Urine Cultures N = 22
Sterile Blood Culture N=22
Sterile Blood Culture N=15
Posive Urine Cultures N = 219
Sterile Blood Culture N=143
Contaminated Blood Culture N=1
Posive Blood Culture N=1
Posive Blood Culture N= 6
Addional Microbiological informaon N = 1
Addional Microbiological informaon N = 6
Posive Blood Culture N = 76
Addional Microbiological informaon N = 4
Fig. 1 Flow chart for the evaluation of blood cultures in pyelonephritis
antibiotic regimen, 94 % of the identified strains were sensitive. Failures of guideline-based ABx regimen were related to Enterococcus infections (n = 5) and three nosocomial situations which identified ESBL-carrying germs. It should be noted that b-lactam-based ABx regimens (mono or dual therapy) were preferentially used in in-
patient management strategies (72/189), whereas, as expected, out-patients benefited preferably from fluoroquinolones (FQ) (47 %). Of the 11 identified patients, 4 did not receive any antibiotics at the ED, but received them in their definitive ward, while 7 others received an effective initial ABx regimen.
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Intern Emerg Med Table 1 Baseline characteristics and managements modalities of acute bacterial pyelonephritis All patients (n = 264)
Out-patient management (n = 75)
In-patient management (n = 189)
0.40
0.36
0.41
62 (17; 99)
51 (19; 92)
66 (18; 99)
Characteristics Sex ratio Mean age (extremes) Median age (IQR) Males
68 (48; 79)
51 (30.5; 70)
71 (55; 81)
n = 76
n = 20
n = 56
Mean age (extremes)
62 (19; 92)
61 (19; 92)
63 (29; 92)
Median age (IQR)
63 (54; 77)
60 (50; 69)
65 (54; 79)
Females
n = 188
n = 55
n = 133
Mean age (extremes)
62 (17; 99)
61 (62; 84)
61 (17; 99)
Median age (IQR)
69 (42; 81)
42 (25; 73)
74 (58; 84)
Identified pathogens GNB GPC Informative blood cultures
212
62
150
24
6
18
11
1
10
IQR interquartile range, GNB gram-negative bacilli, GPC gram-positive cocci
Discussion Our study clearly shows that in the studied population, BCs only provide additional information to UCs in 11/264 (4.2 %) if they are both drawn at the same time without any previous ABx exposure. Kelly et al. [7] and Munro et al. [8] have both questioned the usefulness of blood cultures in EDs, by showing that the tests’ results modified the antibiotic regimen in less than 2 % of the situations. In the case of complicated urinary tract infections, this question is still unanswered. With a simple and robust albeit retrospective methodology, we explored the clinical impact of BC in the management of pyelonephritis. Spoorenberg et al. [5] recently designed an interesting study, based on the concept that in clinical practice, blood cultures are frequently taken before urine samples, as the former can be collected immediately. Their protocol is clearly interesting, showing that in that case, blood cultures have their utility. However, the comparison between the two bacteriological tests is limited by this delay. The fact that there was no significant time span between both bacteriological sampling reinforces our study’s main objective, which was to compare the absolute usefulness of BC. Furthermore, the exclusion of patients with previous exposure to antibiotics clearly limits any risk of false negative results especially with the use of high bactericidal ABx regimens based on 3GC, FQ and aminoglycosides. Our observed rate of 31 % of bacteremic patients is similar to other articles [5, 6] just as our rate of 2 % of BC with additional bacteriological information seems to correspond to other findings [7–9].
