Is Antibiotic Resistance a Problem in the Treatment of Ophthalmic Infections?

Regis P Kowalski


Expert Rev Ophthalmol. 2013;8(2):119-126. 

In This Article

Intrinsically Susceptible Bacteria Become Resistant to Antibiotics

Resistance is more common with endophthalmitis isolates, but as a reminder, this resistance is always interpreted using standards based on the systemic serum standards. Figure 4 presents the antibacterial susceptibilities of staphylococcal endophthalmitis isolates based on serum standards from 1993 to 2011. Others have also reported antibiotic resistance with endophthalmitis.[7,8] Methicillin resistance frequently occurs with coagulase-negative Staphylococcus (48%) and S. aureus (28%), and this often corresponds to resistance among the fluoroquinolones (CNS– Saur; ofloxacin [58–54%], ciprofloxacin [54–50%] and moxifloxacin [39–44%]). As the graph indicates, fluoroquinolone resistance is more common than methicillin (oxacillin) resistance. Based on diagnosis, Figure 5 indicates that methicillin-resistant S. aureus (MRSA) is more prevalent with endophthalmitis (48%) isolates followed by conjunctivitis (39%) and keratitis (34%).

Figure 4.

Antibacterial susceptibilities of staphlococcal endophthalmitis isolates based on serum standards (1993–2011). The bar represents the mean susceptibility value and the error bars represent the yearly deviation.OXA: Oxacillin; Sus: Susceptible.

Figure 5.

Oxacillin susceptibility of Staphylococcus aureus based on diagnosis (1993–2011).

Resistance to the fluoroquinolone anti-infectives with Staphylococcus isolated from endophthalmitis is probably due to topical surgical prophylaxis. These are individual spot mutations that are not passed on by other patients. This phenomenon, with increased resistance after topical fluoroquinolone application, has been reported by others.[9–11] Hwang has reported that fluoroquinolone resistance can arise locally with suboptimal dosing and prolonged usage.[12] Resistance is more likely to occur at tissue concentrations near the MIC. Fluoroquinolone resistance is more common with the second (ciprofloxacin and ofloxacin) and third generation (levofloxacin and purified ofloxacin) because of the single mutation required to convey resistance, whereas a double mutation is required to convey resistance by a fourth-generation fluoroquinolone (moxifloxacin and gatifloxacin).[13] It is important to note that a single mutation by a second- or third-generation fluoroquinolone could provide a step mutation for further resistance to the fourth-generation fluoroquinolone with an additional mutation. Furthermore, moxifloxacin has been reported to be more potent than levofloxacin, ciprofloxacin and ofloxacin with lower MICs against S. aureus isolated from endophthalmitis, keratitis and conjunctivitis.[3,13–15]

Our studies have also indicated that our S. aureus isolates from endophthalmitis correlate more closely with hospital-acquired infection rather than community-acquired infection. This is based on the negative presence of the Panton–Valentine leukocidin marker and the multiresistance nature of the isolates.[16] It is more likely that the staphylococcal isolates are part of the patients' normal flora and developed resistance either through topical prophylaxis or during the infection process.

Erythromycin appears to be the most resistant antibiotic for treating coagulase-negative Staphylococcus from the lid margins of blepharitis patients. This is somewhat paradoxical because erythromycin and azithromycin are frequently prescribed for blepharitis therapy. The in vitro susceptibility testing of erythromycin and now azithromycin may not be appropriate with standard testing because these antibiotics are cell associated.[16,17] Patients may be chronically treated with erythromycin and this is probably the reason for increased resistance. There are other choices for the treatment of bacteria blepharitis (bacitracin, erythromycin, azithromycin and tetracycline) (Figures 6 & 7).

Figure 6.

Antibiotic susceptibility of coagulase-negative Staphylococcus isolated from blepharitis (1993–2011). For each antibiotic, the number of isolates, on which susceptibility was based, is displayed.

Figure 7.

Antibiotic susceptibilities of Staphylococcus aureus isolated from keratitis (n = 454; 1993–2011). The bar represents the mean susceptibility value and the error bars represent the yearly deviation.

Bacterial resistance appears to be less common with bacterial isolates isolated from keratitis. Figures 8 & 9 demonstrate that commonly used antibiotics and alternatives for treating S. aureus (vancomycin, cefazolin and moxifloxacin)[18] and P. aeruginosa (tobramycin, ciprofloxacin and polymyxin B) are available. Fluoroquinolone resistance has been reported with S. aureus but alternative topical treatment, as stated, is available.[19,20] Effective treatment could be problematic for treating fluoroquinolone-resistant (ciprofloxacin, gatifloxacin and moxifloxacin) and aminoglycoside-resistant (tobramycin and gentamicin) P. aeruginosa keratitis. Outbreaks of fluoroquinolone-resistant P. aeruginosa have been reported.[21,22] As of yet, the problem has not compounded and this may be due to antibiotic overuse rather than patient-to-patient spread. Using a rabbit keratitis model, we demonstrated that multi-resistant P. aeruginosa keratitis could be a therapeutic challenge without the availability of alternative effective antibiotics.[23] Figure 9 indicates that S. aureus keratitis infections are on a slight decline and P. aeruginosa keratitis infections are slightly increasing, but both are still prominent infections that must be monitored for antibiotic susceptibility trends (Figure 10).

Figure 8.

Antibiotic susceptibilities of Pseudomonas aeruginosa isolated from keratitis (n = 254; 1993–2011). The bar represents the mean susceptibility value, and the error bars represent the yearly deviation.

Figure 9.

Incidence of Staphylococcus aureus and Pseudomonas aeruginosa keratitis (1993–2011).

Figure 10.

Antibacterial susceptibilities of bacteria isolated from conjunctivitis (1993–2011).

Figure 11 depicts the antibiotic susceptibilities of S. pneumoniae, H. influenzae and S. aureus isolated from conjunctivitis. Except for intrinsic resistance, most topical antibiotics with additional alternatives are available for the coverage of bacterial conjunctivitis.

Figure 11.

Antibacterial susceptibilities of Streptococcus pneumoniae isolated from conjunctivitis (1993–2011). Lines of the antibiotics overlap due to high susceptibility.