Use Of Intravitreal Antibiotics Research Articles

Emerging Antibiotic Resistance Patterns Affect Visual Outcome Treating Acute Endophthalmitis.

Background: Examining the effect of antibiotic resistance, use of intravitreal antibiotics and systemic corticosteroids on visual outcome of eyes with acute endophthalmitis. Methods: We included 226 eyes with acute endophthalmitis, treated using a standardized protocol. Visual outcome up to 12 months was assessed related to biopsy results, antibiotics resistance and treatment regimens. Results: Vitreous biopsies were more likely to be culture-positive (41.1%) than anterior chamber biopsies (21.6%, p < 0.0001). Antibiotic resistance for amikacin was found in 19 eyes (24.7%), vancomycin in 29 eyes (31.5%) and moxiflocacin in 14 eyes (16.1%). At presentation 91.53% of eyes had BCVA < 20/40, reducing by 1 month to 69.94% (p < 0.0001) and remaining stable at 12 months. There was no difference in visual outcome for those receiving early systemic corticosteroids. Endophthalmitis following cataract surgery (OR 1.66, 1.04–2.66 95% CI, p = 0.03) and receiving intravitreal vancomycin (OR 3.15, 1.18–8.42 95% CI, p = 0.02) were associated with a greater chance of final BCVA ≥ 20/40. Conclusion: Using vitreous taps with intravitreal antibiotics, despite an increase in resistance to both vancomycin and moxifloxacin, results in a final BCVA > 20/200 in half of eyes and ≥20/40 in a third. Early treatment with intravitreal antibiotics should not be delayed.

Clinical and visual outcomes following endogenous endophthalmitis: 175 consecutive cases from a tertiary referral center in Taiwan.

To elucidate the linkage between organisms and visual outcome in cases of endogenous endophthalmitis. Patients who presented with signs of endogenous endophthalmitis between January 2008 and December 2015 and underwent a vitreous tapping were enrolled. The patients' demographics and clinical findings were recorded. The outcomes include visual acuity and enucleation. A total of 175 consecutive patients with endogenous endophthalmitis were enrolled. Forty-four percent of the patients had a known distal focus of infection. The most common focus was liver abscess (24.6%), and the major intravitreal isolate was Klebsiella pneumoniae (34.4%). In this series, 51.4% of the intravitreal cultures were positive. The visual acuity of fungal ophthalmitis were better than in bacterial ophthalmitis. Multivariate logistic regression showed that Gram negative vitreous isolates, compared with the negative vitreous culture, were associated with higher risk of enucleation (Odds ratio [OR]: 10.424, 95% confidence interval [95% CI]: 3.019-35.995). The use of intravitreal antibiotics, compared non-users, was associated with a reduced risk of enucleation (OR:0.084, 95% CI: 0.026-0.268). Trans pars plana vitrectomy was not associated with risk of enucleation (OR: 0.307, 95% CI: 0.035-2.693). The post-treatment VA was positively correlated with the presenting VA (r=0.718, p=0.0001). Our study demonstrated that liver abscess is the most common source of endogenous endophthalmitis in Taiwan. The visual outcome is good when the presenting visual acuity is relatively well preserved and when the infecting organism is fungus. The use of intra-vitreal antibiotics reduces the risk of enucleation.

Outbreak of Multidrug-resistant Pseudomonas Aeruginosa Endophthalmitis Due to Contaminated Trypan Blue Solution.

