|Year : 2014 | Volume
| Issue : 1 | Page : 23-25
Use of topical meropenem in management of hospital acquired Pseudomonas ocular infections
Ranjana A Pande, Prajakta V Bhailume
Department of Ophthalmology, BJMC and SGH, Pune, Maharashtra, India
|Date of Submission||10-Apr-2013|
|Date of Acceptance||20-Jun-2013|
|Date of Web Publication||3-Dec-2013|
Ranjana A Pande
B402, Felicita, Baner Pashan Link Road, Baner, Pune - 411 045, Maharashtra
Source of Support: None, Conflict of Interest: None
We report a case series of four eyes of four patients where resistant strains of Pseudomonas aeruginosa in nosocomial ocular infections were treated with topical meropenem with a successful outcome. Pseudomonas infections are known to be very fulminant. We observed strains of P. aeruginosa in four eyes resistant to all routine drugs such as fluoroquinolones, aminoglycosides and cephalosporins. Three eyes presented with infective corneal ulcers and one eye had endophthalmitis. Culture sensitivity of corneal scrape and aqueous tap respectively of each patient showed P. aeruginosa (Gram-negative bacilli) sensitive to carbapenem (meropenem and imipenem) group of drugs. These patients were treated with a topical meropenem 50 mg/ml once in an hour and responded dramaticaly and we could salvage all eyes. Topical meropenem 50 mg/ml, which is not routinely used in ocular infections is thus an effective drug for management of hospital acquired resistant Pseudomonas ocular infections.
Keywords: Sarbapenem, Gram-negative bacilli, meropenem, nosocomial infection, Pseudomonas
|How to cite this article:|
Pande RA, Bhailume PV. Use of topical meropenem in management of hospital acquired Pseudomonas ocular infections. J Clin Ophthalmol Res 2014;2:23-5
|How to cite this URL:|
Pande RA, Bhailume PV. Use of topical meropenem in management of hospital acquired Pseudomonas ocular infections. J Clin Ophthalmol Res [serial online] 2014 [cited 2020 Dec 5];2:23-5. Available from: https://www.jcor.in/text.asp?2014/2/1/23/122637
Gram-negative bacteria are major causative agents of fulminant infections in eye leading to loss of vision. Hence, there is a need for an effective antibiotic for the treatment of these serious bacterial infections.  For specific antibacterial treatment, isolation and identification of bacterial pathogens along with antibiotic susceptibility spectrum is essential. As there is a world-wide problem regarding the emergence of bacterial resistance toward topical antimicrobial agents, which are influenced by characteristics of pathogens, antibiotic-prescribing practices including the use of systemic antibiotics and general health-care need to be regulated.  This development of resistance increases the risk of treatment failure with potentially serious consequences. We observed four cases of Pseudomonas ocular infections, which were resistant to aminoglycosides, fluoroquinolones and cephalosporins, but sensitive to carbapenem group of drugs. The purpose of this report is to highlight the role of topical meropenem in treatment of resistant Pseudomonas hospital acquired ocular infections.
| Case Reports|| |
A 23-year-old medical resident working in medicine ward with a history of contact lens wear presented with corneal ulcer in the left eye (LE). She was asked to stop contact lens wear and was started on topical aminoglycoside (toba eye drop, Milmet Laboratories, India) once in an hour and fluroquinolone (vigamox eye drop, Alcon Laboratories, USA) once in an hour, but worsened within 24 h. She developed 4 mm × 3 mm ulcer with spread to deep corneal stroma associated with hypopyon [Figure 1] and visual acuity was a perception of light (PL) and projection of rays (PR) accurate. Corneal scrape culture sensitivity report showed Pseudomonas aeruginosa sensitive to carbapenem group. Immediately after the report was obtained i.e., 48 h after initial presentation, she was started topical meropenem (50 mg/ml) (Ronem, Venus Remedies Limited, India) once in an hour and responded well with resolution of infection and healing of ulcer within 3-week [Figure 2]. Visual acuity after 3 months was 6/18.
