Endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility: literature review and options for treatment

Abstract

Background

Endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or resistance is an important clinical issue worldwide.

Purpose

To review the published literature on endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance.

Methods

The data were analysed from a PubMed search of endophthalmitis cases caused by Gram-positive organisms with reported reduced vancomycin susceptibility and/or vancomycin resistance from 1990 to 2015.

Results

From 18 publications identified, a total of 27 endophthalmitis cases caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance were identified. The aetiologies of endophthalmitis were exogenous in 19/27 cases (11 post-cataract surgery, 2 post-penetrating keratoplasty, 1 post-glaucoma surgery, 4 post-open globe injury, 1 post-intravitreal injection of ranibizumab), and endogenous in 4/24 cases; no details were available about the four remaining patients. The causative organisms included Enterococcus species (7/27), coagulase-negative staphylococci (4/27), Staphylococcus aureus (4/27), Bacillus species (4/27), Streptococcus species (3/27), Leuconostoc species (3/27), Staphylococcus hominis (1/27), and unidentified Gram-positive cocci (1/27). Visual acuity of 20/400 or better at the final follow-up was recorded in 10/26 patients (38.5%; data were not available for one patient). Treatment options include fluoroquinolones, penicillin, cephalosporins, tetracyclines, and oxazolidinones.

Conclusions

In the current study, visual acuity outcomes were generally poor. Enterococcus and Staphylococcus species were the most common organisms reported and postoperative endophthalmitis after cataract surgery was the most common clinical setting.

INTRODUCTION

Infectious endophthalmitis is a rare but potentially blinding disease caused by bacterial or fungal microbes involving intraocular fluids and tissues of the eye. Gram-positive organisms are the most common cause of postoperative endophthalmitis.¹ Intravitreal antibiotics (broad spectrum drugs covering Gram-positive and Gram-negative organisms) with or without vitrectomy remain standard treatment in suspected bacterial cases.

Vancomycin, a glycopeptide antibiotic, is usually effective against most Gram-positive organisms (Streptococcus, Staphylococcus, and Bacillus species). Vancomycin was discovered in the 1950s and approved for human use by the US Food and Drug Administration (FDA) in 1958, for the management of severe life threatening and organ threatening infections caused by susceptible organisms.² Vancomycin acts by binding irreversibly to D-alanyl-D-alanine moieties of the N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) peptides. This inhibits synthesis and cross-linking of the NAM/NAG polymers that form the backbone of the bacterial cell wall. Intravitreal injection of vancomycin has been reported in the literature to be nontoxic.^3,4 For ocular use, both intravitreal and topical vancomycin are prepared by compounding. The risk of contamination during compounding is very low in pharmacies using the US Pharmacopeia (USP) 797 guidelines in the USA.⁵ As reported in the Endophthalmitis Vitrectomy Study (EVS)⁶ in 1994 and the Antibiotic Resistance Monitoring in Ocular micRoganisms (ARMOR) 2009 surveillance study,⁷ 100% of the Gram-positive organisms from culture positive cases were found to be susceptible to vancomycin. Endophthalmitis may also be caused by organisms which are resistant or have reduced susceptibility to standard antimicrobial regimens. Specifically, there have been recent reports of reduced vancomycin susceptible or vancomycin resistant organisms (Streptococcus, Enterococcus, Staphylococcus, and Leuconostoc species) causing endophthalmitis.^8–25

The current study evaluates the published reports of endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance, and summarises the treatment outcomes in these patients.

METHODS

All endophthalmitis cases caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance, reported on PubMed from the years 1990 to 2015, were reviewed. The data were analysed with respect to clinical presentation, microbiological profile, management, and clinical outcomes.

RESULTS

Using these 18 reports, there were 27 endophthalmitis cases caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance.^8–25 Detailed information of all the cases is summarised in tables 1 and 2. The ages of patients ranged from newborn to 88 years. Fourteen out of 23 patients were males (information not available for remaining four cases). The aetiologies of endophthalmitis were exogenous in 19/27 (11 post-cataract surgery, 2 post-penetrating keratoplasty, 1 post-glaucoma surgery, 4 post-open globe injury, 1 post-intravitreal ranibizumab injection), and endogenous in 4/27; no details were available about the four remaining patients.

Table 1.

