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Article

Methicillin-Resistant Staphylococcus aureus from Diabetic Foot Infections in a Tunisian Hospital with the First Detection of MSSA CC398-t571

by
Ameni Arfaoui
1,
Rym Ben Sallem
1,
Rosa Fernández-Fernández
2,
Paula Eguizábal
2,
Raoudha Dziri
1,
Idris Nasir Abdullahi
2,
Noureddine Sayem
3,
Salma Ben Khelifa Melki
3,
Hadda-Imen Ouzari
1,
Carmen Torres
2 and
Naouel Klibi
1,*
1
Laboratory of Microorganisms and Active Biomolecules, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 1068, Tunisia
2
Biochemistry and Molecular Biology, University of La Rioja, 26006 Logroño, Spain
3
Service of Biology, Carthagene International Hospital of Tunisia, Tunis 1082, Tunisia
*
Author to whom correspondence should be addressed.
Antibiotics 2022, 11(12), 1755; https://doi.org/10.3390/antibiotics11121755
Submission received: 5 November 2022 / Revised: 26 November 2022 / Accepted: 2 December 2022 / Published: 4 December 2022
(This article belongs to the Special Issue Diversity of Antimicrobial Resistance Genes in Clinical Settings)
Review Reports Versions Notes

Abstract

:
This study sought to analyze the antimicrobial resistant phenotypes and genotypes as well as the virulence content of S. aureus isolates recovered from patients with diabetic foot infections (DFIs) in a Tunisian hospital. Eighty-three clinical samples of 64 patients were analyzed, and bacterial isolates were identified by MALDI-TOF. The antimicrobial resistance phenotypes were determined by the Kirby–Bauer disk diffusion susceptibility test. Resistance and virulence genes, agr profile, spa and SCCmec types were determined by PCR and sequencing. S. aureus was detected in 14 of the 64 patients (21.9%), and 15 S. aureus isolates were recovered. Six out of the fifteen S. aureus isolates were methicillin-resistant (MRSA, mecA-positive) (40%). The isolates harbored the following resistance genes (number of isolates): blaZ (12), erm(B) (2), erm(A) (1), msrA (2), tet(M) (2), tet(K) (3), tet(L) (1), aac(6′)-aph(2″) (2), ant(4″) (1) and fexA (1). The lukS/F-PV and tst genes were detected in three isolates. Twelve different spa-types were identified and assigned to seven clonal complexes with the predominance of agr-type III. Furthermore, the SCCmec types III, IV and V were found among the MRSA isolates. Moreover, one MSSA CC398-t571-agr-III isolate was found; it was susceptible to all antimicrobial agents and lacked luk-S/F-PV, tst, eta and etb genes. This is the first report on the prevalence and molecular characterization of S. aureus from DFIs and also the first detection of the MSSA-CC398-t571 clone in human infections in Tunisia. Our findings indicated a high prevalence S. aureus in DFIs with genetic diversity among the MSSA and MRSA isolates.