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However, our population lacked a significant proportion of patients in septic shock or with an obstructive pyelonephritis in whom the identification of a pathogen is crucial and for whom, BC may still have a significant impact [1]. Furthermore, in male patients, the difference between acute pyelonephritis and prostatitis can be difficult to make solely on clinical grounds, while radiological exams do not offer significantly specific diagnostic information [10]. There is no clear border between these two urinary tract infections, which can even be associated, but it seems that microbiological failure rates are higher for urinary tract infections in men than for pyelonephritis in women [11]. Moreover, although male patients represented 28 % of our whole population, they accounted for nearly half of the patients with additional information from their BC, possibly indicating a role in their management. However, more generally, it is still unclear whether a bacteremia needs to be managed differently than a nonbacteremic infection of the same site. Just as Hsu et al. [6] demonstrated, there seems to be a logical relation between bacteremia and mortality by an increased risk of septic shock in pyelonephritis. BC could therefore have a prognostic value rather than a diagnostic one but it still remains unclear whether bacteremic patients should be managed differently [12], whether by prolonging an ABx regimen or changing it. In diagnostic terms and in our population, the application of the edited treatment guidelines allows for an efficient ABx therapy in most cases, while BC do not add any clinically significant information. Excluding patient H (Table 2), who unfortunately was known to be frequently
Intern Emerg Med Table 2 Clinical and bacteriological characteristics of the 11 patients with BC with additional information Patient
Sex/ age
Charlson Index
In/out patient status
Identified bacteria
ABx sensibility
Effective initial regimen
Effective guidelinesbased BL regimen
Effective guidelinesbased FQ regimen
ABx regimen possible simplification
Patient A
M/91
13
In
Citrobacter spp.
Inductible cephalosporinase
Yes
No
Yes
None
Patient B
M/50
1
Out
E. coli
Wild type
Yes
Yes
Yes
Amoxicillin
Patient C
F/88
7
In
Proteus mirabilis
Penicillinase
Yes
Yes
Yes
Amoxicillinclavulanic acid
Patient D
M/81
8
In
Klebsiella oxytoca
Wild type
Yes
Yes
Yes
Amoxicillinclavulanic acid
Patient E
F/94
6
In
Streptococcus dysgalactiae (BC)
Wild type
Yes
Yes
Yes
Amoxicillin
Patient F
M/68
9
In
Klebsiella pneumoniae
Wild type
Yes
Yes
Yes
Patient G
F/62
3
In
E. coli
Wild type
Yes
Yes
Yes
Amoxicillinclavulanic acid Amoxicillin
Patient H
F/78
9
In
E. coli
ESBL, Quinolone resistance, Gentamicine/ Tobramicine resistance
No
No
No
Imipenem
Patient I
F/85
6
In
Proteus mirabilis
Penicillinase
Yes
Yes
Yes
Amoxicillinclavulanic acid
Patient J
F/89
8
In
E. coli
Penicillinase (high-level)
Yes
Yes
No
Ceftriaxone
No
Yes
No
Amoxicillin
E. coli (UC)
Quinolone resistance Patient K
M/19
0
In
Proteus mirabilis
Quinolone resistance
ABx antibiotic, ESBL extended-spectrum beta-lactamase, BC blood culture, UC urine culture
infected with multi-drug resistant GNBs due to prolonged hospitalizations, all empirical ABx regimens were effective against the identified pathogens. One could argue that patient K’s Proteus mirabilis’ resistance to FQ or that patient A’s Citrobacter’s inductible cephalosporinase could have led to a clinical failure but that was fortunately not the case. One can also discuss that, in the absence of mass spectrometry-identification techniques, the delay for the definitive bacteriological identification seems not to be inferior with BC as compared to UC. However, there is a clear superior efficiency with the latter, at least in our study (219 positive UC for 264 total UC versus 83 positive BC for 264 total BC). Furthermore, in dire times as are ours, reducing the prescriptions of such a costly exam could have a clinically significant impact in France, one BC costs around 35€ or 48 USD. If 11 BC were useful for a total of 264 sampled
tests (i.e., one every 24 patients), which represents an approximate cost of a valuable BC to be 840€ or 1150 USD. To further diminish the expenses of BC, Darge`re et al. [13] recently discussed and compared a strategy that collected a large volume of blood (40 mL) in one unique BC to the standard multi-puncture BC strategy in septic ED-patients. The authors argued that with a larger volume of blood drawn in a unique bottle, they outperformed the standard procedure in bacteriological terms with significantly decreased charges. Coupled with our results, these results seem to minimize the importance of BC. The limits of our study are its retrospective nature, but also the main characteristic of the cohort, i.e., the inclusion of patients without any exposure to antimicrobials. One could argue that this specific population does not reflect real-life situations, especially with the uncertainty of the influence of such therapies on the result of BC and UC [5].
