Brett L. Shapiro

Susceptibility testing and clinical outcome in fungal keratitis

Fungal keratitis causes significant morbidity, especially in tropical climates, and is notoriously difficult to manage. The choice of antifungal agent for fungal keratitis remains largely empirical, with no consensus on the role of susceptibility testing in guiding therapy. Studies suggest that susceptibility and outcome may be associated in systemic fungal infections with some dimorphic fungi,1 but this correlation may not exist for filamentous fungi or in ocular disease because of frequent topical dosing and high drug concentration. Given the availability of new topical medications, tailoring antifungal therapy based on microbial sensitivity is important.2 Here, we assess whether fungal susceptibility testing correlates with clinical outcomes in cases of fungal keratitis. This study was a retrospective case review of consecutive patients with culture proven fungal keratitis presenting to the Aravind Eye Hospital cornea clinic between March and July 2004. Of 98 consecutive patients, minimum inhibitory concentration (MIC) data was available for 90.3 Eighty-one corresponding charts were available, and 54 charts had follow-up of at least 3 weeks to allow determination of healing. All cases were …

Trachoma, antibiotics and randomised controlled trials

Role of randomised clinical trials in public health: distribution of mass antibiotics for trachoma control In this issue, Wright et al 1 discuss the role of randomised clinical trials (RCTs) in public health. They suggest that not all decisions can be based on evidence from RCTs, and they use the distribution of mass antibiotics for trachoma control as an example. The authors refer to several reports in which the prevalence of infection was dramatically lower after mass azithromycin distributions, but which had no control groups for comparison.2–5 They contend that a large RCT which randomised communities to different treatment strategies would be too difficult, too expensive and too unethical to conduct, and that treatment recommendations are needed immediately to prevent blindness. The particular example that the authors choose is an interesting one. Antibiotics are clearly effective in eliminating chlamydia.6–8 Infection has stayed low for months, if not years, after a single community-wide antibiotic distribution.2–4 But the long-term efficacy of mass treatment had not been rigorously shown in a group-randomised trial, at least not in time for a Cochrane Collaboration report on the topic (most recently updated in 2005).9,10 The report highlighted the fact that many studies have been uncontrolled and non-blinded. For an outcome, several have relied on clinical activity, which has never been shown to be a particularly good marker for ocular chlamydial infection.11–13 Those trials that did randomise by group typically included far too few …

Amphotericin B and natamycin are not synergistic in vitro against Fusarium and Aspergillus spp. isolated from keratitis

Infectious keratitis is a major cause of monocular blindness worldwide.1 Although fungal ulcers are relatively uncommon in developed nations, they occur frequently in developing countries, especially those in tropical regions. In South India, up to half of infectious ulcers are fungal.2 Fungal ulcers are notoriously difficult to treat compared with bacterial ulcers, and physicians frequently use combination therapy.3 Amphotericin B and natamycin are two commonly used topical agents to treat filamentous fungal keratitis.3 However, combination therapy may increase the risk of potential drug toxicity as well as the cost of therapy. Currently, there are no data on whether natamycin and amphotericin B interact synergistically in vitro against filamentous fungi. Here, we investigate whether amphotericin B and natamycin interact synergistically in vitro when tested against Fusarium and Aspergillus spp. isolated from patients with fungal keratitis. Ten Fusarium spp. and ten Aspergillus spp. isolates were randomly selected from 98 consecutive cases of culture-positive fungal keratitis treated at Aravind Eye Hospital in South India. All patients underwent cornea culture and were treated with natamycin, …