1. Introduction

Staphylococcus aureus (S. aureus) strains have become a leading cause of hospital-associated and community-associated infections worldwide. Two mechanisms confer resistance to β-lactams in staphylococci with the most common being the production of β-lactamase, encoded by blaZ, which produces the hydrolysis of the β-lactam ring, rendering the β-lactam inactive. More than 90% of staphylococcal isolates now produce penicillinases [1]. The second mechanism is due to an altered penicillin-binding protein PBP2a, encoded by mecA, which is carried in a variable mobile element, namely, the staphylococcal chromosome cassette mec (SCCmec) [2]. This mechanism leads to resistance to a semi-synthetic penicillinase-resistant β-lactam called methicillin. Furthermore, the term methicillin resistance manifests as resistance to virtually all β-lactams with the exception of the latest generation of cephalosporin β-lactams [2]. MRSA strains can also acquire additional resistance to several commonly used non-β-lactam antimicrobials (e.g., aminoglycosides, macrolides, fluoroquinolones and tetracycline) and are currently considered as the first class of multidrug-resistant (MDR) pathogens [3].
Diabetic foot infection (DFI), defined as soft tissue or bone infection below the malleoli, is the most common diabetic complication that often leads to hospitalization and non-traumatic lower extremity amputation [4,5,6]. Many studies have shown that DFI is polymicrobial [7,8,9]. Particularly, S. aureus is the bacteria implicated the most [10]. In addition to its ability to acquire antimicrobial resistance (AMR) to many clinically important drugs [11], this microbe plays a significant role in DFIs by causing infections ranging from superficial to severe and potentially fatal systemic infections [12].
The overuse of antibiotics is one of the most serious issues with DFI treatment. The prescription of unsuitable antimicrobial treatment has an impact on the microbiota and encourages the selection and growth of MDR bacteria. Thus, the global emergence of MRSA has considerably restricted the available therapeutic options for staphylococcal infections [13].
The epidemiology of AMR in Tunisia has been very dynamic in recent years, and the available data give insights into the alarming situation, especially in hospital settings [14]. In contrast, only three earlier studies have been conducted on DFI. These studies were limited to the bacteriological profile of DFI patients and showed controversial results. Enterobacteriaceae were the main bacteria causing the infection in diabetics in two of them [8,9], while S. aureus was the most frequent pathogen isolated in the remaining one [15]. Thus, there are currently no data on the molecular characterization of the bacterial strains involved, risk factors or treatment of multi-drug resistance organisms in patients with DFI in Tunisia. The aim of the present study was to evaluate the prevalence of S. aureus isolated from diabetic patients admitted for infected foot ulcers in the multidisciplinary diabetic foot center of the International Hospital, Carthagene in Tunisia during the COVID-19 pandemic and to investigate their genetic relatedness, antibiotic resistance pattern and virulence characteristics.

2. Results

2.1. Patient Characteristics and MRSA Prevalence in Ulcer Samples

As shown in Table 1, 64 patients were included in this study (48 men and 16 women with a mean age of 62.28 years); 6 of them had diabetes type 1 (4 male and 2 female), 57 diabetes type 2 (43 male and 14 female) and 1 male had diabetes secondary to acute pancreatitis. Since the diabetic foot center is international, the patients were from different African countries (Tunisia, Algeria, Libya, Chad and Guinea). Accordingly, the distribution of the nationality among the patients with foot ulcer infection was as follows: Tunisia (51.6%), Libya (39%), Algeria (6.3%), Chad (1.6%) and Guinea (1.6%).
S. aureus was detected in 21.9% of all patients with DFI analyzed in this study (14/64). One isolate per positive sample was included, except in one patient in which two different isolates were recovered and both of them were included making a collection of fifteen S. aureus isolates. Six of these fifteen S. aureus isolates were MRSA (cefoxitin-resistant and mecA positive) (40%), and the remaining nine isolates were methicillin-susceptible S. aureus (MSSA). One of the patients carried one MSSA and one MRSA isolate. Thus, the overall prevalence of MRSA in the ulcers was 9.4% and reflected a proportion of 42.9% of the participants who had S. aureus foot ulcer infections.

2.2. Antimicrobial Resistance Pattern of the S. aureus Isolates

The resistance profiles of MRSA and MSSA isolates to the antimicrobial agents tested are presented in Table 2. All fifteen isolates showed resistance to at least one antibiotic. Multidrug resistance was found in 53.4% of isolates. All six MRSA isolates showed resistance to fusidic acid, four isolates to tetracycline and three isolates to tobramycin and gentamicin. Two MRSA isolates were resistant to ciprofloxacin, levofloxacin, trimethoprim–sulfamethoxazole and erythromycin, and one to clindamycin, minocycline, mupirocin and rifampicin. All the MRSA isolates were susceptible to tigecycline, vancomycin, teicoplanin and linezolid.
Among the nine MSSA isolates, antimicrobial resistance was only shown against penicillin (88.9%), fusidic acid (55.6%) and erythromycin (22.2%).

