-
JAMA Ophthalmology Feb 2021Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this... (Review)
Review
IMPORTANCE
Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this indication. Ophthalmia neonatorum was previously considered a different indication from bacterial conjunctivitis in older children and adults because of uncertain similarities in the cause of disease and the treatment course between the 2 populations. Prospective therapeutic clinical studies were required to demonstrate the effectiveness of treatment for ophthalmia neonatorum.
OBJECTIVE
To review the therapeutic clinical trials for patients with bacterial conjunctivitis to evaluate the similarity in the cause of disease and the treatment response between neonates and older children and adults.
DESIGN, SETTING, AND PARTICIPANTS
In this comparative effectiveness research review of pooled data from the most recent 30 bacterial conjunctivitis trials (N = 2018) submitted to the FDA to support the approval of topical ophthalmic solutions for older children and adults, 95% CIs were constructed from clinical cure rates. Cure rates in 3 neonatal randomized clinical trials (N = 392) of patients treated with ophthalmic anti-infective solutions of ciprofloxacin, gatifloxacin, and moxifloxacin were constructed and compared. The baseline ocular swab cultures were analyzed.
MAIN OUTCOMES AND MEASURES
Cure rates of neonatal trials were compared with the 95% CIs among older children and adults. The bacterial organisms isolated from these 2 populations were compared.
RESULTS
The 3 neonatal trials enrolled a total of 392 patients, and the 30 trials of older children and adults enrolled a total of 2018 patients. Neonatal clinical cure rates for moxifloxacin (day 4, 48%), ciprofloxacin (day 4, 49%; day 5, 61%), and gatifloxacin (day 7, 79%) were within the 95% CI for products approved to treat older children and adults with bacterial conjunctivitis. Bacterial organisms were consistent between these 2 populations.
CONCLUSIONS AND RELEVANCE
Comparison of the pooled analysis of these historical trial data suggests similarity in the cause of disease and the treatment response between neonates and older children and adults with bacterial conjunctivitis. Therefore, it was appropriate to extrapolate the effectiveness from older children and adults to neonates to support the approval of therapies for ophthalmia neonatorum. Based on this analysis, ophthalmic solutions of ciprofloxacin, gatifloxacin, and moxifloxacin are now approved for all age groups. This analysis presents an approach of using pooled data from previously underpowered individual trials to establish the similarities in the cause of disease and in treatment response between children and adults, which are the fundamental elements used to evaluate whether extrapolation of effectiveness can be used to support drug approval.
Topics: Administration, Ophthalmic; Age Factors; Anti-Bacterial Agents; Comparative Effectiveness Research; Conjunctivitis, Bacterial; Drug Approval; Evidence-Based Medicine; Humans; Infant, Newborn; Ophthalmia Neonatorum; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 33331874
DOI: 10.1001/jamaophthalmol.2020.5558 -
Cleveland Clinic Journal of Medicine Dec 2019
Topics: Acute Generalized Exanthematous Pustulosis; Administration, Topical; Aged; Anti-Bacterial Agents; Biopsy; Ciprofloxacin; Conjunctivitis, Bacterial; Diagnosis, Differential; Drug Substitution; Emollients; Glucocorticoids; Humans; Male; Mupirocin; Ophthalmic Solutions; Skin; Treatment Outcome; Withholding Treatment
PubMed: 31821140
DOI: 10.3949/ccjm.86a.19061 -
BMJ Case Reports Jul 2019
Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Coitus; Conjunctivitis, Bacterial; Gonorrhea; Humans; Levofloxacin; Male; Neisseria gonorrhoeae; Orbital Cellulitis; Photophobia; Treatment Outcome
PubMed: 31340941
DOI: 10.1136/bcr-2018-227787 -
American Journal of Ophthalmology Jul 2020To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and inflammatory components of bacterial conjunctivitis.
DESIGN
Randomized, double-masked, multicenter, phase 3 clinical trial.
METHODS
Subjects of all ages (those <3 months had to be full-term) with a diagnosis of bacterial conjunctivitis were randomized 3:1:3 to either PVP-I/DEX, PVP-I alone, or placebo. The primary endpoint was clinical resolution in the study eye, and the key secondary efficacy endpoint was bacterial eradication, both at the day 5 visit. Adverse events (AEs) were documented at all visits.
