Analysis of bacterial spectrum and drug sensitivity in preoperative urine culture of upper urinary calculi

doi:10.21203/rs.3.rs-3105159/v1

Download PDF

Article

Analysis of bacterial spectrum and drug sensitivity in preoperative urine culture of upper urinary calculi

https://doi.org/10.21203/rs.3.rs-3105159/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

OBJECTIVE:

To analyze the distribution of urinary culture pathogenic bacteria and drug resistance in patients with upper urinary calculi combined with urinary tract infections.

METHODS:

Seventy-three patients with upper urinary calculi combined with urinary tract infection who were hospitalized in Taikang Xianlin Drum Tower Hospital from January 2020 to April 2023 were retrospectively analyzed as study subjects. The patients' midstream urine samples was collected in morning, and urine culture and drug sensitivity tests were performed to analyze their pathogenic bacteria distribution and drug resistance.

Results:

In the urine specimens of 73 patients with upper urinary calculi, 80 pathogenic bacteria were detected, including 52 were Gram-negative bacteria (65.00%), 23 were Gram-positive bacteria (28.75%) and 5 were fungi (6.25%). Gram-negative bacteria were mainly Escherichia coli, Gram-positive bacteria were mainly Enterococcus faecalis, and fungi were mainly candida albicans; the top 10 drugs in terms of sensitivity to Gram-negative bacteria were imipenem(100.00%), cefoperazone/sulbactam(100.00%), meropenem (100.00%), amikacin(98.04%), piperacillin/tazobactam (96.08%), cefotetan(93.62%), Nitrofurantoin(84.85%), cefepime(84.44%), aztreonam(81.63%), and tobramycin(76.92%). The top three drug resistance rates were ampicillin(84.62%), piperacillin(56.86%), and ampicillin/sulbactam(46.15%). The drugs with high sensitivity rates to gram-positive bacteria were vancomycin(100%), linezolid(100%), tigecycline(100%), Nitrofurantoin (94%), ampicillin(83%), and penicillin G(79%).

CONCLUSION:

Gram-negative and Gram-positive bacteria are the main pathogens of urinary tract infections in patients with upper urinary calculi, and their major strains differ in their resistance to commonly used antimicrobial drugs.

Biological sciences/Drug discovery/Drug safety

Health sciences/Urology/Ureter

Health sciences/Urology/Urogenital diseases

antibiotic resistance

upper urinary calculi

midstream urine culture

pathogenic bacteria distribution

urinary tract infections

Upper urinary calculi and urinary tract infections are both common diseases in urology [1] . Patients with urinary stones are more prone to various urinary tract infections than other populations [2] , mainly because upper urinary calculi, especially upper urinary calculi, can lead to local urinary tract obstruction, which can cause urinary tract infections, and the presence of infection can lead to local inflammation and aggravate the obstruction, and if the infection is not well controlled, it may lead to recurrence of stones[3] . Urinary tract infections are often retrograde, with Escherichia coli as the main infectious agent, and are prone to recurrence [4]. For patients with upper urinary calculi with urinary tract infection, preoperative anti-infective treatment with antibiotics is required to avoid further aggravation of the patient's infection. However, urine culture usually takes 2 to 3 working days to report the identification and drug sensitivity results, so the clinical need for empirical medication for this type of patients. However, in recent years, due to the widespread use of antimicrobial drugs, the resistance of some pathogenic bacteria has been increasing, and if the antibiotics selected clinically are of the corresponding bacterial resistant type, they are not useful for perioperative infection prevention and may even contribute to the growth and multiplication of drug-resistant bacteria, which may aggravate the patient's infection intraoperatively and may cause sepsis in severe cases [5] . The aim of this study was to analyze the urine culture results and drug sensitivity results of patients with upper urinary tract stone co-infection treated in our hospital in the last two years in order to provide assistance in the use of clinical antibiotics.

1.1 Sample Collection

Retrospective analysis of 73 cases of urinary stones with urinary tract infection treated in our hospital from January 2021 to April 2023, of which 28 (38.4%) were males and 45 (61.4%) were females aged 20 to 87 years, with a mean age of (51.38 ± 18.03) years. The distribution of pathogenic bacteria in clean middle urine specimens and the results of drug sensitivity tests were analyzed in their patients.

