Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

Acute Pyelonephritis in Adults

Acute Pyelonephritis in Adults BackgroundTo formulate a classification tool for early recognition of patients admitted with acute pyelonephritis (AP) who are at high risk for failure of treatment or for death.MethodsA retrospective chart review of 225 patients (102 men) admitted with AP. We considered 13 potential risk factors in a multivariate analysis.ResultsRecent hospitalization, previous use of antibiotics, and immunosuppression were found to be independent correlates of the prevalence of resistant pathogens in both sexes. Additional predictors included nephrolithiasis in women and a history of recurrent AP in men. Prolonged hospitalization should be expected for a man with diabetes and long-term catheterization who is older than 65 years or for a woman of any age with the same characteristics, when the initial treatment was changed according to the results of urine culture. For mortality prediction, we derived an integer-based scoring system with 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for previous antibiotic treatment for men and 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for immunosuppression for women. Among patients with at least 11 points, the risk for in-hospital death was 100% for men and 91% for women.ConclusionsSimple variables available at presentation can be used for risk stratification of patients with AP. The additional identification of certain risk factors by means of a carefully obtained history could contribute to early recognition of patients infected by resistant bacteria and optimize the selection of antimicrobial agents.ACUTE INFECTION of the upper urinary tract (acute pyelonephritis [AP]) occurs in at least 250 000 adults per year in the United States,representing the most severe form of urinary tract infection (UTI).It often requires hospitalization and prolonged therapy, and when accompanied by bacteremia, AP has a mortality rate of 10% to 20%.Efforts to provide emergency department physicians with simple tools for the prediction of antimicrobial resistance and risk for death are justified by the increasing prevalence of resistance of various uropathogens to combined trimethoprim and sulfamethoxazole, β-lactams, and fluoroquinolones (FQs)and the finding in different clinical studies that almost half of the patients who were initially empirically treated with antibiotics received inappropriate treatment.Although numerous studies have focused on antimicrobial resistance of bacteria that cause UTIs in general,data on the ability to predict mortality and failure of treatment due to resistant pathogens in patients with AP are lacking. Moreover, despite the fact that AP in women has been extensively studied, scant information regarding AP in men exists.The aims of the present study were to formulate a classification tool for early recognition of men and women admitted with AP who are at high risk for death, and to identify independent predictors of failure of treatment and of prolonged hospitalization.METHODSDATA COLLECTIONWe conducted a retrospective medical chart review of all admissions to the Third Department of Medicine, Athens University, Sotiria General Hospital, Athens, Greece, that were due to AP from January 1, 1997, through December 31, 2001. Criteria for diagnosis of AP were the isolation of the same pathogen from urine and blood cultures or the simultaneous presence of (1) fever, defined as an axillary temperature of 38°C or greater; (2) pyuria, defined as the presence of 10 or more leukocytes per high-power field in the centrifuged specimen; and (3) positive urine culture (>105colony-forming units [cfu]/mL).In all cases, a positive urine culture was necessary for inclusion in the study. Blood samples were obtained for cultures from all subjects. Factors that defined complicated APs included 1 or more of the following: (1) male sex; (2) age greater than 65 years; (3) the presence of an indwelling catheter or the use of intermittent catheterization; (4) greater than 100 mL of residual urine retained after voiding; (5) obstructive uropathy; (6) vesicoureteral reflux or other urologic abnormalities; (7) azotemia due to intrinsic renal disease; and (8) renal transplantation.Demographic data, medical history, clinical findings, biochemical variables, ultrasonography (US) of the urinary system, record of resistance of microbes to antibiotics, and treatment with antibiotics were recorded. In addition, we assessed the presence of each of the following 13 variables considered to be potential risk factors for death or failure of treatment: age greater than 65 years, change in initial treatment, recent (in the previous month) hospitalization for any reason, prostatic hypertrophy (confirmed by US and defined as a prostate volume >25 mL),recent (in the previous month) use of antibiotics, hydronephrosis (demonstrated on admission by US), nephrolithiasis (confirmed by US), bedridden status, septic shock at presentation, history of recurrent APs (defined as ≥3 episodes of AP documented by means of culture in the past 12 months), diabetes mellitus, immunosuppression, and long-term indwelling catheterization. Antimicrobial agents were administered empirically until the results of urine or blood cultures were known. The duration of hospital stay and outcome (discharge or death) were also recorded.LABORATORY METHODSUrine specimens, obtained by means of the clean-catch midstream technique, in-and-out urethral catheterization, or preexisting long-term indwelling catheterization, were incubated by means of calibrated loops on blood-agar plates with 5% sheep blood. The cultures were incubated for 18 to 24 hours before quantitative reading. All bacterial counts with at least 105cfu/mL in pure culture or a yield of at least 2 species were considered to be significant bacteriuria. For blood cultures, 10 mL of venous blood was obtained from all patients and inoculated into aerobic and anaerobic bottles (Organon Teknika Corp, Durham, NC). At least 2 sets of blood cultures were obtained from each patient. Susceptibility tests were performed using the disk agar diffusion method and interpreted as described by the National Committee for Clinical Laboratory Standards.STATISTICAL ANALYSISStatistical analysis was performed using SPSS software.Acute pyelonephritis due to bacteria resistant to trimethoprim-sulfamethoxazole, to combined ampicillin sodium and sulbactam sodium or combined amoxicillin sodium and clavulanate potassium, or to FQs (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride), prolonged (≥10 days) hospitalization, and death due to AP were used as end points in the analysis.We evaluated univariate correlations using the χ2or the Fisher exact test as appropriate for categorical data and the ttest for continuous variables. All tests of significance were 2-tailed, and a Pvalue of less than .05 was considered to be significant. Variables with a significant univariate correlation with mortality and prolonged hospitalization were considered in a logistic regression analysis using a backward-selection algorithm to identify the respective independent correlates. Furthermore, the coefficients of the regression model, expressed as multiples of a common denominator and rounded to the nearest interval, allowed for the transformation of the multivariate model into an integer-based scoring system, which assigned a weight (number of points) to each predictor and summed the weights of the predictors that were present for a subject.RESULTSClinical and laboratory characteristics of patients according to sex are illustrated in Table 1. Overall median age was 67 years (range, 42-96 years). Women were older than men (median age, 70 and 61 years, respectively [range, 42-96 and 51-92 years, respectively]; P<.001). Women had a decreased level of consciousness on admission in a greater proportion (35.8%) compared with men (12.7%; P<.001).Table 1. Patients' Clinical and Laboratory Characteristics*CharacteristicNo. (%) of PatientsPValueMenWomenOverallOverall102 (45.3)123 (54.7)225 (100)Fever (≥38°C) with chills98 (96.1)119 (96.7)217 (96.4).79Altered level of consciousness13 (12.7)44 (35.8)57 (25.3)<.001Lower abdominal pain/back pain20 (19.6)33 (26.8)53 (23.6).20CVA tenderness22 (21.6)27 (22.0)49 (21.8).94Vomiting/diarrhea19 (18.6)23 (18.7)42 (18.7).99Dysuria24 (23.5)26 (21.1)50 (22.2).67Pyuria90 (88.2)110 (89.4)201 (89.3).78Microscopic hematuria38 (37.3)60 (48.8)98 (43.6).08Leukocytosis102 (100.0)123 (100.0)225 (100.0).18Bacteremia60 (58.8)75 (61.0)135 (60.0).74Elevated SUN or serum creatinine level11 (10.8)12 (9.8)23 (10.2).80US detection of urinary tract obstruction22 (21.6)30 (24.4)52 (23.1).62Abbreviations: CVA, costovertebral angle; SUN, serum urea nitrogen; US, ultrasonography.