The number of complicated skin and soft tissue infections (cSSTIs) in the Arabian Gulf region has risen in recent years, particularly those caused by multi-drug resistant (MDR) pathogens. The high prevalence of diabetes, obesity, and associated cardio-metabolic comorbidities in the region renders medical and surgical management of cSSTI patients with MDR infections challenging. An experienced panel of international and regional cSSTI experts (consensus group on cSSTIs) was convened to discuss clinical considerations for MDR infections from societal, antimicrobial stewardship, and cost perspectives, to develop best practice recommendations. This article discusses antibiotic therapies suitable for treating MDR cSSTIs in patients from the Gulf region and recommends that these should be tailored according to the local bacterial ecology by country and region. The article highlights the need for a comprehensive patient treatment pathway and defined roles of each of the multidisciplinary teams involved with managing patients with MDR cSSTIs. Aligned and inclusive definitions of cSSTIs for clinical and research purposes, thorough and updated epidemiological data on cSSTIs and methicillin-resistant
Complicated skin and soft tissue infections (cSSTIs) comprise a wide group of infections with diverse microbiological causes. These infections may affect the superficial dermis, subcutaneous tissue, fascia, or muscle, and presentation can range from simple superficial infections to severe necrotizing infections [
Robust definitions for cSSTIs are vital for capturing the broader spectrum of these infections and assessing the appropriate treatment. The 1st challenge with the clinical management of cSSTIs is the inconsistencies between the definitions used in published literature and guidelines [
Responsible for a large proportion of infections that require hospitalization, cSSTIs can threaten life and limbs, causing significant morbidity and mortality [
In this review article, the key principles of the management of cSSTIs in 5 Gulf countries (Bahrain, Kuwait, United Arab Emirates (UAE), Oman, and Qatar) are discussed with a focus on current treatment practices, barriers to optimal treatment, and local differences (where data are available). The different therapies available are considered and steps that could be taken to optimize the diagnosis and treatment of cSSTIs in this region are highlighted.
As clinical decision-making in the management of cSSTIs can vary significantly between regions across the globe, the Gulf Consensus Group on complicated skin and soft tissue infections (GCG-cSSTIs) convened to provide experience-based opinions on cSSTI diagnosis and management in the region. This panel was comprised of experts in the field from Bahrain, Kuwait, UAE, Oman, and Qatar who were chosen on the basis of their contributions and roles in their national societies. The group was guided by Prof. Dr. Christian Eckmann, who is an expert in the field of cSSTIs. The panel included microbiologists, infectious disease specialists, and surgeons, some of whom are intensivists in their affiliated institutions.
Panel members received a pre-meeting survey comprising of questions designed to understand their clinical experience and their approach in treating cSSTIs. The results of the survey were presented at a meeting in Kuwait. During the meeting, the panel discussed current microbiological and epidemiological trends, existing antibiotics, and local and international guidelines for the treatment of cSSTIs in the 5 Gulf countries. The overarching goal was to outline unmet needs providing cSSTI management and treatment options which were applicable to the 5 Gulf countries studied. The insights communicated at the meeting were summarized and shared with the participants following the meeting.
A review article thus developed was extensively, critically reviewed by the panel members and the comments were addressed.
Understanding landscape epidemiology is of great importance. By determining local antibiotic resistance patterns and typical causative pathogens, treatments, and patient outcomes can be optimized. Gram-positive bacteria are predominant in cSSTIs (up to 80%), however, treatment is becoming ever more challenging owing to increased antimicrobial resistance [
A Qatar surveillance system report published in 2011, observed that SSTIs were more common in Qatar than in Europe, with rates of 18.5% in Qatar versus 4.8% in Europe [
Although the reason for such a high rate of cSSTIs is not fully understood, countries within the Gulf Cooperation Council (Bahrain, Kuwait, UAE, Oman, Qatar, and Saudi Arabia) have reported high rates of diabetes mellitus in adults [
These data paint an incomplete picture; there are limited published data on the clinical management of associated cSSTIs in Bahrain, Kuwait, UAE, Oman, and Qatar, and causative pathogens are typically underreported, which may preclude the selection of the best treatment strategies. Robust, large-scale epidemiological studies using aligned classifications are needed. Although the Global Antimicrobial Resistance Surveillance System has been developed to facilitate accurate identification of worldwide trends and comparisons, it is limited and it does not cover all drug resistance and bacterial pathogens. Moreover, not all countries have participated. We propose the inclusion of all Gulf countries into such programs. In addition, the implementation of unified local registries could potentially support treatment optimization along with the collection of hard data on the organisms causing infections, demography, risk factors, and patient outcomes according to treatment.