2.3. Genotypic Patterns of Antibiotic Resistance among S. aureus Strains

The mecA gene was found in the six MRSA isolates (40%), and five of these isolates also carried the blaZ gene (encoding penicillin resistance). All tetracycline-resistant isolates carried tet genes (tet(M) (n = 1), tet(K) (n = 1), tet(L) and tet(K) (n = 1) and tet(M) + tet(K) (n = 1)). Concerning the three tobramycin- and gentamicin-resistant isolates, two harbored the aac(6′)-aph(2”) gene, and one co-harbored the aac(6′)-aph(2″) and ant(4′)-Ia genes.
Among the nine MSSA isolates, the blaZ gene was found in seven isolates (77.8%). The presence of erm(B) alone or in association with erm(A) was detected in two erythromycin-resistant isolates. The msrA gene was identified in two isolates and the fexA gene in one isolate. Two strains had no resistance genes (Table 3).

2.4. Molecular Typing of Isolates

Twelve different spa types were identified among the fifteen S. aureus isolates. The spa type t127 was detected in three isolates, while others were detected only once: (t311, t037, t15077, t688, t084, t188, t355, t091, t012, t223 and t571). One of the fifteen isolates could not match any known spa sequence. For one patient, two S. aureus isolates were identified corresponding to two different spa types (t311 and t571). The isolate belonging to spa-type t571 was assigned to the clonal complex CC398.
Among the six isolates that carried the mecA gene, two of them harbored SCCmec type V, one isolate SCCmec type IVb and another SCCmec type III, and the remaining two isolates were not typable. The characterization of the agr system showed a predominance of agr group III (11 isolates, 73.3%). The agr group IV, II and I were detected in four isolates.

2.5. Virulence Profile

The lukF/lukS-PV genes encoding for Panton–Valentine leukocidin (PVL) were detected in two isolates (13.33%) typed as t127-MRSA and t355-MSSA. The tst and eta genes were found, each in one isolate. None of the strains carried genes encoding the ETB toxin.
In addition, all MRSA and seven MSSA isolates carried the scn gene of the IEC system, and they were ascribed to different IEC types (A, B, C, D, E and G). In addition, two MSSA isolates lacked the scn gene (IEC-negative). Thirteen isolates (87%) contained an IEC-converting βC-Φs, as demonstrated by the presence of scn. The predominant IEC variant was type D (sea, sak and scn) found in four isolates (30.7%). Variant E (sak and scn), G (sep, sak and scn), C (chp and scn), A (sea, sak, chp and scn) and B (sak, chp, and scn) were present in three, two, two, one and one isolates, respectively (Table 3).