PurposeTo report the investigation of an outbreak of multidrug-resistant (MDR) Pseudomonas aeruginosa endophthalmitis in 13 patients after cataract surgery and to emphasize on the importance of clinical profile, risk factors, and treatment outcomesMethodsThis was a hospital-based, retrospective case study with 13 consecutive patients who had man- ual small-incision cataract surgery with intraocular lens (IOL) implantation and developed acute postoperative Pseudomonas aeruginosa endophthalmitis. The anterior chamber taps, vitreous aspirates, and environ- mental surveillance specimens were inoculated for culturing. Antibiotic susceptibility testing was performed using the agar diffusion method. Pulsed-field gel electrophoresis (PFGE) was used to determine the relation- ship between bacterial isolates recovered from study patients and contaminated surveillance samples.ResultsPseudomonas aeruginosa was isolated from all 13 eyes with acute postoperative endophthalmitis and the trypan blue solutions used during surgery. Sensitivity tests revealed that all isolates had an identical resistance to multiple drugs and were only susceptible to imipenem. Genomic DNA typing of Pseudomonas aeruginosa isolates recovered from patients and trypan blue solutions showed an identical banding pattern on the PFGE. Despite the prompt use of intravitreal antibiotics and early vitrectomy with IOL explantation in some patients, the outcome was poor in about 50% of patients.ConclusionPositive microbiology and genomic DNA typing results proved that the contaminated trypan blue solutions were the source of infection in this outbreak. Postoperative endophthalmitis caused by Pseudomonas aeruginosa is often associated with a poor visual prognosis despite prompt treatment with intravitreal antibiotics.

Pediatric Posttraumatic Endophthalmitis in China for Twenty Years.

Pediatric posttraumatic endophthalmitis (PTE) is a rare but serious disease that frequently has a poor visual prognosis. To date, only a few English studies have focused on this disease. We perform a systematic review of the Chinese literature on pediatric PTE and describe the epidemiology, management, causative organisms, and visual acuity outcomes of reported cases in twenty years. We found that Staphylococcus epidermidis was the most common isolated organism and the use of a disposable syringe needle was the most common cause of ocular injuries in pediatric PTE in China. In the last ten years, the time from injury to first presentation for treatment has shortened, the proportion of cases resulting from a disposable syringe needle has decreased, the use of intravitreal antibiotics as the initial treatment has increased, and the use of palliative treatment has decreased. Although these favorable changes have occurred in the last ten years, the visual prognosis of pediatric PTE is still poor.

Pharmacokinetics of intravitreal antibiotics in endophthalmitis.

Intravitreal antibiotics are the mainstay of treatment in the management of infectious endophthalmitis. Basic knowledge of the commonly used intravitreal antibiotics, which includes their pharmacokinetics, half-life, duration of action and clearance, is essential for elimination of intraocular infection without any iatrogenic adverse effect to the ocular tissue. Various drugs have been studied over the past century to achieve this goal. We performed a comprehensive review of the antibiotics which have been used for intravitreal route and the pharmacokinetic factors influencing the drug delivery and safety profile of these antibiotics. Using online resources like PubMed and Google Scholar, articles were reviewed. The articles were confined to the English language only. We present a broad overview of pharmacokinetic concepts fundamental for use of intravitreal antibiotics in endophthalmitis along with a tabulated compendium of the intravitreal antibiotics using available literature. Recent advances for increasing bioavailability of antibiotics to the posterior segment with the development of controlled drug delivery devices are also described.

Post-traumatic endophthalmitis

Sir, We read with interest the survey on post-traumatic endophthalmitis by Flynn and co-authors.1 The authors have described the use of systemic or intravitreal antifungal agents in so-called ‘suspected fungal endophthalmitis'. Before instituting antifungal treatment, distinguishing fungal from bacterial post-traumatic endophthalmitis is important because the treatments are different and prophylactic antifungal treatment can be toxic both systemically or locally.2, 3, 4 A clinical feature that suggests fungal infection is a delayed onset of inflammation after injury.2, 3, 4 Literature search has reported that all post-traumatic cases of fungal endophthalmitis became symptomatic between the first and fifth weeks after injury, with minimal discomfort to the patient.3, 4 In the absence of microbiological diagnosis, clinical signs suggesting infection include slow indolent smouldering intraocular inflammation associated with a relatively quiet eye, which may or may not be associated with the presence of an inflammatory mass in the vitreous or anterior chamber that is described as a ‘fungal ball', or white vitreous ‘snowball', or ‘string of pearls'. More often than not, the patients with fungal endophthalmitis may have only minor discomfort.2, 3, 4 Similarly, not all clinicians agree with the routine use of intravitreal antibiotics in prophylaxis.5 In patients with open globe injuries and traumatic endophthalmitis, there is always a risk of associated retinal detachment or choroidal detachment. Pre-operative B-scan is not routinely done in eyes with open globe injury and hence intravitreal injection can pose an additional risk of injection going inadvertently into subretinal or suprachoroidal space. On the other hand, it is important to realize that no large, randomized, prospective study has explicitly demonstrated a decrease in incidence of post-traumatic endophthalmitis with prophylactic antibiotics in eyes without IOFBs. For ruptured globes without IOFBs, until a prospective study shows a clear benefit from a prophylactic treatment protocol, one approach might be to treat all open globe injuries with systemic (oral/intravenous) and topical antibiotics for a few days. Intravitreal antibiotics prophylaxis can be used selectively in eyes with contaminated injuries, greater wound length, or delayed primary closure of the wound, and after ruling out retinal detachment or suprachoroidal haemorrhage, because such cases have an increased risk of endophthalmitis.6