*Percentages have been rounded and may not total 100.†Indicates differences between men and women.The results of urine cultures are presented in Table 2. Escherichia coliaccounted for 56.4% of overall cases, followed by enterococci (10.7%), Staphylococcusspecies (8.0%), Proteus mirabilis(6.7%), Enterobacterspecies (5.3%), and Pseudomonas aeruginosa(5.3%). Bacteriuria was accompanied by bacteremia (with the same pathogen) in 60 men (58.8%) and 75 women (60.9%). Uncomplicated APs accounted for only 5.7% of women (3.1% of the total study population).Table 2. Results of Urine Culture According to Age and SexUrine Culture YieldNo. (%) of PatientsPValueAge, ySex≤65>65MenWomenEscherichia coli70 (59.3)57 (53.3)53 (52.0)74 (60.2).22Enterococci12 (10.2)12 (11.2)14 (13.7)10 (8.1).18Proteus mirabilis7 (5.9)8 (7.5)6 (5.9)9 (7.3).67Enterobacterspecies3 (2.5)9 (8.4)10 (9.8)2 (1.6).02Pseudomonas aeruginosa5 (4.2)7 (6.5)3 (2.9)9 (7.3).14Staphylococcusspecies11 (9.3)7 (6.5)5 (4.9)13 (10.6).12Klebsiellaspecies4 (3.4)7 (6.5)8 (7.8)3 (2.4).09Acinetobacterspecies2 (1.7)02 (2.0)0.12Mixed4 (3.4)01 (1.0)3 (2.4).41*Percentages have been rounded and may not total 100.†Indicates differences between men and women.Amoxicillin-clavulanate or ampicillin-sulbactam was used as the initial empirical treatment in 54% of cases, whereas second-generation cephalosporins were administered in 11%, combined ticarcillin sodium and clavulanate potassium in 10%, FQs in 6%, trimethoprim-sulfamethoxazole in 6%, third-generation cephalosporins in 3%, and the combination of a β-lactam plus an aminoglycoside in 10% of all subjects. The rate of resistance of E colito ampicillin was 27%; to trimethoprim-sulfamethoxazole, 11%; and to at least 2 drugs, 10%. Enterococci were resistant to ampicillin in 7%, ciprofloxacin in 11%, vancomycin hydrochloride in 2%, and teicoplanin in 1% of cases, whereas P aeruginosawas resistant to combined piperacillin sodium and tazobactam sodium in 17%, ticarcillin in 19%, ciprofloxacin in 40%, netilmicin sulfate in 23%, ceftazidime in 30%, and imipenem in 8% of subjects. Overall susceptibility of bacteria isolated from urine culture to amoxicillin-clavulanate or ampicillin-sulbactam was 86%; to trimethoprim-sulfamethoxazole, 67%; to FQs, 91.5%; and to netilmicin, 80%. Overall resistance of bacteria to all of these antibiotics was 4%. Multiresistant pathogens, ie, pathogens resistant to amoxicillin-clavulanate or ampicillin-sulbactam, trimethoprim-sulfamethoxazole, and FQs, included 2 strains of Acinetobacterspecies, 3 strains of P aeruginosa,and 4 strains of Klebsiellaspecies. Among the 9 patients who were infected by multiresistant strains, 4 (44%) had recently used antibiotics (P= .02 compared with recent users of antibiotics who had uropathogens susceptible to at least 1 of the above 4 agents).Men with (49/102 [48.0%]) and without (53/102 [52.0%]) prostatic hypertrophy did not differ in terms of the prevalence of bacteria resistant to trimethoprim-sulfamethoxazole (21/49 [42.9%] vs 16/53 [30.2%]; P= .18), to amoxicillin-clavulanate or ampicillin-sulbactam (3/49 [6.1%] vs 1/53 [1.9%]; P= .35), or to FQs (1/49 [2.0%] vs 2/53 [3.8%]; P= .60). Moreover, no significant differences were found between these groups with regard to mortality (7/49 [14.3%] vs 5/53 [9.4%]; P= .54) and prolonged hospitalization (7/49 [14.3%] vs 5/53 [9.5%]; P= .54).Table 3shows the comparisons between men and women in terms of historical features, antibiotic resistance, and clinical course of the AP episode. The variables identified by univariate analysis to be associated with each of the end points are presented in Table 4and Table 5, whereas the independent risk factors are shown in Table 6. Table 7shows the independent predictors of prolonged hospitalization and death. Although the presence of hydronephrosis was found to be associated with prolonged hospitalization and resistance to trimethoprim-sulfamethoxazole in univariate analysis, it was not isolated as an independent risk factor for the end points in the regression model.Table 3. Comparisons Between Men and Women Regarding Variables Estimated as Risk Factors for Mortality, Prolonged Hospitalization, and the Prevalence of Bacteria Resistant to Antibiotics*VariablesMen (n = 102)Women (n = 123)PValueAge >65 y1791<.001Historical featuresRecent hospitalization1029<.04Prostatic hypertrophy49NARecent use of antibiotics1018.19Nephrolithiasis225<.001Bedridden status1234<.01Septic shock2228.48Recurrent APs1415.44Diabetes mellitus923.04Immunosuppression418<.01Long-term catheterization1145<.001Antibiotic resistanceResistant to combined trimethoprim and sulfamethoxazole3737.32Resistant to combined amoxicillin and clavulanate potassium or to combined ampicillin sodium and sulbactam sodium428<.001Resistant to FQs316.02Clinical course of the AP episodeInitial treatment changed540<.001Prolonged hospitalization1250<.001Early death814.26Overall mortality1215.54Abbreviations: AP, acute pyelonephritis; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); NA, not applicable.*Data are given as number of patients unless otherwise indicated.Table 4. Significant Univariate Correlates of Mortality, Prolonged Hospitalization, and the Prevalence of Bacteria Resistant to Antibiotics in MenVariableNo. of PatientsMortality, No. dead/alive*Age >65 y†10/7Recent hospitalization†6/4Bedridden status†11/1Septic shock†12/10Recent use of antibiotics†9/1Long-term catheterization†10/1Prolonged hospitalization, No. yes/no*Age >65†10/7Recent use of antibiotics‡4/6Bedridden status§5/7Change in initial treatment†3/2Recent hospitalization†8/2Diabetes mellitus†5/4Immunosuppression†4/0Long-term catheterization†5/6Hydronephrosis†10/12Susceptibility of bacteria to trimethoprim-sulfamethoxaxole, No. resistant/susceptible&par;Immunosuppression†3/1Diabetes mellitus†7/2Recent hospitalization†9/1Recent use of antibiotics†9/1Long-term catheterization†7/3Hydronephrosis†16/6Susceptibility of bacteria to amoxicillin-clavulanate or ampicillin-sulbactam, No. resistant/susceptible¶Recent use of antibiotics‡2/8Recent hospitalization†3/7Nephrolithiasis†2/0Bedridden status§2/10Recurrent APs§2/12Diabetes mellitus‡2/7Immunosuppression†2/2Long-term catheterization§2/9Susceptibility of bacteria to FQs, No. resistant/susceptible#Recent hospitalization†3/7Recurrent APs†3/11Immunosuppression†2/2Abbreviations: amoxicillin-clavulanate, combined amoxicillin and clavulanate potassium; ampicillin-sulbactam, combined ampicillin sodium and sulbactam sodium; AP, acute pyelonephritis; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); trimethoprim-sulfamethoxazole, combined trimethoprim and sulfamethoxazole.*N = 12/n = 90.†P<.001.‡P<.01.§P<.05.&par;N = 37/n = 65.¶N = 4/n = 98.#N = 3/n = 99.Table 5. Significant Univariate Correlates of Mortality, Prolonged Hospitalization, and the Prevalence of Bacteria Resistant to Antibiotics in WomenVariableNo. of PatientsMortality, No. dead/alive*Age >65 y†15/76Recent hospitalization‡10/19Bedridden status†14/20Septic shock‡14/14Recurrent APs‡10/5Diabetes mellitus†10/13Nephrolithiasis†7/18Immunosuppression‡11/7Prolonged hospitalization, No. yes/no§Age >65 y‡47/44Change in initial treatment†25/15Nephrolithiasis†16/9Recurrent APs‡13/2Diabetes mellitus†18/5Immunosuppression&par;13/5Long-term catheterization‡17/1Hydronephrosis†20/10Susceptibility of bacteria to trimethoprim-sulfamethoxazole, No. resistant/susceptible¶Age >65 y‡34/57Nephrolithiasis†15/10Immunosuppression&par;11/7Diabetes mellitus&par;12/11Recent hospitalization‡25/4Recent use of antibiotics‡16/2Hydronephrosis‡25/5Susceptibility of bacteria to amoxicillin-clavulanate or ampicillin-sulbactam, No. resistant/susceptible#Recent hospitalization‡14/15Nephrolithiasis†15/10Diabetes mellitus&par;13/10Immunosuppression&par;11/7Susceptibility of bacteria to FQs, No. resistant/susceptible**Age >65 y‡15/76Nephrolithiasis‡15/10Immunosuppression‡10/8Abbreviations: amoxicillin-clavulanate, combined amoxicillin and clavulanate potassium; ampicillin-sulbactam, combined ampicillin sodium and sulbactam sodium; AP, acute pyelonephritis; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); trimethoprim-sulfamethoxazole, combined trimethoprim and sulfamethoxazole.*N = 15/n = 108.†P<.01.‡P<.001.§N = 50/n = 73.&par;P<.05.¶N = 37/n = 86.#N = 28/n = 95.