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Even though, the BC allowed for the definitive identification of 11 additional pathogens, their clinical impact is actually null as the empirical ABx regimen was immediately effective. This particular aspect is of importance as our resistance profiles correspond to those frequently reported in our country [14]. The endorsed guidelines are therefore still a` propos.
2. 3.
4.
Conclusion We did not reveal any significant therapeutic impact of blood cultures in the management of pyelonephritis admitted to an ED before any antibiotic exposure. In this specific context, blood cultures add little information compared to urine cultures, which are of major importance. Whether blood cultures should be drawn systematically or not still remains to be discussed. Further studies are necessary to explore the usefulness of blood cultures in severe cases of acute pyelonephritis and especially in men, where prostatitis cannot be excluded on clinical grounds. Acknowledgments There are no acknowledgements. No organizations funded this research and no Grants were allocated. Conflict of interest
None.
Statement of human and animal rights This article does not contain any additional procedures performed on patients by any of the authors, being an observational retrospective study. Informed consent No informed consent was recquired because of the nature of this study.
5.
6.
7. 8.
9.
10.
11.
12.
13.
References 14. 1. Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for
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management of severe sepsis and septic shock: 2012. Crit Care Med 41(2):580–637 Thanassi M (1997) Utility of urine and blood cultures in pyelonephritis. Acad Emerg Med 4(8):797–800 Ramanujam P, Rathlev NK (2006) Blood cultures do not change management in hospitalized patients with community-acquired pneumonia. Acad Emerg Med 13(7):740–745 Gupta K, Hooton TM, Naber KG et al (2011) Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. 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. Clin Infect Dis 52(5):e103–e120 Spoorenberg V, Prins JM, Opmeer BC, et al (2013) The additional value of blood cultures in patients with complicated urinary tract infections. Clin Microbiol Infect Hsu CY, Fang HC, Chou KJ et al (2006) The clinical impact of bacteremia in complicated acute pyelonephritis. Am J Med Sci 332(4):175–180 Kelly AM (1998) Clinical impact of blood cultures taken in the emergency department. J Accid Emerg Med 15(4):254–256 Munro PT, Howie N, Gerstenmaier JF (2007) Do peripheral blood cultures taken in the emergency department influence clinical management? Emerg Med J 24(3):211–212 Mountain D, Bailey PM, O’Brien D et al (2006) Blood cultures ordered in the adult emergency department are rarely useful. Eur J Emerg Med 13(2):76–79 Etienne M, Pestel-Caron M, Chapuzet C, Bourgeois I et al (2010) Should blood cultures be performed for patients with acute prostatitis? J Clin Microbiol 48:1935–1938 Rubin R, Shapiro E, Andriole V et al (1992) Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis 15(Suppl. 1):S216–S227 Havey TC, Fowler RA, Daneman N (2011) Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis. Crit Care 15(6):R267 Darge`re S, Parienti JJ, Roupie E, et al (2014) The UBC study group. Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study. Clin Microbiol Infect Trystram D, Chardon H, Pe´an Y et al The European Antimicrobial Resistance Surveillance Network (EARS-Net): results 2001-2010 and situation of France in Europe. Bull Epidemiol Hebd N42–N43
