High-level Mupirocin Resistance Research Articles

Antimicrobial susceptibility pattern and mupirocin resistance among methicillin-resistant Staphylococcus aureus isolated from skin and soft-tissue infection patients attending a tertiary care hospital in North India

Background: Antimicrobial susceptibility among bacterial isolates varies from center to center. Mupirocin is a topical antibacterial antibiotic used to treat wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Aim and Objectives: This study was conducted to know the prevalence of high and low levels of mupirocin resistance along with antimicrobial susceptibility in MRSA isolates from skin and soft-tissue infection in patients admitted to a tertiary care hospital in North India. Materials and Methods: A total of 97 non-repetitive isolates of MRSA from various pus samples over a period of 1 year were included in this study. These strains were identified as per standard laboratory protocols given by the Clinical Laboratory Standards Institute. High- and low-level mupirocin resistance of the isolates was tested by using mupirocin discs of 200 μg and 5 μg, respectively. Mupirocin strips of 256 μg and 512 μg were used for the E-test to detect low-level and high-level mupirocin resistance, respectively. The isolates were reported as sensitive to mupirocin, with minimum inhibitory concentrations of <4 mg/L. Results: Overall, 9.27% of mupirocin resistance was found, of which 2.06% of isolates were high-level resistant to mupirocin, while 7.21% had low-level resistance. All MRSA strains were susceptible to vancomycin, followed by linezolid (94.84%), teicoplanin (91.75%), and fusidic acid (88.65%). Conclusion: Regular monitoring, good infection control practices, and proper awareness about utilizing mupirocin therapeutically and prophylactically may help prevent the emergence of mupirocin resistance in health-care facilities.

Antimicrobial susceptibilities and genomic characteristics of methicillin-resistant Staphylococcus aureus resistant to mupirocin in Stockholm, Sweden.

The aim of this study was to investigate antimicrobial susceptibilities and genomic characteristics of mupirocin-resistant MRSA isolates in Stockholm, Sweden. In total, 44 non-duplicate mupirocin-resistant MRSA isolates detected in Stockholm during 2010-2022 were investigated. Antimicrobial susceptibility testing was performed using broth microdilution method and further tested for high-level mupirocin-resistance (MuH) and rifampicin by Etest®. All isolates were subjected to whole genome sequencing. 41 isolates presented MuH with MICs ≥1024 mg/L whilst three isolates displayed low-level mupirocin resistance (MuL). mupA-gene was detected in all MuH isolates. Point mutations in ileS gene leading to N213D and V588F were identified in the three MuL isolates. Mutation in rpoB (H481N) was detected in a rifampicin-resistant isolate. Among the isolates, 15 multi-locus sequence types (MLST) were identified, with the four most common sequence types (ST22, ST72, ST8, and ST125) accounting for 66% of the isolates. Mupirocin-resistant MRSA in Stockholm was uncommon, with a percentage of <0.5% among MRSA cases during 2010-2022. In the present study, most mupirocin-resistant isolates were MuH and mupA-positive, predominantly linked to ST22 or ST72 isolates. MuL-resistance was associated with a point mutation in the IleS protein. A multidrug-resistant ST1-MRSA-IV strain was resistant to both mupirocin and rifampicin.

Prevalence of High and Low-Level Mupirocin Resistance in Clinical Isolates of Staphylococcus Aureus from Skin and Soft Tissue Infection

The skin has an extremely diverse ecology of organisms that may produce infection. The clinical manifestations of skin and soft tissue infection(SSTIs) culminate in a two-step process involving invasion and the interaction of bacteria with host defenses. Approximately 7% to 10% of hospitalized patientsare affected by SSTIs. Mupirocin has been used to treat skin infections and eradicate the nasal carriage of MRSA. Our aim is to estimate the prevalence of lowand high-level Mupirocin resistance among the clinical isolates of Staphylococcus aureus from skin and soft tissue infection. The study was conducted in theDepartment of Microbiology, Krishna Institute of Medical Sciences, Krishna Hospital and Medical Research Centre, Karad, District- Satara. Specimen collectionand processing of samples were performed as per standards. The Kirby -Bauer disc diffusion method was used for the sensitivity to common antibioticsrecommended Clinical and Laboratory Standard Institute (CLSI 2021). Mupirocin resistance was detected using 5μg and 200μg Mupirocin discs to determineLow and High -level resistance. 135 Staphylococcus aureus isolates were obtained from patients admitted to various medical, surgical, and intensive care unitsand patients attending outpatient departments. Out of 415 clinically suspected cases of skin and soft tissue infection, 91.33% were culture positive, and 8.67%were culture negative. Out of 379 microorganisms, 44.06% were Gram-positive cocci, 27.44% were Gram negative bacilli, 24.27% were Gram negative cocci,and 14.22% were Gram-positive bacilli. Out of 167 Gram positive cocci, 135 (80.84%) were Staphylococcus aureus, 22 (13.17%) were Coagulase NegativeStaphylococcus and 10 (5.99%) were Micrococcus. We conclude that the prevalence of Staphylococcus aureus was 32.53%, among which Mupirocin high and lowlevelresistance was 5.92% and 7.41%, respectively.