**N = 16/n = 107.Table 6. Significant Multivariate Correlates of the Prevalence of Bacteria Resistant to Antibiotics*VariableMenWomenOR (95% CI)PercentageOR (95% CI)PercentageSENSSPECPPVNPVSENSSPECPPVNPVBacteria Resistant to Trimethoprim-SulfamethoxazoleRecent hospitalization*4.8 (2.2-6.3)259990706.1 (1.8-29.3)68958687Recent use of antibiotics*7.5 (3.1-4.9)259990703.9 (1.3-47.6)43988980Bacteria Resistant to Amoxicillin-Clavulanate or to Ampicillin-SulbactamImmunosuppression*8.4 (1.2-65.5)509850986.7 (2.1-58.2)32853981Bacteria Resistant to FQsRecurrent APs*7.3 (2.1-55.6)1009330100Nephrolithiasis*5.3 (1.7-16.1)94916099Abbreviations: Amoxicillin-clavulanate, combined amoxicillin and clavulanate potassium; ampicillin-sulbactam, combined ampicillin sodium and sulbactam sodium; AP, acute pyelonephritis; CI, confidence interval; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); NPV, negative predictive value; OR, odds ratio; PPV, positive predictive value; SENS, sensitivity; SPEC, specificity; trimethoprim-sulfamethoxazole, combined trimethoprim and sulfamethoxazole.*P<.01.Table 7. Significant Multivariate Correlates of Prolonged Hospitalization and MortalityVariableOR (95% CI)*MenProlonged hospitalizationChange in initial treatment5.6 (2.3-54.6)Diabetes mellitus4.7 (1.9-45.3)Long-term catheterization3.3 (2.3-69.8)Age >65 y6.2 (3.5-71.1)MortalityAge >65 y8.1 (2.2-69.9)Septic shocks16.4 (4.1-71.5)Bedridden status8.3 (3.1-42.9)Recent use of antibiotics5.2 (2.3-53.7)WomenProlonged hospitalizationChange in initial treatment4.4 (1.4-53.9)Diabetes mellitus5.3 (2.1-44.8)Long-term catheterization*7.6 (2.5-67.1)MortalityAge >65 y8.3 (3.2-68.6)Septic shock15.7 (5.5-72.4)Bedridden status7.9 (2.9-49.6)Immunosuppression4.9 (2.1-51.5)Abbreviations: CI, confidence interval; OR, odds ratio.*For all variables P<.01.The coefficients of the 4 independent correlates of mortality, divided by 0.5 and rounded to the nearest interval, allowed a simpler reexpression of the final regression model, in the form of the following integer-based scoring system:Number of Points (Men) = 6 for Septic Shock + 4 for Bedridden Status + 4 for Age >65 Years + 3 for Previous Antibiotic TreatmentandNumber of Points (Women) = 6 for Septic Shock + 4 for Bedridden Status + 4 for Age >65 Years + 3 for ImmunosuppressionAccording to this prediction tool (Figure 1), most patients (89% of men and 87% of women) could be classified in the subgroups with low scores (<7 points), which predict a very limited risk for death (0%-2.5% for men and 0%-2.3% for women). Patients classified in the highest-score subgroup (≥11 points) had a very high risk for death (100% for men and 91% for women).Performance of an integer-based scoring system regarding mortality due to acute pyelonephritis. The equation we used for calculating the scores is provided in the "Results" section.COMMENTAcute pyelonephritis is the only UTI that may require hospital admission and could be fatal in patients with immunosuppression,elderly individuals,pregnant women,and patients with diabetes.Thus, in patients admitted for AP, the early identification of subgroups of patients at high risk for in-hospital death, prolonged hospitalization, and/or failure of treatment might contribute to ameliorative treatment.In the present study, women admitted for AP were older than men (Table 1), more frequently bedridden, and more likely to undergo long-term catheterization and to be immunosuppressed, and they more often had a history of nephrolithiasis, diabetes mellitus, and recent hospitalization (Table 3). Therefore, they had a higher incidence of infection with resistant bacteria. Because of this difference, and because of the fact that few studies on AP have analyzed data regarding men,we decided to perform separate analyses of data regarding men and women.Our study provides additional support for the view that, although susceptibility patterns have changed, the spectrum of microorganisms that cause community-acquired AP has remained relatively constant. Among the overall population, E coliaccounted for 57% of cases, whereas the rate of its resistance to trimethoprim-sulfamethoxazole (11%) was lower than the corresponding estimated rate in Greece during the same period (17%).Because cost-effectiveness analyses have shown that the threshold trigger for empirical FQ use in E coli– related UTI should be a trimethoprim-sulfamethoxazole resistance of more than 20%,and that the effect of the latter on clinical outcomes depends on the level of resistance in the community,administration of trimethoprim-sulfamethoxazole might be recommended as a first-line treatment for community-acquired AP due to E coliin Greek settings. However, considering that in our study E coliwas responsible for only 57% of APs, 51% of all other bacteria causing AP were resistant to trimethoprim-sulfamethoxazole, and the causative agent of AP is not usually known at the time of admission to the hospital, trimethoprim-sulfamethoxazole is not recommended as a first-line treatment for AP.In accord with previous reports,a history of recent hospitalization and use of antibiotics correlated independently with the prevalence of any trimethoprim-sulfamethoxazole–resistant bacteria in men and women. Thus, clinicians must consider the extent of the patient's exposure to hospital pathogens and the unique bacteriological features of each hospital when devising antibiotic strategies.In contrast to the results of several studies yielding resistance rates as high as 54% in European settings,susceptibility of all bacteria to amoxicillin-clavulanate or to ampicillin-sulbactam was sufficiently high in our population, and immunosuppression was the only independent predictor of the prevalence of bacteria resistant to these drugs in both sexes. The susceptibility pattern in the present study corroborates recent reports by the World Health Organization antimicrobial resistance monitoringand by the first international multicenter epidemiological survey of antimicrobial susceptibility of uropathogens,according to which no firm evidence of increased resistance to these drugs exists so far.Overall resistance rate to FQs in the population studied (8.5%) was comparable to the rate observed in our community (6.5%) at the beginning of the present study (1997)and the rate found in other European settings during the same preriod (6%).In line with previous reports,the present study yielded a history of recurrent APs for men and a history of nephrolithiasis for women as independent determinants of the prevalence of FQ-resistant bacteria. After considering cost-effectiveness and the risk for emergence of resistance, there appears to be little justification for using FQs routinely to treat APs, unless other agents are not well tolerated or are unlikely to be effective.A history of recurrent UTIs, the only independent predictor of multidrug resistance in men in our study, constitutes a well-established risk factor for the prevalence of multiresistant pathogens, especially in elderly patients with underlying diseases.Nevertheless, multivariate analysis isolated only nephrolithiasis as independently associated with multidrug resistance in women, which confirmed the results of previous studies that have shown women with renal lithiasis to have APs more frequently than men.In line with recent reports,the regression model showed that prolonged hospitalization for AP should be expected for a man with diabetes who is undergoing long-term catheterization and is older than 65 years, or for a woman of any age with both additional characteristics, whose initial empirical treatment was changed according to the results of urine culture. Regarding mortality, the multivariate analysis identified 5 factors that have been extensively investigated and found to convey a high risk for death in previous studies. Thus, age greater than 65 years,bedridden status,and the presence of septic shock at presentationwere the common independent predictors of death for both sexes, whereas additional multivariate correlates were recent use of antibiotics in menand immunosuppression in women.The mortality prediction model identified 3 groups of patients. The largest (90% of subjects) consisted of men and women with a score of less than 7 points who had a very limited risk for in-hospital death (<2.5%), whereas the smallest (8%) consisted of patients with a score of at least 11 points who were at high risk for death due to their disease (>90%). The ambiguous zone of patients with a score of 7 to 10 points included only 3 men (2.9%) and 5 women (4.1%) with corresponding risks for death of 67% and 75%, respectively. Thus, the cutoffs for achieving sufficiently high accuracy should be less than 7 or at least 11 points for the prediction of a favorable outcome or death, respectively. Despite significant differences between men and women regarding the mean age and the severity of the illness, risk factors for mortality, prolonged hospitalization, and prevalence of resistant bacteria were quite similar between the 2 sexes. Nevertheless, since the proposed model has been evaluated only in the patients from whom it was derived, its performance requires prospective validation in