3. Discussion

Methicillin-resistant S. aureus is a dominant hospital pathogen in Tunisia and worldwide [16]. Although antibiotic resistance of healthcare-associated staphylococci is well documented in Tunisia, no detailed information is available on antibiotic resistance and the molecular characterization of S. aureus isolated from diabetic ulcers. The current study fills this knowledge gap by analyzing the prevalence and molecular characteristics of S. aureus isolates in the International Tunisian Hospital, Carthagene. Of note, the patients involved were from different countries (Tunisia, Algeria, Libya, Chad and Guinea), thus reflecting the characteristics of S. aureus associated with DFIs not only in Tunisia but also on a wider geographical scale.
Studies have shown that prior use of antibacterial agents, hospitalization, MRSA nasal carriage and chronic wounds are risk factors for MRSA acquisition in patients with DFIs [17].
In our study, the prevalence of S. aureus detected in DFIs was 21.9%. Three previous retrospective studies from different Tunisian hospitals showed that S. aureus was isolated in 9%, 17% and 31% of DFIs [8,9,15]. This variation in percentages might be due to a difference in the geographical areas, the method applied to obtain cultural samples and study periods, especially the case of our study which took place during the COVID-19 pandemic and partly explaining the decrease in the number of consulting patients.
The prevalence of MRSA in this study was six out of fifteen S. aureus isolates (40%), which is a cause for concern given the high clinical significance of this pathogen. Similar studies have been performed in other countries with different prevalences of S. aureus in DFIs / prevalence of MRSA among S. aureus: Ghana (19%/6%), Iran (46.10%/19.48%), Iraq (38.7%/45.8%), Morocco (12.6%/4.7%), Turkey (20%/31%), Jordan (14.2%/93%) and Algeria (30.7%/85.9%) [18,19,20,21,22,23,24]. A recent meta-analysis including 112 studies from a wide range of countries reported S. aureus isolate detection in 109 studies representing 15,670 clinical samples; the proportion of MRSA among these isolates was 18.0% [25].
In our study, multi-resistance was found in 53.4% of isolates. The MDR phenotype is considered a common trait of MRSA isolates from various origins with resistance to several clinically relevant antimicrobial agents typically due to the acquisition of various mobile genetic elements (plasmids and transposons) causing treatment failure and significant associated human health burdens and healthcare costs [26,27]. In Tunisia, the high proportion of isolates showing this resistance phenotype may be related to the abuse of antibiotics with a frequent practice of self-medication. In this study, vancomycin, tigecycline, teicoplanin and linezolid were effective against all the S. aureus isolates. Fortunately, these antibiotics remain the best option to treat MRSA-associated infections, thus appropriate use of these antibiotics is highly recommended to avoid the selection of resistant strains.
Overall, high genetic diversity was found among the S. aureus isolates demonstrated by thirteen spa types and four agr groups with the predominance of agr-type III and spa-type t127 (CC1). These results are consistent with those of a recent review which highlighted that S. aureus strains isolated from diabetic foot ulcers in different countries are genetically diverse [28].
The spa type t127 was the predominant (three isolates, 20%). It was previously reported that t127 is associated with serious human infections in the United States and Germany [29,30,31]. In addition to a clinical origin, the spa type t127 has recently been reported in processed foods in China and in animals, indicating the risk of MRSA transfer from food and animal origins to humans or vice versa [32,33].
Interestingly, an MSSA isolate belonging to the spa type t571 (CC398 lineage) was found in one of the patients in our study. To our knowledge, this is the first report of MSSA-CC398 in human infections in Tunisia. Even though livestock-associated (LA)-MRSA-CC398 is closely related to food-producing animals [34], this MSSA-CC398-t571 subclade seems to be livestock-independent and has been detected in human invasive infections in different countries [35,36,37]. Similarly, a national French study showed a consistent and significant association between MSSA-CC398 and diabetic foot osteomyelitis [38].
The Panton–Valentine leukocidin is the most studied toxin produced by S. aureus [39]. In our study, only two S. aureus isolates contained the genes of PVL (13.3%). It has been suggested that PVL-positive strains are less frequently detected among DFIs as this gene is mostly prevalent in community species [20]. However, some studies reported higher PVL gene rates reaching 14.1% and 57% in Algeria and India, respectively [24,40].
The tst gene, encoding toxic shock syndrome toxin-1, was found in one isolate. Other studies reported different rates of tst positive strains in cases of diabetic foot ulcers ranging from 13% to 19% [40,41,42], whereas no strains of S. aureus from DFIs were positive to tst in a previous African study [43].
Among our fifteen S. aureus isolates, one of them (6.7%) harbored the eta gene and none harbored the etb gene. This result was similar to a previous report from France showing that 3% of S. aureus strains from diabetic foot ulcers were eta-positive, but no strain harbored the etb gene [41]. Another European study noted that 13% and 17% of the strains from DFIs harbored eta and etb genes, respectively [42]. However, these virulence factors were not detected in cases of DFIs previously reported in Algeria [24] or in diabetic foot osteomyelitis in France [38]. S. aureus is an extremely versatile pathogen in humans with different virulence phenotypes, suggesting that the virulence determinants did not spread homogeneously among various genetic backgrounds.