Chronicity of high and low level mupirocin resistance in Staphylococcus aureus from 30 Indian hospitals

Mupirocin is one of the most effective topically used antibiotic for the treatment of dermatitis, nasal carriage, decolonization of methicillin susceptible Staphylococcus aureus and eradication of methicillin resistant Staphylococcus aureus. Extensive use of this antibiotic has resulted in mupirocin resistance in Staphylococcus aureus which is a matter of concern. This study was conducted to evaluate the high and low level of mupirocin resistance in Staphylococcus aureus collected from various Indian hospitals. A total of 600 samples, of which 436 were pus specimens and 164 wound site swabs were collected from 30 Indian hospitals. Disc diffusion and agar dilution methods were used to test mupirocin susceptibility in methicillin resistant Staphylococcus aureus. Out of 600 Staphylococcus aureus isolates, 176 isolates (29.33%) were found to be methicillin resistant Staphylococcus aureus (MRSA). Out of 176 non-duplicate MRSA strains, 138 isolates were found to be mupirocin sensitive, 21 isolates had high level resistance whereas 17 isolates had low level resistance to mupirocin, which contributed 78.41%, 11.93% and 9.66% respectively. Multidrug resistant susceptibility was tested for all the MRSA with Cefuroxime, Cotrimoxazole and Vancomycin antibiotics. All the high and low level resistant strain were subjected to genome screening for mupA ileS gene respectively. mupA gene was found positive in all the high level resistant strain and out of 17 low level resistant strain, 16 strain were found point mutation in V588F of ileS gene. Overall, high rate of mupirocin resistance was found in the studied samples which might be a result of indiscriminate use of mupirocin in the population of studied region. This data emphasizes the urgent need for formulation of a well-defined and regulated guidelines for mupirocin use. Moreover, continuous surveillance is needed for the use of mupirocin and routine test should be performed to detect MRSA in patients and health care personnel to prevent MRSA infections.

Molecular Characteristics of Staphylococcus aureus Strains to Carry Panton-Valentine Leukocidin Genes Isolated from Hospitalized Patients in Tehran, Iran

Background: Staphylococcus aureus with concurrent resistance to antibacterial agents is emerging globally. This emergence might be due to the production of different virulence determinants, notably Panton-Valentine leukocidin (PVL). Objectives: This study aimed to investigate the genetic characteristics of PVL-positive S. aureus strains isolates from clinical samples. Methods: An epidemiological study was conducted on 65 S. aureus isolates carrying pvl genes. An antibiogram test by the disk diffusion and broth microdilution methods was conducted to assess antimicrobial resistance profiles. Results: All detected methicillin-resistant S. aureus (MRSA) isolates were confirmed by mecA polymerase chain reaction (PCR) assays. The PVL-positive isolates were characterized using multiplex PCR assay to detect staphylococcal cassette chromosome mec (SCCmec) and agr types. The PVL frequency was 19.5% and 17.6% in MRSA and methicillin-susceptible S. aureus (MSSA), respectively. Among the PVL-positive isolates, 66.2% and 33.8% were MRSA and MSSA, respectively. Multidrug resistance amounted to 84.6% of the isolates (MRSA: 61.5%, MSSA: 23.1%). Staphylococcal cassette chromosome mec III was dominated (55.8%; 24/43). The most commonly identified agr was type III (53.8%; 35/65). Resistance to vancomycin amounted to 12.3% of the isolates, and all belonged to agr type III and SCCmec type III. The frequency of inducible and constitutive clindamycin resistance among PVL-positive MRSA strains (12.3% and 26.1%) was higher than PVL-positive MSSA strains (7.7% and 15.4%). Most constitutive and inducible clindamycin resistance isolates belonged to agr type III (26.2% and 18.5%) and SCCmec type III (each 27.9%). In the present study, 32.3% of the isolates were confirmed as mupirocin resistant, and all were MRSA, 9 (42.9%) and 12 (57.1%) isolates of which exhibited high-level mupirocin resistant (HLMUPR) and low-level mupirocin resistant phenotypes. All HLMUPR MRSA isolates belonged to SCCmec III and recovered from wound samples. Conclusions: The emergence of vancomycin-resistant S. aureus strains among PVL-positive S. aureus strains in Iran is a serious alarm and seems to be becoming the greatest concern in the treatment of staphylococcal infections in the healthcare setting. The present study reinforces plausible direct transfers between community and nosocomial PVL-positive S. aureus types.

