No sign of chloramphenicol resistance in bacterial conjunctivitis

Chloramphenicol remains effective against Gram-positive bacteria, the most common agent in bacterial conjunctivitis, researchers say.

Making the antibiotic available over the counter has not increased bacterial resistance to it, wrote Alexander Silvester, Royal Liverpool University Hospital, Liverpool, United Kingdom, and colleagues. They published the finding in BMJ Open Ophthalmology.

The incidence of acute infective conjunctivitis is about 135 per 10,000 in the United States. In severe cases it can cause conjunctival scarring and damage to the ocular surface.

Antimicrobials have the positive effect of improving remission rates, but many cases of conjunctivitis are self-limiting, and inappropriate use of antimicrobials can lead to increased bacterial resistance.

A global movement is underway to reduce prescribing of antimicrobials, and general practitioners in the United Kingdom have been writing fewer chloramphenicol prescriptions for conjunctivitis. However, the use of the drug has increased several-fold since 2005 when it became the first antibiotic available over the counter.

Research into trends in prescription patterns and antimicrobial resistance can help guide prescription decisions. Researchers in the United States have undertaken such investigations, though chloramphenicol is not widely used there because of concerns about aplastic anaemia – a concern dismissed by reviewers studying its use in the United Kingdom, Silvester and colleagues reported.

To examine whether resistance to chloramphenicol was developing in the United Kingdom, Silvester and colleagues analysed laboratory records for all bacterial swabs taken from adult patients with suspected bacterial conjunctivitis presenting to the Royal Liverpool University Hospital from 2001 to 2012.

Samples were incubated for the presence of pathogens, and starting in 2006 were analysed for viruses using real time polymerase chain reaction (PCR). Bacteria were tested for susceptibility to chloramphenicol, ciprofloxacin, and gentamicin.

The researchers used British Society for Antimicrobial Chemotherapy (BSAC) guidelines and templates to interpret zone inhibition diameters for chloramphenicol, ciprofloxacin, and gentamicin.

Out of 8209 conjunctival swabs, 1300 (15.9%) were considered positive for bacteria. Of these, 977 (74.2%) were Gram-positive and 323 (24.8%) were Gram-negative. The most prevalent organism identified was Staphylococcus aureus.

The researchers counted 3293 viral samples, of with 707 were adenovirus. They counted 21 (2.97%) in which both viruses and bacteria were identified.

Resistance to chloramphenicol varied from 3.0% to 16.4% in bacterial culture-positive samples. Most of the resistant organisms were Gram-negative. The rate of resistance to chloramphenicol did not appear to change after 2005 when it became available over the counter.

The researchers calculated that 16.4% of samples were resistant to ciprofloxacin, of which 80.1% were Gram-positive and 14.0% were resistant to gentamicin. Of those, 69.2% were Gram-positive.

Antimicrobial resistance

They found no significant association between antimicrobial resistance and isolation rate for any year under study, but they found a significant reduction in methicillin resistance among S. aureus isolates, ranging from a maximum of 13.4% to a minimum of 1.3%.

Although more samples were infected with viruses than with bacteria, it is hard to distinguish them, so “it is not unreasonable to prescribe broad-spectrum antimicrobials prior to obtaining culture results,” the researchers wrote.

Compared with many other topical antibacterial agents, chloramphenicol penetrates well following topical application, they pointed out.

However, they warned against using chloramphenicol in contact lens related cases of conjunctivitis, or when Pseudomonas aeruginosa is suspected.

The prevalence of S. aureus was lower in these samples than in studies in Japan and the United States, even though it was the most common organism identified. Researchers looking at other organisms have also documented a reduction of resistance to methicillin in S. aureus over time. They have attributed it to enhanced screening and decolonisation.

Silvester et al. advised caution in interpreting their results because BSAC breakpoints are derived for systemically rather than topically delivered antimicrobials. Breakpoints are becoming available for keratitis, they noted, but are not yet available for conjunctivitis.

They also acknowledged a low-positive isolation rate as a limitation of this study. Such rates have varied in other studies, they said. They explained this variation by the inclusion of all bacteria isolated in some studies rather than pathogenic bacteria only.

They also pointed out that bacterial swabs in this study were taken from all patients with suspected conjunctivitis, including those with viral conjunctivitis. Many patients have already started topical antibiotic treatment by the time the patients present at clinics, which may have reduced the positive isolation rate.

“Despite the ready availability of chloramphenicol over the counter during the last seven years, there has been no increase in chloramphenicol resistance nor a change in the bacterial spectrum in this cohort of patients,” the researchers concluded.