1 Introduction

Orthopedic implant infections have continued to rise in recent years and constitute a major health and economic burden due to increasing needs for revision surgery.^1,2 Infections with multi-drug-resistant (MDR) organisms have increased, significantly contributing to morbidity in such cases. MDR pathogens most commonly isolated in such infections are ESBLs, MRSA, and MDR pseudomonas, which are more common in immunocompromised patients such as those with diabetes, COPD, and open wounds.³ Risk factors such as irrational use of antibiotics, prolonged hospital stay, delay in initiation of treatment, prolonged bed rest, incomplete debridement, and poor aseptic technique have contributed to the emergence of resistance in such infections^4. Moreover, they have a significant economic impact on healthcare resources owing to complications such as the need for revision surgeries, prolonged length of stay, and prolonged duration of treatment and rehabilitation.⁵ Guidelines have been developed to help guide antibiotic treatment in orthopedic implant infections⁶ however, local resistance patterns and antibiograms should be consulted when commencing specific antibiotic therapy. In Rawalpindi, Pakistan, a public hospital's orthopedic section served as the study's setting. It discusses the local resistance patterns in patients with orthopedic implant-related infections, along with the prevalence of MDR pathogens in the subjects.

2 Subjects and methods

This study was conducted in the Department of Orthopedics at Benazir Bhutto Hospital from January 2022 to August 2023 after getting consent from the patients and approval from the ethical review board. Blood samples from indoor patients were analyzed for culture and sensitivity after non-probability convenience sampling. The samples were collected in blood culture bottles containing Tryptic Soy Broth with Sodium Polyanethole Sulphonate and incubated for 7 days at 35 °C, after which they were inoculated on MacConkey agar and blood agar.

All gram-negative, oxidase-positive, and catalase-positive colonies were identified by standard microbiological testing. Kirby-Bauer's method was applied to assess antibiotic sensitivity and resistance. Antibiotic discs of Amikacin, Amoxicillin/Clavulanic Acid, Cefoparazone/Sulbactam, Cefalexin, Fosfomycin, Meropenem, Methicillin, Moxifloxacin, Tazobactam/Piperacillin, Aztreonam, Ceftazidime, and Ciprofloxacin were placed on an agar plate and incubated at 35 °C for 16–24 h. The zones of growth around each disc were then measured and assessed as resistant. The data was analyzed using Statistical Package for Social Sciences (SPSS) version 26.

3 Results

The results of our study showed varying trends of resistance for different pathogens. The majority of the infected samples showed growth of Staph Aureus (54 %), Pseudomonas (14 %), and E. coli (12 %), respectively. The pie chart representing the most common organisms is displayed in Fig. 1.

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Fig. 1 Graphic representation of the percentage of bacterial organisms in orthopedic implant infections.

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Of all the samples showing growth of Staph Aureus, Methicilin-Resistant Staph Aureus (MRSA) was detected in 82.2 % of the samples. It was resistant to Amoxicillin + Clavulanic acid in 66.9 % of the samples and to Moxifloxacin in 70.3 % of the samples, showing high resistance for the above-mentioned drugs. However, drugs such as Amikacin, Cefoparazone + Sulbactam, Fosfomycin, Meropenem, Ceftazidime, and Ciprofloxacin had less than 4 % resistance against Staph Aureus.

Out of the 31 samples having Pseudomonas, alarmingly, 80.6 % were resistant to Meropenem, 77.4 % to Cefoparazone + Sulbactam, 74.2 % to Amikacin, and 70.9 % to Tazobactam + Piracillin. In these samples, Pseudomonas was the least resistant to Ciprofloxacin (35.5 %).

In 96.3 % of the samples, E. coli was resistant to Amikacin, in 85.3 % to Cefoparazone + Sulbactam, in 81.5 % to Meropenem, and in 77.7 % to Tazobactam + Piracillin. The least resistance was against Ceftazidime (11 %). Klebsiella was highly resistant to Meropenem (90 %), Amikacin(80 %), and Methicillin (5 %).

Half of the samples positive for Acinetobacter were resistant to Cefoparazone and Sulbactam; all samples for Streptococcus were resistant to Amoxicillin, Clavulanic Acid, Cephalexin, and Methicillin. Proteus showed 100 % resistance against Meropenem.

The following Table 1, illustrates resistance patterns of microbes for various Antimicrobial agents.

4 Discussion

The pathogen present in more than half of our infected samples was Staphylococcus aureus, comparable to other studies worldwide.^7,8 Staphylococci have contributed to almost 2/3 of the infections associated with orthopedic implants.⁹ These implants have a surface that facilitates tissue adhesion and proliferation; however, this feature also promotes the growth of pathogens, leading to implant infections.¹⁰ Studies have shown infection rates varying from 1 to 3 % in open fractures treated with internal fixation and reaching up to 50 % in fractures involving high-energy trauma.¹¹

Out of all samples showing growth of Staph Aureus, 82 % were methicillin-resistant (MRSA). MRSA is one of the most notorious pathogens for prolonging hospital stays due to its biofilm-forming ability, which makes it resistant to multiple antibiotics.¹² Nasal MRSA colonization is one of the major risk factors for surgical-site infections.¹³ Therefore, decolonization of MRSA before procedures involving the use of orthopedic devices has been shown to significantly improve the outcomes.¹⁴ IV glycopeptides (Vancomycin and Teicoplanin) are the recommended first-line antibiotics against orthopedic infections due to MRSA, after which oral agents such as Clindamycin, Co-Trimoxazole, Doxycycline, and Linezolid can be used to complete treatment course.¹⁵

In our study, Staph Aureus was highly resistant to amoxicillin and clavulanic acid. This may be due to the decreased concentration of amoxicillin and clavulanic acid in bone as compared to serum due to their lesser penetration,¹⁶ hence making it difficult to achieve the minimum inhibitory concentration (MIC) inside bones. Interestingly, although previous studies have shown high sensitivity and efficacy towards Moxifloxacin,^17,18 in our study, Staph Aureus was highly resistant to it.