MINIMUM INHIBITORY CONCENTRATION LEVELS OF MUPIROCIN BY E-TEST AMONG STAPHYLOCOCCUS AUREUS ISOLATES AND THEIR ANTIMICROBIAL SUSCEPTIBILITY PATTERN

Objective: This study was done to evaluate the susceptibility of Staphylococcus aureus to mupirocin and to determine the antimicrobial susceptibility pattern of Staphylococcus aureus among various clinical isolates. Methods: All the consecutive, non-duplicative Staphylococcus aureus isolates collected during the year 2020 were subjected to the disk diffusion method to evaluate the antimicrobial susceptibility pattern and were stocked. Mupirocin susceptibility for all stocked Staphylococcus aureus was detected by Minimal inhibitory concentration (MIC) determination by Epsilometer test (E-test). Results: The total number of Staphylococcus aureus was 52. The maximum number of Staphylococcus aureus was isolated from pus sample 40 (76.9%). Among the 52 isolates, 26 (50%) were found to be methicillin-resistant Staphylococcus aureus (MRSA). All the isolates were susceptible to tetracycline (100%), vancomycin (100%), teicoplanin (100%), and linezolid (100%). By E-test, the overall prevalence of mupirocin resistance was 63.5%. Low-level Mupirocin resistance (MupRL) of 8-256 µg/ml was 59.6% and high-level mupirocin resistance (MupRH) of ≥512 µg/ml was 3.9%. Conclusion: The present study shows a high prevalence of mupirocin resistance (63.5%) which is a serious concern. Therefore, indiscriminate use of topical mupirocin in carriers is not advisable. It may be recommended only in case of an outbreak of skin and soft tissue infection attributed to Staphylococcus aureus.

Comparison of Disk Diffusion and Agar Dilution Method for the Detection of Mupirocin Resistance in Staphylococcal Isolates from Skin and Soft Tissue Infections.

Aims and Objectives Mupirocin is a widely used topical antibiotic for the treatment of skin and soft tissue infections. This has resulted in resistance leading to treatment failure. Hence, the present study aimed to determine the prevalence of mupirocin resistance among staphylococcal isolates obtained from the skin and soft tissue infections. Also, comparison of disc diffusion and agar dilution method in detecting mupirocin resistance was done. Materials and Methods This cross-sectional study was conducted in the Department of Microbiology of a tertiary health care center in Karnataka from January to December, 2018. Clinical samples such as wound swabs, tissues, and pus were included in the study. All staphylococcal isolates were screened for mupirocin resistance using 5 µg and 200 µg discs for low-level (MuL) and high-level mupirocin resistance (MuH), respectively. Minimum inhibitory concentration (MIC) was determined using the agar dilution method. Results Out of 100 staphylococcal isolates, 68 were Staphylococcus aureus and 32 were CoNS. MuH was detected in 11 isolates. MuH was more common in CoNS (10/11) compared with S. aureus (1/11). MuL was not found in the study. Discussion In our study, 10 out of 11 mupirocin-resistant isolates were methicillin resistant, which is statistically significant ( p < 0.05). The correlation between results of disc diffusion and MIC were appropriate in this study. Conclusion Judicial prescription of mupirocin after knowing the susceptibility report should become the standard practice. Screening for mupirocin resistance can be done by disc diffusion in resource-limited settings.

Dissemination of Methicillin-Resistant Staphylococcus aureus Sequence Type 764 Isolates with Mupirocin Resistance in China.