MRSA continues to be a leading cause of morbidity and mortality among hospitalized patients, particularly in those who are critically ill. In contrast to the European trend where there is a reduction in the prevalence of MRSA strains [
Previously confined to healthcare settings, MRSA strains are frequently the source of infection in community settings in the 5 Gulf countries. Studies report varying rates for CA-MRSA infections over time: in Kuwait and Saudi Arabia, CA-MRSA comprised of about 60% of infections [
Risk factors for developing MRSA may differ, depending on whether the infection was HA or CA (
Across the 5 Gulf countries, MRSA has been shown to be resistant to many antimicrobials used to treat SSTI, including fusidic acid, ciprofloxacin, erythromycin, tetracycline, trimethoprim, streptomycin, kanamycin, and gentamicin (
Identifying and addressing MRSA as early as possible has far-reaching effects on clinical outcomes, particularly because patients with more complex or severe cSSTI, or risk factors, are slower to respond to treatment [
Furthermore, inappropriate treatment is a significant risk factor for treatment failure [
Novel and rapid molecular methods of detecting pathogens from blood cultures in cSSTIs in 2006 offered the promise of reducing morbidity by controlling infection and guiding appropriate antimicrobial choice [
Cell culture is a common technique for MRSA surveillance [
The high rate of MRSA infections in the 5 Gulf countries studied warrants careful consideration of the available anti-MRSA options. In the last decade, several agents for treating MRSA, have become available, such as ceftaroline, ceftobiprole, telavancin, oritavancin, dalbavancin, tedizolid, and delafloxacin. While newer agents offer promise for dealing with multi-resistant organisms in the region, there remains a need for an affordable oral agent which can reliably treat MRSA, as well as the relevant Gram-negative pathogens. This would allow outpatient treatment, where possible. Delafloxacin, which was approved in 2017 by the US Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs), offers these advantages [
Ceftaroline, recently introduced in the 5 Gulf countries, is an advanced 5th generation cephalosporin that has been approved for use against CA-pneumonia and cSSTI.
Ceftaroline possesses bactericidal activity against Gram-positive bacteria, including MRSA, and Gram-negative bacteria [
Ceftobiprole is another 5th-generation cephalosporin that is currently available in Saudi Arabia and is expected to be available in 5 Gulf countries in the near future. Ceftobiprole also possesses broad bactericidal activity against Gram-positive bacteria, including MRSA, and Gram-negative bacteria, such as Pseudomonas [
A clear diagnostic and therapeutic pathway is a crucial part of the patient diagnostic process. This should span everything from the initial Emergency Department admission through diagnosis and treatment, until hospital discharge. A multidisciplinary approach based on clear hospital-based guidelines is recommended, including diagnostic testing ahead of surgery, referring the patient to an appropriate team of specialists including the surgeon, clinical pharmacist, clinical microbiologist, intensivist, and infectious disease specialist. In the cases of severe infections, the treatment decision could take place prior to diagnosis, and if empirical therapy is used, it should focus on patient profile, as well as the local epidemiology of cSSTIs.