Pseudomonas is a gram-negative bacterium that, although less common than gram-positive cocci, can complicate orthopedic infections as it is difficult to eradicate and requires a long duration of treatment.¹⁹ In our samples, Pseudomonas was highly resistant to meropenem (80.6 %). Some studies have shown good results with increasing the dose of Meropenem to achieve a higher MIC in serum,^20,21 however, more work needs to be done in this regard. The most effective and least resistant drugs against pseudomonal orthopedic infections were combinations of Ciprofloxacin in combination with beta lactams such as Cefepime and Ceftazidime,^19,22,23 which was consistent with our study where Pseudomonas was least resistant to Ciprofloxacin.

According to our data, the highest resistance of E. coli was towards amikacin(96.3 %), followed by cefoparazone, sulbactam, meopenem, tazobactam, and piperacillin. E. coli has also been reported in other studies to have a high resistance to amikacin.²⁴ It stimulates osteoclastic activity while inhibiting osteoblast differentiation,²⁵ therefore, it is a difficult pathogen to eliminate, often requiring the need for implant removal to treat the infection.²⁶ The recommended treatments for E. coli are drugs such as beta-lactam antibiotics (cephalosporins, carbapenems), trimethoprim-sulfamethoxazole, Fluoroquinolones.²⁷ For Extended Spectrum Beta-Lactamase (ESBL)-producing E. coli, Meropenem is the drug of choice, and in the case of carbapenemase-producing E. coli, Ceftazidime-Avibactam is preferred.²⁸ This indicates the possibility that most of the subjects in our study were infected by ESBL and carbapenemase-producing E. coli, as the majority were resistant to beta-lactams and Meropenem and least resistant to ceftazidime.

Nine percent of our participants had Klebsiella infections, and these patients had severe resistance to amikacin and meropenem. Klebsiella is a multi-drug-resistant pathogen that contributes to adverse outcomes and an exhausting recovery in orthopedic infections as it is difficult to eradicate and requires prolonged stay and treatment with multiple drug combinations.²⁹ It has been shown to develop resistance against carbapenems due to its carbapenemase-producing ability, which greatly contributes to worsening morbidity and mortality in such patients.³⁰ Studies have shown satisfactory eradication of Klebsiella with Ceftazidime-Avibactam³¹ and Fosfomycin,³² consistent with our study where these drugs were less resistant to Klebsiella.

One of the less common pathogens isolated from our samples was Acinetobacter. Compared to other microbes, the incidence of infection with Acinetobacter is less; however, orthopedic implant infections complicated by this pathogen need to be treated aggressively and are associated with much higher morbidity and mortality.^33,34 Among our samples, all Streptococci strains were resistant to amoxicillin and clavulanic acid, compared to another study where all strains were susceptible.³⁵ Proteus was highly resistant to multiple antibiotics, although only a few isolates were examined. This microbe possesses the genetic support that enables it to acquire resistance to multiple antibiotic agents.³⁶

Hospital-acquired infections in orthopedic surgeries represent a major health challenge, with multi-drug-resistant (MDR) organisms becoming increasingly common.³⁷ The most common pathogens leading to MDR orthopedic infections in our patients were MRSA, Pseudomonas, and E. coli, respectively. This may lead to poor surgical outcomes due to the increased likelihood of inadequate empiric treatment as these pathogens were resistant to multiple broad-spectrum antibiotics. It highlights the need and importance of regional antibiograms to guide empiric treatment in such cases. Timely initiation of an appropriate antibiotic regimen can help reduce morbidity in orthopedic infections. Moreover, due to self-medication being particularly common in our community,³⁸ the incidence of infections with MDR bacteria has greatly increased. Appropriate measures to raise awareness in both the public and healthcare communities need to be taken to overcome this alarming issue.

The limitations of this study are: 1) This was a retrospective study conducted in a single orthopedic unit with a limited number of subjects. Studies on a larger population in multiple centers of the region can help guide antibiotic treatment more accurately. 2) Data was unavailable on resistance against Vancomycin, which is often preferred as prophylaxis or treatment of orthopedic infections due to its broad spectrum as MRSA coverage.^39,40 3) The sensitivities of microbes against anti-microbials were not discussed in this study.

Informed consent statement

Consent was taken before taking cultures.

Ethical statement

Ethical approval was taken from the Head of the Department, and the study was performed under his direct observation.

Credit author statement

Dr.Ameer Hamza Mahmood Ul Hassan contributed to the acquisition, interpretation, drafting, revision, and final draft for approval.

Dr.Nehala Nooz contributed to the initial drafting and final draft.

Dr. Humayoon Ashraf approved the final manuscript and contributed to the acquisition.

Dr Obaid ur Rehman approved the final manuscript and supervised the whole project.