Ocular Bacterial Infections In Northern China: A Retrospective Study Of Pathogen Distribution And Antibiotic Sensitivity

Ocular bacterial infections,which are associated with many risk factors including trauma,surgery,contact lenses,age,dry eye state,chronic nasolacrimal duct obstruction and previous ocular infections,are common in ophthalmology and vary from self-limiting to sight-threatening.Bacterial infections can involve conjunctiva,cornea,lens,vitreous body,eyelid,lacrimal duct and other ocular tissues.In the treatment of bacterial infections,it is necessary to determine the pathogenic bacteria to ensure proper antibacterial treatment.Due to the influence of geographical location and environment,the distribution of pathogenic bacteria in different studies may be different.We carried out a retrospective study on the bacteria isolated from the eye specimens suspected of microbial infection in northern China,and classified bacteria according to the gram staining method,in order to obtain more accurate distribution results of pathogenic bacteria.Before the results of drug sensitivity test,broad-spectrum antibiotics are usually the first choice for the treatment of ocular bacterial infections.However,due to the wide use or even unreasonable use of broad-spectrum antibiotics,the sensitivity of bacteria to some frequently used antibiotics has gradually decreased.Some scholars believe that topical use of antibiotics may enhance the development of drug resistance and jeopardize the availability of antimicrobial treatment for ocular infection in the future.Other scholars believed that most bacterial drug resistance is due to the results of systematic treatment,so this concern should not be extrapolated to the local use of antibiotics.Antibiotic sensitivity changes with time,so it is necessary to summarize it regularly.There have been many studies on antibiotic sensitivity.These studies only classify bacteria into gram-positive bacteria(GPB)and gram-negative bacteria(GNB)or directly list antibiotic sensitivity.In a retrospective study of 1664 ocular specimens conducted in New York,USA,the pathogen distribution in the study results divided the bacteria into GPB and GNB,and selected the most common bacteria in GPB and GNB respectively for antibiotic sensitivity analysis.In a retrospective study conducted in Japan,242 patients with ocular infection or trauma were studied.The pathogen distribution of the study results divided the bacteria into GPB and GNB,and the drug sensitivity results only listed the sensitivity rate of bacteria isolated from different parts of the eye to leofloxacin.In a retrospective study of 235 ocular specimens conducted in India,the results directly listed the distribution of common bacteria in each site and the antibiotic susceptibility rates corresponding to common bacteria.A retrospective study conducted in Malaysia analyzed 1,267 isolated strains of ocular bacterial infections.The results listed the distribution of 10 common bacterial genera and showed the sensitivity of staphylococcus aureus and pseudomonas aeruginosa to several commonly used antibiotics in the form of bar charts.In a previous study conducted in China,737 isolated strains of ocular bacterial infections were retrospectively analyzed.In the results of pathogen distribution,the bacteria were divided into GPB and GNB.Antibiotic sensitivity was analyzed according to the classification of different ocular diseases.None of the antibiotic sensitivity analyses in these studies involved statistical methods.Can the bacteria be divided into four categories according to the gram staining method,and the sensitivity rate of various antibiotics be compared through statistical analysis to obtain more accurate analysis results?This hypothese has not been confirmed.The minimum inhibitory concentration(MIC)can only reflect the antibiotic sensitivity in a single drug sensitivity report,and our research plans to analyze and compare the antibiotic sensitivity through a large number of drug sensitivity test results,so as to find more sensitive antibiotics for different types of pathogens,and help ophthalmologists make more effective decisions on the treatment of bacterial infections in the eyes.AIM:To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections.METHODS:This retrospective study was approved by the institutional review board of Shandong Eye Institute.Because of its retrospective nature,the requirement of informed consent was waived.All study conduct adhered to the tenets of the Declaration of Helsinki.A retrospective review of the records of ocular isolates was conducted from January 2013 to December 2017 at Shandong Eye Institute,a major tertiary eye center in northern China.Clinical specimens were obtained from the conjunctiva,cornea,aqueous humor,vitreous body,eyelid margin,lacrimal passage,orbital contents,and other ocular sites of the patients in the inpatient wards and outpatient clinics.The collection method of conjunctival sac samples was as follows:We let the patient take the sitting position,instructed the patient’s eyes to gaze upward,and opened the lower eyelid.We dipped the cotton swab in the normal saline,gently twisted and wiped the lower eyelid conjunctival sac(including the inner canthus),and then conducted the bacterial culture after the completion of the collection.The method of collecting cornea specimen was as follows:We let the patient take the recumbent position.After surface anesthesia,the necrotic tissue on the surface of corneal ulcer was scraped under the microscope first,and the corneal lesions were exposed.The corneal tissue with as many obvious lesions was scraped with the ophthalmic microsurgery knife as possible,and the bacterial culture was carried out.The collecting method of palpebral margin specimen was as follows:We let the patient take the sitting position,applied hot compress and massaged the meibomian glands.We dipped the cotton swab into the normal saline and gently wiped the lipid secretions excluded from the meibomian glands and then cultured the secretions.The ocular specimens