There is a tendency to overuse or misuse antibiotics in the Gulf Cooperation Council countries (Bahrain, Kuwait, UAE, Oman, Qatar, and Saudi Arabia) [
Severe infections are characterized by failure of oral antimicrobial treatment, failure of incision and drainage, systemic signs of infection, an immunocompromised state, and clinical signs of deeper infections or evidence of organ dysfunction [
The most commonly observed cSSTIs in the 5 Gulf countries studied are the major cutaneous abscesses, erysipelas, surgical-site infections, cellulitis, infected ischemic ulcers/infected venous stasis ulcers, and infected decubitus ulcers. These cSSTIs along with their causative pathogens, primary disciplines involved in its management, surgical treatment options, and available antimicrobial substances are presented in
For patients with severe infections, intravenous antimicrobial treatment is generally recommended. Clinicians should determine the likelihood of; (1) a monomicrobial MRSA infection (e.g. an extended abscess of an extremity); or (2) a polymicrobial infection including MRSA, and susceptible Gram-negative organisms (e.g. perineal abscess in a patient known to be colonized with MRSA); or (3) a polymicrobial infection with the involvement of resistant Gram-positive (MRSA) and Gram-negative (ESBL-producing or Carbapenem-resistant enterobacterales) pathogens (e.g. necrotizing fasciitis in a multimorbid patient with multiple recent hospitalizations). Tigecycline is an option in hemodynamically stable patients, even in elderly patients [
Many mild-to-moderate infections require only surgical source control, meaning that use of antibiotics can be spared. In general, antibiotic treatment courses in cSSTI requiring surgical intervention, should be short. The standard antibiotic treatment duration for mild infections is 5–7 days, which can be extended to 7–10 days in severe infections, especially in critically ill patients [
Due to limited national guidance for the everyday clinical management of cSSTIs, of the 5 Gulf countries, rely on local hospital guidelines or international guidelines. This highlights the need for a more comprehensive approach to the clinical management of cSSTIs and greater alignment on the guidelines across the 5 Gulf countries studied. Using clear, recognized classification systems, particularly for describing disease severity and assessment, these should clarify the position of novel agents in the treatment paradigm. Recognized staging/ scoring systems should be used for patient diagnosis and stratification, which should be based on the local patient population and their risk factors, and the importance of infection source control must underpin the management of all cSSTIs [
Crucially, recommendations must encourage antimicrobial stewardship in both inpatient and outpatient settings, involving all healthcare professionals in the treatment pathway of a patient, including guidance for general practitioners and family physicians. This information in the guidelines should be used by the entire multidisciplinary team involved in managing cSSTIs, including infectious disease specialists, clinical microbiologists, Emergency Department healthcare providers, intensive care physicians, infectious disease physicians, and surgeons. Treatment can then be optimized and standardized whilst maintaining antimicrobial stewardship standards. For example, by electing simple surgery to avoid the overuse of oral antibiotics, or by relaxing restrictions on certain antibiotics in pre-specified cases, such as those with sepsis.
To tackle the rise of multi-antibiotic resistant bacteria, and remove barriers to optimize treatment in Bahrain, Kuwait, UAE, Oman, and Qatar, the management and treatment of cSSTIs needs to be reconsidered with special attention to the following areas:
Application of an inclusive definition of cSSTIs which aligns with clinical and research purposes.
Collection of comprehensive up-to date epidemiological data on cSSTIs and MRSA in a region, using local and regional registries, financed by centralized and regional health authorities.
Clear indications in place for the use of novel agents and a comprehensive assessment of comparative agents to be factored into the decision-making for treatment of cSSTIs.
Guidance for the management of patients with cSSTI which is applicable to Bahrain, Kuwait, UAE, Oman, and Qatar.
Improved access and availability to rapid diagnostics and treatments for MRSA from a cost perspective and a patient need perspective.
Improved education and awareness of cSSTIs and their management among newly qualified physicians, those in training, and primary care physicians is essential.
Antimicrobial stewardship initiatives to reduce the inappropriate use of antibiotics and aid judicious use and appropriate duration of use of antibiotics.
cSSTIs comprise multifaceted infections and present numerous challenges for patients and those who care for them. We present our recommendation hoping that this collaborative guidance will help clinicians optimize the management and treatment of cSSTIs in patients across Bahrain, Kuwait, UAE, Oman, and Qatar, and reduce the burden on the local healthcare system.
The authors of this review convened an expert panel in a sponsored meeting and were not appointed by national societies or regulatory authorities in the respective countries. Medical writing and editorial assistance were provided by Aisling Koning and Kyle Lambe (Synergy Medical Communications, London, UK), and was supported by Pfizer, Inc. Additional editorial support was provided by Vaidehi Wadhwa (Center of Excellence, Emerging Markets, Pfizer).
