European Journal of Cardiovascular Medicine

Implantation of cardiac implantable electrophysiological devices (CIEDs), including permanent pacemakers and implantable cardioverter-defibrillators has been on the rise over the past years, largely due to the expanded indications for CIED implantation for primary prevention. Infection associated with implantable devices is a serious complication with high morbidity leading to mortality. ( ) Infection in a permanently implanted pacemaker is a serious complication. It may occur either as a surgical site infection (SSI), occurring within 1 year after implantation or as late-onset lead endocarditis. ( ) The microbiology of CIED infections is relevant to the pathogenesis of infection and the selection of both antimicrobial prophylaxis and empirical treatment regimens.

Several studies indicate that the incidence of CDIs has increased over time with a 12-month infection rate for de novo device implant and for other generator procedures ranging between 0.3-2.5 %.( ) 

The effective management in infections following interventional cardiac care includes antimicrobial treatment. The importance of appropriate empirical antibiotic coverage is illustrated by studies that document the association between inappropriate selection and increased mortality in patients with permanent pacemaker implantation. Over the last two decades most of the micro-organisms have developed increased resistance and this poses a problem in treatment management of such patients. Reasons for this increasing multi drug resistance problem could be due to mutations, over use of broad-spectrum antibiotics, across the counter availability of antibiotics and lack of infection control policy in the hospital settings.

Keeping these factors in mind this study was planned to understand the Antimicrobial Susceptibility Profile of the microbial flora in CIED infections at a tertiary care hospital in Himachal Pradesh.

STUDY DESIGN & SETTING

It was a prospective observational study conducted at Indira Gandhi Medical College (IGMC), Shimla, the major tertiary care centre of the State of Himachal Pradesh, for duration of one year. The study included the patients admitted in the Department of Cardiology.

The patients admitted, w.e.f. 1st June, 2017 to 31st July, 2018, were observed for having any sign or symptom suggestive of nosocomial infection and their samples were processed in the Department of Microbiology, for bacteriological profile and sensitivity pattern.

Patients who had undergone interventional cardiology procedure and developing any sign or symptom of general or systemic infection were included in the study after informed consent.

QUALITY CONTROL: The quality check was performed using standard strains as per the manufacturer’s instructions.

STATISTICAL ANALYSIS:  The data collected was entered in Excel spreadsheet and accuracy of data entered was checked by cross-verification of the data entered. Categorical variables are expressed as frequencies and percentages.

ETHICAL CONSIDERATIONS: The investigator and supervisor were aware of the ethics in biomedical research policy of IGMC, Shimla. Keeping this in view, written informed consent of all participants was obtained before gathering any information. The information collected was kept strictly confidential and individual identity was kept strictly confidential and individual identity was not disclosed under any circumstances. The study did not involve any risk to the patient and any extra financial burden. Result of the study will be used only for academic purposes and for framing recommendations for the improvement in services and for no other purpose.

MICROBIOLOGICAL WASTE DISPOSAL: The Biomedical Waste (Management & Handling) Rules, 2016 were strictly followed as regards disposal of all biomedical waste generated during the study.

SAMPLE COLLECTION PROCEDURES

Pus sample was aspirated under all aseptic measures using sterile syringe which was firmly stoppered after collection of sample. If the pus sample could not be aspirated then two sterilized cotton swabs were used to collect samples from the depth of the wound or incision site and transported immediately to the Department of Microbiology for further processing. Simultaneously blood sample was collected for blood culture sensitivity testing by obscuring aseptic technique as follows: - eight to ten ml of blood was collected under all aseptic conditions with sterile disposable syringe for blood culture preferably from median cubital vein. The venepuncture site was disinfected by applying 70% alcohol upside down and allowed to dry followed by applying either chlorhexidine or tincture iodine concentric inside out and was allowed to dry. The blood collected was directly injected at the bedside through the rubber cap into the BD BACTEC TM plus Aerobic/F culture vials after cleaning the bottle top with alcohol wipe to avoid contamination from the external environment. The samples were preferably collected prior to starting antibiotic.

PROCESSING OF SAMPLES:

PUS:

The aspirated sample or one swab was inoculated onto one plate of  sheep blood agar medium (B/A) and one plate of  MacConkey agar medium (M/A) After inoculation, the plates were incubated at 37℃ for 18-24 hours. Remaining sample or the second swab was used for direct smear examination after staining with Gram’s Method and interim report was conveyed to the respective Department. The direct smear examination was done to ascertain presence of organisms and their differentiation into Gram positive, Gram negative, morphology and arrangement. Even if the direct smear examination gave a negative report, the cultures were done as per protocol.