RESULTS
Overall, 753 subjects were randomized (intent-to-treat [ITT] population; PVP-I/DEX [n = 324]; PVP-I [n = 108]; placebo [n = 321]); mean and standard deviation (SD) age was 44.3 (22.9) years, and most were female (61.2%) and white (78.1%). In all treatment groups, mean treatment compliance was >98%. The modified ITT population for the efficacy analysis comprised 526 subjects. In the study eye at the day 5 visit, clinical resolution was achieved by 50.5% (111/220) subjects in the PVP-I/DEX group vs 42.8% (95/222) in the placebo group (P = .127), and bacterial eradication was achieved by 43.3% (94/217) and 46.8% (102/218), respectively (P = .500). Treatment-emergent AEs were experienced by 32.8% (106/323), 39.8% (43/108), and 19.0% (61/321) of subjects in the safety population treated with PVP-I/DEX, PVP-I, and placebo, respectively (most mild in severity).
CONCLUSION
In this study, PVP-I/DEX did not demonstrate additional benefit in clinical efficacy compared with placebo in subjects with bacterial conjunctivitis.
Topics: Acute Disease; Administration, Ophthalmic; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteria; Conjunctivitis, Bacterial; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Glucocorticoids; Humans; Male; Middle Aged; Ophthalmic Solutions; Povidone-Iodine; Prospective Studies; Treatment Outcome
PubMed: 32222367
DOI: 10.1016/j.ajo.2020.03.018 -
The British Journal of General Practice... Dec 2005Uncertainty remains about the extent to which findings from our previously published systematic review and meta-analysis of double-blind, randomised controlled trials of... (Meta-Analysis)
Meta-Analysis Review
Uncertainty remains about the extent to which findings from our previously published systematic review and meta-analysis of double-blind, randomised controlled trials of topical antibiotics compared with placebo in the management of patients with acute bacterial conjunctivitis treated in secondary care outpatient settings are generalisable to the management of the condition in primary care settings. We updated our review, undertaking searches, methodological assessment, data extraction and analysis according to a pre-defined protocol. In addition to the previous three included studies, we identified two additional double-blind primary care trials, one which compares fusidic acid gel with placebo gel and one which compares chloramphenicol eye drops with placebo eye drops in children. Meta-analyses of clinical and microbiological remission data reveal that topical antibiotics are of benefit in improving early (days 2-5) clinical (relative risk [RR] = 1.24, 95% confidence interval [CI] = 1.05 to 1.45) and microbiological (RR = 1.77, 95% CI = 1.23 to 2.54) remission rates; later (days 6-10) data reveal that these early advantages in clinical (RR = 1.11, 95% CI = 1.02 to 1.21) and microbiological cure rates are reduced (RR 1.56, 95% CI = 1.17 to 2.09), but persist. Most cases of acute bacterial conjunctivitis resolve spontaneously. While topical antibiotics are associated with significantly improved rates of early (days 2-5) clinical remission, this benefit is marginal for later remission (days 6-10).
Topics: Acute Disease; Administration, Topical; Anti-Bacterial Agents; Conjunctivitis, Bacterial; Humans; Randomized Controlled Trials as Topic
PubMed: 16378567
DOI: No ID Found -
Saudi Pharmaceutical Journal : SPJ :... Dec 2020Conjunctivitis, caused by bacterial infections, represents health concern and diagnosis of the disease is pivotal for the proper selection of the treatment. The main...
Conjunctivitis, caused by bacterial infections, represents health concern and diagnosis of the disease is pivotal for the proper selection of the treatment. The main causes of bacterial conjunctivitis vary in different countries. The current study investigated the common bacterial causes of bacterial conjunctivitis from eye clinics' attendants and evaluated the effectiveness of different therapeutic approaches. Eye swabs from patients, diagnosed with conjunctivitis, were assessed microbiologically and the isolated bacteria were identified using the standard biochemical identification and sequencing of the 16S rRNA gene. Antibiotics' susceptibility of the conjunctivitis-associated bacterial pathogens was evaluated against nineteen broad-spectrum antibiotics. In the meanwhile, cell-free preparations from probiotic and strains were used to evaluate their antagonistic activities. Findings from this study showed that out of 52 specimen, 17 eye swabs from patients with conjunctivitis were bacterial culture-positive. The identity of the bacterial species, using the biochemical identification system, was (4 isolates) and (13 isolates). spp. showed susceptibility to linezolid, vancomycin, novobiocin, and fluoroquinolones (norfloxacin, ofloxacin, ciprofloxacin and levofloxacin). However, isolates from the two spp. expressed resistance to penicillin G, oxacillin, and cephalexin. As alternatives to antibiotics, the growth of spp., including isolates with antibiotic resistance, was inhibited by cell-free preparations of the 4 probiotic and the 2 strains. These findings provide evidence that topical antibiotics such as fluoroquinolones are still effective antimicrobial agents against staphylococci associated with conjunctivitis whereas probiotic preparations could be promising for further research to pave the way for their therapeutic applications against ophthalmic diseases.
