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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2016  |  Volume : 59  |  Issue : 4  |  Page : 496-498
In vitro activity of ceftaroline: A novel antibiotic against methicillin-resistant Staphylococcus aureus


Department of Microbiology, Government Medical College and Hospital, Latur, Maharashtra, India

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Date of Web Publication10-Oct-2016
 

   Abstract 

Introduction: Staphylococcus is one of the most common causes of nosocomial infection, especially pneumonia, surgical site infections, blood stream infections, and continues to be a major cause of community-acquired infections. The emergence of penicillin resistance followed by the development and spread of strains resistant to the semisynthetic penicillins such as methicillin, oxacillin and nafcillin, macrolides, tetracycline, and aminoglycosides has made the treatment of staphylococcal infection a global challenge. To treat this multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), the only option available is glycopeptides such as vancomycin. However, recently, vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains have emerged with different resistance mechanism. There are newer drugs in the pipeline against MRSA such as ceftaroline, dalbavancin, oritavancin, and tedizolid; however, very little data are available for their use. Recently, ceftaroline has been approved by the US Food and Drug Administration for the treatment of acute bacterial skin and soft tissue infections and community-acquired bacterial pneumonia due to MRSA. Hence, we tried to evaluate in vitro activity of ceftaroline against MRSA. Aim: The aim of this study was to detect in vitro activity of new cephalosporin, ceftaroline, against MRSA. Materials and Methods: Thirty nonduplicate MRSA strains were collected from various clinical samples, and minimum inhibitory concentration (MIC) was detected using ceftaroline E-test strips. Results: Twenty-eight MRSA isolates (93.33%) were found to be susceptible to ceftaroline. Conclusion: Ceftaroline demonstrated promising potency and coverage against MRSA isolates and can be considered an effective alternative treatment keeping vancomycin and linezolid as a reserved option.

Keywords: Ceftaroline, minimum inhibitory concentration, methicillin-resistant Staphylococcus aureus

How to cite this article:
Gaikwad V, Gohel T, Panickar S, Chincholkar V, Mangalkar S. In vitro activity of ceftaroline: A novel antibiotic against methicillin-resistant Staphylococcus aureus. Indian J Pathol Microbiol 2016;59:496-8

How to cite this URL:
Gaikwad V, Gohel T, Panickar S, Chincholkar V, Mangalkar S. In vitro activity of ceftaroline: A novel antibiotic against methicillin-resistant Staphylococcus aureus. Indian J Pathol Microbiol [serial online] 2016 [cited 2019 Nov 22];59:496-8. Available from: http://www.ijpmonline.org/text.asp?2016/59/4/496/191798



   Introduction Top


Methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat in an era of increasing antimicrobial resistance. Due to increased drug resistance, very limited treatment options are available. Patients admitted in hospitals with open wounds, invasive devices, and immunocompromised are at greater risk with MRSA infection. Furthermore, the emergence of highly virulent community-associated MRSA causing skin infections, sepsis, toxic shock syndrome, and necrotizing pneumonia is the another concern. [1] For treatment of multidrug-resistant MRSA, glycopeptides such as vancomycin and teicoplanin are considered the drug of choice. [2] Since the emergence of vancomycin resistance in enterococci in 1988 and its in vitro demonstration that its resistance genes (Van A and Van B) are transmissible to other bacterial species including S. aureus, the emergence of vancomycin-intermediate-resistant S. aureus and vancomycin-resistant S. aureus in the clinical sample has become a great concern. [3]

For the treatment of this MRSA infection, newer drugs such as ceftaroline, dalbavancin, oritavancin, and tedizolid are available. This antimicrobial agent binds to penicillin-binding proteins (PBP) inhibiting cell wall synthesis and has a high affinity for PBP 2a, which is associated with methicillin resistance. The ability of ceftaroline to bind the PBP 2a, an MRSA-specific protein, makes it unique among cephalosporin. Ceftaroline is consistently active against multidrug-resistant Streptococcus pneumoniae, S. aureus, and some Gram-negative organisms. As ceftaroline is a newer agent with only limited knowledge about its susceptibility pattern, the present study was conducted to know the in vitro activity of ceftaroline against MRSA.


   Materials and Methods Top


A total of thirty nonduplicate methicillin-resistant S. aureus strains isolated from various clinical samples were included in the study. Methicillin resistance was detected using cefoxitin 30-μg disc. Ceftaroline minimum inhibitory concentrations (MIC) were detected for all the thirty isolates using ceftaroline E-strips (Biomerieux). The Clinical and Laboratory Standards Institute clinical break points were applied for interpretation of ceftaroline MIC (sensitive ≤1 μg/ml, 2 μg/ml intermediate, and resistant ≥ 4 μg/ml). S. aureus ATCC 29213 was used as a control strain for MIC detection.