IDENTIFICATION OF CULTURE ISOLATE

Next morning, the inoculated culture plates of the pus samples were examined for colony characters.Blood agar plates were studied particularly for size of colonies e.g. pin head, pin point or otherwise, shape, surface and margins. Colour of colonies: golden yellow, white, grayish white and type of haemolysis: α or β type.MacConkey agar plates were observed for growth and presence of lactose fermenter or non lactose fermenter colonies. Smears from both the plates were examined by Gram’s method to check Gram positive and Gram negative organisms. For further identification of Gram positive isolates the rapid biochemical tests like catalase, coagulase were carried out .For catalase test, growth from the bacterial colony was transferred to the surface of a glass slide with a wooden applicator stick. A drop of 3% hydrogen peroxide was added to it and any bubble formation was observed. The rapid and sustained appearance of bubbles or effervescence was taken as a positive result. No formation of bubbles or a few tiny bubbles formed after 20 to 30 seconds was considered as negative result. After this, Slide coagulase test was performed. Catalase positive colony was emulsified in a drop of normal saline on a slide. If the isolate did not form a smooth, milky suspension, the test was not proceeded with. Similar suspensions of a positive and negative control strains were also made to confirm proper reactivity of the plasma. A sterile inoculating wire was dipped in the undiluted plasma at room temperature, withdrawn and the adhering traces of plasma was stirred into the colony suspension on the slide. Similar procedure was repeated for suspensions of control strains. After this tube coagulase test was performed by using1 ml of 1:6 dilution of the plasma in saline solution (0.85% NaCl) in a small sterile test tube. A colony of catalase and slide coagulase test positive organism was emulsified in the diluted plasma. With each batch of tests, coagulase positive and negative organisms as control were included and a tube of unseeded diluted plasma was also included to confirm that it does not clot spontaneously. The tubes were incubated at 37℃, preferably in a water bath, for upto 4 hours and were examined at 1, 2 and 4 hours for clot formation by tilting the tubes at 90 degree angle. The negative tubes were left at room temperature overnight and re-examined for clot formation. The test was read as positive in which the plasma was converted into a stiff gel, best recognized by remaining in place, when the tube was tilted or inverted. The test was read as negative in which the plasma remained as such.

Identification (ID) of microorganism and Antimicrobial Susceptibility Testing (AST) by BD PHOENIXTM AUTOMATED ID/AST SYSTEM

The BD Phoenix™ Automated Microbiology System is intended for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically significant bacteria. Most tests used in the Phoenix ID panels are slight modifications of the classical methods including tests for fermentation, oxidation, degradation and hydro lysis of various substrates. In addition to these, the Phoenix System utilize chromogenic and fluorogenic substrates as well as single carbon source substrates in the identification of organisms. The micro-broth doubling dilution technique is involved in the AST by the system. As per the BD Phoenix System user’s manual, maximum of 100 identification and antimicrobial susceptibility tests can be performed in the System at a time using Phoenix combination panels. A sealed and self-inoculating molded polystyrene tray, with 136 micro-wells containing dried reagents, serves as the Phoenix disposable panel. The combination panel includes a 51 well ID side with dried substrate for the identification of the organism and an 85 well AST side with varying concentrations of antimicrobial agent, growth and fluorescent controls at appropriate well locations. The ID side contains 49 well with dried biochemical substrates and 2 fluorescent control wells. The AST side potentially contains up to 84 wells with dried antimicrobial agents and 1 growth control well. The system utilizes an optimized colorimetric redox indicator for AST, and a variety of colorimetric and fluorometric indicators for ID. The AST broth is cation-adjusted (e.g., Ca++ and Mg++ ) to optimize susceptibility testing performance.

