Contact Lens Associated Bacterial Keratitis: Common Organisms, Antibiotic Therapy, and Global Resistance Trends: A Systematic Review

Introduction Contact lens wearing has been increased globally during recent decades, which is one of the main risk factors for developing microbial keratitis. Microbial keratitis is a severe and dangerous condition that causes cornea inflammation. It can lead to corneal scarring and perforation or even endophthalmitis and visual loss if it remains untreated. Among bacterial, fungal, protozoal, and viral agents which can cause microbial keratitis, bacteria are the most common cause. Therefore, in this study, we aim to find common causative bacteria, sensitivity, and resistance to antibiotics and the outcome of antibiotic therapy in contact lens-related bacterial keratitis. Methods A systematic search was carried out in PubMed/Medline, EMBASE, and Web of Science for published studies and medRxiv for preprints up to February 30, 2021, and May 14, 2021, respectively. A combination of the following keywords was used: “Infection”, “Corneal infection”, “Keratitis”, “Microbial keratitis”, and “Contact lens”, Also, we used the “Contact lenses” MeSH term. Lists of references for each selected article and relevant review articles were hand-searched to identify further studies. Results Twenty-six articles were included. From 1991 to 2018, 2,916 episodes of contact lens-related microbial keratitis) CLMK(with 1,642 episodes of proven bacterial keratitis have been reviewed in these studies. Studies were conducted in 17 countries with different geographical regions, and four studies were conducted in Iran, which is the highest number of studies among these countries. According to 20 studies, the mean age of patients was 30.77 years. Females with 61.87% were more than males in 19 studies. A percentage of 92.3% of patients used soft contact lenses, and 7.7% of patients used hard contact lenses (including RGP), according to 16 studies. Pseudomonas aeruginosa, Staphylococcus spp., and Serratia marcescens were the three most common bacteria isolated from samples of patients with contact lens-related bacterial keratitis. Overall, isolated bacteria were most sensitive to fluoroquinolones and aminoglycosides, especially ciprofloxacin and gentamicin respectively, and most resistant against penicillin and cephalosporins especially cefazolin and chloramphenicol. Almost all patients responded well to antibiotic therapy, with some exceptions that needed further surgical interventions. Conclusion Antibiotics are efficient for treating almost all patients with contact lens-related bacterial keratitis if they are appropriately chosen based on common germs in every geographical region and the sensitivity and resistance of these germs against them. In this regard, Pseudomonas aeruginosa is the most common causative germ of contact lens-associated bacterial keratitis all over the world and is almost fully sensitive to ciprofloxacin. Because of some different results about the sensitivity and resistance of germs against some antibiotics like gentamicin, vancomycin, and chloramphenicol in the Middle East region, especially Iran, more in vitro and clinical studies are suggested.


INTRODUCTION
During the recent decades, contact lens wearing has been increased globally from approximately 32 million in 2002 to 40.9 million adult (>18 years old) wearers in 2014 only in the USA, and this number was 140 million worldwide (1,2). The contact lens global market is estimated at 19.45 billion US dollars in 2024 (3). There are many types of contact lenses available for therapeutic and non-therapeutic purposes; soft and hard or rigid gas permeable (RGB) are two main types (4). Although modern contact lenses are safer than old ones, adverse events like corneal edema due to hypoxia, corneal abrasion, neovascularization, conjunctivitis, midday fogging, inflammation, and infection may occur (5). Contact lens wearing is a prevalent risk factor for microbial keratitis (MK), with an incident rate of approximately 2-20 cases per 10,000 wearers each year (6,7). Various factors can increase the risk of contact lens-related microbial keratitis like professional occupation compared with being a student, discarding lenses yearly versus fewer periods, showering daily with wearing lenses versus never showering in lenses, and sleeping in lenses (8,9). Procrastination of therapy results in corneal scarring and perforation, then maybe endophthalmitis and visual loss (10). MK could occur via bacterial, fungal, protozoal, and viral agents (11).
Bacterial keratitis is the most common cause of MK, which accounts for about 90% of cases (12); manifestation of bacterial keratitis includes eye discomfort and redness, eyelid swelling, decreased sight, and photophobia (10). Correct identification of the causative pathogen and its virulence factors and using appropriate antibiotics can reduce extended and drastic treatment and avoid further antibiotic resistance. It is also associated with better outcomes and decreased surgical interventions (13).
This systematic review aimed to find common causative germs, sensitivity and resistance to antibiotics, and antibiotic therapy outcomes in contact lens-related bacterial keratitis.