Predictive factors and outcomes for posterior segment intraocular foreign bodies

Sir, We read with interest the article on ‘Predictive factors and outcomes of posterior segment intraocular foreign bodies' by Choovuthayakorn et al.1 In the results section, 4 (4.76%) of the 84 eyes with intraocular foreign bodies (IOFB) underwent primary enucleation. Given the trend to avoid primary enucleation following trauma, it would have been helpful if the authors had described the indications for primary enucleation in these eyes and why enucleation was preferred over evisceration. One of the key conclusions drawn, and perhaps the most controversial, is that good outcome can be achieved even if there is delay in removal of IOFB. The incidence of endophthalmitis reported by the authors in this series was 9.1% that, though comparable with the literature, was still quite high. In another case series of 1421 eyes with IOFB by Zhang et al,2 the reported rate of endophthalmitis was much higher at 16.76%, pointing possibly to the influence of IOFB presence. The two referenced papers3, 4 citing low-risk or no risk of endophthalmitis with delayed removal of IOFB were in the context of war injuries, whereby high-velocity explosives and the heat generated before impact could potentially partially account for the relatively lower incidence of endophthalmitis. Furthermore, there was no mention about the use of intravitreal antibiotics in this case series, which has a major role in prevention and treatment of post traumatic endophthalmitis.5 In conclusion, we are concerned that the article may create the impression that delayed removal of IOFB can achieve good visual outcome by giving systemic antibiotics and prompt primary repair. On the contrary, especially if there is presence of a vegetative foreign body, prompt wound closure with simultaneous removal of IOFB with systemic and intravitreal antibiotics should be the preferred practice pattern for most ophthalmologists.5 Second sitting removal of IOFB should be considered only in patients with significantly large corneoscleral wounds that may leak during vitrectomy and in cases with associated retinal detachment requiring complex vitreoretinal surgery.5

Role of Inflammation in Endophthalmitis

Inflammation originating from infection of the vitreous cavity is called endophthalmitis. Attention has been focused on the epidemiologic, microbiologic reports, and treatment options; unfortunately, the role of the host immune reaction in the visual function damage is still not well understood. Endophthalmitis occurs most frequently after cataract surgery. In this paper we review the published literature regarding inflammatory mediators and apoptosis during the course of endophthalmitis. Toll-like receptors, cytokines, high-mobility group box 1 proteins, aB-crystallin and apoptosis have been studied during clinical and experimental cases of endophthalmitis. Further understanding of the host-immune reaction to vitreous infection is essential for the development of new therapies. The use of intravitreal antibiotics and corticosteroids, vitrectomy and systemic antibiotics for the preservation of visual function is still discouraging.

Endophthalmitis following open-globe injuries.

The incidence of traumatic endophthalmitis may be decreasing due to earlier wound closure and prompt initiation of antibiotics. Risk factors for endophthalmitis include retained intraocular foreign body, rural setting of injury, disruption of the crystalline lens, and a delay in primary wound closure. The microbiology in the post-traumatic setting includes a higher frequency of virulent organisms such as Bacillus species. Recognizing early clinical signs of endophthalmitis, including pain, hypopyon, vitritis, or retinal periphlebitis may prompt early treatment with intravitreal antibiotics. Prophylaxis of endophthalmitis in high-risk open-globe injuries may include systemic broad-spectrum antibiotics, topical antibiotics, and intravitreal antibiotics to cover both Gram-positive and Gram-negative bacteria. For clinically diagnosed post-traumatic endophthalmitis, intravitreal vancomycin, and ceftazidime are routinely used. Concurrent retinal detachment with endophthalmitis can be successfully managed with vitrectomy and use of intravitreal antibiotics along with a long acting gas or silicone oil tamponade. Endophthalmitis is a visually significant complication of open-globe injuries but early wound closure as well as comprehensive prophylactic antibiotic treatment at the time of injury repair may improve visual acuity outcomes.