PANEL PREPARATION

First the Gram stain reaction of the isolate was confirmed as Gram positive or Gram negative, before proceeding with the inoculums preparation for use in the Phoenix instrument. The PMIC Phoenix panel or NMIC Phoenix panel was then selected for inoculation for Gram positive or Gram negative bacteria respectively. The respective panel was removed from pouch. Panels were inoculated within 2 hours of being removed from the pouch. The panel was placed on the Inoculation Station with the inoculation ports on top and the pad on the bottom. Phoenix ID broth tube was labeled with the patient’s specimen number. Using aseptic technique, colonies of the same morphology were picked with the tip of a sterile cotton swab or a wooden applicator stick from one of the recommended media. The colonies were suspended in the Phoenix ID Broth (4.5 mL) tube and tube was capped and vortexed for five seconds.The tube was inserted into the BD Phoenix Spec nephelometer, to confirm the inoculum density of 0.5 McFarland, following which this Broth was used to inoculate the Phoenix AST Broth and/or Phoenix Panel. A Phoenix AST Broth tube (8.0 mL) was labeled with the patient’s specimen number and one drop of AST Indicator solution added to the AST broth tube. This was inverted to mix and taking caution not to vortex. After  the addition of the Indicator to AST broth, the mixed solution was stored in the dark, at room temperature and must be used within 2 hours after the addition of AST indicator solution if exposed to light. 25µL of the bacterial suspension is now transferred from the ID tube into the AST broth tube and Panels must be inoculated within 30 minutes of preparation of AST broth inoculums.  The AST tube was capped and inverted several times to mix and wait a few seconds for air bubbles to surface and Then the ID tube inoculum was poured into the fill port on ID side of the panel (51-well side) and allowed to traverse down the tracks before moving the panel. The AST broth inoculum was then poured into the fill port on AST side of the panel (85-well side), and panels snapped close with the closures. Panels were loaded into the instrument within 30 minutes of inoculation and incubated at 35℃. The instrument tests panels every 20 minutes; on the hour, at 20 minutes past the hour, again at 40 minutes past the hour for upto16 hours if necessary. The Phoenix panels can be read only by the Phoenix System and cannot be read manually.

ORGANISMS IDENTIFICATION

The ID portion of the Phoenix panel utilizes a series of conventional, chromogenic, and fluorogenic biochemical tests to determine the identification of the organism. Both growth-based and enzymatic substrates are employed to cover the different types of reactivity within the range of taxa. The tests are based on microbial utilization and degradation of specific substrates detected by various indicator systems. Acid production is indicated by a change in phenol red indicator when an isolate is able to utilize a carbohydrate substrate. Chromogenic substrates produce a yellow color upon enzymatic hydrolysis of either P-nitrophenyl or P-nitroanilide compounds. Enzymatic hydrolysis of fluorogenic substrates results in the release of a fluorescent coumarin derivative. Organisms that utilize a specific carbon source reduce the resazurin-based indicator. In addition, there are other tests that detect the ability of an organism to hydrolyze, degrade, reduce, or otherwise utilize a substrate.

ANTIMICROBIAL SUSCEPTIBILITY TESTING

The Phoenix AST method is a broth based micro-dilution test. The Phoenix system utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Continuous measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations. Organism identification is used in the interpretation of the MIC values of each antimicrobial agent. All procedures were performed as per the user’s manual of the BD Automated Systems and AST Reporting proforma generated. Gram positive isolates were put on PMIC panels and Gram-negative isolates on NMIC panels, both of which reported sensitivity for a separate group of drugs. The PMIC panels reported the sensitivity for Gentamicin-Syn, Gentamicin, Cefazoline, Cefoxitin, Ampicillin, Penicillin G, Oxacillin, Daptomycin, Trimethoprim-sulfamethoxazol, Teicoplanin, Vancomycin, Clindamycin, Erythromycin, Quinupristin-dalfopristin, Linezolid, Levofloxacin, Moxifloxacin, Rifampin, and Tetracycline. Whereas, the NMIC panels reported the sensitivity for Amikacin, Gentamicin, Imipenem, Meropenem, Cefazolin, Cefoxitin, Ceftazidime, Cefotaxime, Cefepime, Aztreonam, Ampicillin, Piperacillin, Amoxicillin-Clavulanate, Piperacillin-Tazobactam, Colistin, Trimethoprim-Sulfamethoxazole, Chloramphenicol, Ciprofloxacin, Levofloxacin and Tetracycline.

The study was conducted in the Department of Microbiology, Indira Gandhi Medical College and Hospital, Shimla, Himachal Pradesh during the period starting from 1^st July, 2017 to 30^th June, 2018.

GRAM STAINING FROM THE CLINICAL SAMPLES

On direct Gram staining of clinical samples, microorganisms were seen in 12 (70.58%) samples and in 5 (29.41%) samples no microorganism seen.

Table 1:  Direct Gram staining from the clinical sample

The samples which were positive on Gram staining showed a visible growth on subsequent culture on solid medium. However no growth was obtained in samples which were negative for organisms on Gram staining.