METHODS
This systematic review was conducted according to the "Preferred Reporting Items for Systematic Reviews and Metaanalyses" (PRISMA) statement (14).

Search Strategy
A systematic search was carried out in the literature from the following bibliographical databases: PubMed/Medline, EMBASE, and Web of Science for published studies and medRxiv for preprints up to February 30, 2021, and May 14, 2021, respectively. Keyword searches were done with combinations of the terms "infection", "corneal infection", "keratitis", "microbial keratitis", and "contact lens". Also, we used the "contact lenses" MeSH term. Lists of references of selected articles and relevant review articles were hand-searched to identify further studies. There was no restriction on publication date, but only studies written in English were selected.

Study Selection
All potentially relevant English articles were screened in two stages for eligibility. Two reviewers independently reviewed titles and abstracts in the first stage. Study types that were included in this stage were clinical retrospective or prospective reviews of patients, case series, and cross-sectional studies that were about infectious keratitis and fit the full-text evaluation criteria. Review articles and case reports were excluded. Discrepancies at this step were discussed with a third reviewer. In the second assessment stage with full-text evaluation, we included studies that discussed contact lens-related bacterial keratitis and examined the sensitivity, resistance, and outcome of antibiotic therapies on common bacterial germs. Therefore, studies that had discussed about other etiological microorganisms such as amoebic, fungal, or viral agents or had focused on infectious keratitis due to factors other than contact lens such as traumatic or post-surgical keratitis were excluded. Other exclusion criteria were studies that discussed about rare causative bacteria, molecular or animal studies, and studies that discussed the protective use of antibiotics as antimicrobial solutions. Disagreements and technical uncertainties were discussed and resolved between review authors.

Data Extraction
The following variables were extracted from all included studies: first author, study interval, type of study, countries where the study was conducted, study population, number of patients with proven bacterial keratitis, sex and mean age of patients, contact lens regime, diagnostic microbiological tests for bacterial keratitis, and three common isolated bacteria. The three most common sensitive antibiotics and the most resistant ones, and the outcome of antibiotic therapy, were extracted from some studies. Two authors independently extracted the data from the selected studies. The data were jointly reconciled, and disagreements were discussed and resolved between review authors.

The Most Common Isolated Bacteria
Twenty-four of 26 studies perused the most common isolated bacteria from cultured samples; two of them (16,38) only had Pseudomonas spp. in their survey. Among these 24 studies, Pseudomonas spp. especially Pseudomonas aeruginosa was the most common isolated bacteria from cultured samples (625 episodes among three common germs in studies with raw data) and were the first common bacteria in 18 studies and the second common bacteria in five studies. Only the study by Inoue et al. (18) had not reported Pseudomonas among its three common isolated bacteria. Staphylococcus spp. especially coagulase-negative staphylococcus spp. (CoNS) Staphylococcus epidermidis was the second most common bacteria from cultured samples. In five studies, they were the first common bacteria (438 episodes of Staphylococcus spp. and 364 episodes of coagulase-negative staphylococcus spp. among three common germs in studies with raw data). Serratia spp. was the third common bacteria, and in the study by Cheng et al. (35), Serratia  (17), gram-positive bacteria like staphylococcus species were the most common bacteria in soft and hard contact lenses. The three most common bacteria that were isolated from samples in each study are shown in Table 3.