An Outbreak of Post-Cataract Surgery Endophthalmitis Caused by Pseudomonas aeruginosa

Infectious endophthalmitis is among the most serious complications of cataract surgery. Gram-negative bacteria, including Pseudomonas aeruginosa, are responsible for less than 30% of cases; however, their rapidity of infection and virulence often results in poor visual outcome despite prompt antibiotic treatment. The purpose of this study was to investigate an outbreak of post-cataract surgery P. aeruginosa endophthalmitis in India. Hospital-based case series. Twenty patients with acute postoperative endophthalmitis who underwent cataract surgery at one of the peripheral centers of Joseph Eye Hospital, Tiruchirapalli, Tamil Nadu, India, from February 23 to April 2, 2008. Vitreous aspirates and environmental surveillance specimens were inoculated for culture. Antibiotic susceptibility testing was performed by agar diffusion method. Polymerase chain reaction (PCR) with enterobacterial repetitive intergenic consensus (ERIC) primers (ERIC-PCR) was used to establish the clonal relationship between clinical and environmental isolates. Post-cataract surgery P. aeruginosa endophthalmitis. Pseudomonas aeruginosa was isolated from 20 eyes with postoperative endophthalmitis, the phacoemulsifier's internal tubes, the povidone-iodine solution, and the operating theater air-conditioning system. All strains were multidrug-resistant to cefazolin, chloramphenicol, tetracycline, aminoglycosides, and fluoroquinolones; conversely, most of them were susceptible to polymyxin B. Polymerase chain reaction with enterobacterial repetitive intergenic consensus primers disclosed 2 major clusters: six genetically identical clinical isolates shared 94% of similarity with the air-conditioning isolate; 11 other clinical isolates had 88% of similarity with the former strain. Despite the prompt use of intravitreal antibiotics, 10 patients had evisceration or phthisis of the affected eye. The outcome of cataract surgery-related P. aeruginosa endophthalmitis is poor. The detection of multidrug-resistant isolates is a serious problem, jeopardizing an appropriate choice of treatment. Polymerase chain reaction with enterobacterial repetitive intergenic consensus results strongly suggest that the main source of infection in this outbreak was the contaminated air-conditioning system. Polymerase chain reaction with enterobacterial repetitive intergenic consensus is an inexpensive, fast, reproducible, and discriminatory DNA typing tool for effective epidemiologic surveillance of clinical and environmental isolates of P. aeruginosa.

Polymerase chain reaction identification in aqueous humor of patients with postoperative endophthalmitis

To identify bacterial agents in the aqueous humor of patients with postoperative endophthalmitis using eubacterial polymerase chain reaction (PCR) and conventional culture. University Hospital of Lyon E. Herriot, Lyon, France. Broad-range eubacterial PCR amplification followed by direct sequencing was used to identify microbial pathogens in ocular samples from 30 patients with acute or delayed-onset endophthalmitis, mainly after cataract surgery. Ocular samples included aqueous humor collected before the first intravitreal injection of antibiotics and vitreous samples collected at the time of the therapeutic pars plana vitrectomy. Cultures were positive in 32% of cases and PCR in 61% of cases with aqueous humor samples. When associated, culture and PCR of aqueous humor samples allowed for a microbiological diagnosis in 71% of cases. Microorganisms cultured by conventional techniques matched those identified by PCR. When applied on vitreous pretreated with intravitreal antibiotics, PCR increased the identification rate from 18% to 62%. Polymerase chain reaction assay of initial aqueous humor samples contributed to the diagnosis of endophthalmitis in 30% of cases. Previous use of intravitreal antibiotics did not seem to affect the ability to PCR-amplify DNA in the short term. Polymerase chain reaction-based technology was a useful adjunct to conventional culture because when used with aqueous humor samples only, the association of both techniques allowed for a microbiological diagnosis in 71% of cases of postoperative acute and delayed-onset endophthalmitis.