independent, external populations before it is routinely applied.Taking into account the rates of resistance in our study, patients with AP due to E colicould be treated with trimethoprim-sulfamethoxazole, whereas when the pathogen is not known, empirical treatment with trimethoprim-sulfamethoxazole is not recommended. Amoxicillin-clavulanate or ampicillin-sulbactam might be recommended as first-line treatment for APs acquired in communities with susceptibility patterns similar to those of our country. Fluoroquinolones should not be administered empirically as first-line treatment for AP, except in cases in which the risk factors for prevalence of bacteria resistant to other antibiotics are present and in men with hypertrophy of the prostate, for whom the penetration of FQs is superior compared with that of other agents.The proposed prediction model requires the application of simple information available at the emergency department and transformed to an easily remembered score. If validated, the model could be used to confirm the necessity of hospitalization for seriously ill patients who require intravenous treatment. Therefore, the model may contribute to a more objective risk stratification of patients presenting with AP, thus optimizing the selection of antimicrobial agents, ensuring prompt management of high-risk individuals, and directing those at low risk to less intensive and less costly levels of care.WEStammSRNorrbyUrinary tract infections: disease panorama and challenges.J Infect Dis.2001;183(suppl 1):S1-S4.JWWarrenEAbrutynJRHebelJRJohnsonAJSchaefferWEStammGuidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women: Infectious Diseases Society of America (IDSA).Clin Infect Dis.1999;29:745-758.WEStammUrinary tract infections.In: Root RK, Waldvogel F, Corey L, Stamm WE, eds. Clinical Infectious Diseases: A Practical Approach.New York, NY: Oxford University Press Inc; 1999:649-656.PIspahaniNJPearsonDGreenwoodAn analysis of community and hospital-acquired bactaeremia in a large teaching hospital in the United Kingdom.Q J Med.1987;63:427-440.FJRobertsIWGeereAColdmanA three-year study of positive blood cultures, with emphasis on prognosis.Rev Infect Dis.1991;13:34-46.AJSchaefferUrinary tract infections: antimicrobial resistance.Curr Opin Urol.2000;10:23-24.MLCohenEpidemiology of drug resistance: implications for a post-antimicrobial era.Science.1992;257:1050-1055.LLeiboviciSGreenshtainOCohenAJWysenbeekToward improved empiric management of moderate to severe urinary tract infections.Arch Intern Med.1992;152:2481-2486.CSvanborgResistance to urinary tract infection.N Engl J Med.1993;329:802-803.IEDyerTMSankaryJADawsonAntibiotic resistance in bacterial urinary tract infections, 1991 to 1997.West J Med.1998;169:265-268.KGuptaDFSahmDMayfieldWEStammAntimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis.Clin Infect Dis.2001;33:89-94.BALipskyUrinary tract infections in men: epidemiology, pathophysiology, diagnosis, and treatment.Ann Intern Med.1989;110:138-150.AJSchaefferUrinary tract infection in men—state of the art.Infection.1994;22(suppl 1):S19-S21.RHRubinEDShapiroVTAndrioleRJDavisWEStammEvaluation 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.1992;15(suppl 1):S216-S227.MHoferUltrasound Teaching Manual.New York, NY: Thieme-Stratton Inc; 1999.National Committee for Clinical Laboratory StandardsPerformance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard.5th ed. Villanova, Pa: National Committee for Clinical Laboratory Standards; 1993. NCCLS document M2-A5.SPSS IncStatistical Package for the Social Sciences.Chicago, Ill: SPSS Inc; 2000. Windows version, release 10.0.MSadek SabbourTAbd-el-HamidSKHusseinInfection in immunosuppressed patients.Chemioterapia.1984;3:19-24.LENicolleUrinary tract pathogens in complicated infection and in elderly individuals.J Infect Dis.2001;183(suppl 1):S5-S8.LCGilstrap IIISMRaminUrinary tract infections during pregnancy.Obstet Gynecol Clin North Am.2001;28:581-591.ARonaldELudwigUrinary tract infections in adults with diabetes.Int J Antimicrob Agents.2001;17:287-292.ACVatopoulosVKalapothakiNJLegakisfor the Greek Network for the Surveillance of Antimicrobial ResistanceAn electronic network for the surveillance of antimicrobial resistance in bacterial nosocomial isolates in Greece.Bull World Health Organ.1999;77:595-601.TPLeLGMillerEmpirical therapy for uncomplicated urinary tract infections in an era of increasing antimicrobial resistance: a decision and cost analysis.Clin Infect Dis.2001;33:615-621.KGuptaTMHootonWEStammIncreasing antimicrobial resistance and the management of uncomplicated community-aquired urinary tract infections.Ann Intern Med.2001;135:41-50.PBemer-MelchiorLGillyKJugroot-KlotzTBrunPNevotGPaulResistance to amoxicillin and amoxicillin–clavulanic acid combination of 231 clinical strains of Escherichia coli, isolated in 1992 at the Cochin Hospital [in French].Pathol Biol (Paris).1995;43:760-765.DVanakCSauvagetCMuller-SerieysGMillotEBergogne-Berezinβ-Lactamase producing Escherichia coli: in vitro susceptibility of clinical strains to β-lactamase inhibitors.In: Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology; Washington, DC; 1983.Washington, DC: American Society for Microbiology; 1983:143. Abstract 132.CHenquellDSirotCChanalFrequency of inhibitor-resistant TEM β-lactamases in Escherichia coliisolates from urinary tract infections in France.J Antimicrob Chemother.1994;34:707-714.World Health OrganizationReport on Infectious Diseases: Removing Obstacles to Healthy Development.Geneva, Switzerland; World Health Organization; 1999.GKahlmeterThe ECO.SENS Project: a prospective, multinational, multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens: interim report.J Antimicrob Chemother.2000;46(suppl 1):15-22.ACVatopoulosVKalapothakiNJLegakisfor the Greek Network for the Surveillance of Antimicrobial ResistanceBacterial resistance to ciprofloxacin in Greece: results from the National Electronic Surveillance System.Emerg Infect Dis.1999;5:471-476.NJLegakisLSTzouvelekisATsakrisJNLegakisACVatopoulosOn the incidence of antibiotic resistance among aerobic gram-negative rods isolated in Greek hospitals.J Hosp Infect.1993;24:233-237.RDazaJGutierrezGPiedrolaAntibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections.Int J Antimicrob Agents.2001;18:211-215.HGiamarellouFleroxacin in complicated urinary tract infections.Chemotherapy.1996;42(suppl 1):17-27.JEnaCAmadorCMartinezVOrtiz de la TablaRisk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant Escherichia coli.J Urol.1995;153:117-120.AJSchaefferReview of norfloxacin in complicated and recurrent urinary tract infections.Eur Urol.1990;17(suppl 1):19-23.AUlmannJClavelDDestreeCDuboisAMombetJMBrissetNatural history of renal calcium lithiasis: data obtained from a cohort of 667 patients [in French].Presse Med.1991;20:499-502.CYPakNephrolithiasis.Curr Ther Endocrinol Metab.1997;6:572-576.JARobertsManagement of pyelonephritis and upper urinary tract infections.Urol Clin North Am.1999;26:753-763.SJEykynUrinary tract infections in the elderly.Br J Urol.1998;82(suppl 1):79-84.JMHamilton-MillerIssues in urinary tract infections in the elderly.World J Urol.1999;17:396-401.MDewandreJFranckJLecomteAMutsersPTaziauxThe hazards of bed rest in the elderly [in French].Rev Med Liege.1981;36:894-902.CAllenPGlasziouCDel MarBed rest: a potentially harmful treatment needing more careful evaluation.Lancet.1999;354:1229-1233.EProcaRRadulescuCCalinNCalomfirescuJNasaudeanANatuClinical comments on management of urosepsis in a general urological department.Acta Urol Belg.1992;60:41-56.JTMageeELPritchardKAFitzgeraldFDDunstanAJHowardAntibiotic prescribing and antibiotic resistance in community practice: retrospective study, 1996-8.BMJ.1999;319:1239-1240.DJAustinKGKristinssonRMAndersonThe relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance.Proc Natl Acad Sci U S A.1999;96:1152-1156.GPedersenHCSchonheyderFHSteffensenHTSorensenRisk of resistance related to antibiotic use before admission in patients with community-acquired bacteraemia.J Antimicrob Chemother.1999;43:119-126.DTSteinkeRASeatonGPhillipsTMMacDonaldPGDaveyPrior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors.J Antimicrob Chemother.2001;47:781-787.JARobertsGJDomingueLNMartinJCKimSRRanganImmunology of pyelonephritis in the primate model, II: effect on immunosuppression.Investig Urol (Berl).1981;19:148-153.Corresponding author and reprints: Angelos V. Pefanis, MD, Third Department of Medicine, Athens University, Medical School, Sotiria General Hospital, 152 Mesogion Ave, Athens 11527, Greece (e-mail: gpp@hol.gr).Accepted for publication August 16, 2002. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Internal Medicine American Medical Association

Loading next page...