Sensitivity and Resistance to Antibiotics
Fifteen studies reported the sensitivity and resistance of isolated bacteria to antibiotics. Eight studies reported the sensitivity and resistance of each bacteria separately. In the remaining seven studies, only the overall sensitivity and resistance of discussed bacteria to antibiotics were reported. In studies by Mohammadpour et al. (38) and Bourkiza et al. (16) which only discussed the treatment of Pseudomonas spp., isolated bacteria were 100% sensitive to fluoroquinolones, especially ciprofloxacin. Also, isolated bacteria in the study by Mohammadpour et al. (38) were 100% sensitive to ceftazidime. Green et al. (29) reported that none of the cultured isolates of P. aeruginosa was resistant to fluoroquinolones. Lai et al. (27) and Moriyama et al. (22) noticed that cultured Pseudomonas aeruginosa samples were 100% sensitive to ciprofloxacin and gentamicin in the former study and ciprofloxacin, ofloxacin, gatifloxacin, amikacin, and tobramycin in the latter. Hoddenbach et al. (17) showed that P. aeruginosa is sensitive to ofloxacin and gentamicin by 98.7% and 97.3%, respectively, and Bennett et al. (21) noticed that P. aeruginosa is 100% sensitive to oxacillin. On the other hand, Rahim et al. (31) represented that P. aeruginosa had 82% sensitivity to ciprofloxacin and was most sensitive to imipenem with 84.4% sensitivity. In the study by Singh et al. (40), P. aeruginosa had only 57.1% and 14.2% sensitivity to other fluoroquinolones like moxifloxacin and levofloxacin, respectively. According to studies by Hedayati et al. (37) and Rasoulinejad et al. (39), P. aeruginosa is 100% resistant to gentamicin. Hoddenbach et al. (17) noticed that resistance to cefazolin in P. aeruginosa is 99.3%. Isolated P. aeruginosa in the study by Bourkiza et al. (16) showed 100% resistance to chloramphenicol, but Mohammadpour et al. (38) showed 100% resistance for cefazolin and vancomycin and 97% for chloramphenicol.
S. epidermidis and S. aureus, according to Rahim et al. (31), had the most sensitivity to imipenem with 100% sensitivity. In this study, ciprofloxacin is in second place in which S. aureus showed 100% sensitivity and S. epidermidis 92.9% sensitivity to it. Moriyama et al. (22) represented that coagulase-negative staphylococcus spp. had 100% sensitivity to ciprofloxacin, ofloxacin, amikacin, tobramycin, gentamicin, cephalothin, and oxacillin. S. aureus and CoNS in the study by Bennett et al. (21) showed 87% and 83% sensitivity to oxacillin, respectively. Conversely, Singh et al. (40) reported that the S. aureus sensitivity to moxifloxacin, levofloxacin, and amikacin was 33.3%, and S. epidermidis was 50% sensitive to moxifloxacin. In the study by Hedayati et al. (37), all three S. aureus samples were resistant to ciprofloxacin but were sensitive to gentamicin.
Hoddenbach et al. (17) showed that Serratia spp. were 100% sensitive to gentamicin and 90% sensitive to ofloxacin but were 90% resistant to cefazolin. Also, Karaca et al. (23) reported that both Serratia marcescens and P. aeruginosa were 100% sensitive to vancomycin and ceftazidime.
Among studies that reported the overall sensitivity and resistance of all discussed bacteria (gram-negative and grampositive bacteria like P. aeruginosa, Serratia spp., S. epidermidis, S. aureus, etc.) to antibiotics, bacteria were most sensitive to ciprofloxacin in studies by Hedayati et al. (37) and Rasoulinejad et al. (39) with 86% and 71.4% sensitivity in each study respectively. Also, ciprofloxacin was the second and third antibiotics in the studies by Sharma et al. (26)and Faghri et al. (30) in which bacteria had the most sensitivity to it, with 88% and 86.8%, respectively. In these two studies, gentamicin was the first antibiotic in that order, in which bacteria had 100%   (26). Other fluoroquinolones were discussed in the study by Konda et al. (15), and gatifloxacin, ofloxacin, and gentamicin were the first three antibiotics that bacteria were most sensitive to, with 89%, 88%, and 86% sensitivity to each of them, respectively. Green et al. (29) reported that P. aeruginosa, S. epidermidis, and S. aureus had 100% sensitivity to vancomycin. Bacteria had 100% resistance to penicillin in two studies (37,39) and 71.1% resistance in another study (30). Konda et al. (15) reported that Pseudomonas spp., Serratia spp., and CoNS were most resistant to chloramphenicol, while in the study by Faghri et al. (30), these bacteria had 94.7% sensitivity to chloramphenicol. Bacteria in the study by Green et al. (29) were most resistant against cephalosporins. For example, all bacteria excluding Enterobacter had 100% resistance against cefixime in the study by Rasoulinejad et al. (39) and had 56% resistance against cefazolin in Sharma et al. (26). The three most effective antibiotics and the most ineffective ones are shown in Table 4.