4. Materials and Methods

4.1. Bacteria Collection and Identification

Between September 2019 and October 2020, a total of 83 samples (tissue biopsy and/or deep swab and/or aspiration) were analyzed from 64 patients who were admitted for DFI at the diabetology department of the International Hospital Carthagene of Tunisia; this hospital has a capacity of 300 beds and 55 intensive care beds. Inclusion criteria were diabetic patients with any type of diabetes and aged ≥18. Patients who received antibiotic therapy within 3 months before the consultation, pregnant patients and those with a mental disorder that precluded understanding the scope of the study were excluded from the work.
Samples (aspirations (n = 5), deep swabs (n = 42), and tissue biopsies (n = 36)) were collected after wound debridement and cleansing with sterile physiological saline (as part of part of the routine clinical work of the hospital). Swabs were taken from open wounds by sterile cotton swabs from the base of the ulcer wound and aspirations were taken for closed lesions (abscesses and other fluctuant infected tissues) by needle aspirates after cleaning with polyvidone-iodin solution. In operated patients, intra-operative samples were obtained by infected soft tissues biopsies in the operating room. The samples were transported in sterile tubes without transport medium and were processed immediately upon arrival for bacteria recovery in the clinical laboratory as part of the routine diagnosis at the hospital.
The samples were inoculated on blood agar (Oxoid, UK, CM0271) and incubated in stove at 37 °C for 24 h. Colonies suspected to be Staphylococcus were subcultured on mannitol salt agar selective medium (Oxoid, UK, CM0085) for specific detection of S. aureus. All isolates were identified by MALDI-TOF-MS system using the standard extraction protocol recommended by Bruker (Bruker, Bremen, Germany). The identification of the S. aureus colonies was also confirmed by PCR of the gene nuc [44].

4.2. Antimicrobial Susceptibility Profile of S. aureus Isolates

The antimicrobial susceptibility tests on all the S. aureus isolates were performed by the Kirby–Bauer disk diffusion method on Mueller–Hinton agar medium (MH) (BioRad, Marne-la-Coquette, France). The antibiotic discs (BioRad, Marne-la-Coquette, France) tested were the following ones (μg/disk): penicillin (1 unit), cefoxitin (30), tobramycin (10), gentamicin (10), ciprofloxacin (5), levofloxacin (5), trimethoprim–sulfamethoxazole (1.25 + 23.75), clindamycin (2), erythromycin (15), fusidic acid (10), tetracycline (30), minocycline (30), mupirocin (200), chloramphenicol (30), linezolid (10), tigecycline (15) and rifampicin (5). The breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) guidelines [45] were followed. The double-disc diffusion test (D-test) with erythromycin and clindamycin disks was implemented for all isolates to detect inducible clindamycin resistance. Vancomycin and teicoplanin MICs were determined using the broth microdilution method according to CLSI [45]. Isolates displaying resistance to three or more antimicrobial classes were considered multidrug-resistant (MDR).

4.3. Screening of Methicillin-Resistant S. aureus Isolates (MRSA)

Isolates resistant to cefoxitin (FOX, 30 µg) on MH agar according to CLSI recommendations were confirmed for the presence of the mecA gene by PCR technique as described previously [45,46]. mecA-positive isolates were considered as MRSA isolates.

4.4. Detection of Antimcrobial Resistannce Genes (ARGs)

The presence of genes associated with resistance to β-lactams (mecA and blaZ), erythromycin (erm(A), erm(B), erm(C) and msr(A)), tetracycline (tet(K), tet(L) and tet(M)), chloramphenicol (fexA and fexB) and aminoglycosides (aac(6′)-aph(2″) and ant(4)-Ia) were analyzed using PCR and confirmed by sequencing [46].

4.5. Molecular Typing of Isolates

All S. aureus isolates were characterized by amplification and sequencing of the polymorphic region of the staphylococcal protein A-encoding gene (spa) [47]. The obtained sequences were analyzed using Ridom Spa-type software version 1.5.21 (Ridom GmbH, Würzburg, Germany) to determine the spa type. In addition, a specific PCR was carried out to identify the CC398 lineage, targeting the CC398-specific variant of sau1-hsdS1 [48]. The clonal complex of the remaining isolates was assigned, when possible, according to the spa-type.
MRSA isolates were subjected to SCCmec typing by PCR strategy to determine the mec gene complex and the ccr gene complex as described by Zhang et al. [49]. The identification of the agr allele group (I–IV) was also determined by multiplex PCR as described earlier [50].