Figure I: Culture on solid medium

MICROORGANISMS ISOLATED

Out of 12 positive samples, Gram positive cocci were isolated from ten samples accounting for 83.33% of total isolates, while Gram negative bacilli were isolated from one sample (8.33%) and both Gram positive cocci and Gram-negative bacilli were isolated from single sample accounting for 8.33% of total isolates.

Majority of the isolates were S.aureus (46%), followed by S.epidermidis (38%). Pseudomonas aeruginosa and Achromobacter spp. were 8% each.

Figure II : Isolates obtained

Distribution of Staphylococcus species isolate

Out of 11 Staphylococcus isolates, 6 (54.54%) were identified as Staphylococcus aureus (S.aureus) and 5 (45.45%) were Staphylococcus epidermidis (S.epidermidis).

Figure III: Staphylococcus species isolates

Antimicrobial susceptibility profile of Staphylococcus species isolates

There was 100% sensitivity to Vancomycin, Daptomycin and Linezolid. Almost 64% samples were resistant to Oxacillin, Cefoxitin, Cefazolin and Erythromycin; 45% were resistant to Co-trimoxazole and Clindamycin; 18% were resistant to Gentamicin and 9% were resistant to teicoplanin and Rifampicin. All the isolates were resistant to Ampicillin and Penicillin G.

Figure IV :  Antimicrobial susceptibility profile of Staphylococcus species isolates

Distribution of Methicillin Resistant S.aureus (MRSA) isolates

Out of 6 isolates of S.aureus, 3 (50%) were MRSA.

Figure V: Distribution of MRSA isolates

Distribution of Methicillin resistant S.epidermidis isolates

Out of 5 isolates of S.epidermidis 4 (80%) were Methicillin resistant.

Figure VI: Methicillin resistant S.epidermidis among S.epidermidis isolates

Comparison of Antimicrobial susceptibility profile of MRSA and MSSA

All the MRSA isolates were sensitive to daptomycin, teicoplanin, vancomycin, linezolid and rifampicin but they were resistant to erythromycin, ampicillin and penicillin G. 67% isolates were sensitive to gentamicin, co-trimoxazole and clindamycin.

Figure VII: Comparison of Antimicrobial susceptibility profile of MRSA and MSSA

Comparison of antimicrobial susceptibility profile of MR S.epidermidis and MS S.epidermidis.

All Methicillin resistant S.epidermidis were sensitive to daptomycin, vancomycin and linezolid. 75% were sensitive to gentamicin, teicoplanin and rifampicin and only 25% were sensitive to  co-trimoxazole. However all were resistant to erythromycin and clindamycin.

Figure VIII : Comparison of antimicrobial susceptibility profile of MR and MS  S.epidermidis

Proportion distribution of antimicrobial susceptibility profile of MRSA and MR S.epidermidis

Figure IX : Antimicrobial susceptibility profile (MRSA vs. MR S.epidermidis)

Antimicrobial susceptibility profile of Gram negative bacilli.

In single isolate of Achromobacter spp resistance was observed for gentamicin, imipenem, meropenem, ciprofloxacin, levofloxacin and tetracycline. The isolate was sensitive to ceftazidime, piperacillin-tazobactam and co-trimoxazole.

Single isolate of Pseudomonas aeruginosa was sensitive to amikacin, gentamicin, imipenem, meropenem, ceftazidime, cefepime, aztreonam, ciprofloxacin, levofloxacin and piperacillin-tazobactam.

In our study out of 12 positive samples, Gram positive cocci were isolated from ten samples accounting for 83.33% of total isolates, while Gram negative bacilli were isolated from one sample (8.33%) and both Gram positive cocci and Gram negative bacilli were isolated from single sample accounting for 8.33% of total isolates. In a study done by Bongiorni MG, Tascini C, Tagliaferri E et.al ( ) similar results were found where Gram-positive organisms were most frequently isolated (92.5% of isolates).

In our study among the positive isolates Majority of the isolates were S.aureus (46%), followed by S.epidermidis (38%) which is in concordance with a study done by Hemal M. Nayak et.al.( ) where Staphylococcal species remained the most common pathogens in CIED infections (68.4%).