A 56-year-old male, one eyed came with a history of LE vegetative trauma with sugarcane. He was noted to have corneal ulcer 4 mm × 5 mm with typical characteristics of fungal infection. Visual acuity was 1/60. Corneal scrape of ulcer edge showed fungal filaments on potassium hydroxide mount. Patient was admitted and started on topical antifungals and responded well initially. However after 1 week, he deteriorated showing deep spread to the corneal stroma with hypopyon and vision was PL and PR accurate [Figure 3]. Culture sensitivity of corneal scrape was repeated and report showed P. aeruginosa sensitive to carbapenem group. Immediately, after the report was obtained i.e., 48 h after scrape was taken, he was started topical meropenem (50 mg/ml) (Ronem, Venus Remedies Limited) once in an hour and responded well [Figure 4]. Visual acuity after 6 months was 5/60.
A 64-year-old female came with the right eye (RE) fulminant corneal ulcer 4 mm × 5 mm with hypopyon and visual acuity PL + PR accurate. She was on topical steroids for herpetic keratouveitis since 3 weeks and used to come for frequent follow-up in the out-patient department. Corneal scrape culture sensitivity report of ulcer edge showed P. aeruginosa sensitive to carbapanem. She was started on topical meropenem (50 mg/ml) (Ronem, Venus Remedies Limited) immediately after the scrape report was obtained, i.e., 48 h after the presentation and responded well to treatment with a resolution of infection. Visual acuity after 3 months was 2/60.
A 62-year-old female who underwent an uneventful small incision cataract surgery in the LE developed post-operative endophthalmitis on the post-operative day one. Intravitreal ceftazidime 2.25 mg/0.1 cc and vancomycin 1 mg/0.1 cc were given. Patient developed corneal infiltrates within a few hours. Then, vitrectomy was performed. Vitreous tap and aqueous tap showed Pseudomonas aeruginousa sensitive to carbapanem. Immediately after the report as obtained i.e., 48 h after corneal involvement, we started topical meropenem (50 mg/ml) (Ronem, Venus Remedies Limited) once in an hour for corneal involvement. Though her vision was not restored, we could salvage her eye.
| Discussion|| |
Bacterial keratitis is an ophthalmic emergency that needs immediate institution of treatment. In the absence of laboratory diagnosis, the initial therapy is usually broad spectrum intensive treatment. Specific therapy should be based on the laboratory data, which identifies the causative agent and provides antibacterial susceptibility results.
Pseudomonas is a virulent corneal pathogen associated with rapid, liquefactive necrosis of the cornea. P. aeruginosa is a highly relevant opportunistic pathogen commonly seen in contact lens wearers and hospital infections. Analysis of the bacterial trends of keratitis reveals that Pseudomonas spp. is the second most important cause of bacterial keratitis in India after Gram-positive bacteria.  In vitro studies of antibacterial susceptibility tests by various authors have shown an increased resistance of various bacteria to commonly used antimicrobials.  One of the most worrisome characteristics of P. aeruginosa is its low antibiotic susceptibility. This low susceptibility is attributed to the low permeability of the bacterial cellular envelopes and easily develops acquired resistance by mutation in chromosomally-encoded genes. 
In these four cases, we have observed strains of P. aeruginosa resistant to all routine drugs including fluoroquinolones, aminoglycosides and cephalosporins. However, they were sensitive to meropenem (carbapenem group).
Meropenem, a new beta-lactam antibiotic, is stable against inactivation by most beta-lactamases and has a broad antibacterial spectrum generally similar to that of imipenem; although, there are some important differences between the two carbapenems. For one, imipenem is degraded by human renal dehydropeptidase-I (DHP-I) and consequently must be given in combination with the DHP-I enzyme inhibitor (cilastatin) to avoid low antimicrobial activity in urine and potential nephrotoxicity associated with renal metabolism. Meropenem, however, is relatively stable to DHP-I and thus does not need to be administered with an enzyme inhibitor. Meropenem also appears to have less epileptogenic activity than imipenem. Meropenem is more active than imipenem against Gram-negative aerobes, including those in the Enterobacteriaceae family, P. aeruginosa, Haemophilus influenzae and Neisseria More Details gonorrhoeae. 