Hypopyon and Pseudoendophthalmitis Associated With Chronic Vitreous Hemorrhage

Infectious endophthalmitis is an uncommon but potentially devastating eye disease. Although the presence of a hypopyon is considered one of the hallmark clinical signs of infectious endophthalmitis, hypopyon associated with non-infectious causes may occur. Two patients with hypopyon and pseudoendophthalmitis secondary to chronic vitreous hemorrhage are described. In both cases, the hypopyon improved without the use of intravitreal antibiotics.

Endophtalmie à Penicillium chrysogenum: À propos d’un cas

We report a case of Penicillium chrysogenum endophthalmitis after penetrating ocular trauma in a 9-year-old child, describing the initial management and the therapeutic adaptation after biopsy culture. After a review of endophthalmitis treatment, we discuss mycotic endophthalmitis treatment and recommend the use of intravitreal antibiotics. In this case, we used amphotericin B to treat the fungal disorder with success.

Retained Intraocular Fore ign Bodies and Endonhthalmltls

Retained intraocular foreign bodies (IOFBs) are associated with endophthalmitis in approximately 7 to 13% of cases. The role of prompt surgical removal of the foreign body along with the use of intravitreal antibiotics in reducing this figure is uncertain. Retained IOFBs presenting to The Medical College of Wisconsin between July 1986 and June 1989 were reviewed. A total of 27 cases were evaluated and surgically treated. None of the 27 cases presented with or developed clinical signs of endophthalmitis, yet bacterial cultures of the removed intraocular material were positive in seven cases (foreign body in 5 cases, the aqueous fluid and the vitreous fluid in 1 case each). All eyes presenting within 24 hours of injury underwent immediate surgery (average, 4.5 hours after presentation). Of the seven eyes with positive intraocular cultures, all had pars plans vitrectomy removal of the IOFB and three of these eyes received intravitreal antibiotics at the time of surgery over concern of a high risk of infection. Two of these eyes eventually grew out the Bacillus sp. All eyes received subconjunctival antibiotics and postoperative topical and systemic antibiotics. Even after the positive cultures, no signs of clinical infection developed in any of the eyes. All seven eyes retained excellent visual acuity of 20/70 or better at an average of 10 months' follow-up. Follow-up ranged from 1 to 37 months. Prompt surgical intervention, the use of intravitreal antibiotics in high-risk-type injuries, and the possible use of vitrectomy surgery may reduce the incidence and severity of endophthalmitis.

Staphylococcus epidermidis Endophthcilmitis: Visual Outcome Following Noninvasive Therapy

Staphylococcus epidermidis has been reported with increasing frequency as a cause of bacterial endophthalmitis. Over the past eight years 18 consecutive postsurgical cases have been treated by combined anti biotic-corticosteroid therapy without intravitreal antibiotics or vitrectomy. Fourteen (78%) achieved a final visual acuity of 20/50 or better. When these cases were added to similarly reported cases in the literature, 72% achieved this level of vision. By contrast, 42% of adequately documented cases in the literature treated by intravitreal antibiotics, and 42% treated additionally by vitrectomy, achieved a vision of 20/50 or better. S. epidermidis is an organism with a low order of virulence. The use of intravitreal antibiotics and vitrectomy do not appear to be necessary for effective treatment.

The experimental and clinical use of intravitreal antibiotics to treat bacterial and fungal endophthalmitis

The experimental data involving the use of 14 antibacterial and two antifungal agents have been used to establish a rationale for the management of human endophthalmitis. Twelve cases of endophthalmitis treated under our supervision have been described in detail. The eventual visual outcome is related to two factors: (1) time interval between diagnosis and institution of adequate therapy, and (2) the severity of the organism and its ability to produce exotoxins and proteolytic enzymes. Eleven of 12 cases were cured with the recommended dosages of gentamicin and dexamethasone (400 mcg and 360 mcg, respectively). Eight of the 12 patients retained useful vision of 20/200 or better.