 
/lp/american-medical-association/acute-pyelonephritis-in-adults-g3oZeqj7Pu
Publisher
American Medical Association
Copyright
Copyright 2003 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6106
eISSN
2168-6114
DOI
10.1001/archinte.163.10.1206
pmid
12767958
Publisher site
See Article on Publisher Site

Abstract

BackgroundTo formulate a classification tool for early recognition of patients admitted with acute pyelonephritis (AP) who are at high risk for failure of treatment or for death.MethodsA retrospective chart review of 225 patients (102 men) admitted with AP. We considered 13 potential risk factors in a multivariate analysis.ResultsRecent hospitalization, previous use of antibiotics, and immunosuppression were found to be independent correlates of the prevalence of resistant pathogens in both sexes. Additional predictors included nephrolithiasis in women and a history of recurrent AP in men. Prolonged hospitalization should be expected for a man with diabetes and long-term catheterization who is older than 65 years or for a woman of any age with the same characteristics, when the initial treatment was changed according to the results of urine culture. For mortality prediction, we derived an integer-based scoring system with 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for previous antibiotic treatment for men and 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for immunosuppression for women. Among patients with at least 11 points, the risk for in-hospital death was 100% for men and 91% for women.ConclusionsSimple variables available at presentation can be used for risk stratification of patients with AP. The additional identification of certain risk factors by means of a carefully obtained history could contribute to early recognition of patients infected by resistant bacteria and optimize the selection of antimicrobial agents.ACUTE INFECTION of the upper urinary tract (acute pyelonephritis [AP]) occurs in at least 250 000 adults per year in the United States,representing the most severe form of urinary tract infection (UTI).It often requires hospitalization and prolonged therapy, and when accompanied by bacteremia, AP has a mortality rate of 10% to 20%.Efforts to provide emergency department physicians with simple tools for the prediction of antimicrobial resistance and risk for death are justified by the increasing prevalence of resistance of various uropathogens to combined trimethoprim and sulfamethoxazole, β-lactams, and fluoroquinolones (FQs)and the finding in different clinical studies that almost half of the patients who were initially empirically treated with antibiotics received inappropriate treatment.Although numerous studies have focused on antimicrobial resistance of bacteria that cause UTIs in general,data on the ability to predict mortality and failure of treatment due to resistant pathogens in patients with AP are lacking. Moreover, despite the fact that AP in women has been extensively studied, scant information regarding AP in men exists.The aims of the present study were to formulate a classification tool for early recognition of men and women admitted with AP who are at high risk for death, and to identify independent predictors of failure of treatment and of prolonged hospitalization.METHODSDATA COLLECTIONWe conducted a retrospective medical chart review of all admissions to the Third Department of Medicine, Athens University, Sotiria General Hospital, Athens, Greece, that were due to AP from January 1, 1997, through December 31, 2001. Criteria for diagnosis of AP were the isolation of the same pathogen from urine and blood cultures or the simultaneous presence of (1) fever, defined as an axillary temperature of 38°C or greater; (2) pyuria, defined as the presence of 10 or more leukocytes per high-power field in the centrifuged specimen; and (3) positive urine culture (>105colony-forming units [cfu]/mL).In all cases, a positive urine culture was necessary for inclusion in the study. Blood samples were obtained for cultures from all subjects. Factors that defined complicated APs included 1 or more of the following: (1) male sex; (2) age greater than 65 years; (3) the presence of an indwelling catheter or the use of intermittent catheterization; (4) greater than 100 mL of residual urine retained after voiding; (5) obstructive uropathy; (6) vesicoureteral reflux or other urologic abnormalities; (7) azotemia due to intrinsic renal disease; and (8) renal transplantation.Demographic data, medical history, clinical findings, biochemical variables, ultrasonography (US) of the urinary system, record of resistance of microbes to antibiotics, and treatment with antibiotics were recorded. In addition, we assessed the presence of each of the following 13 variables considered to be potential risk factors for death or failure of treatment: age greater than 65 years, change in initial treatment, recent (in the previous month) hospitalization for any reason, prostatic hypertrophy (confirmed by US and defined as a prostate volume >25 mL),recent (in the previous month) use of antibiotics, hydronephrosis (demonstrated on admission by US), nephrolithiasis (confirmed by US), bedridden status, septic shock at presentation, history of recurrent APs (defined as ≥3 episodes of AP documented by means of culture in the past 12 months), diabetes mellitus, immunosuppression, and long-term indwelling catheterization. Antimicrobial agents were administered empirically until the results of urine or blood cultures were known. The duration of hospital stay and outcome (discharge or death) were also recorded.LABORATORY METHODSUrine specimens, obtained by means of the clean-catch midstream technique, in-and-out urethral catheterization, or preexisting long-term indwelling catheterization, were incubated by means of calibrated loops on blood-agar plates with 5% sheep blood. The cultures were incubated for 18 to 24 hours before quantitative reading. All bacterial counts with at least 105cfu/mL in pure culture or a yield of at least 2 species were considered to be significant bacteriuria. For blood cultures, 10 mL of venous blood was obtained from all patients and inoculated into aerobic and anaerobic bottles (Organon Teknika Corp, Durham, NC). At least 2 sets of blood cultures were obtained from each patient. Susceptibility tests were performed using the disk agar diffusion method and interpreted as described by the National Committee for Clinical Laboratory Standards.STATISTICAL ANALYSISStatistical analysis was performed using SPSS software.Acute pyelonephritis due to bacteria resistant to trimethoprim-sulfamethoxazole, to combined ampicillin sodium and sulbactam sodium or combined amoxicillin sodium and clavulanate potassium, or to FQs (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride), prolonged (≥10 days) hospitalization, and death due to AP were used as end points in the analysis.We evaluated univariate correlations using the χ2or the Fisher exact test as appropriate for categorical data and the ttest for continuous variables. All tests of significance were 2-tailed, and a Pvalue of less than .05 was considered to be significant. Variables with a significant univariate correlation with mortality and prolonged hospitalization were considered in a logistic regression analysis using a backward-selection algorithm to identify the respective independent correlates. Furthermore, the coefficients of the regression model, expressed as multiples of a common denominator and rounded to the nearest interval, allowed for the transformation of the multivariate model into an integer-based scoring system, which assigned a weight (number of points) to each predictor and summed the weights of the predictors that were present for a subject.RESULTSClinical and laboratory characteristics of patients according to sex are illustrated in Table 1. Overall median age was 67 years (range, 42-96 years). Women were older than men (median age, 70 and 61 years, respectively [range, 42-96 and 51-92 years, respectively]; P<.001). Women had a decreased level of consciousness on admission in a greater proportion (35.8%) compared with men (12.7%; P<.001).Table 1. Patients' Clinical and Laboratory Characteristics*CharacteristicNo. (%) of PatientsPValueMenWomenOverallOverall102 (45.3)123 (54.7)225 (100)Fever (≥38°C) with chills98 (96.1)119 (96.7)217 (96.4).79Altered level of consciousness13 (12.7)44 (35.8)57 (25.3)<.001Lower abdominal pain/back pain20 (19.6)33 (26.8)53 (23.6).20CVA tenderness22 (21.6)27 (22.0)49 (21.8).94Vomiting/diarrhea19 (18.6)23 (18.7)42 (18.7).99Dysuria24 (23.5)26 (21.1)50 (22.2).67Pyuria90 (88.2)110 (89.4)201 (89.3).78Microscopic hematuria38 (37.3)60 (48.8)98 (43.6).08Leukocytosis102 (100.0)123 (100.0)225 (100.0).18Bacteremia60 (58.8)75 (61.0)135 (60.0).74Elevated SUN or serum creatinine level11 (10.8)12 (9.8)23 (10.2).80US detection of urinary tract obstruction22 (21.6)30 (24.4)52 (23.1).62Abbreviations: CVA, costovertebral angle; SUN, serum urea nitrogen; US, ultrasonography.