Dynamic Changes of the Microflora Sensitivity to Antibiotics in Patients with Chronic Calculous Pyelonephritis

 

N.G. Kulchenko¹, S.M. Chibisov¹, I.Z. Eremina¹, M.A. Vekilyan ², S.P. Syatkin¹, A.S. Skorik¹, G.I. Myandina¹, N.A. Shevkun¹, E.V. Neborak¹

¹Federal State Budgetary Institution of Higher Professional Education “People’s Friendship University of Russia”, Mikloukho-Macklay Street, 6, Moscow, 117198

²Department of Urology of Non-Governmental Healthcare Institution of Regional Clinical Hospital at the station Volgograd-1, JSC "Russian Railways", Avtotransportnaya Street, 75, Volgograd, 400131

 

ABSTRACT:

Secondary pyelonephritis occurs in 48.3% - 89.3% of cases and complicates the states of the disease. The effectiveness of therapy and prognosis of the disease depends on chosen methods of antibiotic prophylaxis of pyoinflammatory kidney diseases.

The purpose of the research: To improve the results of patients’ treatment with complicated calculous pyelonephritis.

Materials and methods: We have examined 179 people. This was a retrospective pharmacoepidemiological analysis of medical documents of patients, treated in 2009 and in 2013 in a hospital of Volgograd. The number of women, taking part in the research was 99 (55.4%) and men - 80 (44%). All patients underwent a standard clinical examination, with the mandatory bacteriological urinalysis, renal ultrasound.

Results: Among patients with chronic calculous pyelonephritis, the most common infectious agents are the following: E.coli - 72,4%, Staph. epidermidis - 20,8%, P. aeruginosa - 26,8%. The greatest sensitivity to infectious agents possess the next preparations: carbopenems (meronems) - 92%, amoxicillin + clavulanic acid - 86.4%, cefotaxime - 89.4%. The greatest resistance of E.Coli is to ciprofloxacin and ampicillin.

Conclusions: The regular review of recommendations for antimicrobial therapy of urinary tract infections is necessary, due to the constant changes in the level of uropathogens resistance.

 

 

 

INTRODUCTION:

Urinary tract infections are one of the most urgent problems of modern urology [1, 7, 9]. Often urolithiasis combines with urinary tract infection, that causes the development of pyelonephritis [2, 6, 11]. Among all kidneys diseases, 15-25% of elderly persons have pyelonephritis [4]. Secondary pyelonephritis occurs in 48.3% - 89.3% of cases and complicates the states of the disease [4, 12].

 

The seeds of secondary pyelonephritis are various: the infection of urinary tract with pathogens, the influence of the obstruction factor to the urinary tract and caused them urinary stasis, including diabetes [3, 5, 9, 10]. The therapy effectiveness and disease prognosis depends on chosen methods of antibiotic prophylaxis of pyoinflammatory kidney diseases[7].

 

The purpose of the research is to improve the results of patients’ treatment with complicated calculous pyelonephritis.

 

MATERIALS AND METHODS:

This research was carried out on the basis of the Department of Urology of Non-Governmental Healthcare Institution of Regional Clinical Hospital at the station Volgograd-1, JSC "Russian Railways".

 

We carried out pharmacoepidemiological retrospective research, the object of which was primary medical documentation (medical records) over 2009 and 2013.

 

We divided the research into 3 stages:

1. Retrospective analysis of medical records of 2009, - the first group of patients.

2. Retrospective analysis of medical records of 2013, - the second group of patients.

3. Comparative analysis of both groups of patients.

 

503 medicals cases with an established diagnosis of urolithiasis, chronic pyelonephritis were analyzed in 2009. Bacteriological examination of urine was performed among 88 persons, 17.4% of cases. In 2013 564 medical cases were analyzed, the examination of urine on the bacteriological flora was performed in 91 patients, 16.1% of cases. Among the remaining patients, bacteriological examination was not carried out, due to the absence of any clinical findings of pyelonephritis or previous intake of antibacterial drugs within 14 days before hospitalizing.

 

Consequently, 179 patients with a diagnosis of "chronic calculous pyelonephritis" were included in the research. The first group comprised of 88 (49.1%) patients, the second group comprised of 91 persons (50,9%). The patients were divided by gender as follows: 179 patients - 80 men (44.6%) and 99 women (55.4%).

 

At the time of the research, the patients’ age ranged from 18 to 80 years, average age was 49 + 31 years.

 

All patients underwent standard clinical examination, with the mandatory bacteriological urinalysis, ultrasound of the kidneys.

 

Determination of the sensitivity of microorganisms’ isolated strains to antibiotics was carried out by the disco-diffusion method on the agar of Mueller - Hinton, in accordance with the Municipal Cultural Institution recommendations from 1994. The quality control of defining the sensitivity we conducted in parallel with testing of studied pathogens, using strains of E. coli ATCC 25922, S. aureus ATCC 25923, Ps. aeruginosa ATCC 27853, Streptococcus pneumoniae ATCC 49619, E.coli ATCC 35218.