EM - ORIGINAL
Relevance of blood cultures in acute pyelonephritis in a single-center retrospective study Stanislas Ledochowski1 • Paul-Samuel Abraham1 • Xavier Jacob2 • Oana Dumitrescu3,4,5 • Ge´rard Lina3,4,5 • Alain Lepape1,4 • Vincent Piriou1,4 Florent Wallet1,4 • Arnaud Friggeri1,4,
•
Received: 26 June 2014 / Accepted: 5 August 2014 Ó SIMI 2015
Abstract Pyelonephritides are frequently encountered diagnosis in Emergency Departments. Urinalyses have a central place in the management of this situation but the usefulness of blood cultures is not clear. We conducted a single-center retrospective study of 24 months to study the microbiological relevance of blood cultures in pyelonephritis. We included patients with blood cultures (BC) and urine cultures (UC) drawn at the same time, if they were not exposed to antibiotics prior to these tests. Of our 264 patients, 39 (15 %) had no bacteriological documentation. There were 83 (31 %) bacteremic patients. Seven patients had contaminated or sterile UC with positive BC. Four patients had positive UC and BC with the latter allowing identification of a pathogen absent from the UC (n = 1) or identifying the main pathogen in three cases. A total of 11 patients theoretically benefited from BC representing 4.2 % of our population. Excluding one patient who was known to be infected with multi-drug resistant bacteria, all empirical antibiotics regimens were & Arnaud Friggeri [email protected] 1
Service d’Anesthe´sie-Re´animation Me´dicale et Chirurgicale, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, 69395 Lyon, Pierre-Be´nite, France
2
Service d’Accueil des Urgences, Centre Hospitalier LyonSud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, Lyon, Pierre-Be´nite, France
3
Laboratoire de Microbiologie, Centre de Biologie Sud, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, Lyon, Pierre-Be´nite, France
4
Universite´ Claude Bernard Lyon 1, 69007 Lyon, France
5
Inserm U1111 CIRI, Universite´ Claude Bernard Lyon I, 69007 Lyon, France
effective against the identified pathogens. We did not reveal any significant therapeutic impact of blood cultures in the management of pyelonephritis, when BC and UC are performed before any antimicrobials treatment. Keywords Pyelonephritis Blood cultures Bacteriology Costs and cost-analysis
Introduction Pathogen identification is a main concern in sepsis, with blood cultures (BC) being the most recommended technique [1]. However, when available and compared, other bacteriological samples than blood cultures, such as sputum or urine, have proved to be just as useful and even allow their questioning [2, 3]. For acute pyelonephritis, urine cultures (UC) have a central place in their management and the IDSA/ESCMID 2011 guidelines [4] do not precisely develop the role of BC. Recently, Spoorenberg et al. [5] argued that in real-life conditions with hard to obtain urine samples, blood cultures allow for more bacterial identification. Hence, to precisely evaluate the additional value of blood cultures compared to urine samples in acute pyelonephritis, we designed the present study to include only patients with confirmed pyelonephritis who had urine and blood cultures taken at the same time and whose samples were taken before any exposure to antibiotics.