*Percentages have been rounded and may not total 100.†Indicates differences between men and women.The results of urine cultures are presented in Table 2. Escherichia coliaccounted for 56.4% of overall cases, followed by enterococci (10.7%), Staphylococcusspecies (8.0%), Proteus mirabilis(6.7%), Enterobacterspecies (5.3%), and Pseudomonas aeruginosa(5.3%). Bacteriuria was accompanied by bacteremia (with the same pathogen) in 60 men (58.8%) and 75 women (60.9%). Uncomplicated APs accounted for only 5.7% of women (3.1% of the total study population).Table 2. Results of Urine Culture According to Age and SexUrine Culture YieldNo. (%) of PatientsPValueAge, ySex≤65>65MenWomenEscherichia coli70 (59.3)57 (53.3)53 (52.0)74 (60.2).22Enterococci12 (10.2)12 (11.2)14 (13.7)10 (8.1).18Proteus mirabilis7 (5.9)8 (7.5)6 (5.9)9 (7.3).67Enterobacterspecies3 (2.5)9 (8.4)10 (9.8)2 (1.6).02Pseudomonas aeruginosa5 (4.2)7 (6.5)3 (2.9)9 (7.3).14Staphylococcusspecies11 (9.3)7 (6.5)5 (4.9)13 (10.6).12Klebsiellaspecies4 (3.4)7 (6.5)8 (7.8)3 (2.4).09Acinetobacterspecies2 (1.7)02 (2.0)0.12Mixed4 (3.4)01 (1.0)3 (2.4).41*Percentages have been rounded and may not total 100.†Indicates differences between men and women.Amoxicillin-clavulanate or ampicillin-sulbactam was used as the initial empirical treatment in 54% of cases, whereas second-generation cephalosporins were administered in 11%, combined ticarcillin sodium and clavulanate potassium in 10%, FQs in 6%, trimethoprim-sulfamethoxazole in 6%, third-generation cephalosporins in 3%, and the combination of a β-lactam plus an aminoglycoside in 10% of all subjects. The rate of resistance of E colito ampicillin was 27%; to trimethoprim-sulfamethoxazole, 11%; and to at least 2 drugs, 10%. Enterococci were resistant to ampicillin in 7%, ciprofloxacin in 11%, vancomycin hydrochloride in 2%, and teicoplanin in 1% of cases, whereas P aeruginosawas resistant to combined piperacillin sodium and tazobactam sodium in 17%, ticarcillin in 19%, ciprofloxacin in 40%, netilmicin sulfate in 23%, ceftazidime in 30%, and imipenem in 8% of subjects. Overall susceptibility of bacteria isolated from urine culture to amoxicillin-clavulanate or ampicillin-sulbactam was 86%; to trimethoprim-sulfamethoxazole, 67%; to FQs, 91.5%; and to netilmicin, 80%. Overall resistance of bacteria to all of these antibiotics was 4%. Multiresistant pathogens, ie, pathogens resistant to amoxicillin-clavulanate or ampicillin-sulbactam, trimethoprim-sulfamethoxazole, and FQs, included 2 strains of Acinetobacterspecies, 3 strains of P aeruginosa,and 4 strains of Klebsiellaspecies. Among the 9 patients who were infected by multiresistant strains, 4 (44%) had recently used antibiotics (P= .02 compared with recent users of antibiotics who had uropathogens susceptible to at least 1 of the above 4 agents).Men with (49/102 [48.0%]) and without (53/102 [52.0%]) prostatic hypertrophy did not differ in terms of the prevalence of bacteria resistant to trimethoprim-sulfamethoxazole (21/49 [42.9%] vs 16/53 [30.2%]; P= .18), to amoxicillin-clavulanate or ampicillin-sulbactam (3/49 [6.1%] vs 1/53 [1.9%]; P= .35), or to FQs (1/49 [2.0%] vs 2/53 [3.8%]; P= .60). Moreover, no significant differences were found between these groups with regard to mortality (7/49 [14.3%] vs 5/53 [9.4%]; P= .54) and prolonged hospitalization (7/49 [14.3%] vs 5/53 [9.5%]; P= .54).Table 3shows the comparisons between men and women in terms of historical features, antibiotic resistance, and clinical course of the AP episode. The variables identified by univariate analysis to be associated with each of the end points are presented in Table 4and Table 5, whereas the independent risk factors are shown in Table 6. Table 7shows the independent predictors of prolonged hospitalization and death. Although the presence of hydronephrosis was found to be associated with prolonged hospitalization and resistance to trimethoprim-sulfamethoxazole in univariate analysis, it was not isolated as an independent risk factor for the end points in the regression model.Table 3. Comparisons Between Men and Women Regarding Variables Estimated as Risk Factors for Mortality, Prolonged Hospitalization, and the Prevalence of Bacteria Resistant to Antibiotics*VariablesMen (n = 102)Women (n = 123)PValueAge >65 y1791<.001Historical featuresRecent hospitalization1029<.04Prostatic hypertrophy49NARecent use of antibiotics1018.19Nephrolithiasis225<.001Bedridden status1234<.01Septic shock2228.48Recurrent APs1415.44Diabetes mellitus923.04Immunosuppression418<.01Long-term catheterization1145<.001Antibiotic resistanceResistant to combined trimethoprim and sulfamethoxazole3737.32Resistant to combined amoxicillin and clavulanate potassium or to combined ampicillin sodium and sulbactam sodium428<.001Resistant to FQs316.02Clinical course of the AP episodeInitial treatment changed540<.001Prolonged hospitalization1250<.001Early death814.26Overall mortality1215.54Abbreviations: AP, acute pyelonephritis; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); NA, not applicable.*Data are given as number of patients unless otherwise indicated.Table 4. Significant Univariate Correlates of Mortality, Prolonged Hospitalization, and the Prevalence of Bacteria Resistant to Antibiotics in MenVariableNo. of PatientsMortality, No. dead/alive*Age >65 y†10/7Recent hospitalization†6/4Bedridden status†11/1Septic shock†12/10Recent use of antibiotics†9/1Long-term catheterization†10/1Prolonged hospitalization, No. yes/no*Age >65†10/7Recent use of antibiotics‡4/6Bedridden status§5/7Change in initial treatment†3/2Recent hospitalization†8/2Diabetes mellitus†5/4Immunosuppression†4/0Long-term catheterization†5/6Hydronephrosis†10/12Susceptibility of bacteria to trimethoprim-sulfamethoxaxole, No. resistant/susceptible&par;Immunosuppression†3/1Diabetes mellitus†7/2Recent hospitalization†9/1Recent use of antibiotics†9/1Long-term catheterization†7/3Hydronephrosis†16/6Susceptibility of bacteria to amoxicillin-clavulanate or ampicillin-sulbactam, No. resistant/susceptible¶Recent use of antibiotics‡2/8Recent hospitalization†3/7Nephrolithiasis†2/0Bedridden status§2/10Recurrent APs§2/12Diabetes mellitus‡2/7Immunosuppression†2/2Long-term catheterization§2/9Susceptibility of bacteria to FQs, No. resistant/susceptible#Recent hospitalization†3/7Recurrent APs†3/11Immunosuppression†2/2Abbreviations: amoxicillin-clavulanate, combined amoxicillin and clavulanate potassium; ampicillin-sulbactam, combined ampicillin sodium and sulbactam sodium; AP, acute pyelonephritis; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); trimethoprim-sulfamethoxazole, combined trimethoprim and sulfamethoxazole.*N = 12/n = 90.†P<.001.‡P<.01.§P<.05.&par;N = 37/n = 65.¶N = 4/n = 98.#N = 3/n = 99.Table 5. Significant Univariate Correlates of Mortality, Prolonged Hospitalization, and the Prevalence of Bacteria Resistant to Antibiotics in WomenVariableNo. of PatientsMortality, No. dead/alive*Age >65 y†15/76Recent hospitalization‡10/19Bedridden status†14/20Septic shock‡14/14Recurrent APs‡10/5Diabetes mellitus†10/13Nephrolithiasis†7/18Immunosuppression‡11/7Prolonged hospitalization, No. yes/no§Age >65 y‡47/44Change in initial treatment†25/15Nephrolithiasis†16/9Recurrent APs‡13/2Diabetes mellitus†18/5Immunosuppression&par;13/5Long-term catheterization‡17/1Hydronephrosis†20/10Susceptibility of bacteria to trimethoprim-sulfamethoxazole, No. resistant/susceptible¶Age >65 y‡34/57Nephrolithiasis†15/10Immunosuppression&par;11/7Diabetes mellitus&par;12/11Recent hospitalization‡25/4Recent use of antibiotics‡16/2Hydronephrosis‡25/5Susceptibility of bacteria to amoxicillin-clavulanate or ampicillin-sulbactam, No. resistant/susceptible#Recent hospitalization‡14/15Nephrolithiasis†15/10Diabetes mellitus&par;13/10Immunosuppression&par;11/7Susceptibility of bacteria to FQs, No. resistant/susceptible**Age >65 y‡15/76Nephrolithiasis‡15/10Immunosuppression‡10/8Abbreviations: amoxicillin-clavulanate, combined amoxicillin and clavulanate potassium; ampicillin-sulbactam, combined ampicillin sodium and sulbactam sodium; AP, acute pyelonephritis; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); trimethoprim-sulfamethoxazole, combined trimethoprim and sulfamethoxazole.*N = 15/n = 108.†P<.01.‡P<.001.§N = 50/n = 73.&par;P<.05.¶N = 37/n = 86.#N = 28/n = 95.