The Outcome of Antibiotic Therapy
The outcome of experimental or antibiogram-guided antimicrobial therapy was discussed in 11 studies. Therapeutic penetrating keratoplasty, therapeutic graft, amniotic membrane transplantation, anterior lamellar keratoplasty, anterior lamellar corneal transplants, RGB lens, and phototherapeutic keratectomy were additional therapies in patients that did not respond to antibiotic therapy and had complications like corneal perforation. Singh et al. (40) represented that treatment outcome was good among all cases with prescribed topical antimicrobials, and none of them have required surgical interventions; also, in the study by Konda (17) reported that three perforating keratoplasties were managed in an emergency setting because of corneal perforation due to Pseudomonas aeruginosa. Karaca et al. (23) studied that the mean best-corrected visual acuity (BCVA) increased with antibiotic therapy, and according to culture results, P. aeruginosa infections were associated with significantly worse BCVA. In the study by Green et al. (29), only one 68-year-old female had a poor outcome due to cultured MRSA from scraping cornea resistant to multiantibiotics like cephalosporins and fluoroquinolones. Finally, she was treated with topical vancomycin while her visual acuity was hand movements. Twenty-one patients (6.5%) with CLMK required surgical interventions or showed complications in this study. The outcome of antibiotic therapy is shown in Table 5.

DISCUSSION
Among the reviewed articles, the most common isolated bacteria were Pseudomonas aeruginosa which was considered separately in the two articles due to its high prevalence and importance of treatment. Although it was not reported as a common germ in some studies, no other bacteria were mentioned besides P. aeruginosa in all reviewed studies. The next common organism was Staphylococcus spp. especially coagulase-negative spp. such as Staphylococcus epidermidis, and the third organism was Serratia marcescens. In some articles' rankings, these agents fluctuated, but because of different geographical areas where studies were conducted, somehow variation in the frequency of microorganisms is acceptable and not so far unexpected.
In the treatment approaches, Pseudomonas is most considered in the studies, and there is a consensus on notable sensitivity to fluoroquinolones, especially ciprofloxacin as a drug of choice in this issue. Ofloxacin and gatifloxacin are two effective antibiotics against Pseudomonas, but moxifloxacin and levofloxacin which are other members of fluoroquinolones were not effective in this regard; these antibiotics are known as respiratory fluoroquinolones, and their inefficacy as a topical drug is presumable (41).

Author
The first most common bacteria The second most common bacteria The third most common bacteria We should also consider that the studies by Mohammadpour et al. (38) and Rahim et al. (31) were conducted in two proximal geographical areas respectively in Iran and Pakistan, so we do not expect so many differences between these two studies. This difference may be related to the source of the isolated bacteria in the study by Rahim et al. (31) which was from the conjunctiva, but this hypothesis needs more investigation. Using ciprofloxacin as an antibiotic for Staphylococcus spp. was confirmed by the study of Rahim et al. (31) in which S. aureus had complete sensitivity to ciprofloxacin, but conversely, in a study held by Hedayati et al. (37), all three S. aureus samples were resistant to ciprofloxacin. It can be supposed that this is due to the small sample size and therefore a sampling bias, but a 100% resistance even in a small sample size is remarkable. The study by Rahim et al. (31)

Author
The first most effective antibiotic The second most effective antibiotic The third most effective antibiotic study was about 6 years later, we can assume developing a new emerging antibiotic resistance among the S. aureus species in this area, but due to the small sample size, our evidence has not enough strength to prove it. Another assumption can be related to the microbiological tests that in the study by Hedayati et al.  (27) performed the study in about the same time as Hedayati et al. (37) and Rasoulinejad et al. (39) did between 2010 to 2013; therefore, this resistance is probably regional, and at least when the studies were conducted, the resistance was not spread to other regions. Most of these studies used the corneal culture method for identifying the bacteria, so we cannot attribute it to the sampling method. We should notice that there was another study in this area, Iran, which is conducted by Mohammadpour et al. (38) between 2009 to 2010 who studied on 52 patients with Pseudomonas keratitis exclusively and declared that Pseudomonas is 93% sensitive to gentamicin. This controversy between these three studies which were all held in Iran is doubtful, and antibiotic resistance mutation occurrence in about a 2-year interval seems impossible. This issue needs more investigations, and this resistance in Iran and probably surrounding countries should be considered in the treatment of P. aeruginosa keratitis and gentamicin prescription for bacterial keratitis should be avoided.