 

The criteria for inclusion of patients in the research: individuals of both sexes at the age of 18 years, the presence of established diagnosis "urolithiasis + chronic pyelonephritis", the presence of bacteriological examination of urine.

 

The criteria for exclusion of patients: coexisting cancer diseases; tuberculosis (pulmonary and out pulmonary form); the existence of permanent urethral catheter in patients at the time of hospitalization; pregnancy and lactation; if the patient has another disease that requires systemic antibacterial therapy; acute or chronic renal failure; patients with HIV infection.

 

Statistical analysis of the material was carried out using the spreadsheet "EXCEL" and the program "STATISTICA 6.0". The significance of differences assessment between quantitative parameters was performed using the criteria of Mann - Whitney. The differences were considered as significant when p <0,05.

 

RESULTS AND DISCUSSION:

In the process of analysis of diseases duration, the large group consisted of patients who had chronic calculous pyelonephritis more than three years - 120 (67,2%). Among them, the first group included people who had the disease from 3 to 5 years – 38 persons (43.1%), the second group included 61 persons (34%), respectively. Comparative characteristic of two patients groups, on the basis of disease duration is shown in Table 1.

 

All the patients of the first research group (n = 88) underwent medical tests on urine culture, among them 12 persons (13.6%) hadn’t an abnormal growth of flora, 76 persons (86.4%) had an abnormal growth. 52 patients (59%) had bacteriuria (10x5 cfu/ml or more).

 

Also, all the patients of the second research group (n = 91) underwent medical tests on urine culture, among them 19 persons (20.8%) hadn’t an abnormal growth of flora, 72 persons (79.2%) had an abnormal growth. 63 patients (69.2%) had bacteriuria (10x5 cfu/ml or more).

 

 

Table 1. Comparative characteristic of the researched groups of patients, on the basis of disease duration

Note: * - p <0.05 when compared the terms of patients’ admission to hospital, depending on the research groups

 

In making an assessment of comparative characteristics of the pathogen titer in patients of the first and the second groups, we found that the largest part of the two groups made up the bacteria identified in the titer 10x5 CFU. Moreover, in 2013, we recorded an increase in the number of patients with a titer 10x6 CFU up to 25%, and with a titre 10x7 CFU up to 20%, respectively. This phenomenon can be explained by an increase in the virulence of pathogens, which can subsequently lead to the emergence of drug-resistant forms.

 

Comparative characteristic of the first and the second research groups of patients on the basis of pathogen titer is presented in Table 2.

 

Table 2. The pathogen titer in the first group of patients

The pathogen titer (cfu/ml)	The 1st group		The 2nd group
	n	%		n	%
<103	3	3,4		5	5,4
103	11	12,5		12	13,1
104	22	25		11	12
105	34	38,6		36	39,5
106	13	14,7		19	20,8
107	5	5,6		8	8,7

 

Among all the surveyed patients, 36 persons (40.9%) had an abnormal flora in the form of one infection, the rest - 52 persons (59.1%) - had mixed infection of different bacterial combinations. Comparison of patients on the basis of the identified microflora spectrum is presented in Table 3.

 

In 2009, patients from the research group had the most common pathogens of upper urinary tract the E.coli - 63,3%, Enterococcus faecalis - 29,5%, Pseudomonas aeruginosa - 37,5 and Klebsiella pneumonia - 20,4%.

 

Table 3. The spectrum of microflora in patients of both research groups

Note: * - Detected number of pathogens is more than the total number of patients (n = 179), because in some research cases there were several pathogens.

 

In 2013, patients from the research group had the most frequent pathogens of upper urinary tract, such as: E.coli – 79.1%, Enterococcus faecalis – 24.1%, Pseudomonas aeruginosa – 29.6% and Klebsiella pneumonia – 26.3%.

 

Among all patients of the first group, 36 persons (40.9%) had an abnormal flora in the form of one infection, the rest - 52 persons (59.1%) - had mixed infection of different bacterial combinations. Consequently, in 2009, patients of the first research group had the most frequent pathogen of the upper urinary tract - E.coli - 44,4% and Staph. epidermidis - 19,4%.

 

All the patients of the second research group (n = 91) underwent medical tests on urine culture, among them 19 persons (20.8%) hadn’t an abnormal growth of flora, 72 persons (79.2%) had an abnormal growth. The bacterial flora in the form of mono - pathogen in patients’ research group of 2013, with chronic pyelonephritis is presented by E.coli - 72,4% and Staph.epidermidis - 20,8%, P. aeruginosa - 26,8%.