**N = 16/n = 107.Table 6. Significant Multivariate Correlates of the Prevalence of Bacteria Resistant to Antibiotics*VariableMenWomenOR (95% CI)PercentageOR (95% CI)PercentageSENSSPECPPVNPVSENSSPECPPVNPVBacteria Resistant to Trimethoprim-SulfamethoxazoleRecent hospitalization*4.8 (2.2-6.3)259990706.1 (1.8-29.3)68958687Recent use of antibiotics*7.5 (3.1-4.9)259990703.9 (1.3-47.6)43988980Bacteria Resistant to Amoxicillin-Clavulanate or to Ampicillin-SulbactamImmunosuppression*8.4 (1.2-65.5)509850986.7 (2.1-58.2)32853981Bacteria Resistant to FQsRecurrent APs*7.3 (2.1-55.6)1009330100Nephrolithiasis*5.3 (1.7-16.1)94916099Abbreviations: Amoxicillin-clavulanate, combined amoxicillin and clavulanate potassium; ampicillin-sulbactam, combined ampicillin sodium and sulbactam sodium; AP, acute pyelonephritis; CI, confidence interval; FQs, fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin hydrochloride); NPV, negative predictive value; OR, odds ratio; PPV, positive predictive value; SENS, sensitivity; SPEC, specificity; trimethoprim-sulfamethoxazole, combined trimethoprim and sulfamethoxazole.*P<.01.Table 7. Significant Multivariate Correlates of Prolonged Hospitalization and MortalityVariableOR (95% CI)*MenProlonged hospitalizationChange in initial treatment5.6 (2.3-54.6)Diabetes mellitus4.7 (1.9-45.3)Long-term catheterization3.3 (2.3-69.8)Age >65 y6.2 (3.5-71.1)MortalityAge >65 y8.1 (2.2-69.9)Septic shocks16.4 (4.1-71.5)Bedridden status8.3 (3.1-42.9)Recent use of antibiotics5.2 (2.3-53.7)WomenProlonged hospitalizationChange in initial treatment4.4 (1.4-53.9)Diabetes mellitus5.3 (2.1-44.8)Long-term catheterization*7.6 (2.5-67.1)MortalityAge >65 y8.3 (3.2-68.6)Septic shock15.7 (5.5-72.4)Bedridden status7.9 (2.9-49.6)Immunosuppression4.9 (2.1-51.5)Abbreviations: CI, confidence interval; OR, odds ratio.*For all variables P<.01.The coefficients of the 4 independent correlates of mortality, divided by 0.5 and rounded to the nearest interval, allowed a simpler reexpression of the final regression model, in the form of the following integer-based scoring system:Number of Points (Men) = 6 for Septic Shock + 4 for Bedridden Status + 4 for Age >65 Years + 3 for Previous Antibiotic TreatmentandNumber of Points (Women) = 6 for Septic Shock + 4 for Bedridden Status + 4 for Age >65 Years + 3 for ImmunosuppressionAccording to this prediction tool (Figure 1), most patients (89% of men and 87% of women) could be classified in the subgroups with low scores (<7 points), which predict a very limited risk for death (0%-2.5% for men and 0%-2.3% for women). Patients classified in the highest-score subgroup (≥11 points) had a very high risk for death (100% for men and 91% for women).Performance of an integer-based scoring system regarding mortality due to acute pyelonephritis. The equation we used for calculating the scores is provided in the "Results" section.COMMENTAcute pyelonephritis is the only UTI that may require hospital admission and could be fatal in patients with immunosuppression,elderly individuals,pregnant women,and patients with diabetes.Thus, in patients admitted for AP, the early identification of subgroups of patients at high risk for in-hospital death, prolonged hospitalization, and/or failure of treatment might contribute to ameliorative treatment.In the present study, women admitted for AP were older than men (Table 1), more frequently bedridden, and more likely to undergo long-term catheterization and to be immunosuppressed, and they more often had a history of nephrolithiasis, diabetes mellitus, and recent hospitalization (Table 3). Therefore, they had a higher incidence of infection with resistant bacteria. Because of this difference, and because of the fact that few studies on AP have analyzed data regarding men,we decided to perform separate analyses of data regarding men and women.Our study provides additional support for the view that, although susceptibility patterns have changed, the spectrum of microorganisms that cause community-acquired AP has remained relatively constant. Among the overall population, E coliaccounted for 57% of cases, whereas the rate of its resistance to trimethoprim-sulfamethoxazole (11%) was lower than the corresponding estimated rate in Greece during the same period (17%).Because cost-effectiveness analyses have shown that the threshold trigger for empirical FQ use in E coli– related UTI should be a trimethoprim-sulfamethoxazole resistance of more than 20%,and that the effect of the latter on clinical outcomes depends on the level of resistance in the community,administration of trimethoprim-sulfamethoxazole might be recommended as a first-line treatment for community-acquired AP due to E coliin Greek settings. However, considering that in our study E coliwas responsible for only 57% of APs, 51% of all other bacteria causing AP were resistant to trimethoprim-sulfamethoxazole, and the causative agent of AP is not usually known at the time of admission to the hospital, trimethoprim-sulfamethoxazole is not recommended as a first-line treatment for AP.In accord with previous reports,a history of recent hospitalization and use of antibiotics correlated independently with the prevalence of any trimethoprim-sulfamethoxazole–resistant bacteria in men and women. Thus, clinicians must consider the extent of the patient's exposure to hospital pathogens and the unique bacteriological features of each hospital when devising antibiotic strategies.In contrast to the results of several studies yielding resistance rates as high as 54% in European settings,susceptibility of all bacteria to amoxicillin-clavulanate or to ampicillin-sulbactam was sufficiently high in our population, and immunosuppression was the only independent predictor of the prevalence of bacteria resistant to these drugs in both sexes. The susceptibility pattern in the present study corroborates recent reports by the World Health Organization antimicrobial resistance monitoringand by the first international multicenter epidemiological survey of antimicrobial susceptibility of uropathogens,according to which no firm evidence of increased resistance to these drugs exists so far.Overall resistance rate to FQs in the population studied (8.5%) was comparable to the rate observed in our community (6.5%) at the beginning of the present study (1997)and the rate found in other European settings during the same preriod (6%).In line with previous reports,the present study yielded a history of recurrent APs for men and a history of nephrolithiasis for women as independent determinants of the prevalence of FQ-resistant bacteria. After considering cost-effectiveness and the risk for emergence of resistance, there appears to be little justification for using FQs routinely to treat APs, unless other agents are not well tolerated or are unlikely to be effective.A history of recurrent UTIs, the only independent predictor of multidrug resistance in men in our study, constitutes a well-established risk factor for the prevalence of multiresistant pathogens, especially in elderly patients with underlying diseases.Nevertheless, multivariate analysis isolated only nephrolithiasis as independently associated with multidrug resistance in women, which confirmed the results of previous studies that have shown women with renal lithiasis to have APs more frequently than men.In line with recent reports,the regression model showed that prolonged hospitalization for AP should be expected for a man with diabetes who is undergoing long-term catheterization and is older than 65 years, or for a woman of any age with both additional characteristics, whose initial empirical treatment was changed according to the results of urine culture. Regarding mortality, the multivariate analysis identified 5 factors that have been extensively investigated and found to convey a high risk for death in previous studies. Thus, age greater than 65 years,bedridden status,and the presence of septic shock at presentationwere the common independent predictors of death for both sexes, whereas additional multivariate correlates were recent use of antibiotics in menand immunosuppression in women.The mortality prediction model identified 3 groups of patients. The largest (90% of subjects) consisted of men and women with a score of less than 7 points who had a very limited risk for in-hospital death (<2.5%), whereas the smallest (8%) consisted of patients with a score of at least 11 points who were at high risk for death due to their disease (>90%). The ambiguous zone of patients with a score of 7 to 10 points included only 3 men (2.9%) and 5 women (4.1%) with corresponding risks for death of 67% and 75%, respectively. Thus, the cutoffs for achieving sufficiently high accuracy should be less than 7 or at least 11 points for the prediction of a favorable outcome or death, respectively. Despite significant differences between men and women regarding the mean age and the severity of the illness, risk factors for mortality, prolonged hospitalization, and prevalence of resistant bacteria were quite similar between the 2 sexes. Nevertheless, since the proposed model has been evaluated only in the patients from whom it was derived, its performance requires prospective validation in