Reported cases of reduced vancomycin susceptible organisms causing exogenous endophthalmitis: clinical features, microbiology and treatment outcomes^8–25

Category (Author/year)	Age/sex	VA (initial)	VA (final)	Treatment	Topical antibiotics	Systemic antibiotics	Isolates	Comment (outcome/ coexisting pathology)
After cataract surgery
Kumudhan et al, 2004	76/M	LP	HM	VB+IOAB (V+A)	CFC, G	CFC	Leuconostoc mesenteroides	(U)
Durkin et al, 2008	43/M	CF	20/40	VB+IOAB (V+C), PPV+IOAB (V+C)	NA	None	Leuconostoc species	(F)
Sharma et al, 2010	73/F	CFCF	20/200	PPV+IOAB (V+C)	Ch, G	Linezolid	Enterococci species	(F) ARMD
Das et al, 2011	57/M	HM	20/60	VB+IOAB (V+A)	MFC	None	CNS	(F) RD
Hernandez-Da Mota et al, 2011	55/M	HM	20/40	VB+IOAB (Q/D+C+D)	NA	None	CNS	(F)
Stroh et al, 2012	83/M	HM	20/50	PPV+ACW+RW+IOAB (Q/D+C)	V,C	Linezolid+minocycline—21 days,	Staphylococcus aureus	(F)
				IOAB−Q/D+A		and R+M—3 months
	78/M	LP	CF	PPV+ACW+RW+IOAB (V+C)	V,C	Linezolid + minocycline—21 days,	Staphylococcus aureus	(F) CRVO
				IOAB (V+C)		and R+M—3 months
				IOAB (Q/D+A)
Khera et al, 2013	70/F	LP	LP	PPV+IOAB+IOL explants	V+A	Gatifloxacin	Staphylococcus epidermidis	(U)
	70/M	LP	20/20	PPV+IOAB	V+A	CFC	Bacillus species	(F)
	60/M	LP	LP	PPV+IOAB	V+C	CFC	Enterococcus faecalis	(U)
Won et al, 2013	80/M	CF	20/400	VB+IOAB (V+C) PPV+SOI +IOL explant	Tp+V	–	Staphylococcus hominis	(F)
After PK
Bains et al, 2007	73/F	LP	20/80	PPV+IOAB (V+A)	V+G	Linezolid+ampicillin	Enterococcus faecium	(F) Pale disc
Hernandez et al, 2012	51/F	LP	LP	PPV+IOAB (V+C+D)	MFC, Cef	Linezolid for 1 week (iv)	Enterococcus species	(U)
After glaucoma surgery
Tang et al, 2007	79/F	HM	HM (30 cm)	PPV+PPL+IOAB (V+A) IOAB – ampicillin	NA	Penicillin G	Enterococcus faecalis	(U)
After open globe
Hillier et al, 2013	88/M	HM	20/200	PPV+PPL+IOFB−R+IOAB (V+C+D) IOAB – ampicillin +Amikacin	G	Ampicillin+clindamycin followed by MFC	Enterococcus gallinarum	(F) RD
Khera et al, 2013	20/M	LP	CF 1 m	CTR+PPV+IOAB (V+C) and PPV+membranectomy+IOAB (C+T)	CFC	CFC	Bacillus macerrans	(U)
	5/M	LP	LP	CTR+PPL+PPV+IOAB (V+C+A)	CFC	CFC	Bacillus cereus	(U)
	4/F	HM	LP	CTR+PPL+PPV+IOAB (V+C)	CFC	CFC	Bacillus species	(U)
After intravitreal injection
Damasceno et al, 2015	89/M	LP	NLP	VB+IOAB (V+A), IOAB (A) twice	MFC	Gatifloxacin	Leuconostoc species	(U)

This table excludes the four cases reported in references 5 and 6 as complete details were not available.

(F), favourable outcome; (U), unfavourable outcome; A, amikacin; ACW, anterior chamber wash; ARMD, age related macular degeneration; C, ceftazidime; Cef, ceftriaxone; CF 1 m, counting fingers at 1 m; CFC, ciprofloxacin; CFCF, counting fingers close to face; CF, counting fingers; Ch, chloramphenicol; CNS, coagulase-negative staphylococci; CRVO, central retinal vein occlusion; CTR, corneal tear repair; d, days; D, dexamethasone; F, female; G, gentamicin; HM, hand motions; IOAB, intravitreal antibiotics; IOFB-R, intraocular foreign body removal; iv, intravenous; LP, light perception; M, male; MFC, moxifloxacin; M, minocycline; NA, information not available; NLP, no light perception; PK, penetrating keratoplasty; PPL, pars plana lensectomy; PPV, pars plana vitrectomy; Q/D, quinupristin/dalfopristin; RD, retinal detachment; R, rifampin; RW, resuturing of wound; SOI, silicone oil injection; Tp, teicoplanin; T, triamcinolone; V, vancomycin; VA, visual acuity; VB, vitreous biopsy.

Table 2.