   Results Top


Of 30 MRSA isolates tested, 28 (93.3%) were sensitive to ceftaroline. Ceftaroline MIC values ranged from 0.25 to 4 μg/ml. One isolate with intermediate susceptibility showed MIC of 2 μg/ml. Moreover, one isolate resistant to ceftaroline showed MIC of 4 μg/ml. All the remaining isolates showed MIC ≤1 μg/ml. The MIC50 and MIC90 of the isolates were 0.38 μg/ml and 0.75 μg/ml, respectively [Table 1].
Table 1: Antimicrobial susceptibility pattern of methicillin - resistant Staphylococcus aureus (n=30)

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All thirty isolates of MRSA were sensitive to linezolid, teicoplanin, and tigecycline by Kirby-Bauer disc diffusion method [Table 2].
Table 2: Minimum inhibitory concentration of vancomycin and ceftaroline by E-test

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All isolates showed 100% susceptibility to vancomycin, while ceftaroline susceptibility was 93.33% [Figure 1].
Figure 1: Ceftaroline E-test showing minimum inhibitory concentration 0.38 μg/ml

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   Discussion Top


In this study, 28 MRSA (93.33%) isolates were sensitive to ceftaroline with the MIC90 being 0.75 μg/ml. These findings correlate well with the surveillance studies. In the Assessing Worldwide Antimicrobial Resistance Evaluation [4] program, 98.4% of the MRSA were inhibited at MIC value of 1 μg/ml. The highest MIC in their study was 2 μg/ml. In a study by Jones et al., 94.8% of the MRSA isolates from the USA were inhibited at a concentration of 1 μg/ml, whereas only 82.6% European isolates were inhibited at 1 μg/ml. [5]

In the study conducted by Basireddy et al., [6] 50 MRSA isolates were sensitive to ceftaroline. Ceftaroline MIC values ranged from 0.125 to 1.5 mg/L. Only two isolates showed the maximum MIC of 1.5 mg/L, which is in the intermediate susceptible range. Similarly, this study showed MIC range from 0.25 to 4 μg/ml, of which one isolate with intermediate susceptibility showed MIC of 2 μg/ml and one isolate resistant to ceftaroline showed MIC of 4 μg/ml. Moreover, all the remaining isolates showed MIC ≤1 μg/ml. Furthermore, a study conducted by Vidaillac et al. found that MIC ranged between 0.125 and 2 μg/ml for ceftaroline. [7]

The MIC50 and MIC90 of the isolates in the study conducted by Basireddy et al. [6] were 0.5 and 1 mg/L, respectively, which was similar to our study.

A study conducted by Vidaillac et al. found that MIC ranged between 0.5 and 2 μg/ml for vancomycin. [7] While MIC of vancomycin was found to be <2 μg/ml for all isolates in this study

Ho et al. reported series of six patients, in which ceftaroline was utilized as salvage monotherapy in persistent MRSA bacteremia or endocarditis. All six patients experienced rapid clearance of their bacteremia after starting ceftaroline suggesting sterilization within 13 days of starting ceftaroline. [8]

Advancement of modern medicine may have prolonged the lifespan of man, but it has also brought problems such as "Drug resistance." The spread of superbugs in the community might mean the "End of Antibiotic Era." It is with a view to increase awareness in the health-care community that the WHO declared following slogan in 2011 - "No action today, no cure tomorrow."


   Conclusion Top


MRSA continues as a major problem in the community. Vancomycin remains the gold-standard treatment option for MRSA infections. The pattern of antibiotic use for MRSA has significantly changed over the past 10 years limiting their use suggesting the need for newer antimicrobials. Considering patient-specific parameters, cost and relevant clinical data demonstrating drug safety and efficacy should be employed for the selection of the appropriate alternative agent. The approval of ceftaroline fosamil for MRSA provides a new empirical option that addresses the need to cover today's infections while preserving the well-recognized tolerability profile of the cephalosporin class. Ceftaroline showed good in vitro activity against MRSA isolates and can be considered an effective alternative for the treatment of these infections.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Fraimow HS, Tsigrelis C. Antimicrobial resistance in the intensive care unit: Mechanisms, epidemiology, and management of specific resistant pathogens. Crit Care Clin 2011;27:163-205.  Back to cited text no. 1
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2.
Lowy FD. Staphylococcal infections. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al., editors. Harrison's Principles of Internal Medicine. 17 th ed. New York: McGraw-Hill; 2008. p. 872-81.  Back to cited text no. 2
    
3.
Bhateja P, Mathur T, Pandya M, Fatma T, Rattan A. Detection of vancomycin resistant Staphylococcus aureus: A comparative study of three different phenotypic screening methods. Indian J Med Microbiol 2005;23:52-5.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
4.
Flamm RK, Sader HS, Farrell DJ, Jones RN. Summary of ceftaroline activity against pathogens in the United States, 2010: Report from the assessing worldwide antimicrobial resistance evaluation (AWARE) surveillance program. Antimicrob Agents Chemother 2012;56:2933-40.  Back to cited text no. 4
[PUBMED]    
5.
Jones RN, Mendes RE, Sader HS. Ceftaroline activity against pathogens associated with complicated skin and skin structure infections: Results from an international surveillance study. J Antimicrob Chemother 2010;65 Suppl 4:iv17-31.  Back to cited text no. 5
[PUBMED]    
6.
Basireddy S, Singh M, Ali S, Kabra V. In vitro activity of ceftaroline against methicillin-resistant Staphylococcus aureus isolates. Indian J Med Microbiol 2015;33:464-5.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.
Vidaillac C, Leonard SN, Rybak MJ. In vitro activity of ceftaroline against methicillin-resistant Staphylococcus aureus and heterogeneous vancomycin-intermediate S. aureus in a hollow fiber model. Antimicrob Agents Chemother 2009;53:4712-7.  Back to cited text no. 7
[PUBMED]    
8.
Ho TT, Cadena J, Childs LM, Gonzalez-Velez M, Lewis JS 2 nd . Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy. J Antimicrob Chemother 2012;67:1267-70.  Back to cited text no. 8
    

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Correspondence Address:
Vaishali Gaikwad
B/30-2, Rajmudra HSG SOC, Gulab Nagar, Dhankawdi, Pune - 411 043, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.191798

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    Figures

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    Tables

  [Table 1], [Table 2]

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