In a review article by Pandozi C, Matteucci A, Pignalberi C et. al.( ) it was seen that initial broad-spectrum therapy typically includes a combination of ampicillin, cloxacillin, ceftriaxone, or vancomycin with gentamicin. This regimen was maintained until the pathogen identification is confirmed to optimize treatment efficacy. When streptococci were isolated, the recommended treatment for native valve endocarditis (NVE) usually consisted of ceftriaxone combined with gentamicin for four weeks, while in prosthetic valve endocarditis (PVE), the treatment duration was extended to six weeks because of the increased risk and complexity associated with prosthetic materials. In staphylococcal NVE infections, the options included flucloxacillin, cefazolin, or vancomycin, with treatment duration of four to six weeks. In cases of PVE, a combination of flucloxacillin or vancomycin with gentamicin and rifampin for six weeks was recommended to address the biofilmogenic nature of staphylococci on prosthetic valves. The enterococcal species, on the other hand, required regimens for both NVE and PVE that included ampicillin with gentamicin, vancomycin with gentamicin, or ampicillin with ceftriaxone, with a treatment duration of six weeks.

In our study, antibiogram of the Staphylococcus species showed that all the Staphylococcus species were sensitive to Vancomycin, Daptomycin and Linezolid whereas all the isolates were resistant to ampicillin and penicillin G. Among aminoglycosides, maximum isolates were sensitive to Gentamicin (81.82%).

In our study, 50% of Staphylococcus aureus were methicillin resistant and 80% of Staphylococcus epidermidis were resistant to methicillin. Study by Kratz JM et al ( )  also reported 50% methicillin resistant Staphylococcus aureus from pacemaker site infection. Bongiorni MG et al( )  reported 13% methicillin resistant Staphylococcus aureus and 33% methicillin resistant Staphylococcus epidermidis while Jan E et al ( )  reported 30.5% methicillin resistant Staphylococcus aureus.

In our study, no MRSA isolate was found to be sensitive to penicillin G and ampicillin. Tahnkiwale SS et al( ) and Vidhani S et al ( ), in their respective studies reported similar finding. Farzana et al ( ) in their study found that less than 20% of S.aureus isolates were sensitive to penicillin and ampicillin. Sensitivity to co-trimoxazole was found to be 66.67%. Other studies (9, 10, 11) however, have shown lower sensitivity (3%-40%) to co-trimoxazole. Erythromycin proved to be resistant in MRSA isolates in our study. A sensitivity ranging from 20% to 50% was reported in other studies for erythromycin (9, 10, 11). The lower sensitivity of the MRSA isolates against the commonly used antibiotics could be attributed to factors like misuse and overuse of antibiotics. Antibiotic use provides selective pressure favouring resistant bacterial strains. Inappropriate use increases the risk for selection and dissemination of antibiotic resistant bacteria which are placed at competitive advantage. In our study 100% of the MRSA isolates were found to be sensitive to Rifampicin. Study by Askarian et al ( )found that 97% of the MRSA isolates were sensitive to Rifampicin.

MSSA isolates were more sensitive to Gentamicin, erythromycin and Clindamycin as compared to MRSA isolates. This was in agreement with the studies conducted by Askarian et al(12) and Vidhani et al [10].

Methicillin sensitive S.epidermidis isolates were found to be more sensitive to Gentamicin, erythromycin, Clindamycin, co-trimoxazole, teicoplanin and rifampicin as compared to Methicillin resistant S.epidermidis.

Methicillin resistant S.epidermidis were found to be more resistant to co-trimoxazole, rifampicin and Clindamycin as compared to MRSA strains. In our study 25% Methicillin resistant S.epidermidis were resistant to teicoplanin. Study by Jan E et al, 2012, France (8) reported teicoplanin resistance in 15% of Coagulase negative Staphylococci isolated from cardiac device associated infections.

Vancomycin has remained the treatment of choice for serious infections caused by MRSA. MRSA strains usually remain sensitive to vancomycin as shown by various studies (9,10,11). This is consistent with the finding in our study also as all isolates were sensitive to vancomycin.

In our study, among the 2 (16%) Gram-negative isolates, one was Pseudomonas aeruginosa (8%) and another was Achromobacter species (8%).Gram-negative pathogens are infrequent causes of cardiac device infections accounting for 6% to 9% of infections ( ). Study by Bongiorni MG et al(8) reported 6.1% of Gram-negative isolates from cardiac device infections. The isolation of Gram-negative bacteria most likely suggest a causative organism, because they are not skin flora and rarely show false positive results (13). In our study Pseudomonas aeruginosa was sensitive to amikacin, gentamicin, imipenem, meropenem, ceftazidime, cefepime, aztreonam, ciprofloxacin, levofloxacin and piperacillin-tazobactam. While in case of Achromobacter spp resistance was observed for gentamicin, imipenem, meropenem, ciprofloxacin, levofloxacin and tetracycline, and it was sensitive to ceftazidime, piperacillin-tazobactam and co-trimoxazole.