such as aqueous humor,vitreous body,lacrimal passage,orbital contents and so on were from intraoperative sampling.Cultures were performed using liquid(nutrient broth)and solid(chocolate agar,blood agar,and MacConkey agar)media.Bacterial isolates were identified,and dilution antimicrobial susceptibility testing was made and interpreted using automated microbiology systems,i.e.,VITEK II compact 30 before 2016 and Microscan Walkaway 96 after 2016,at the clinical microbiology laboratory of our institution according to the Clinical and Laboratory Standards Institute’s Guidelines.The parameters assessed mainly included the distribution of isolated bacteria and the results of susceptibility tests for antibiotics.Only nonrepetitive isolates that underwent susceptibility testing were included in this study,and not all antimicrobials were tested against each isolate.Positive results were inputted into a Microsoft Excel spreadsheet file,which included patient name,patient ID number,patient age,collection date,ward type,collection site,organism isolated and minimum inhibitory concentration values against various antibiotics.For a small amount of uncertain data,such as"intraoperative specimen",the patients’ medical records were checked to ensure the accurate collection site.We also obtained a five-year statistical report on the antibiotic sensitivity from the Laboratory Information System.In the analysis of antibiotic sensitivities,the bacteria were divided into four groups according to gram staining,and statistical methods were used to compare their antibiotic sensitivities.Data were analyzed using the SPSS(version 19.0;SPSS,Inc.,Chicago,IL,USA).The spearman correlation analysis was used to study the correlation between two variables.Comparisons of categorical variables were conducted using the Chi-square test.A P-value<0.05 at 95%CI was considered statistically significant.RESULTS:A total of 11530 ocular specimens with suspected microbial infections were submitted for microbiological evaluation.Among these specimens,3625(31.44%)showed bacterial growth,and 3690 bacterial strains were isolated.The positivity rates of the bacterial cultures from years 2013 to 2017 were 30.82%,35.26%,25.76%,25.88%,and 36.56%,respectively.The change in the annual culture positivity rate was not statistically significant(P=0.747).Among the patients corresponding to positive bacterial culture specimens,1513 were male and 2112 were female,with a male-female ratio of 1:1.40.The average age of the patients was 49.65±22.21(range 4d-102y).Among the 3625 bacterial specimens,2849(78.59%)were obtained from the conjunctiva,569(15.70%)from the cornea,and 111(3.06%)from the aqueous humor or vitreous body.The remaining 96(2.65%)specimens were gathered from the lacrimal passage,eyelid margin,orbital contents and other ocular sites.A total of 3690 strains(32 genera and 140 species)were isolated by bacterial culture.Among these strains,3037 were G+C(gram-positive cocci,82.30%),407 were G-B(gram-negative bacilli,11.03%),221 were G+B(gram-positive bacilli,5.99%),and 25 were G-C(gram-negative cocci,0.68%).The most common bacterial genera were Staphylococcus(2706,73.33%),Corynebacterium(161,4.36%),Neisseria(19,0.51%),and Pseudomonas(91,2.47%)in G+C,G+B,G-C,and G-B,with Staphylococcus epidermidis(2007,54.39%),Corynebacterium xerosis(160,4.34%),Neisseria mucosa(7,0.19%),and Pseudomonas aeruginosa(77,2.09%)being the main isolates,respectively.The predominant bacterial isolate was S,epidermidis(2007,54.39%),followed by Staphylococcus aureus(260,7.05%),C.xerosis(160,4.34%),Staphylococcus hominis(125,3.39%),Staphylococcus haemolyticus(115,3.12%),and P.aeruginosa(77,2.09%).Neither the annual changes in the proportions of the above major strains nor those in the proportions of G+C,G+B,G-C,and G-B were statistically significant(P>0.05).S.epidermidis was the predominant bacterial isolate in the conjunctiva,cornea,aqueous humor or vitreous body,and other ocular sites,respectively.In addition,S.aureus was one of the most common bacteria in the conjunctiva,cornea,as well as aqueous humor or vitreous bodyThe sensitivity rate of the total isolates to gatifloxacin was up to 90.01%,with G+C,G+B,G-C,and G-B being all highly sensitive.For levofloxacin,the sensitivity rate of the total isolates was only 51.91%,whereas that of G-B was 83.66%,significantly higher than that of G+C,G+B,and G-C(P<0.05).For vancomycin,the sensitivity rate of GPB was as high as 97.92%(3112/3178),while that of GNB was only 68.97%(60/87).Moreover,the sensitivity rates of G+C and G+B to vancomycin were significantly higher than those of G-C and G-B(P<0.05).For fusidic acid,the sensitivity rate of GPB was as high as 88.91%(2702/3039),whereas that of GNB was only 32.00%(64/200).In addition,the sensitivity rate of G+C to fusidic acid was significantly higher than that of G-C and G-B,and the sensitivity rate of G+B was significantly higher than that of G-B(P<0.05).For cefuroxime,the sensitivity rate of GNB was as low as 59.25%(269/454),but it was only G-B whose sensitivity rate was 57.28%,while the sensitivity rate of G-C was 89.29%,significantly higher than that of G-B(P=0.001).For moxifloxacin,the sensitivity rate of GPB was as high as 80.28%(2121/2642),but it was only G+C whose sensitivity rate was 81.21%,while the sensitivity rate of G+B was just 32.00%,significantly lower than that of G+C(P=0.000).Antibiotic sensitivities of fusidic acid and ciprofloxacin increased year by year(Rs=0.900,P=0.037),whereas the changes in other antibiotics were not statistically significant(P>0.05).CONCLUSION:In northern China,Staphylococcus epidermidis is the predominant isolate in all ocular specimens with bacteria;Gatifloxacin is a broad-spectrum and highly sensitive antibiotic,which is more suitable for topical use in perioperative ophthalmology than levofloxacin;Vancomycin and fusidic acid both have better effects on GPB than GNB.By further classifying the bacteria and comparing their sensitivity to antibiotics through statistical analysis,more accurate antibiotic sensitivity analysis results can be obtained.