Author Outcome
Konda et al. (15) Approximately all patients were treated with choosing antibiotics via antibiogram. Among 61 pseudomonas spp., four of them showed in vitro resistance to multiple antibiotics containing aminoglycosides, fluoroquinolones, and third cephalosporins. Three cases showed suitable clinical result to ciprofloxacin eye drops. One case needs penetration of keratoplasty due to insufficiency of medical therapy. Bourkiza et al. (16) At presentation to the hospital, the chloramphenicol group had a larger size of ulcer and worse VA than the non-chloramphenicol group, while final VA was not statistically different in the final examination. The average period follow-up of patients for the chloramphenicol group was 37 days versus 21 days for the non-chloramphenicol group. Six complications including 3 vascularized scar and 3 therapeutic graft happen in the chloramphenicol group versus 2 therapeutic graft in the non-chloramphenicol group. Hedayati et al. (37) Among all cases, 57.7% were treated outpatients; 34.6% and 7.7% of them were admitted and need to surgical interventions, respectively. The median treatment interval was 31 ± 6 days in the outpatient case and 84 ± 12 days in the inpatient case. Treatment outcomes were excellent in 24.2%, good in 45.5%, and poor in 30.3% based on results. Mohammadpour et al. (38) 39 cases (75%) required hospitalization, while 13 cases (25%) were managed in outpatient and none of the patients needed hospitalization during the follow-up. A prosperous clinical response of 81% was seen with antibiotic therapy. Ten cases (10%) with mean age of 21 years and 4 × 4 mm corneal ulcer on average required amniotic membrane transplantation and 58% of them had hypopyon. Hoddenbach et al. (17) Corneal transplantation was needed for 22 eyes (20.2%), including 17 perforating keratoplasties, 3 deep anterior lamellar keratoplasties, and 2 anterior lamellar corneal transplants. Due to corneal perforation, three patients with perforating keratoplasty were managed in emergency settings and 19 keratoplasties were conducted for culture-positive samples of P. aeruginosa due to major loss of visual acuity because of scarring. None of the cases required evisceration or enucleation. Forty-seven patients (43.1%) needed rigid gas permeable (RGP) lenses for achieving proper vision, whereas 33 patients (30.3%) did not need further interventions like RGP or surgery.

Rasoulinejad et al. (39)
Outcome of treatment was excellent in 23.5%, good in 47.1%, and poor in 29.4% of patients that required penetrating keratoplasty intervention Singh et al. (40) Treatment outcome was good among all cases with prescribed topical antimicrobials, and none of them required surgical interventions. Karaca et al. (23) There was a significant negative correlation between best-corrected visual acuity (BCVA) and P. aeruginosa keratitis.
At the end of follow-up, the mean BCVA was increased from 0. On presentation, the mean logMAR visual acuity of all patients was 0.99 and was increased to 0.34 and 0.26 at 1 and 3 months after treatment, respectively. Only 37 and 19 cases were recorded at 1 and 3 months, respectively, due to neglecting follow-up or being released from clinic. The mean logMAR visual acuity was improved -0.77 at 3 months in between 19 patients. Green et al. (29) Among all CLMK cases only one 68-year-old female had a poor outcome related to cultured MRSA from scraping cornea that was resistant to multi-antibiotics like cephalosporins and fluoroquinolones. Finally, she was treated with topical vancomycin while her visual acuity was hand movements. 21 patients (6.5%) with CLMK required surgical interventions or showed complications, which included penetrating keratoplasty in 18 (6.1%) patients, phototherapeutic keratectomy in 2 cases, and 2 patients had corneal perforation.
Konda et al. (15) (29) made an investigation in Australia, from January 1999 to December 2015, with 372 episodes of CLMK that were proved by corneal scraping cultures. These studies had non-different methods for isolation and identification of the organisms, and these differences cannot be attributed to the methodological issues. Also, as mentioned previously, the type of contact lens (therapeutic or cosmetic) could be an essential factor. In the study by Mohammadpour et al. (38), only 14% of the patients had therapeutic contact lenses. However, in the study by Karaca et al. (23), 85.5% of the patients had therapeutic contact lenses, and we previously mentioned that low education level in the cosmetic contact lens users might be related to the consequent outcomes. It also can be attributed to the different subspecies with various vancomycin genetic resistances, but according to the proximity of Iran and Turkey, this meaningful difference needs to be investigated more in the future.
While most of the similar articles were narrative review studies, we considered all of the related articles over time as a systematic review in this article. One of the strengths of the present study is that it reveals the controversies among different studies and, according to the standard and rational events, suggests some assumptions or logical reasons. On the other hand, there is an agreement in most of the details between this article and other previous similar systematic review studies that were written by Willcox (42) (45). There has been a consensus on this issue in which Pseudomonas is the most common bacterial organism in microbial keratitis, and the fluoroquinolone family, especially ciprofloxacin, is the first-line treatment. Another essential strength point of this study is its recency; the last review study in this issue was performed by Willcox (42) in 2012, and in the last 9 years, there were no similar studies. Most of the previous studies did not focus on bacterial keratitis exclusively and reviewed Acanthamoeba keratitis alone or along with bacterial keratitis. They also usually discussed other risk factors rather than focusing on contact lens-induced keratitis, and sometimes they approached the risk factors, epidemiologic factors, and other issues but did not focus on antibiotic treatment and antibiotic sensitivity profile. However, in this article, we discussed that bacterial keratitis only related to contact lens wear and its antibiotic treatment and antibiotic sensitivity profile.
There were also limitations in this study. Some of the articles which were selected for the review were written in a language other than English, e.g., Chinese, and we could not use them for review. On the other hand, the total number of articles that met the inclusion criteria was limited. In reviewing the treatment approaches, we did not consider combination therapy, while some studies like those of Willcox (42) and Zimmerman et al. (45) paid great attention to combination therapy instead of monotherapy. Corticosteroid therapy is also considered in the study of Zimmerman et al. (45) as an important part of treatment, unlike our study.