4.6. Occurrence of Virulence and Immune Evasion Cluster (IEC) Genes

All S. aureus isolates were screened using PCR for the following staphylococcal virulence genes: Panton–Valentine leukocidin (lukS/F-PV), toxic shock syndrome toxin (tst) and the exfoliative toxins (eta and etb) as previously described [51]. The immune evasion cluster (IEC) genes (scn, chp, sak, sea and sep) were examined by PCR and, based on the genes obtained, the isolates were classified into seven IEC types [51,52]. The scn gene (encoding the staphylococcal complement inhibitor) was used as a marker of the IEC system. Positive controls from the collection of the University of La Rioja were included in all PCR assays.

5. Conclusions

This is the first study to report the prevalence rate, the antimicrobial resistance profile, virulence genes and molecular typing of S. aureus isolates obtained from diabetic foot wounds in Tunisia. Our results indicate a high prevalence of S. aureus in DFIs with genetic diversity among the MSSA and MRSA isolates. A high number of MDR isolates harbored various AMR and virulence genes.
This study elucidates the recent regional epidemiological data on S. aureus implicated in DFIs which will be relevant for better guidelines for antibiotic use in clinical settings. These findings highlight the need for further studies focusing on the molecular surveillance of AMR for optimal management of DFI.

Author Contributions

N.K., R.B.S. and A.A. conceived the study. A.A., N.S. and S.B.K.M. contributed to acquisition of the data and sample collection. A.A., R.F.-F., P.E. and I.N.A. analysed the resistance phenotypes, resistance genes and virulence. R.D., R.B.S. and A.A. studied the genetic diversity of the strains. N.K. and C.T. analysed the data and interpreted the results. A.A., R.B.S. and N.K. wrote the manuscript. N.K., C.T. and H.-I.O. revised it critically for important intellectual content. All authors agree with the article submission. All authors have read and agreed to the published version of the manuscript.

Funding

A. Arfaoui has a grant from the Tunisian Ministry of Higher Education and Scientific Research. The work performed at the University of La Rioja was financed by MCIN/AEI/10.13039/501100011033 of Spain (project PID2019-106158RB-I00); also, it received funding from the European Union’s H2020 research and innovation programme under the Marie Sklodowska–Curie grant agreement No. 801586 (for Idris Nasir Abdullahi). R. Fernández-Fernández has a predoctoral contract with the Ministry of Spain (FPU18/05438). P. Eguizábal has a predoctoral contract FPI with the University of La Rioja (Spain).