The peak concentrations of meropenem in the aqueous humor ranged from 0.17-0.93 mg/l and the peak tear-fluid concentration was 1.25 mg/l after a 500-mg intravenous dose. The Minimum nhibition oncentrationof meropenem for P. aeruginosa is 0.25-1 mcg/0.1 ml. 
Meropenem drops were prepared using 1 g vial containing powdered meropenem (Ronem, Venus Remedies Limited). It was diluted using 20 ml distilled water to get concentration of 50 mg/ml. 
These drops were instilled once in an hour until patient showed response followed by lesser frequency over 3 weeks. All patients showed dramatic improvement within 1 week and we could salvage their eyes.
Though our case series was small consisting of four eyes, it showed promising results with topical meropenem in treating Pseudomonas infections about which detail information is not available in the literature. This drug was used as intravenous therapy in recalcitrant Pseudomonas keratitis.  The cost of meropenem therapy is 5-6 times costlier than fluoroquinolones and aminoglycosides.
Though this drug showed promising results, it should not be used as first line of treatment as a routine. It should be used only after culture sensitivity report and non-responding cases.
Topical meropenem 50 mg/ml, which is not routinely used in ocular infections, is an effective alternative for management of hospital acquired resistant Pseudomonas corneal infections and may become an additional agent in the armamentarium of treating ophthalmologist and cornea specialist.
| References|| |
|1.||Smitha S, Lalitha P, Prajna VN, Srinivasan M. Susceptibility trends of Pseudomonas species from corneal ulcers. Indian J Med Microbiol 2005;23:168-71. |
|2.||Sharma S. Antibiotic resistance in ocular bacterial pathogens. Indian J Med Microbiol 2011;29:218-22. |
|3.||Srinivasan M, Gonzales CA, George C, Cevallos V, Mascarenhas JM, Asokan B, et al. Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India. Br J Ophthalmol 1997;81:965-71. |
|4.||Srikanth K, Kalavathy CM, Thomas PA, Jesudasan CA. Susceptibility of common ocular bacterial pathogens to antibacterial agents. Journal of Tamil Nadu Ophthalmic Association 1998;39:49-50. |
|5.||Craig WA. The pharmacology of meropenem, a new carbapenem antibiotic. Clin Infect Dis 1997;24 Suppl 2:S266-75. |
|6.||Sueke H, Kaye S, Neal T, Murphy C, Hall A, Whittaker D, et al. Minimum inhibitory concentrations of standard and novel antimicrobials for isolates from bacterial keratitis. Invest Ophthalmol Vis Sci 2010;51:2519-24. |
|7.||Sharma N, Jindal A, Bali SJ, Titiyal JS. Recalcitrant Pseudomonas keratitis after epipolis laser-assisted in situ keratomileusis: Case report and review of the literature. Clin Exp Optom 2012;95:460-3. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
|This article has been cited by|
||A shell-less henís egg test as infection model to determine the biocompatibility and antimicrobial efficacy of drugs and drug formulations against Pseudomonas aeruginosa
| ||Paul Warncke,Sarah Fink,Cornelia Wiegand,Uta-Christina Hipler,Dagmar Fischer |
| ||International Journal of Pharmaceutics. 2020; : 119557 |
|[Pubmed] | [DOI]|
||Surfactin Like Broad Spectrum Antimicrobial Lipopeptide Co-produced With Sublancin From Bacillus subtilis Strain A52: Dual Reservoir of Bioactives
| ||Deepika Sharma,Shelley Sardul Singh,Piyush Baindara,Shikha Sharma,Neeraj Khatri,Vishakha Grover,Prabhu B. Patil,Suresh Korpole |
| ||Frontiers in Microbiology. 2020; 11 |
|[Pubmed] | [DOI]|