Inclusion criteria: ( 1) Upper urinary tract stone as the primary diagnosis; ( 2) positive preoperative urine culture results; (3) with the results of routine urine report of the middle segment collected on the same day. Exclusion criteria: urine culture results did not specify the specific strains of bacteria; combined with other infections.

1.2 Methodology

1.2.1 Collection of specimens

Collection method: Before collecting urine, the patient was instructed to clean and disinfect the external urethral orifice, and take the middle urine in a disposable sterile urine cup with a volume of about 10 ml.

1.2.2 Bacterial culture, identification and drug sensitivity determination The suspect colonies were picked and identified and sensitized on a Vitek2-Compact60 bacterial identification and drug sensitivity instrument. ATCC29213, Pseudomonas aeruginosa ATCC 90028.

1.3 Statistical methods

The data were statistically tested and analyzed using Graph Pad Prism 8.0 software: continuous variables were expressed as mean ± standard deviation ( 𝑥̅ ± sd).P < 0.05 was considered a statistically significant difference.

2.1 Distribution and composition ratio of pathogenic bacteria in specimens from patients with urinary stones

In 73 urine specimens from patients with upper urinary calculi, 80 cases of pathogenic bacteria were detected, 52 were Gram-negative (65.00%), 23 were Gram-positive (28.75%), and 5 were fungal (6.25%) strains (Figure 1). Gram-negative bacteria were predominantly Escherichia coli, Gram-positive bacteria were predominantly Enterococcus faecalis, and fungi were predominantly candida albicans (Figure 2). The differences in strains between men and women were not significant (P > 0.05) in the comparative study. Figure 3

2.2 Drug resistance characteristics of gram-negative bacteria in the urine of patients with urinary stones

Of the 52 Gram-negative strains, the main causative agent, Escherichia coli (36 strains, 69.23%), the top 10 drugs ranked in terms of sensitivity to Gram-negative bacteria were imipenem(100.00%),cefoperazone/sulbactam(100.00%),meropenem (100.00%), amikacin(98.04%), piperacillin/tazobactam (96.08%),cefotetan(93.62%), Nitrofurantoin(84.85%), cefepime(84.44%), aztreonam(81.63%), and tobramycin(76.92%). The top three drug resistance rates were ampicillin(84.62%), piperacillin(56.86%), and ampicillin/sulbactam(46.15%). Table 1.

G-bacteria were highly resistant to β-lactam antibiotics, but showed good susceptibility to the combination of β-lactam antibiotics combined with β-lactamase inhibitor-sulbactam/tazobactam and significantly lower resistance (P < 0.05) Figure 4&5.

2.3 Drug resistance characteristics of Gram-positive bacteria in the urine of patients with urinary stones

Among the 23 gram-positive strains, the main causative organism was Enterococcus faecalis (9 strains, 39.13%). The drugs with high sensitivity to gram-positive bacteria were: vancomycin(100%), linezolid(100%), tigecycline(100%),Nitrofurantoin (94%), ampicillin(83%), and penicillin G(79%)Table 2.

Table 1 Composition of the drug sensitivity profile of patients with gram-negative bacilli ( %)

Drugs	Imipenem	Cefoperazone/Sulbactam	MeropeneM	Amikacin	Piperacillin/Tazobactam	Cefotetan	Nitrofurantoin	Cefepime	Aztreonam	Tobramycin	Compound SMZ	Ceftazidime
Sensitivity rate	100	100	100	98	96	94	85	84	82	77	76	73
Mediation rate	0.	0	0	0	1.96	2.13	9.09	0	0	15.38	0	1.96
resistance rate	0	0	0	1.96	1.96	4.26	6.06	15.56	18.37	7.69	24.49	25.49

Drugs		Gentamicin	Levofloxacin	Ciprofloxacin	Tigecycline	cefuroxime sodium	Cefazolin	Ceftriaxone	Cefuroxime Axetil	Piperacillin	Ampicillin/Sulbactam	Ampicillin
Sensitivity rate	73		67	67	60	60	57	56	54	39	31	15
Mediation rate	2.50		13.46	7.69	0	0	2.86	0	6.25	3.92	23.08	0.00
resistance rate	25.00		19.23	25.00	40.00	40.43	40.00	43.90	39.58	56.86	46.15	84.62

S. I and R respectively represent bacterial sensitivity, mediation, and resistance to corresponding antibiotics; Sensitivity rate=S/(S+R+I); Resistance rate=R/(S+R+I)

Table 2 Composition of the drug sensitivity profile of patients with Gram-positive bacilli ( %)