Institutional Review Board Statement

The Ethics Committee of the International Hospital Carthagene of Tunisia approved the protocols in this study.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Table
Table 1. Characteristics of 64 patients included in this study.
Table 1. Characteristics of 64 patients included in this study.
Case NumberThe Reason Why the Patient Entered the CenterSexAge (Years)CountryType of Diabetes/Duration (Years)
1Infected plantar perforating disease of the right footM62TunisiaII/30
24th left toe infectionM53LibyaII/5
3Phlegmon of the sole of the right footM55TunisiaII/12
4Superinfection of the right transmetatarsal amputation stumpM67LibyaII/10–19
5Left big toe infectionM77LibyaII/20
6Infected plantar perforating disease of the right Charcot footM60LibyaII/10–19
7Gangrene of the 4th and 5th right toeF68LibyaI/20
8Phlegmon of the left footM50TunisiaI/28
9Patient with sepsis (left heel infection)M55LibyaII/10
102nd right toe infectionM55LibyaII/20
11Left 4th toe stump infectionM68AlgeriaII/20
12Right hallux gangreneF68LibyaII/30
13Phlegmon of the plantar surface of the left footF79LibyaII/19
14Right foot infectionM84TunisiaII/10
15Patient with sepsis (right plant gangrene)M71TunisiaII/20
16Infected plantar perforating disease of the right footM58AlgeriaII/21
17Left foot phlegmonF66TunisiaII/27
18Gangrene of the 2nd right toeF77AlgeriaII/30
19Right big toe infectionM67LibyaII/+30
20Left foot infection with purulent dischargeM69LybiaII/25
21Right hallux gangreneM64TunisiaII/25
22Superinfection of the 4th right toeM80LybiaII/30
23Left hallux infectionM62LibyaII/19
24Infected intertrigo inter toe of the 3rd and 4th space of the right footF51LibyaII/+20
25Left big toe infectionF64TunisiaII/18
26Phlegmon of the flexor sheaths of the left footM43TunisiaII/14
27Infected right footM47LibyaII/4 months
28Infected left footM43TunisiaII/10
29Infected right heelF53LibyaII/20
30Charcot infection of the left footM59TunisiaII/10
31Right hallux gangreneM45TunisiaI/30
32Phlegmon and plantar perforating disease of the right and left footM46TunisiaII/15
33Right hallux infectionM67AlgeriaII/10
343rd left toe gangreneM56LibyaII/25
353rd left toe infectionM92TunisiaII/30
36Left big toe gangreneM74TunisiaII/26
37Infected ulceration of the 2nd right and left toeF69LibyaII/15
38Phlegmon in the sole of the left footM42ChadII/10
39Right big toe gangreneM67TunisiaII/25
40Infection of the big toe and the 3rd left toeM63LibyaI /50
412nd left toe infectionF58LibyaII/10–19
42Superinfection of the amputation stump of the right halluxF71GuineaII/1
43Left hallux infectionM52LibyaII/36
445th left toe gangreneM53LibyaII/20
45Left hallux flexor sheath phlegmonM74TunisiaII 10
46Left big toe gangreneM39LibyaII/20
47Plantar perforating disease on Charcot foot of the left footM66LibyaII/36
48Gangrene of the 1st and 3rd left toeM57TunisiaII/25
49Right foot infectionM80TunisiaII/15
50Infected ulceration of the 5th right toeM60TunisiaII/36
51Right 2nd toe gangreneM52TunisiaII/20
52Superinfection of the left heelM58Tunisiadiabetes secondary to acute pancreatitis/23
53Left 2nd toe gangreneF43TunisiaII/10
54Infected ulceration of the plantar surface of the right halluxM65TunisiaII/20
55Right foot phlegmonM68TunisiaII/20
56Left 5th toe infectionM64TunisiaII/15
57Right foot transmetatarsal amputation stump infectionM64TunisiaII/40
58Superinfection of the amputation stump of the right 1st rayM60TunisiaI/19
59Left heel infectionF62TunisiaI/30
60Left big toe infectionF58TunisiaII/20
61Phlegmon of the 4th left toeM81TunisiaII/+20
62Right hallux gangreneF66TunisiaII/25
63Right heel infectionF67TunisiaII/37
64Left foot infectionM72LibyaII/25
F, female; M, male.
Table
Table 2. Antibiotic resistance rate of the 15 S. aureus isolates from DFIs.
Table 2. Antibiotic resistance rate of the 15 S. aureus isolates from DFIs.