Mupirocin, a topical antimicrobial agent, is an important component in the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization. The molecular characteristics of 46 mupirocin-resistant MRSA (MR-MRSA) clinical isolates were analyzed by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec element (SCCmec) typing, spa typing, and analysis of virulence genes. All 26 MRSA isolates with low-level mupirocin resistance possessed a V588F mutation in ileS. Among 20 MRSA isolates with high-level resistance to mupirocin, all carried mupA; 2 isolates also possessed the V588F mutation in ileS, and 1 possessed the V631F mutation in ileS (isoleucyl-tRNA synthetase). The majority of MR-MRSA isolates were resistant to erythromycin, clindamycin, tetracycline, ciprofloxacin, and gentamicin, but the rates of resistance to rifampin and fusidic acid were 8.7% and 6.5%, respectively. Eight sequence types (STs) were found among the 46 MR-MRSA isolates, of which ST764 was the most prevalent (76.1%). The most frequent spa type identified was t1084 (52.2%). The SCCmec type most frequently found was type II (80.4%). The most common clone among low-level MR-MRSA isolates was ST764-MRSA-SCCmec type II-t1084 (23 isolates), while ST764-MRSA-SCCmec type II-t002 (9 isolates) was the most common clone among high-level MR-MRSA isolates. Additionally, all toxin genes except the seb gene were not identified among ST764 isolates. Among clonal complex 5 (CC5) isolates, immune evasion cluster (IEC)-associated genes (chp, sak, and scn) and seb were present in ST764 but absent in ST5, while sec, sel1, tsst-1, and hlb genes were identified in ST5 but absent in ST764. In conclusion, the spread of CC5 clones, especially a novel ST764-MRSA-SCCmec type II-t1084 clone with high-level resistance to mupirocin, was responsible for the increase in mupirocin resistance. These findings indicated that the emergence of the ST764 MR-MRSA clone involves a therapeutic challenge for treating serious MRSA infections. IMPORTANCE Mupirocin, a topical antibiotic that is commonly used for the nasal decolonization of MRSA and methicillin-sensitive Staphylococcus aureus in hospital settings and nursing homes, was introduced as a highly effective antibiotic against MRSA. Mupirocin acts by competitively binding isoleucyl-tRNA synthetase, thereby disrupting protein synthesis. This drug shows bacteriostatic and bactericidal activity at low and high concentrations, respectively. However, with the increase in mupirocin use, low-level and high-level resistance during nasal mupirocin treatment has been reported. In a previous study, the proportion of MRSA strains with high-level mupirocin resistance in a Canadian hospital increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% (2000 to 2004).

Mupirocin-Resistant Staphylococcus aureus in Iran: A Biofilm Production and Genetic Characteristics.

The spread of mupirocin-resistant Staphylococcus aureus strains in hospitals and communities is a universal challenge. Limited data is available on the genetic features of high-level mupirocin resistant- (HLMUPR-) S. aureus isolates in Tehran. In the present research, we investigated 48 high-level mupirocin resistance S. aureus by antimicrobial activity, virulence analysis, biofilm formation, multilocus sequence typing (MLST), and staphylocoagulase (SC) typing. All the HLMUPR strains were positive for mupA gene. The frequency of multidrug resistance was 97.9%. Twenty-one (43.8%) were toxinogenic with 14 producing pvl (29.2%), 5 tst (10.4%), and two eta (4.2%). Among the HLMUPR isolates, biofilm production was detected in 45 (89.6%) isolates with complete dominance clfB, clfA genes, and a noticeably high frequency fnbA (95.8%), followed by fnbB (93.8%), eno and icaD (each 83.3%), sdrC (81.3%), ebps (79.2%), icaA (75%), sdrD (66.7%), fib (60.4%), sdrE (50%), cna (41.7%), and bap (4.2%). Coagulase typing distinguished isolates into four genotypic patterns including III (50%), II (27.1%), and type IVa (22.9%). A total of three clonal complexes (CCs) and 4 sequence types (STs) including CC/ST22 as the most prevalent (52.1%), CC8/ST239 (20.8%), CC/ST8 (16.7%), and CC/ST5 (10.4%) were identified in current work. According to our analysis, nonbiofilm producer isolates belonged to CC8/ST239 (6.3%) and CC/ST8 (4.2%). Fusidic acid-resistant isolates belonged to CC/ST45 (n = 3) and CC8/ST239 (n = 1). Observations highlighted the circulation of the CC/ST22 HLMUPR S. aureus strains with strong biofilm-production ability in our hospitals, indicating the possibility of transmission of this type between community and hospital.

Detection and Distribution of Low Level and High Level Mupirocin Resistance among Clinical Methicillin Resistant Staphylococcus aureus Isolates