independent, external populations before it is routinely applied.Taking into account the rates of resistance in our study, patients with AP due to E colicould be treated with trimethoprim-sulfamethoxazole, whereas when the pathogen is not known, empirical treatment with trimethoprim-sulfamethoxazole is not recommended. Amoxicillin-clavulanate or ampicillin-sulbactam might be recommended as first-line treatment for APs acquired in communities with susceptibility patterns similar to those of our country. Fluoroquinolones should not be administered empirically as first-line treatment for AP, except in cases in which the risk factors for prevalence of bacteria resistant to other antibiotics are present and in men with hypertrophy of the prostate, for whom the penetration of FQs is superior compared with that of other agents.The proposed prediction model requires the application of simple information available at the emergency department and transformed to an easily remembered score. If validated, the model could be used to confirm the necessity of hospitalization for seriously ill patients who require intravenous treatment. Therefore, the model may contribute to a more objective risk stratification of patients presenting with AP, thus optimizing the selection of antimicrobial agents, ensuring prompt management of high-risk individuals, and directing those at low risk to less intensive and less costly levels of care.WEStammSRNorrbyUrinary tract infections: disease panorama and challenges.J Infect Dis.2001;183(suppl 1):S1-S4.JWWarrenEAbrutynJRHebelJRJohnsonAJSchaefferWEStammGuidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women: Infectious Diseases Society of America (IDSA).Clin Infect Dis.1999;29:745-758.WEStammUrinary tract infections.In: Root RK, Waldvogel F, Corey L, Stamm WE, eds. Clinical Infectious Diseases: A Practical Approach.New York, NY: Oxford University Press Inc; 1999:649-656.PIspahaniNJPearsonDGreenwoodAn analysis of community and hospital-acquired bactaeremia in a large teaching hospital in the United Kingdom.Q J Med.1987;63:427-440.FJRobertsIWGeereAColdmanA three-year study of positive blood cultures, with emphasis on prognosis.Rev Infect Dis.1991;13:34-46.AJSchaefferUrinary tract infections: antimicrobial resistance.Curr Opin Urol.2000;10:23-24.MLCohenEpidemiology of drug resistance: implications for a post-antimicrobial era.Science.1992;257:1050-1055.LLeiboviciSGreenshtainOCohenAJWysenbeekToward improved empiric management of moderate to severe urinary tract infections.Arch Intern Med.1992;152:2481-2486.CSvanborgResistance to urinary tract infection.N Engl J Med.1993;329:802-803.IEDyerTMSankaryJADawsonAntibiotic resistance in bacterial urinary tract infections, 1991 to 1997.West J Med.1998;169:265-268.KGuptaDFSahmDMayfieldWEStammAntimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis.Clin Infect Dis.2001;33:89-94.BALipskyUrinary tract infections in men: epidemiology, pathophysiology, diagnosis, and treatment.Ann Intern Med.1989;110:138-150.AJSchaefferUrinary tract infection in men—state of the art.Infection.1994;22(suppl 1):S19-S21.RHRubinEDShapiroVTAndrioleRJDavisWEStammEvaluation 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.1992;15(suppl 1):S216-S227.MHoferUltrasound Teaching Manual.New York, NY: Thieme-Stratton Inc; 1999.National Committee for Clinical Laboratory StandardsPerformance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard.5th ed. Villanova, Pa: National Committee for Clinical Laboratory Standards; 1993. NCCLS document M2-A5.SPSS IncStatistical Package for the Social Sciences.Chicago, Ill: SPSS Inc; 2000. Windows version, release 10.0.MSadek SabbourTAbd-el-HamidSKHusseinInfection in immunosuppressed patients.Chemioterapia.1984;3:19-24.LENicolleUrinary tract pathogens in complicated infection and in elderly individuals.J Infect Dis.2001;183(suppl 1):S5-S8.LCGilstrap IIISMRaminUrinary tract infections during pregnancy.Obstet Gynecol Clin North Am.2001;28:581-591.ARonaldELudwigUrinary tract infections in adults with diabetes.Int J Antimicrob Agents.2001;17:287-292.ACVatopoulosVKalapothakiNJLegakisfor the Greek Network for the Surveillance of Antimicrobial ResistanceAn electronic network for the surveillance of antimicrobial resistance in bacterial nosocomial isolates in Greece.Bull World Health Organ.1999;77:595-601.TPLeLGMillerEmpirical therapy for uncomplicated urinary tract infections in an era of increasing antimicrobial resistance: a decision and cost analysis.Clin Infect Dis.2001;33:615-621.KGuptaTMHootonWEStammIncreasing antimicrobial resistance and the management of uncomplicated community-aquired urinary tract infections.Ann Intern Med.2001;135:41-50.PBemer-MelchiorLGillyKJugroot-KlotzTBrunPNevotGPaulResistance to amoxicillin and amoxicillin–clavulanic acid combination of 231 clinical strains of Escherichia coli, isolated in 1992 at the Cochin Hospital [in French].Pathol Biol (Paris).1995;43:760-765.DVanakCSauvagetCMuller-SerieysGMillotEBergogne-Berezinβ-Lactamase producing Escherichia coli: in vitro susceptibility of clinical strains to β-lactamase inhibitors.In: Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology; Washington, DC; 1983.Washington, DC: American Society for Microbiology; 1983:143. Abstract 132.CHenquellDSirotCChanalFrequency of inhibitor-resistant TEM β-lactamases in Escherichia coliisolates from urinary tract infections in France.J Antimicrob Chemother.1994;34:707-714.World Health OrganizationReport on Infectious Diseases: Removing Obstacles to Healthy Development.Geneva, Switzerland; World Health Organization; 1999.GKahlmeterThe ECO.SENS Project: a prospective, multinational, multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens: interim report.J Antimicrob Chemother.2000;46(suppl 1):15-22.ACVatopoulosVKalapothakiNJLegakisfor the Greek Network for the Surveillance of Antimicrobial ResistanceBacterial resistance to ciprofloxacin in Greece: results from the National Electronic Surveillance System.Emerg Infect Dis.1999;5:471-476.NJLegakisLSTzouvelekisATsakrisJNLegakisACVatopoulosOn the incidence of antibiotic resistance among aerobic gram-negative rods isolated in Greek hospitals.J Hosp Infect.1993;24:233-237.RDazaJGutierrezGPiedrolaAntibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections.Int J Antimicrob Agents.2001;18:211-215.HGiamarellouFleroxacin in complicated urinary tract infections.Chemotherapy.1996;42(suppl 1):17-27.JEnaCAmadorCMartinezVOrtiz de la TablaRisk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant Escherichia coli.J Urol.1995;153:117-120.AJSchaefferReview of norfloxacin in complicated and recurrent urinary tract infections.Eur Urol.1990;17(suppl 1):19-23.AUlmannJClavelDDestreeCDuboisAMombetJMBrissetNatural history of renal calcium lithiasis: data obtained from a cohort of 667 patients [in French].Presse Med.1991;20:499-502.CYPakNephrolithiasis.Curr Ther Endocrinol Metab.1997;6:572-576.JARobertsManagement of pyelonephritis and upper urinary tract infections.Urol Clin North Am.1999;26:753-763.SJEykynUrinary tract infections in the elderly.Br J Urol.1998;82(suppl 1):79-84.JMHamilton-MillerIssues in urinary tract infections in the elderly.World J Urol.1999;17:396-401.MDewandreJFranckJLecomteAMutsersPTaziauxThe hazards of bed rest in the elderly [in French].Rev Med Liege.1981;36:894-902.CAllenPGlasziouCDel MarBed rest: a potentially harmful treatment needing more careful evaluation.Lancet.1999;354:1229-1233.EProcaRRadulescuCCalinNCalomfirescuJNasaudeanANatuClinical comments on management of urosepsis in a general urological department.Acta Urol Belg.1992;60:41-56.JTMageeELPritchardKAFitzgeraldFDDunstanAJHowardAntibiotic prescribing and antibiotic resistance in community practice: retrospective study, 1996-8.BMJ.1999;319:1239-1240.DJAustinKGKristinssonRMAndersonThe relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance.Proc Natl Acad Sci U S A.1999;96:1152-1156.GPedersenHCSchonheyderFHSteffensenHTSorensenRisk of resistance related to antibiotic use before admission in patients with community-acquired bacteraemia.J Antimicrob Chemother.1999;43:119-126.DTSteinkeRASeatonGPhillipsTMMacDonaldPGDaveyPrior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors.J Antimicrob Chemother.2001;47:781-787.JARobertsGJDomingueLNMartinJCKimSRRanganImmunology of pyelonephritis in the primate model, II: effect on immunosuppression.Investig Urol (Berl).1981;19:148-153.Corresponding author and reprints: Angelos V. Pefanis, MD, Third Department of Medicine, Athens University, Medical School, Sotiria General Hospital, 152 Mesogion Ave, Athens 11527, Greece (e-mail: gpp@hol.gr).Accepted for publication August 16, 2002.

Journal

JAMA Internal MedicineAmerican Medical Association

Published: May 26, 2003

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$499/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month