 

We conducted a comparative analysis of the pathogen characteristics in patients of the first (2009) and the second group (2013) and noted that over these years, the leading pathogen of the upper urinary tract is E.coli. Our research confirms that E.coli is the cause of inflammatory diseases of the kidneys more than in two-thirds of clinical cases. The identifying growth of E.coli in 2013 amounted to 15,8%, the Klebsiella pneumoniae growth was 5,9%, Staphilococcus growth was 7.2% over the specified period (p <0,05).

 

Comparing the sensitivity of E.coli isolated strains to antimicrobial agents, in patients of the first and the second groups, over 2009 and 2013 respectively, we have found a general tendency to reducing the sensitivity of E.coli to virtually all the antimicrobial agents. The most significant was decreasing sensitivity of E.coli to fluoroquinolones: to norfloxacin by 12,9% (p<0,05), to ciprofloxacin by 23,5% (p <0,01). It was noticed steady dynamic decline of E.coli sensitivity to aminoglycosides: to gentamicin by 5.6%; to ampicillin by nearly 4%, to third-generation cephalosporins by 7.4%; to levofloxacin by 4.8%.

 

However, despite the growing E.coli resistance to antibiotics, there is a high sensitivity to amoxicillin/ clavulanate - 90.9%, cefatoxime - 91.4%, ceftazidime - 91.1%, amikacin - 92.3%, imipenem – 97.7%, which allows to use these drugs for empiric antibiotic therapy in patients with chronic calculous pyelonephritis.

 

The results of sensitivity comparison of K. pneumonia strains to antimicrobial agents in patients of the first and the second groups, found common dynamic tends to decrease the sensitivity of K. pneumonia to antimicrobial agents. We have defined statistically evidential lower sensitivity of K. pneumonia to ampicillin, cotrimoxazole (p <0,05). We also revealed the dynamics of the decrease in sensitivity of K. pneumonia to cephalosporins of the second generation (cefuroxime) by 12,1% (p <0,05), and to aminoglycosides (gentamicin) by14,3% (p<0,01).

 

Consequently, according to received in vitro data, the greatest pharmacodynamic activity against K. pneumonia had carbapenems and fluoroquinolones. Gentamicin, aminopenicillin, cephalosporins of the second generation, as well as co-trimoxazole could not be recommended as antibiotics for empirical therapy.

 

Over the five-year research period, we also recorded steady decrease of P. aeruginosa sensitivity to the main spectrum of antibacterial agents: cefuroxime by 12,1% (p <0,05), gentamicin by 14,3% (p <0,05). Carrying out comparative analysis of the P. aeruginosa sensitivity to antibiotics in both groups of patients, we noted the continuing high sensitivity to ceftazidime - 96.5%, to amikacin - 86.8%, to imipenem - 100%, which allows the use of these drugs as empirical therapy.

 

So, ceftazidime, imipenem, amikacin were the most active against P. aeruginosa. Taking into account the small number of researched strains, it is possible to say only with a certain probability, that other antibiotics with own antipseudomonal activity (except fluoroquinolones) had good activity against P aeruginosa. In case of presence in patients with upper urinary tract infection, indications in a history about previous surgical or instrumental urological intervention as empirical antibiotic therapy, it is appropriate to use antibiotics with antipseudomonal activity.

 

We found low sensitivity of Enterococcus spp. strains to aminoglycosides (gentamicin, amikacin), fluoroquinolones, cotrimoxazole, ampicillin, which prevents the use of these drugs as empirical antibiotic therapy. The results of comparing the dynamics of sensitivity changes of Enterococcus spp. showed continuing high activity of protected penicillins (amoxicillin/ clavulanate) and carbapenems (p <0,05).

 

Consequently, for the treatment of upper urinary tract infections in patients with chronic calculous pyelonephritis, when the pathogen is assumed as Enterococcus spp., protected penicillins and carbapenems may be recommended.

 

So, the use of antibiotic therapy for elimination of uropathogenic pyelonephritis bacteria is complex and not always solvable problem. Knowledge of modern characteristics of pathogens, the approaches to its diagnosis and treatment has great significance for practical urology.

 

CONCLUSIONS:

In patients with infection of the upper urinary tract and diabetes, there has been observed a strong tendency of decreasing sensitivity to all groups of antibiotics. Sensitivity to unprotected penicillins and fluoroquinolones steadfastly declined almost twice, that could not allow to assign these agents as empirical therapy. The sensitivity to the protected beta-lactam penicillins (amoxicillin/ clavulanate) declined by almost 10%. The resistance to aminoglikozides increased by 23% among the patients of this group.

 

Today, patients with chronic calculous pyelonephritis has a high sensitivity of the main infectious agents to cephalosporins of the third and fourth generation - 89.4%, to the protected beta-lactam penicillins (amoxicillin/ clavulanate) - 86.4%, to derivatives of carbapenems - 92% (p <0,05).

 

Due to the constant changes in the level of uropathogens resistance, it is required regular review of recommendations for antimicrobial therapy of urinary tract infections.

 

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Accepted on 02.01.2017           © RJPT All right reserved