Method We conducted a single-center teaching-hospital retrospective study for 24 months (June 2011–June 2013) to evaluate the clinical utility of blood cultures in acute
123
Intern Emerg Med
pyelonephritis. Clinical utility was determined by a BC identifying a pathogen not present in UC, whether because these were sterile or contaminated, or if it was a supplemental pathogen only present in the BC. If that was the case, the patient was added to the ‘‘Additional information’’ group. We included adult patients admitted to our Emergency Department (ED), whether they were managed as in-patients or out-patients. The final diagnosis was retrieved through a diagnosis-based search through our ED program (Cristal-NetÒ AlmaÒ, Saint Martin d’He`res, France.), double-checked by the encoded diagnosis in case of in-patient management and hand-checked by comparing to the clinical findings and all available documents. UC and BC were both taken at the ED, at the same time, and before any antibiotic (ABx) exposure, including the time between the blood and urine sampling. BC and UC were referred to as ‘‘positive’’ when a bacterial pathogen was discovered and considered as being qualitatively and quantitatively (more than 10,000 colony forming units per milliliter) pathogenic by the microbiologist and reported with a susceptibility pattern. A contaminated culture was labeled by the microbiologist if the BC revealed only coagulasenegative staphylococci (excluding Staphylococcus saprophyticus) or if the UC revealed more than three bacterial pathogens. A ‘‘sterile’’ culture was defined when no proof of bacterial culture was found. Laboratory practices concerning collection of BC are based on a closed system through the sampling bottles BacT/ ALERTÒ FN Plus (bioMe´rieuxÒ, Marcy l’Etoile, France) and culture system BACT ALERTÒ 3D (BioMe´rieuxÒ Marcy l’Etoile, France) that is used in our labs. Our practices consist of a single sample of series of four blood culture bottles (two aerobic and anaerobic bottles). Urinary cultures are exclusively aerobic and incubated at 36° C on URIÒ 4 or URISELECT4Ò mediums (Bio-RadÒ, Hercules, USA) to allow bacterial count and identification. Processing is automated for BC, but is manual for UC. The local Ethics Committee exempted our study from their approval.
Results For the study period, we initially analyzed 553 patients with acute pyelonephritis, 264 of whom had both urine cultures (UC) and blood cultures (BC) drawn and were not exposed to antibiotics (ABx) (Fig. 1).
189 (72 %) were hospitalized. An emergent urinary diversion was performed in 14 (5 %) of them and 8 (3 %) were in septic shock or were admitted to an ICU. Comparison of findings from BC and UC Only 83 patients (31 %) were bacteremic while 219 patients had a positive UC. Forty-five patients (17 %) had sterile or contaminated UC. In that group of patients, seven had positive BC allowing a definitive bacterial identification. In the group of patients with positive UC (n = 219), 76 patients had positive BC. Seventy-two patients had concordant bacteriological results between their UC and BC. Only four patients with positive UC and BC had additional information provided by the BC. In one case the BC allowed the identification of a pathogen absent from the UC, while in three cases it allowed the identification of the main pathogen (UC with more than one pathogen at 100,000 colony forming units per milliliter of urine and BC identifying only one pathogen). Thirty-eight patients (15 %) had, in fine, no bacteriological documentation: 22 had both, sterile UC and BC, 15 had a contaminated UC and sterile BC, and one had a contaminated UC and BC. A total of 11/264 patients theoretically benefited from BC representing 4.2 % of those patients with both microbiological samples analyzed but less than 2 % of all pyelonephritis treated at our ED during the study period (Table 2). Microbiological findings Overall, 239 bacterial strains were isolated in the 264 patients. Fourteen pyelonephritides (5 %) were polymicrobial. Gram-negative bacilli (GNB) accounted for 92 % of all identified germs with Escherichia coli (74 %) being the dominant pathogen, followed by Klebsiella spp. (8 %) and Proteus spp. (4 %). As for the gram-positive cocci, Enterococcus faecalis was the main pathogen, representing 6 % of all identifications. For the GNB, 47 % of them had a preserved sensitivity to amoxicillin. Regarding their resistance profiles, 35 % of all GNB-strains were resistant to amoxicillin, with a preserved sensitivity to amoxicillin–clavulanate. Ten percent were resistant to 3rd generation cephalosporins (3GC). Quinolone resistance accounted for 9 % of GNB-strains. A single community labeled E. coli with an extended-spectrum b-lactamase (ESBL) was identified, representing less than 0.5 % of all E. coli strains.