PubMed: 33424249
DOI: 10.1016/j.jsps.2020.10.002 -
The Cochrane Database of Systematic... Sep 2020Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ophthalmia neonatorum is an infection of the eyes in newborns that can lead to blindness, particularly if the infection is caused by Neisseria gonorrhoeae. Antiseptic or antibiotic medication is dispensed into the eyes of newborns, or dispensed systemically, soon after delivery to prevent neonatal conjunctivitis and potential vision impairment.
OBJECTIVES
1. To determine if any type of systemic or topical eye medication is better than placebo or no prophylaxis in preventing ophthalmia neonatorum. 2. To determine if any one systemic or topical eye medication is better than any other medication in preventing ophthalmia neonatorum.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers, date of last search 4 October 2019. We also searched references of included studies and contacted pharmaceutical companies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials of any topical, systemic, or combination medical interventions used to prevent ophthalmia neonatorum in newborns compared with placebo, no prophylaxis, or with each other.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane. Outcomes were: blindness or any adverse visual outcome at 12 months, conjunctivitis at 1 month (gonococcal (GC), chlamydial (CC), bacterial (BC), any aetiology (ACAE), or unknown aetiology (CUE)), and adverse effects. MAIN RESULTS: We included 30 trials with a total of 79,198 neonates. Eighteen studies were conducted in high-income settings (the USA, Europe, Israel, Canada), and 12 were conducted in low- and middle-income settings (Africa, Iran, China, Indonesia, Mexico). Fifteen of the 30 studies were quasi-randomised. We judged every study to be at high risk of bias in at least one domain. Ten studies included a comparison arm with no prophylaxis. There were 14 different prophylactic regimens and 12 different medications in the 30 included studies. Any prophylaxis compared to no prophylaxis Unless otherwise indicated, the following evidence comes from studies assessing one or more of the following interventions: tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%. None of the studies reported data on the primary outcomes: blindness or any adverse visual outcome at any time point. There was only very low-certainty evidence on the risk of GC with prophylaxis (4/5340 newborns) compared to no prophylaxis (5/2889) at one month (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.24 to 2.65, 3 studies). Low-certainty evidence suggested there may be little or no difference in effect on CC (RR 0.96, 95% CI 0.57 to 1.61, 4874 newborns, 2 studies) and BC (RR 0.84, 95% CI 0.37 to 1.93, 3685 newborns, 2 studies). Moderate-certainty evidence suggested a probable reduction in risk of ACAE at one month (RR 0.65, 95% 0.54 to 0.78, 9666 newborns, 8 studies assessing tetracycline 1%, erythromycin 0.5%, povidone-iodine 2.5%, silver nitrate 1%, colostrum, bacitracin-phenacaine ointment). There was only very low-certainty evidence on CUE (RR 1.75, 95% CI 0.37 to 8.28, 330 newborns, 1 study). Very low-certainty evidence on adverse effects suggested no increased nasolacrimal duct obstruction (RR 0.93, 95% CI 0.68 to 1.28, 404 newborns, 1 study of erythromycin 0.5% and silver nitrate 1%) and no increased keratitis (single study of 40 newborns assessing silver nitrate 1% with no events). Any prophylaxis compared to another prophylaxis Overall, evidence comparing different interventions did not suggest any consistently superior intervention. However, most of this evidence was of low-certainty and was extremely limited.
AUTHORS' CONCLUSIONS
There are no data on whether prophylaxis for ophthalmia neonatorum prevents serious outcomes such as blindness or any adverse visual outcome. Moderate-certainty evidence suggests that the use of prophylaxis may lead to a reduction in the incidence of ACAE in newborns but the evidence for effect on GC, CC or BC was less certain. Comparison of individual interventions did not suggest any consistently superior intervention, but data were limited. A trial comparing tetracycline, povidone-iodine (single administration), and chloramphenicol for GC and CC could potentially provide the community with an effective, universally applicable prophylaxis against ophthalmia neonatorum.