Introduction: Prolonged and improper use of antibiotics increases the resistance among pathogens and leads to life threatening implications and increases mortality. The incidence of mupirocin resistance in Methicillin Resistant Staphylococcus aureus (MRSA) clinical isolates were reportedly increasing. Aim: To determine the rate of high level and low level mupirocin resistance in clinical MRSA isolates in a tertiary care hospital. Materials and Methods: A cross-sectional study was carried out for a period of three months from December 2019- February 2020 in Department of Microbiology, PSG Institute of Medical Sciences and Research (PSG IMSR), Coimbatore, Tamil Nadu, India. A total of 100 non duplicate Staphylococcus aureus isolates from different specimens were subjected to mupirocin susceptibility by Kirby-Bauer disc diffusion method as per Clinical and Laboratory Standards Institute (CLSI) 2019 standards. The low (MuL) and high (MuH) level mupirocin resistance were detected by using 5 and 200 μg mupirocin discs (Himedia) respectively. The isolate exhibiting diameter of ≥14 mm indicates its susceptibility. The isolate exhibiting diameter ≤13 mm for both 5 and 200 μg indicates MuL and MuH strains respectively. Pearson’s Chi-square test calculated, p-value of &lt;0.05 was considered as statistically significant. Results: About 51 out of 100 (51%) Staphylococcus aureus isolates were found to be MRSA. In present study, 6 out of 51 (11.7 %) MRSA isolates were found to exhibit MuL and 5 out of 51 (9.8%) MRSA isolates were found to be having MuH. Low level and high level mupirocin resistance were not observed in Methicillin Sensitive Staphylococcus aureus (MSSA). Conclusion: The incidence of MuH and MuL resistance among MRSA were found to be 9.8% and 11.7% respectively. Screening for mupirocin resistant MRSA to be carried out periodically and stringent infection control practices to be in place to prevent further spread of mupirocin resistant MRSA.

Mupirocin Resistance of Staphylococcus aureus in Clinical Isolates of National Hospital and in the Nasal Carriage of Healthy Undergraduates in Colombo, Sri Lanka

Introduction and Objectives : Mupirocin resistance in Staphylococcus aureus is increasingly reported in many parts of the world. This study was conducted with the objective of describing high-level and low-level mupirocin resistance of S. aureus in clinical isolates and nasal carriage. Materials and Methods : A descriptive study was conducted including 45 nasal isolates of S. aureus collected from healthy university students in Colombo and 249 clinical isolates of S. aureus from the patient specimens in National Hospital of Sri Lanka. All of the confirmed S. aureus strains were tested for methicillin resistance using cefoxitin disc (30μg). S. aureus isolates were considered methicillin-resistant if the diameter of zone of inhibition was 21mm or less (CLSI, 2017). The S. aureus isolates were then tested for mupirocin resistance. Disk diffusion method was utilized with 5μg and 200μg mupirocin discs to determine low-level and high-level resistances respectively. The criterion employed for interpretation of mupirocin resistance was a combination of the widely accepted criterion described by Finlay, Miller, and Poupard (1997) for low-level mupirocin resistance and CLSI (2017) criterion for high-level mupirocin resistance. If both inhibition zone diameters for 5μg disk and 200μg were ≥14mm, the isolate was considered mupirocin sensitive. If 5μg disc displays &lt;14mm and 200 μg disk displayed ≥14mm inhibition zone diameter, the isolate was considered to be mupirocin low level resistant. If there is no inhibition zone in 200μg disk, the isolate was considered as mupirocin high level resistant. Results : From the 45 nasal carriage isolates, 33 (73%) were Methicillin sensitive Staphylococcus aureus (MSSA) and 12 (27%) were Methicillin Resistant Staphylococcus aureus (MRSA). Among the clinical isolates, majority (n=158, 63%) were MRSA while only 91 (37%) MSSA. An overall mupirocin resistance rate of 4.4% among S. aureus was observed. Low-level mupirocin resistance was observed in 3.7% Staphylococcus aureus isolates and high-level mupirocin resistance was observed in 0.7% isolates. Mupirocin low-level and high-level resistance in MRSA isolates were 5.3% and 0.6% respectively. MSSA isolates demonstrated 1.6% (n=2) and 0.8% (n=1) mupirocin low-level and high-level resistances respectively. None of the nasal isolates were resistant to mupirocin while 6% (n=15) mupirocin low-level resistance and 0.8% (n=2) mupirocin high-level resistance was observed in clinical isolates. Conclusion : This initial survey of mupirocin resistance among S. aureus in a country with fairly high usage of mupirocin emphasizes that although the overall mupirocin resistance is relatively low in this population, regular surveillance of mupirocin resistance remains a necessity.