Clinical findings Treatment modalities and ABx regimens Women accounted for 189 (60 %) of our patients, their clinical characteristics are summarized in Table 1. Outpatient treatment was performed in 75 (28 %) patients and
123
The initial antibiotic treatment was in line with the IDSA/ ESCMID 2011 guidelines In the case of a guideline-based
Intern Emerg Med
Pyelonephris N= 553
Excluded N = 288 (Anbiocs prior to admission N= 94 Missing either Urine or Blood Cultures or both N= 194)
Pyelonephris with Urine and Blood Cultures
Sterile Urine Cultures N = 23
Contaminated Urine Cultures N = 22
Sterile Blood Culture N=22
Sterile Blood Culture N=15
Posive Urine Cultures N = 219
Sterile Blood Culture N=143
Contaminated Blood Culture N=1
Posive Blood Culture N=1
Posive Blood Culture N= 6
Addional Microbiological informaon N = 1
Addional Microbiological informaon N = 6
Posive Blood Culture N = 76
Addional Microbiological informaon N = 4
Fig. 1 Flow chart for the evaluation of blood cultures in pyelonephritis
antibiotic regimen, 94 % of the identified strains were sensitive. Failures of guideline-based ABx regimen were related to Enterococcus infections (n = 5) and three nosocomial situations which identified ESBL-carrying germs. It should be noted that b-lactam-based ABx regimens (mono or dual therapy) were preferentially used in in-
patient management strategies (72/189), whereas, as expected, out-patients benefited preferably from fluoroquinolones (FQ) (47 %). Of the 11 identified patients, 4 did not receive any antibiotics at the ED, but received them in their definitive ward, while 7 others received an effective initial ABx regimen.
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Intern Emerg Med Table 1 Baseline characteristics and managements modalities of acute bacterial pyelonephritis All patients (n = 264)
Out-patient management (n = 75)
In-patient management (n = 189)
0.40
0.36
0.41
62 (17; 99)
51 (19; 92)
66 (18; 99)
Characteristics Sex ratio Mean age (extremes) Median age (IQR) Males
68 (48; 79)
51 (30.5; 70)
71 (55; 81)
n = 76
n = 20
n = 56
Mean age (extremes)
62 (19; 92)
61 (19; 92)
63 (29; 92)
Median age (IQR)
63 (54; 77)
60 (50; 69)
65 (54; 79)
Females
n = 188
n = 55
n = 133
Mean age (extremes)
62 (17; 99)
61 (62; 84)
61 (17; 99)
Median age (IQR)
69 (42; 81)
42 (25; 73)
74 (58; 84)
Identified pathogens GNB GPC Informative blood cultures
212
62
150
24
6
18
11
1
10
IQR interquartile range, GNB gram-negative bacilli, GPC gram-positive cocci
Discussion Our study clearly shows that in the studied population, BCs only provide additional information to UCs in 11/264 (4.2 %) if they are both drawn at the same time without any previous ABx exposure. Kelly et al. [7] and Munro et al. [8] have both questioned the usefulness of blood cultures in EDs, by showing that the tests’ results modified the antibiotic regimen in less than 2 % of the situations. In the case of complicated urinary tract infections, this question is still unanswered. With a simple and robust albeit retrospective methodology, we explored the clinical impact of BC in the management of pyelonephritis. Spoorenberg et al. [5] recently designed an interesting study, based on the concept that in clinical practice, blood cultures are frequently taken before urine samples, as the former can be collected immediately. Their protocol is clearly interesting, showing that in that case, blood cultures have their utility. However, the comparison between the two bacteriological tests is limited by this delay. The fact that there was no significant time span between both bacteriological sampling reinforces our study’s main objective, which was to compare the absolute usefulness of BC. Furthermore, the exclusion of patients with previous exposure to antibiotics clearly limits any risk of false negative results especially with the use of high bactericidal ABx regimens based on 3GC, FQ and aminoglycosides. Our observed rate of 31 % of bacteremic patients is similar to other articles [5, 6] just as our rate of 2 % of BC with additional bacteriological information seems to correspond to other findings [7–9].