Topics: Anti-Infective Agents; Bias; Blindness; Erythromycin; Humans; Infant, Newborn; Ophthalmia Neonatorum; Povidone-Iodine; Randomized Controlled Trials as Topic; Silver Nitrate; Tetracycline; Trachoma; Vision Disorders
PubMed: 32959365
DOI: 10.1002/14651858.CD001862.pub4 -
International Journal of Ophthalmology 2021To detect the quantitative expression levels of the pro-inflammatory interleukin-8 (IL8), antimicrobial peptides human beta defense-2 (HBD2), and human beta defense-3...
AIM
To detect the quantitative expression levels of the pro-inflammatory interleukin-8 (IL8), antimicrobial peptides human beta defense-2 (HBD2), and human beta defense-3 (HBD3) genes in bacterial conjunctivitis.
METHODS
The human conjunctival epithelial cells were obtained using the impression cytology technique from healthy controls and patients. The genes expression levels were determined utilizing a reverse transcription quantitative polymerase chain reaction (RT-qPCR). The contribution of causative agent type, the number of isolates and severity of clinical features, in the increase of genes expression was also determined.
RESULTS
The RT-qPCR showed that IL8, HBD2, and HBD3 expression increased in bacterial conjunctivitis as compared to healthy control (<0.001). In gram-negative bacterial conjunctivitis, HBD2 was highly up-regulated (<0.001) compared to other types of bacterial conjunctivitis. In mixed bacterial conjunctivitis, a direct correlation between HBD2 up-regulation and HBD3 up-regulation was observed (<0.05). The severity of clinical features was related to the up-regulation of IL8 and HBD2 (<0.05).
CONCLUSION
IL8, HBD2, and HBD3 are immune-effectors in infectious conjunctivitis. HBD2 is active during different bacterial conjunctivitis but is more released with gram-negative bacteria compared to gram-positive bacteria. HBD3 is an obvious defender in different bacterial conjunctivitis.
PubMed: 34012880
DOI: 10.18240/ijo.2021.05.05 -
Scientific Reports Jan 2021Haemophilus influenzae is a predominant pathogen for conjunctivitis, acute otitis media and acute bacterial paranasal sinusitis in children. We undertook this study to...
Haemophilus influenzae is a predominant pathogen for conjunctivitis, acute otitis media and acute bacterial paranasal sinusitis in children. We undertook this study to investigate the possible association among these diseases. Children younger than 18-year-old with a diagnosis of bacterial conjunctivitis plus acute otitis media and/or acute bacterial paranasal sinusitis during 2009-2018 were included. Sampling for bacterial cultures was obtained from the lower palpebral conjunctiva and/or ear discharge with cotton-tipped swabs. A total of 67 children were recruited and the age was 29.5 (± 22.4) months in average. Fifty-seven children had conjunctivitis-otitis media syndrome and eight of them had a concurrent diagnosis of acute paranasal sinusitis. Ten children had conjunctivitis and acute paranasal sinusitis simultaneously. Clusters in household were observed in 50.7% children. Most common isolates were Haemophilus influenzae (70%), Moraxella catarrhalis (18%), and Staphylococcus aureus (8%). Antibiotic resistance rate of H. influenzae was 80% for ampicillin, 18% for amoxicillin-clavulanate, and 11% for the second or third-generation cephalosporins. Apart from well-known conjunctivitis-otitis media syndrome, acute paranasal sinusitis may also be linked to conjunctivitis with a similar pathogenic process. Simultaneous presence of these infections may guide the choice of empiric antibiotics toward H. influenzae.
Topics: Acute Disease; Child; Child, Preschool; Conjunctivitis, Bacterial; Drug Resistance, Microbial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Sinusitis
PubMed: 33420151
DOI: 10.1038/s41598-020-79680-6 -
Journal Francais D'ophtalmologie Jan 2020
Topics: Azithromycin; Chlamydia trachomatis; Conjunctivitis, Inclusion; Conjunctivitis, Viral; Diagnosis, Differential; Humans; Male; Young Adult
PubMed: 31753423
DOI: 10.1016/j.jfo.2019.03.036