Prolonged outbreak of clonal, mupirocin-resistant methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit: association with personnel and a possible environmental reservoir, analyzed using whole genome sequencing

BackgroundOutbreaks of MRSA occur in NICUs and may be difficult to control. We describe an outbreak of mupirocin-resistant MRSA, molecular epidemiology of isolates and control. MethodsMedical record review of personnel contact with infants. MRSA isolates were analyzed by whole genome sequencing (WGS); single nucleotide polymorphisms (SNPs) were identified. ResultsA 31-month outbreak of MRSA infection occurred. Weekly colonization surveillance of infants was initiated; initial prevalence was 45%. Isolates exhibited high level mupirocin-resistance. There were 3 periods of increased colonization and new infections despite implementation of multiple infection prevention interventions. During the second period, an analysis identified a frontline staff member associated with newly colonized infants whose nasal culture grew the clonal MRSA. A marked reduction in colonization followed removal from patient contact. WGS of isolates from years 1-3 showed clonality with maximum SNP differences of 33. Importantly, the year 3 isolates were more closely related to the early year 1 isolates (15-20 SNP differences) than to the late year 1 or year 2 isolates (18-33 SNP differences). Discussion/ConclusionsDuring a recrudescent MRSA outbreak due to a clonal strain, both contact with a colonized staff member and a putative environmental or personnel reservoir were associated with MRSA acquisition.

Molecular characterization of high-level mupirocin resistance in methicillin-resistant staphylococci isolated from companion animals

High-level mupirocin resistance (HLMR) is determined by the plasmid-located ileS2 gene flanked by two copies of the insertion sequence 257 (IS257). The molecular epidemiology of high-level mupirocin-resistant isolates could be assessed by the determination of their IS257-ileS2 spacer regions conformation. In this study, 188 isolates of methicillin-resistant staphylococci were subjected to the detection of HLMR, and analysis of the conformation of the IS257-ileS2 spacer regions. Mupirocin resistance was detected in five (2,6%) isolates, among which two were recognized as Staphylococcus pseudintermedius, two as Staphylococcus haemolyticus, and one as Staphylococcus aureus. High-level mupirocin resistance was revealed by the agar disk diffusion method, and MIC values, and was confirmed by the detection of the ileS2 gene. The conformations of the IS257-ileS2 spacer regions were homologous in two S. haemolyticus strains tested. The remaining three isolates showed diverse IS257-ileS2 conformations. The results of this study indicate that HLMR occasionally occurs in staphylococci isolated from companion animals. The heterogeneity and the homogeneity of the IS257-ileS2 spacer regions confirm that the ileS2 gene spread among staphylococci of animal origin by the transfer of different as well as the same plasmids. Surveillance of the occurrence of mupirocin resistance and molecular characterization of resistant isolates are strongly recommended due to the possibility of plasmid-located resistance gene transfer between staphylococci.

In vitro activity and resistance rates of topical antimicrobials fusidic acid, mupirocin and ozenoxacin against skin and soft tissue infection pathogens obtained across Canada (CANWARD 2007-18).

Current antimicrobial susceptibility/resistance data versus skin and soft tissue infection (SSTI) pathogens help to guide empirical treatment using topical antimicrobials. To assess the in vitro activity and resistance rates of fusidic acid, mupirocin, ozenoxacin and comparator agents against pathogens isolated from patients with SSTIs in Canada. SSTI isolates of MSSA (n = 422), MRSA (n = 283) and Streptococcus pyogenes (n = 46) obtained from CANWARD 2007-18 were tested using CLSI broth microdilution. Fusidic acid low-level resistance was defined as an MIC of ≥2 mg/L and high-level resistance as an MIC ≥512 mg/L. Mupirocin high-level resistance was defined as an MIC ≥512 mg/L and low-level resistance was an MIC of 2-256 mg/L. Low-level and high-level fusidic acid resistance in MSSA was 10.9% and 1.7%, respectively. Low-level and high-level fusidic acid resistance in MRSA was 10.6% and 3.5%, respectively. High-level mupirocin resistance was identified in 1.4% of MSSA and 14.1% of MRSA, respectively. Versus MSSA, ozenoxacin demonstrated MIC50 and MIC90 of 0.004 and 0.25 mg/L, respectively. Against MRSA, ozenoxacin inhibited all isolates at an MIC of ≤0.5 mg/L, including isolates with ciprofloxacin MICs >2 mg/L, clarithromycin-resistant, clindamycin-resistant, high-level fusidic acid-resistant and high-level mupirocin-resistant isolates. We conclude that fusidic acid low-level resistance exceeded 10% for both MSSA and MRSA while fusidic acid high-level resistance was ≤3.5%. Mupirocin high-level resistance exceeded 10% in MRSA. Ozenoxacin is active versus SSTI pathogens including MRSA resistant to fluoroquinolones, macrolides, clindamycin, fusidic acid and mupirocin.

Molecular characterization of invasive Staphylococcus aureus strains isolated from patients with diabetes in Iran: USA300 emerges as the major type.