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However, our population lacked a significant proportion of patients in septic shock or with an obstructive pyelonephritis in whom the identification of a pathogen is crucial and for whom, BC may still have a significant impact [1]. Furthermore, in male patients, the difference between acute pyelonephritis and prostatitis can be difficult to make solely on clinical grounds, while radiological exams do not offer significantly specific diagnostic information [10]. There is no clear border between these two urinary tract infections, which can even be associated, but it seems that microbiological failure rates are higher for urinary tract infections in men than for pyelonephritis in women [11]. Moreover, although male patients represented 28 % of our whole population, they accounted for nearly half of the patients with additional information from their BC, possibly indicating a role in their management. However, more generally, it is still unclear whether a bacteremia needs to be managed differently than a nonbacteremic infection of the same site. Just as Hsu et al. [6] demonstrated, there seems to be a logical relation between bacteremia and mortality by an increased risk of septic shock in pyelonephritis. BC could therefore have a prognostic value rather than a diagnostic one but it still remains unclear whether bacteremic patients should be managed differently [12], whether by prolonging an ABx regimen or changing it. In diagnostic terms and in our population, the application of the edited treatment guidelines allows for an efficient ABx therapy in most cases, while BC do not add any clinically significant information. Excluding patient H (Table 2), who unfortunately was known to be frequently
Intern Emerg Med Table 2 Clinical and bacteriological characteristics of the 11 patients with BC with additional information Patient
Sex/ age
Charlson Index
In/out patient status
Identified bacteria
ABx sensibility
Effective initial regimen
Effective guidelinesbased BL regimen
Effective guidelinesbased FQ regimen
ABx regimen possible simplification
Patient A
M/91
13
In
Citrobacter spp.
Inductible cephalosporinase
Yes
No
Yes
None
Patient B
M/50
1
Out
E. coli
Wild type
Yes
Yes
Yes
Amoxicillin
Patient C
F/88
7
In
Proteus mirabilis
Penicillinase
Yes
Yes
Yes
Amoxicillinclavulanic acid
Patient D
M/81
8
In
Klebsiella oxytoca
Wild type
Yes
Yes
Yes
Amoxicillinclavulanic acid
Patient E
F/94
6
In
Streptococcus dysgalactiae (BC)
Wild type
Yes
Yes
Yes
Amoxicillin
Patient F
M/68
9
In
Klebsiella pneumoniae
Wild type
Yes
Yes
Yes
Patient G
F/62
3
In
E. coli
Wild type
Yes
Yes
Yes
Amoxicillinclavulanic acid Amoxicillin
Patient H
F/78
9
In
E. coli
ESBL, Quinolone resistance, Gentamicine/ Tobramicine resistance
No
No
No
Imipenem
Patient I
F/85
6
In
Proteus mirabilis
Penicillinase
Yes
Yes
Yes
Amoxicillinclavulanic acid
Patient J
F/89
8
In
E. coli
Penicillinase (high-level)
Yes
Yes
No
Ceftriaxone
No
Yes
No
Amoxicillin
E. coli (UC)
Quinolone resistance Patient K
M/19
0
In
Proteus mirabilis
Quinolone resistance
ABx antibiotic, ESBL extended-spectrum beta-lactamase, BC blood culture, UC urine culture
infected with multi-drug resistant GNBs due to prolonged hospitalizations, all empirical ABx regimens were effective against the identified pathogens. One could argue that patient K’s Proteus mirabilis’ resistance to FQ or that patient A’s Citrobacter’s inductible cephalosporinase could have led to a clinical failure but that was fortunately not the case. One can also discuss that, in the absence of mass spectrometry-identification techniques, the delay for the definitive bacteriological identification seems not to be inferior with BC as compared to UC. However, there is a clear superior efficiency with the latter, at least in our study (219 positive UC for 264 total UC versus 83 positive BC for 264 total BC). Furthermore, in dire times as are ours, reducing the prescriptions of such a costly exam could have a clinically significant impact in France, one BC costs around 35€ or 48 USD. If 11 BC were useful for a total of 264 sampled
tests (i.e., one every 24 patients), which represents an approximate cost of a valuable BC to be 840€ or 1150 USD. To further diminish the expenses of BC, Darge`re et al. [13] recently discussed and compared a strategy that collected a large volume of blood (40 mL) in one unique BC to the standard multi-puncture BC strategy in septic ED-patients. The authors argued that with a larger volume of blood drawn in a unique bottle, they outperformed the standard procedure in bacteriological terms with significantly decreased charges. Coupled with our results, these results seem to minimize the importance of BC. The limits of our study are its retrospective nature, but also the main characteristic of the cohort, i.e., the inclusion of patients without any exposure to antimicrobials. One could argue that this specific population does not reflect real-life situations, especially with the uncertainty of the influence of such therapies on the result of BC and UC [5].