Antibiotic (Disc Charge)All Isolates (Total = 15)
n (%)		MRSA (Total = 6)
n (%)		MSSA (Total = 9)
n (%)
penicillin14 (93.3%)6 (100%)8 (88.9%)
cefoxitin6 (40%)6 (100%)0
tobramycin3 (20%)3 (50%)0
gentamicin3 (20%)3 (50%)0
ciprofloxacin2 (13.3%)2 (33.3%)0
levofloxacin2 (13.3%)2 (33.3%)0
trimethoprim–sulfamethoxazole2 (13.3%)2 (33.3%)0
clindamycin1 (6.7%)1 (16.7%)0
erythromycin2 (13.3%)02 (22.2%)
fusidic acid11 (73.3%)6 (100%)5 (55.6%)
tetracycline4 (26.7%)4 (66.7%)0
minocycline1 (6.7%)1 (16.7%)0
mupirocin1 (6.7%)1 (16.7%)0
chloramphenicol1 (6.7%)1 (16.7%)0
linezolid000
tigecycline000
vancomycin000
teicoplanin000
rifampicin1 (6.7%)1 (16.7%)0
Table
Table 3. Characteristics of the six MRSA and nine MSSA isolates recovered from diabetic foot infections in this study.
Table 3. Characteristics of the six MRSA and nine MSSA isolates recovered from diabetic foot infections in this study.
StrainSample TypeMolecular TypingAntimicrobial ResistanceVirulence GenesIEC f
Spa TypeCC cAgr-TypeSCCmec-TypePhenotype eGenotype
X3653 aAspirationt311CC5IVVPEN, FOX, CIP, LVX, FAmecA, blaZ E
X3655Aspirationt037CC8IVIV bPEN, FOX, SXT, FA, TET, CHLmecA, blaZ, tet(M), fexA G
X3656Deep swabt127CC1IIIND dPEN, FOX, TOB, GEN, SXT, FA, TET, MUPmecA, blaZ, tet(L), tet(K), aac6′-aph2”lukS/F-PVD
X3657Deep swabt15077 IIINDPEN, FOX, FAmecA E
X3659Deep swabt688CC5IIIIIIPEN, FOX, TOB, GEN, CIP, LVX, FA, TET, MIN, RIFmecA, blaZ, tet(M), tet(K), aac6′-aph2” D
X3654Deep swabt084CC15IIVPEN, FOX, TOB, GEN, FA, TETmecA, blaZ, tet(K), aac6′-aph2”, ant4′-la C
X3694Deep swabt127CC1III-PEN, FAblaZ D
X3695Deep swabNC b III-PENblaZ -
X3697Tissue biopsyt118 III-PEN, ERY, FA,blaZ, erm(B), msr(A)eta-
X3698Tissue biopsyt355 III-PENblaZlukS/F-PVE
X3693Tissue biopsyt091 III-PENblaZ G
X3699Deep swabt012CC12III-PEN, ERY, CLI *blaZ, erm(A), erm(B), msr(A)tstA
X3700Tissue biopsyt223CC22III-PEN, FAblaZ B
X3692Tissue biopsyt571CC39III-FA- C
X3696 aDeep swabt127CC1I-PEN, FA- D
a, isolates obtained from the same patient; b NC, novel combination: the repetitions detected in spa-type were as follows: r03-r16-r21-r17-r23-r12; c CC: they were assumed according to the spa type, except for CC398 that was determined by specific PCR; d ND, non-determined; e PEN, penicillin; FOX, cefoxitin; ERY, erythromycin; TET, tetracycline; CIP, ciprofloxacin; LVX, levofloxacin; FA, fusidic acid; SXT, trimethoprim–sulfamethoxazole; TOB, tobramycin; GEN, gentamycin; MIN, minocycline; CHL, chloramphenicol; MUP, mupirocin; RIF, rifampicin; CLI *, inducible resistance; f IEC, immune evasion cluster.
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Arfaoui, A.; Sallem, R.B.; Fernández-Fernández, R.; Eguizábal, P.; Dziri, R.; Abdullahi, I.N.; Sayem, N.; Ben Khelifa Melki, S.; Ouzari, H.-I.; Torres, C.; et al. Methicillin-Resistant Staphylococcus aureus from Diabetic Foot Infections in a Tunisian Hospital with the First Detection of MSSA CC398-t571. Antibiotics 2022, 11, 1755. https://doi.org/10.3390/antibiotics11121755

AMA Style

Arfaoui A, Sallem RB, Fernández-Fernández R, Eguizábal P, Dziri R, Abdullahi IN, Sayem N, Ben Khelifa Melki S, Ouzari H-I, Torres C, et al. Methicillin-Resistant Staphylococcus aureus from Diabetic Foot Infections in a Tunisian Hospital with the First Detection of MSSA CC398-t571. Antibiotics. 2022; 11(12):1755. https://doi.org/10.3390/antibiotics11121755

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Arfaoui, Ameni, Rym Ben Sallem, Rosa Fernández-Fernández, Paula Eguizábal, Raoudha Dziri, Idris Nasir Abdullahi, Noureddine Sayem, Salma Ben Khelifa Melki, Hadda-Imen Ouzari, Carmen Torres, and et al. 2022. "Methicillin-Resistant Staphylococcus aureus from Diabetic Foot Infections in a Tunisian Hospital with the First Detection of MSSA CC398-t571" Antibiotics 11, no. 12: 1755. https://doi.org/10.3390/antibiotics11121755

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