There have been few studies focused on the molecular characterization of invasive Staphylococcus aureus strains in patients with diabetes in Iran. In the present study, 20 invasive S. aureus strains recovered from the patients with diabetes characterized by the virulence and resistance analysis, biofilm formation, staphylocoagulase (SC) typing, S. aureus protein A locus (spa) typing staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing (MLST). Virulence gene detection indicated a high prevalence of strains encoding the pvl genes (50%), a low prevalence of the tst and seg gene (each of them was 5%) and a markedly high prevalence of fnbB (95%), fnbA (85%), icaD (75%), icaA (65%). A total of 3 coagulase types (III, 85%; II, 10%; V, 5%), 2 agr types (I, 90%; II 10%) and 2 SCCmec types (IV, 65%; III, 35%) and four different clones namely ST8-MRSA-IV/t008 (50%) (USA300), ST239-MRSA-III/t030 (35%), ST5-MRSA-IV/t002 (10%), and ST45-MRSA-IV/t038 (5%) were detected in this study. Eighty-five percent of the isolates were biofilm producers. All the 4 high-level mupirocin resistance (HLMUPR) strains belonged to CC/ST8-MRSA-IV/t008 clone and carried mupA gene. Fusidic acid-resistant isolate belonged to ST239-SCCmec III/t030 clone. One vancomycin-intermediate resistance isolates was detected in our study, which belonged to ST5-MRSA-IVt002. Circulating clone in MRSA strains (USA300) isolated from the patients with diabetes highlighting the possibility of transmission of these microorganisms' clones between hospital, community, and environments. However, further studies require providing critical insights into the importance of continued controlling and treatment of S. aureus infections in patients with diabetes.

Antibiotic resistance and typing of the methicillin-resistant Staphylococcus aureus clones in Kuwait hospitals, 2016\u20132017

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) belong to diverse genetic backgrounds that differ in antibiotic resistance. Knowledge of the local clonal composition of MRSA strains is important for patients’ management and for designing effective control and eradication methods. The aim of this study was to compare the antibiotic resistance patterns and genotypic characteristics of MRSA isolates obtained in public hospitals in Kuwait in 2016 and 2017 for changes in their resistance patterns and clonal composition.MethodsA total of 4726 MRSA isolates obtained in 2016–2017 from clinical specimens in Kuwait public hospitals were characterized using antibiogram, SCCmec typing, spa typing and DNA microarray.ResultsThe isolates expressed resistance to fusidic acid (52.9%), kanamycin (41.6%), gentamicin (32.5%) and erythromycin (36.2%). The prevalence of high-level mupirocin resistance decreased from 3.7% in 2016 to 2.4% in 2017, while the proportion of resistance to other antibiotics remained relatively stable. A total of 382 spa types were detected with eight spa types, t688 (N = 547), t304 (N = 428), t860 (N = 394), t127 (N = 306), t044 (N = 230), t311 (N = 243), t223 (N = 184) and t002 (N = 181) constituting 53.1% of the MRSA isolates in 2016–2017. Of the 3004 MRSA isolates obtained in 2016 (N = 1327) and 2017 (N = 1677) selected for DNA microarray analysis, 26 clonal complexes (CCs) were identified. Most of the isolates belonged to CC1 (N = 248), CC5 (N = 833), CC6 (N = 241), CC8 (N = 292), CC22 (N = 421), CC30 (N = 177), CC80 (N = 177) and CC97 (N = 171). The prevalence of CC5 isolates has significantly (p ≤ 0.05) increased from 294 isolates in 2016 to 539 isolates in 2017. Although CC22 increased from 196 isolates in 2016 to 225 isolates in 2017, CC1 increased from 112 isolates in 2016 to 136 isolates in 2017, CC6 increased from 103 isolates in 2016 to 138 isolates in 2017, these changes were not significant (p ≥ 0.05).ConclusionThese results revealed the diversity in the genetic backgrounds of MRSA isolates and the stable maintenance of the dominant MRSA clones in Kuwait hospitals in 2016 and 2017 suggesting an on-going transmission of these clones. Novel and creative infection prevention and control measures are required to curtail further transmission.