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Intern Emerg Med
Even though, the BC allowed for the definitive identification of 11 additional pathogens, their clinical impact is actually null as the empirical ABx regimen was immediately effective. This particular aspect is of importance as our resistance profiles correspond to those frequently reported in our country [14]. The endorsed guidelines are therefore still a` propos.
2. 3.
4.
Conclusion We did not reveal any significant therapeutic impact of blood cultures in the management of pyelonephritis admitted to an ED before any antibiotic exposure. In this specific context, blood cultures add little information compared to urine cultures, which are of major importance. Whether blood cultures should be drawn systematically or not still remains to be discussed. Further studies are necessary to explore the usefulness of blood cultures in severe cases of acute pyelonephritis and especially in men, where prostatitis cannot be excluded on clinical grounds. Acknowledgments There are no acknowledgements. No organizations funded this research and no Grants were allocated. Conflict of interest
None.
Statement of human and animal rights This article does not contain any additional procedures performed on patients by any of the authors, being an observational retrospective study. Informed consent No informed consent was recquired because of the nature of this study.
5.
6.
7. 8.
9.
10.
11.
12.
13.
References 14. 1. Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for
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management of severe sepsis and septic shock: 2012. Crit Care Med 41(2):580–637 Thanassi M (1997) Utility of urine and blood cultures in pyelonephritis. Acad Emerg Med 4(8):797–800 Ramanujam P, Rathlev NK (2006) Blood cultures do not change management in hospitalized patients with community-acquired pneumonia. Acad Emerg Med 13(7):740–745 Gupta K, Hooton TM, Naber KG et al (2011) Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. 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. Clin Infect Dis 52(5):e103–e120 Spoorenberg V, Prins JM, Opmeer BC, et al (2013) The additional value of blood cultures in patients with complicated urinary tract infections. Clin Microbiol Infect Hsu CY, Fang HC, Chou KJ et al (2006) The clinical impact of bacteremia in complicated acute pyelonephritis. Am J Med Sci 332(4):175–180 Kelly AM (1998) Clinical impact of blood cultures taken in the emergency department. J Accid Emerg Med 15(4):254–256 Munro PT, Howie N, Gerstenmaier JF (2007) Do peripheral blood cultures taken in the emergency department influence clinical management? Emerg Med J 24(3):211–212 Mountain D, Bailey PM, O’Brien D et al (2006) Blood cultures ordered in the adult emergency department are rarely useful. Eur J Emerg Med 13(2):76–79 Etienne M, Pestel-Caron M, Chapuzet C, Bourgeois I et al (2010) Should blood cultures be performed for patients with acute prostatitis? J Clin Microbiol 48:1935–1938 Rubin R, Shapiro E, Andriole V et al (1992) Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis 15(Suppl. 1):S216–S227 Havey TC, Fowler RA, Daneman N (2011) Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis. Crit Care 15(6):R267 Darge`re S, Parienti JJ, Roupie E, et al (2014) The UBC study group. Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study. Clin Microbiol Infect Trystram D, Chardon H, Pe´an Y et al The European Antimicrobial Resistance Surveillance Network (EARS-Net): results 2001-2010 and situation of France in Europe. Bull Epidemiol Hebd N42–N43