Wadha Alfouzan reports payment for advisory board meetings, presentation and research funding from Pfizer, Inc., MSD, and Sanofi. Nervana Habashy reports employment from Pfizer, Inc. Ayman Kurdi reports employment and stock ownership from Pfizer, Inc. Christian Eckmann reports personal fees from Pfizer, Inc. during the conduct of the study; and personal fees from Menarini, Nabriva and Pfizer, Inc. outside the submitted work. All other authors report no potential conflicts of interest.
This research did not involve any human or animal experiment.
Characteristics of complicated skin and soft tissue infections according to patient, wound specific factors and causative pathogen.
Overview of updated FDA guidance on SSTI.
FDA (1998) [ |
FDA (2013) [ | |
---|---|---|
Indication |
cSSTI |
ABSSSI |
Type of infection |
Large abscess, wound infection, cellulitis, DFI, chronic ulcer |
Large abscess, wound infection, cellulitis |
Infection severity |
Intermediate/ severe |
Severe |
Primary endpoints |
Subjective endpoint: Clinicians assessment at 7–14 days after EOT |
Objective endpoints for treating ABSSI for clinical trials: A bacterial infection of the skin with a lesion size area of ≥ 75 cm2 (lesion size measured by the area of redness, edema, or induration Defines anatomical extension of infected area |
Secondary endpoints |
Varied → Low potential for differentiation |
Primary endpoint sustained to EOT Clinicians’ assessment at EOT → High potential for differentiation |
ABSSI = acute bacterial skin and skin structure infections; cSSTI = complicated skin and soft tissue infections; DFI = diabetic foot infection; EOT = end of therapy; FDA = Food and Drug Administration; WSES/SIS-E = the World Society of Emergency Surgery and Surgical Infection Society Europe.
Summary of studies investigating cSSTIs and MRSA in 5 Gulf countries.
Reference | Region | Source | Study findings |
---|---|---|---|
Al Jalaf -2018 [ |
UAE |
CA-MRSA among ambulatory patients presenting with SSTI |
The prevalence of MRSA was 23% (18/78) among 78 culture-positive isolates and 29% (18/62) among |
Udo & Boswihi -2017 [ |
Kuwait |
Of the MRSA isolates tested 2011—2015, 2,290/6,016 (38%) were HA and 3,651/6,016 (61%) were CA 2,835/6,922 (40.9%) from SSTI |
All 6,922 MRSA isolates from 2011–2015 were susceptible to linezolid, vancomycin, and teicoplanin. However, some were resistant to kanamycin (2,979; 43%), ciprofloxacin (2,955; 43%), erythromycin and clindamycin (2,935; 42%), fusidic acid (2,858; 41%), gentamicin (2,665; 39%), tetracycline (2,652; 38%), and trimethoprim (2,324; 34%) |
Alfouzan et al -2019 [ |
Kuwait |
Of the MRSA isolates, 39.7% were HA and 60.3% were CA |
The MRSA isolates were susceptible to vancomycin, teicoplanin, rifampicin, ceftaroline fosamil, and linezolid but were resistant to gentamicin, tetracycline, erythromycin, fusidic acid, chloramphenicol and ciprofoxacin. 164/ 209 (78.5%) of the isolates expressed multi-resistance and 45/209 (21.5%) isolates were non-multi-resistant |
El-Mahdy et al -2014 [ |
Qatar |
MRSA isolates represented 21% (176/840 isolates) of the total A subset of 61 MRSA isolates were mostly believed to be CA (58/61) whereas the remaining 3 were HA |
12 (20%) isolates were resistant to clindamycin and 5 (8%) were resistant to mupirocin |
Udo et al -2008 [ |
Bahrain |
Of the MRSA isolates, 44/53 (87%) were HA and 7/53 (13%) were thought to be CA |
All 53 MRSA isolates were susceptible to vancomycin, teicoplanin, rifampicin, and linezolid. MRSA was resistant to fusidic acid (92.5%), ciprofloxacin (92.5%), erythromycin (90.6%), tetracycline (88.7%), trimethoprim (88.7%), streptomycin (88.7%), kanamycin (83.0%), and gentamicin (73.6%) |