Suggestions
Around the world, Pseudomonas is sensitive and responds well to gentamicin, but in the Iran region, in different studies, converse results have been observed (37,39).
S. aureus was sensitive to ciprofloxacin, but in the study conducted by Hedayati et al. (24), all three S. aureus samples were resistant to it.
As a broad-spectrum antibiotic, vancomycin is a potent antibiotic that most germs respond to and is prescribed empirically (23,29). It has been proven in various studies that vancomycin is an effective anti-Pseudomonas agent. However, the existence of 100% resistance to this antibiotic in a study (38) with a considerable sample size can be indicative of a developing resistance among the bacteria in the Middle East, and because of the broad use of this antibiotic in hospital settings, developing resistance is an important and serious issue.
In addition, although resistance to chloramphenicol has been proven in most studies, in a study conducted in Iran (30), a significant sensitivity was reported.
Almost all of these converse results were detected in the Middle East region, especially Iran and Pakistan, so more investigation is needed to reveal the underlying reason for these events. We suggest future in vitro molecular studies to identify different subspecies, developing antibiotic resistance and genetic mutations in this regard.
Sampling from various places such as conjunctiva or corneal scrapings may significantly affect the final result of the sensitivity profile test in the reviewed articles. Consequently, different sources of isolated bacteria may lead to different antibiotic sensitivity profiles even in the same geographical areas. In this regard, it is suggested to evaluate the effect of sampling from different places in future studies.
For systemic Pseudomonas infections in nosocomial settings, piperacillin/tazobactam as an anti-Pseudomonas antibiotic is commonly used (46). Also, for the treatment of non-contact lens-related keratitis, topical piperacillin/tazobactam is used in resistant keratitis cases as an effective antibiotic and has promising outcomes (47). Therefore, for future studies, the response to treatment with this antibiotic in the severe resistant cases of contact lens-related bacterial keratitis can be evaluated.

CONCLUSION
Among the reviewed articles, Pseudomonas aeruginosa was the most common bacteria, and Staphylococcus spp. such as S. aureus and Coagulase-negative spp. were the second, and Serratia marcescens was the third one. Commonly isolated bacteria were most sensitive to fluoroquinolones and aminoglycosides, especially ciprofloxacin and gentamicin, respectively, and most resistant against penicillin, cephalosporins, and chloramphenicol. Almost all patients responded well to antibiotic therapy, and some untreated cases needed further surgical interventions. In most of the reviewed studies, bacteria were susceptible to gentamicin and vancomycin and fully resistant against chloramphenicol. However, in the Middle East region, especially Iran, there were some different results about these antibiotics, which need more in vitro and clinical studies about the sensitivity and resistance of germs against them.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.