The present study indicated an infection rate of 8.1% following permanent pacemaker implantation. 84% of the causative organisms were Staphylococcus species and out of which 64% were methicillin resistant. Staphylococcus has been reported as a major cause of community and hospital acquired infections. Infections caused by Staphylococcus used to respond to β-lactam and related group of antibiotics. However, due to development of MRSA, treatment of these infections has become problematic. Vancomycin has been used as the drug of choice for treating MRSA infections. However, a regular monitoring of vancomycin sensitivity and routine testing of other newer glycopeptides like teicoplanin should be carried out. Further, the regular surveillance of hospital associated infections including monitoring antibiotic sensitivity pattern of MRSA and formulation of definite antibiotic policy may be useful for reducing the incidence of MRSA infection.

1. Greenspon, Arnold J., et al. "16-Year Trends in the Infection Burden for Pacemakers and Implantable Cardioverter-Defibrillators in the United States: 1993 to 2008." Journal of the American College of Cardiology, vol. 58, no. 10, 2011, pp. 1001–1006. https://doi.org/10.1016/j.jacc.2011.04.033.
2. Mangram, A. J., et al. "Guideline for Prevention of Surgical Site Infection, 1999." Infect Control Hosp Epidemiol, vol. 20, 1999, pp. 250–278.
3. Russo, A., et al. "New Advances in Management and Treatment of Cardiac Implantable Electronic Devices Infections." Infection, vol. 52, 2024, pp. 323–336. https://doi.org/10.1007/s15010-023-02130-8.
4. Bongiorni, M. G., et al. "Microbiology of Cardiac Implantable Electronic Device Infections." Europace, vol. 14, no. 9, 2012, pp. 1334–1339. https://doi.org/10.1093/europace/eus044.
5. Hussein, A. A., et al. "Microbiology of Cardiac Implantable Electronic Device Infections." JACC Clinical Electrophysiology, vol. 2, 2016, pp. 498–505. https://doi.org/10.1016/j.jacep.2016.01.019.
6. Pandozi, C., et al. "Antibiotic Prophylaxis and Treatment for Cardiac Device Infections." Antibiotics, vol. 13, no. 10, 2024, pp. 991. https://doi.org/10.3390/antibiotics13100991.
7. Kratz, J. M., and Toole, J. M. "Pacemaker and Internal Cardioverter Defibrillator Lead Extraction: A Safe and Effective Surgical Approach." Annals of Thoracic Surgery, vol. 90, 2010, pp. 1411–1417.
8. Bongiorni, M. G., et al. "Microbiology of Cardiac Implantable Electronic Device Infections." Europace, vol. 14, 2012, pp. 1334–1339.
9. Jan, E., et al. "Microbiologic Characteristics and In Vitro Susceptibility to Antimicrobials in a Large Population of Patients with Cardiovascular Implantable Electronic Device Infections." Journal of Cardiovascular Electrophysiology, vol. 23, 2012, pp. 375–381.
10. Tahnkiwale, S. S., Roy, S., and Jalgaonkar, S. V. "Methicillin Resistance Among Isolates of Staphylococcus aureus: Antibiotic Sensitivity Pattern and Phage Typing." Indian Journal of Medical Sciences, vol. 56, 2002, pp. 330–334.
11. Vidhani, S., Mehndiratta, P. L., and Mathur, M. D. "Study of Methicillin Resistant aureus (MRSA) Isolates from High Risk Patients." Indian Journal of Medical Microbiology, vol. 19, no. 2, 2001, pp. 13–16.
12. Farzana, K., Rashid, Z., and Akhtar, N. "Nasal Carriage of Staphylococci in Health Care Workers: Antimicrobial Susceptibility Profile." Pakistani Journal of Pharmaceutical Sciences, vol. 21, no. 3, 2008, pp. 290–294.
13. Askarian, M., Zeinalzadeh, A., and Japoni, A. "Prevalence of Nasal Carriage of Methicillin-resistant Staphylococcus aureus and Its Antibiotic Susceptibility Pattern in Healthcare Workers at Namazi Hospital, Shiraz, Iran." International Journal of Infectious Diseases, vol. 13, 2009, pp. 241–247.
14. Arnold, C. J., and Chu, V. H. "Cardiovascular Implantable Electronic Device Infections." Infectious Disease Clinics of North America, vol. 32, 2018, pp. 811–825.