Alkharsah et al -2018 [ |
Saudi Arabia (KSA) |
Of the MRSA isolates, 19/51 (37%) were HA and 32/51 (63%) were CA |
All 51 MRSA isolates were sensitive to vancomycin and linezolid, while 90—100% were resistant to chloramphenicol, fusidic acid, teicoplanin and tigecycline; 78.4% and 60.8% were resistant to erythromycin and ciprofloxacin, respectively. |
Matar et al -2017 [ |
Saudi Arabia (KSA) |
Population in hospitals in Saudi Arabia ( |
Longer hospital duration (35.5 vs 14.5 d) and rehospitalization rate for cSSTI (5% vs 3%,) in Saudi Arabia vs Lebanon, respectively |
Zigmond et al -2014 [ |
Middle East |
MRSA reported in 50% of SSTIs in Middle East (vs 32% in Arabian Peninsula, 70% in Northern Africa, 25% in Sub-Saharan Africa) |
MRSA infection rates were ≥ 60% for the region (where data available), whereas MRSA colonization was 5—9% in Saudi Arabia and 10—14% in Iraq |
Reference | Region | MRSA infection and/ or colonization rates |
---|---|---|
Alfouzan et al -2019 [ |
Kuwait |
34/112 (30.3%) pregnant women who contracted an infection following caesarean section had MRSA; 265/453 (58%) |
Mahmood et al -2016 [ |
Qatar |
1,064 hemodialysis patients were screened, detecting 15 patients with MRSA infections, giving an overall MRSA infection prevalence of 1.1% |
Balkhair et al -2014 [ |
Oman |
35/329 (10.6%) of MDRO identified in a tertiary care hospital were identified as MRSA |
Al Jalaf et al -2018 [ |
UAE |
The prevalence of MRSA was 23% (18/78) among 78 culture-positive isolates and 29% (18/62) among |
CA = community-acquired; cSSTI = complicated skin and soft tissue infection; HA = hospital-acquired; MDRO = multidrug-resistant organism; MRSA = methicillin-resistant
Risk factors for H-or CA-MRSA.
Source of MRSA | HA-MRSA [ |
CA-MRSA [ |
---|---|---|
Risk factor |
Elderly age Prolonged hospitalization Invasive procedures Prior colonization or infection Recent antimicrobial exposure Comorbidities such as ○ Cancer ○ Cardiovascular disease ○ Chronic kidney disease |
Children < 2 y Athletes Injection drug users Homosexual males Military personnel Inmates of correctional facilities Residential homes, or shelters Vets, pet owners, and pig farmer Patients with post-flu-like illness and/or severe pneumonia Patients with concurrent SSTI, history of colonization or recent infection with CA-MRSA Individuals with a history of antibiotic consumption in the previous year, particularly quinolones, or macrolide |
CA = community-acquired; HA, hospital-acquired; MRSA = methicillin-resistant
Frequent cSSTIs in the Gulf and current treatment pathways.
Type of cSSTI | Cellulitis | Erysipelas | Major cutaneous abscess | Infected decubitus ulcer | Surgical site infection | Infected ischemic ulcer/infected venostasis ulcer |
---|---|---|---|---|---|---|
Frequently isolated pathogens |
|
S. pyogenes A (B) |
Extremities
S. aureus/MRSA Polymicrobial, including Gram positive and Gram negative bacteria |
Polymicrobial: Gram positive bacteria (MRSA), Gram negative bacteria (ESBL-producing, CRE) and anaerobes |
Ortho / cardiothoracic/ vascular surgery:
Polymicrobial, including Gram negative bacteria (Non ESBL/ESBL-producing ESBL-producing) and Gram positive |
Polymicrobial, mainly Gram negative (ESBL-producing, CRE, Pseudomonas, Acinetobacter |
Surgical intervention necessary |
For more complex cases |
Primarily no but may be necessary in more complex cases |
Yes |
Yes |
Yes (debridement/ drainage/ clip removal) |
Yes |
Primarily responsible specialty |
Internal medicine/ surgery |
Internal medicine/ surgery |