Drugs	Linazolamide	Vancomycin	Tigecycline	Furantoin	Penicillin G	Ampicillin	Levofloxacin	Ciprofloxacin	Gentamicin	Streptavidin	Quenuptine
Sensitivity rate	100	100	100	94.44	78.95	83.33	73.68	68.42	71.43	69.23	21.43
Mediation rate	0	0	0	0	0	0	5.26	0	0	0	0
resistance rate	0	0	0	5.56	21.05	16.67	21.05	31.58	28.57	30.77	78.57

S. I and R respectively represent bacterial sensitivity, mediation, and resistance to corresponding antibiotics; Sensitivity rate=S/(S+R+I); Resistance rate=R/(S+R+I)

Urinary stones are common in clinical urology, and their incidence is increasing year by year [6] . Urinary tract infection is an inflammatory manifestation caused by pathogens invading the mucosa or tissues of the urinary system. Urinary tract infection is one of the most common bacterial infections, with a much higher incidence in women than in men[7] . Urinary stones and urinary tract infections interact with each other. Urinary stones, especially upper urinary calculi, can lead to urinary tract obstruction and infection, while urinary tract infections also play an important role in the occurrence and development of stones .[8]

At present, the clinical treatment of urinary tract infection combined with urinary tract stones is mainly the application of antibiotic therapy, and then surgical treatment to deal with the stones after the infection is controlled, but due to the bacterial culture and drug sensitivity identification need a certain amount of time, the clinical use of empirical drugs, but the pathogenic bacteria causing urinary tract infection more, blindly administered, not only antibacterial effect is not significant, but also will increase the resistance of pathogenic bacteria, affecting the patient's follow-up Treatment[9] . Therefore, it is important to understand the type of pathogenic bacteria and drug sensitivity results for the treatment of upper urinary calculi combined with urinary tract infections.

The most predominant strain of Escherichia coli causing urinary tract infections detected in this study, ranked second and third are Enterococcus faecalis and Proteus mirabilis, but there is some chance due to the relatively small number of these two strains. However, combined with some current studies, we found that Escherichia coli and Enterococcus faecalis, on the other hand, are the most common G- and G+ strains causing urinary tract infections[10-12] .

In the analysis of the drug sensitivity results of G- bacteria we found that the sensitivity rate of G- bacteria to carbapenem antibiotics (imipenem, meropenem) was 100%. And the sensitivity rate of cefoperazone/sulbactam was also 100% in this study. Due to the small sample size of cefoperazone/sulbactam, combined with the relevant literature, we found that cefoperazone/sulbactam had a good effect on G-bacteria[11、12] . In this study, we found that G-bacteria had relatively high sensitivity to amikacin, piperacillin/tazobactam and cefotetan, but relatively low sensitivity to quinolones (norfloxacin, ciprofloxacin). G-bacteria had very low sensitivity to β-lactam antibiotics (ampicillin, piperacillin), but showed good sensitivity to β-lactam antibiotics combined with β-lactamase inhibitors-sulbactam/tazobactam The combination showed good sensitivity and significantly reduced resistance. Moreover, it has been shown that the success rate of piperacillin/tazobactam in the treatment of urinary tract infections with ESBL(+) infections was not significantly different compared to carbapenems[13] . The current study found higher susceptibility to cefotetan, cefepime and ceftazidime among the three generations of cephalosporins but lower susceptibility to ceftriaxone.

In the analysis of the drug sensitivity results of G+ bacteria were found that the G+ group had 100% sensitivity to vancomycin, linezolid and tigecycline. The susceptibility to Nitrofurantoin and ampicillin was also relatively high, and in comparison we can see that Nitrofurantoin has a good susceptibility in both G- and G+ flora. And like G-, the quinolones (levofloxacin, ciprofloxacin) also had a very high resistance. This result is similar to the results of a study by Kraszewska Z et al.[14] , thus testifying to the correctness of the present analysis.

In addition, five fungal strains were detected this time, including four cases of candida albicans and one case of Candida glabrata. The detected fungi had high susceptibility to 5-fluorocytosine, fluconazole, itraconazole and voriconazole, but had extremely high resistance to benomycin B. Due to the small sample size this time, the relevant drug susceptibility needs to be analyzed in a large sample.