Increasing Mupirocin Resistance Among MRSA Nasal Surveillance Isolates in the Chicago Area

Background: In 2005, our healthcare system began universal admission screening for nasal colonization with MRSA and decolonization of MRSA positive patients with mupirocin. In 2010–2012, we studied the impact of nasal MRSA decolonization and concluded that it does not add benefit when contact precautions are used; plus, it resulted in increased rates of mupirocin resistance up to 9.4% in 2012. In September 2012 routine decolonization of hospitalized patients was discontinued. In the 2 years following discontinuation of mupirocin use for decolonization of MRSA carriers, the rate of mupirocin resistance gradually declined. We undertook a contemporary review of mupirocin resistance rates to ensure that the rates were stable. Methods: NorthShore University HealthSystem, Illinois, consists of 4 hospitals in the northern suburbs of Chicago, with 750 beds and 60,000 annual admissions. Admission nasal swab samples were collected from at-risk hospitalized patients based on a risk-adjusted algorithm. Nasal swabs were tested using the BD MAX MRSA assay. Positive samples were cultured onto BD BBL CHROMagar MRSA to recover the organism and were tested for the mupA gene, which confers high-level mupirocin resistance using an in-house PCR test. Data for mupirocin orders were provided by the pharmacy. Results: Mupirocin resistance rates and prescription orders are shown in Figs. 1 and 2. Conclusions: Mupirocin resistance rates plateaued between 2012 and 2014 and then increased from 9.1% in 2015 to 18.1% in 2019, despite discontinuation of routine decolonization of hospitalized patients. The reason for the increase is unclear; inpatient mupirocin orders were stable from 2015 to 2017.Funding: NoneDisclosures: None

Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution.

Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is an effective measure to prevent clinical infection but resistance is a concern. We aim to evaluate the impact of mupirocin (MUP) ointment formulary removal, plateauing use of chlorhexidine gluconate (CHG), and hospital-wide introduction of octenidine (OCT)-based products on the minimum inhibitory concentration (MIC) of MRSA to MUP, CHG, and OCT in our hospital. A prevalence study was conducted at three time points (TP) on consecutive MRSA screening isolates to evaluate for their MICs to MUP, CHG, and OCT using broth microdilution sensititre plates and detection of the ileS-2 gene encoding high-level MUP resistance in 2013 (pre-intervention TP1; n = 160), 2016 (early post-intervention TP2; n = 99) and 2017 (late post-intervention TP3; n = 76). Statistical analyses were performed using Chi square test with reference from TP1. There was a significant improvement in MUP susceptibility (MIC < 4 mcg/ml) from 71.9% (TP1) to 86.9% (TP2; p = 0.006) to 88.2% (TP3; p = 0.007). The prevalence of MUP high-level resistance (MIC > 256 mcg/ml) reduced from 25.0% (TP1) to 12.1% (TP2; p = 0.014) to 5.3% (TP3; p = 0.001). Likewise, the prevalence of isolates harboring the ileS-2 gene decreased from 28.1% (TP1) to 18.2% (TP2; p = 0.072) to 9.2% (TP3; p = 0.002). OCT MIC range remains stable at 0.5 to 1 mcg/ml across all three TPs. The proportion of isolates with reduced CHG susceptibility (MIC ≥ 4 mcg/ml) increased over the three TPs from 23.1 to 27.2% (p = 0.45) to 42.1% (p = 0.003). Active formulary regulations have an impact on the resistance profile of MRSA and can be used as a strategy to preserve the MRSA decolonization armamentarium.

Localization and Characterization of MupA Gene in High and Low-Level Mupirocin Resistant Methicillin Resistant Staphylococcus Aureus

Background: Two types of mupirocin resistance among methicillin resistant Staphylococcus aureus (MRSA) have been reported; low-level mupirocin resistance (LL-MR), and high-level mupirocin resistance (HL-MR). The mupA gene is typically located on mobile genetic elements which facilitate the resistance dissemination. Objective: The aim of this work was to identify the mupA gene location, as well as the restriction fragment length polymorphism (RFLP) patterns in high and low-level mupirocin resistant MRSA. Methodology: This study was conducted on 100 MRSA isolates; seven of them were mupirocin resistant. The E test was used to identify high and low level mupirocin resistance. Amplification of mupA gene in total and plasmid DNA was performed. We also detected the spacer region (trsLM–IS257-like–mupA) in the 7 isolates by PCR then we investigated its RFLP patterns. Results: Four MR MRSA isolates had low level resistance, their MupA gene was located on chromosomal DNA, whereas, three isolates showed high level MR, their MupA gene was located on plasmid DNA. Four types of different RFLP patterns of the spacer region were identified; type-1 included two LL-MR isolates, each of type-2 and 3 included both HL-MR and LL-MR isolates, and type-4 included one HL-MR isolate. Conclusions: Staphylococcus aureus mupA gene responsible for LL-MR is located on the chromosome while that responsible for HL-MR is plasmid-mediated. The spacer region variations appear to occur in both chromosomal and plasmid-located mupA gene regardless the type of mupirocin resistance.

Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus with mupirocin, fusidic acid and/or retapamulin resistance

BackgroundThe data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).ResultsOverall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates.ConclusionsMUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.