Surgery |
Internal medicine/ surgery |
Surgery |
Vascular surgery/ internal medicine |
Total hospitalization (days) |
5–14 |
5–14 |
5–14 |
≤ 28 |
≤ 28 |
≤ 21 |
Frequently of comorbidities (estimated prevalence) |
Diabetes (30–40%) Obesity (30–40%) |
Obesity (50%) Renal insufficiency (40%) Age > 65 y (30%) Diabetes (30%) Cancer/ transplant (10%) |
Obesity (50%) Age > 65 y (30%) Diabetes (30%) Cancer/transplant (10%) Renal insufficiency (5–10%) |
Age > 65 y Diabetes Stroke |
Obesity (50%) Renal insufficiency (40%) Age > 65 y (30%) Diabetes (30%) Cancer/transplant (10%) |
Diabetes Renal insufficiency |
Frequently prescribed 1st line antibiotics |
Cloxacillin/ fluxcloxacillin Amoxicillin/ clavulanic acid |
Amoxicillin/ clavulanic acid Cephalexin Clindamycin |
Extremities
Amoxicillin/ clavulanic acid Clindamycin Cloxacillin or similar isoxazole penicillin (e.g., flucloxacillin) Vancomycin Teicoplanin Linezolid Amoxicillin/ clavulanic acid Piperacillin-tazobactam |
Piperacillin/ tazobactam + Vancomycin or Teicoplanin Ampicillin/ Sulbactam Tigecycline |
Gram positive
Cefazolin Amoxicillin/ clavulanic acid Clindamycin Co-trimoxazole Vancomycin |
Piperacillin–tazobactam Tigecycline |
Frequently prescribed 2nd line antibiotics |
Vancomycin Teicoplanin Linezolid Piperacillin/ tazobactam +Vancomycin |
Linezolid |
Extremities
Linezolid Meropenem + vancomycin/ linezolid/ teicoplanin Tigecycline + Colistin (CRE) |
Carbapenems OR aminoglycosides to spare carbapenems Carbapenems + vancomycin/ teicoplanin for MRSA |
Linezolid (MRSA) |
Carbapenem |
Only available in Qatar.
In stable patients.
CRE = Carbapenem-resistant Enterobacteriaceae; cSSTI = complicated skin and soft tissue infection; ESBL = extended-spectrum beta-lactamase; MRSA = methicillin-resistant
Empirical treatment of MRSA in cSSTIs in 5 Gulf countries: Clinical conditions, limitations, and available alternatives.
Drug/drug combinations (reference) | Route | Microbiology | Severity of disease/ comorbidity | Issues/comments | Available alternative [reference] |
---|---|---|---|---|---|
Clindamycin |
P.O. |
Gram positive bacteria (including MRSA) Anaerobic bacteria |
Mild/moderate -Varying comorbidity |
Varying MRSA susceptibility Induction of CDI |
Cotrimoxazole [ Linezolid [ Doxycycline [ |
Vancomycin |
I.V. |
Gram positive bacteria (including MRSA) |
Moderate to severe Significant comorbidity |
Nephrotoxicity Complex monitoring Increased mortality if MIC > 1 mg/mL |
Daptomycin [ Linezolid [ Ceftaroline [ |
Vancomycin + Piperacillin- tazobactam +Amoxicillin/ clavulanic acid |
I.V. |
Gram positive bacteria (including MRSA) Gram negative bacteria Anaerobic bacteria |
Severe Significant comorbidity |
See Vancomycin Nephrotoxicity Piperacillin tazobactam overuse & unnecessary coverage of Pseudomonas (stewardship) |
Ceftaroline [ |
Vancomycin + Meropenem |
I.V. |
Gram positive bacteria (including MRSA) Gram negative bacteria (including multidrug resistant Gram negative organisms) Anaerobic bacteria |
Severe Significant comorbidity |
See Vancomycin Carbapenem resistance due to overuse (stewardship) |
Linezolid + Fosfomycin [ Tigecycline [ |
Tigecycline |
I.V. |
Gram positive bacteria (including MRSA) Gram negative bacteria (including multidrug resistant Gram negative organisms) Anaerobic bacteria |
Severe Significant comorbidity |
No Pseudomonas activity Not recommended in septic shock as monotherapy |
Linezolid + Meropenem [ |
CDI = Clostridioidium difficile infection; cSSTI = complicated skin and soft tissue infection; I.V. = intravenous; MIC = minimum inhibitory concentration; MRSA = methicillin-resistant