The results of the analysis in this paper suggest that there are more pathogenic bacteria in the urine of patients with urinary stones with urinary tract infection, and the degree of drug resistance varies, so in clinical treatment, antimicrobial drug therapy should be selected as reasonably as possible according to the results of the drug sensitivity test to improve clinical efficacy. For patients whose drug sensitivity test is to be returned, three generations of cephalosporins (cefotetan, cefepime and ceftazidime) or β-lactam antibiotics combined with β-lactamase inhibitor-sulbactam/tazobactam combination drugs (such as piperacillin/tazobactam) can be selected for treatment first, and drugs with higher resistance such as quinolones can be avoided for treatment as far as possible, and drug adjustment will be made after the drug sensitivity results are returned. In addition, bacterial resistance changes over time, so continuous attention and timely reporting are needed.

Ethics statement：

The studies involving human participants were reviewed and approved by the EthicsCommittee of Taikang Xianlin Drum Tower Hospital. All methods were carried out in accordance with relevant guidelines and regulations. This experiment has obtained informed consent from all subjects and/or their legal guardian(s).

Data availability：

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Ye Z, Wu C, Xiong Y, et al. Obesity, metabolic dysfunction, and risk of kidney stone disease: a national cross-sectional study. Aging Male. 2023;26(1) :2195932.
Gharbi C, Tostivint I, Bagnis CI. Infections urinaires récidivantes et risque de lithiase rénale [Renal stones and urinary tract infections]. Rev Prat. 2014;64(7):978-979.
Ahmed AE, Abol-Enein H, Awadalla A, Shokeir AA, El-Shehaby OA, Harraz AM. Metabolic stone workup abnormalities are not as important as stone culture in patients with recurrent stones undergoing percutaneous nephrolithotomy. Urolithiasis. 2023;51(1):47. Published 2023 Mar 13.
York A. Uropathogenic E. coli creates a memory. Nat Rev Microbiol.2023;21(6):345.
Boutzoukas AE, Komarow L, Chen L, et al. International epidemiology of carbapenemase-producing Escherichia coli [published online ahead of print. 2023 May 8]. Clin Infect Dis. 2023;ciad288.
Zhang D, Li S, Zhang Z, et al. Urinary stone composition analysis and clinical characterization of 1520 patients in central China. Sci Rep. 2021;11(1) :6467. :6467. Published 2021 Mar 19.
Geerlings SE. Clinical Presentations and Epidemiology of Urinary Tract Infections.Microbiol Spectr. 2016;4(5):10.1128/microbiolspec.UTI- 0002-2012.
Gu J, Chen X, Yang Z, Bai Y, Zhang X. Gender differences in the microbial spectrum and antibiotic sensitivity of uropathogens isolated from patients with urinary stones. J Clin Lab Anal. 2022;36(1):e24155.
Gu J, Song P, Chen X, Yang Z, Zhang X, Bai Y. Comparative study of the bacterial distribution and antimicrobial susceptibility of uropathogens in older and younger patients with urinary stones. BMC Geriatr. 2022;22(1):195. Published 2022 Mar 12.
Kasew D, Eshetie S, Diress A, Tegegne Z, Moges F. Multiple drug resistance bacterial isolates and associated factors among urinary stone patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. BMC Urol. 2021;21(1):27. Published 2021 Feb 23.
Zhang J, Xie L, Cao Y, et al. Characteristics of and antibiotic resistance in urinary tract pathogens isolated from patients with upper urinary tract stones. stones.
Li J, Jiang F, Xie A, Jiang Y. Analysis of the Distribution and Drug Resistance of Pathogens in Patients with Urinary Tract Infection in the Eastern Chongming Area of Shanghai from 2018 to 2020. Infect Drug Resist. 2022;15:6413-6422. Published 2022 Nov 1.
Stefanos SS, Sakaan S, Samarin M, et al. Assessing clinical cure of empirical piperacillin/tazobactam for ESBL urinary tract infections (ACCEPT- UTI). JAC Antimicrob Resist. 2023;5(3):dlad055. Published 2023 May 11.
Kraszewska Z, Skowron K, Kwiecińska-Piróg J, et al. Antibiotic Resistance of Enterococcus spp. Isolated from the Urine of Patients Hospitalized in Antibiotics (Basel). 2022;11(12):1749. Published 2022 Dec 3.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Analysis of bacterial spectrum and drug sensitivity in preoperative urine culture of upper urinary calculi

Status:

Version 1

Abstract

Figures

Introduction

Data and Methods

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1