Reported cases of reduced vancomycin susceptible organisms causing endogenous endophthalmitis: clinical features, microbiology and treatment outcomes^16,23–25

Category (author/year)	Age/ sex	VA (initial)	VA (final)	Treatment	Topical antibiotics	Systemic antibiotics	Isolates	Comments (outcome)
Esmaeli et al, 2003	70/F	LP	Enuc	IOAB (V+C)	NA	Rifampin+cefepime +trovafloxacin+alatrofloxacin	Enterococci	(U) Enucleation
Khera et al, 2013	16/F	LP	Enuc	PPV+IOAB	CFC	CFC	Staphylococcus aureus	(U) Enucleation
Dedania et al, 2014	48/F	HM	LP	IOAB (V+C) IOAB (clinda+amika)	NA	Vancomycin, daptomycin	Staphylococcus aureus	(U)
Relhan et al, 2015	18d/M	–	FL	VB+IOAB (V+C+D), IOAB (P/T)	CFC	Cefpodoxime	Coagulase-negative staphylococci	Good

(F), favourable; (U), unfavourable; Amika, amikacin; C, ceftazidime; CFC, ciprofloxacin; D, dexamethasone; Enuc, enucleation; F, female; FL, follows light; HM, hand motions; IOAB, intravitreal antibiotics; LP, light perception; M, male; NA, information not available; P/T, piperacillin-ticarcillin; PPV, pars plana vitrectomy; V, vancomycin; VA, visual acuity; VB, vitreous biopsy.

The causative organisms included Enterococcus species (7/27, 6 exogenous and 1 endogenous), coagulase-negative staphylococci (4/27, 3 exogenous and 1 endogenous), Staphylococcus aureus (4/27, 2 exogenous and 2 endogenous), Bacillus species (4/27, all exogenous), Streptococcus species (3/27 cases), Leuconostoc species (3/27, both exogenous), and Staphylococcus hominis (1/27, exogenous). Microbiological methods used to determine antibiotic susceptibility in these reported cases included broth microdilution, disk diffusion, and culture analysis (table 3).

Table 3.

Sensitivities of reduced vancomycin susceptible isolates reported in literature^{12–21,23,25}

Report (Author/year)	Isolates	Sample used	Susceptibility method used	Alternative sensitive antibiotics	Resistance in addition to vancomycin
Sharma et al, 2010	Enterococcus species	Vitreous culture	Vitek-2	Ch, linezolid, Q/D	Ampicillin, LFC, erythromycin, penicillin, streptomycin, tetracycline, CFC
Das et al, 2011	CNS	Vitreous culture	Disk diffusion	–	GFC, OFC, CFC, MFC (I), piperacillin-tazobactam (I)
Hernandez-Da Mota et al, 2011	CNS	Vitreous culture	In vitro tests not performed. Clinically responsive to Q/D	NA	–
Stroh et al, 2012	Staphylococcus aureus	Aqueous & Vitreous culture	Vitek-2	Ch, linezolid, Q/D	MFC, clindamycin, imipenem, methicillin,
Bains et al, 2007	Enterococcus faecium	Aqueous, Vitreous & donor corneal rim culture	MIC—broth microdilution (MIC 64 mg/mL)	NA	–
Tang et al, 2007	Enterococcus faecalis	Vitreous culture	Information not available	Ampicillin, penicillin	All common antibiotics (not mentioned in paper)
Hillier et al, 2013	Enterococcus gallinarum	Vitreous culture	Information not available	Ampicillin, clindamycin	–
Esmaeli et al, 2003	Enterococcus species	Vitreous culture	Information not available	NA	–
Khera et al, 2013	Bacillus, Staphylococcus, Enterococcus species	Vitreous culture	Disk diffusion	CFC, G, amikacin CFC, GFC –	Cefazolin, chloramphenicol Ofloxacin, A, Ch, G Cefazolin, CFC, OFC, A, G Ch, ceftazidime
Hernandez-Camarena et al, 2012	Enterococcus faecium	Vitreous culture	MIC—broth microdilution (MIC 32 mg/mL)	Linezolid, tetracycline	–
Won et al, 2013	Staphylococcus hominis	Vitreous culture	MIC—broth microdilution (MIC 8–16 mg/mL)	TMP/SMZ, teicoplanin	LFC, MFC, CFC, cefazolin
Relhan et al, 2014	CNS	Vitreous culture	Disk diffusion	G, piperacillin-tazobactam	Ampicillin, erythromycin

(I), intermediate sensitivity; A, amikacin; CFC, ciprofloxacin; Ch, chloramphenicol; CNS, coagulase-negative staphylococci; GFC, gatifloxacin; G, gentamicin; LFC, levofloxacin; MFC, moxifloxacin; MIC, minimum inhibitory concentration; NA, data not available; OFC, ofloxacin; Q/D, quinupristine-dalfopristine; TMP/SMZ, trimethoprim-sulfamethoxazole.

In the current series of the reports of endophthalmitis caused by Gram-positive organisms with reduced susceptibility and/or resistance to vancomycin, antibiotic susceptibility patterns were reported for 14 patients and nine were found to be multidrug resistant. These organisms were resistant to other drugs including fluoroquinolones (5 patients), penicillins (5 patients), cephalosporins (3 patients), and aminoglycosides (2 patients). Systemic treatment was administered in 19/27 patients. These included fluoroquinolones (11/19 cases), linezolid (5/19 cases), daptomycin (1/19 cases), and others (including rifampicin, penicillins, and cefpodoxime (tables 1 and 2)). Intravitreal antibiotics were administered in all cases. In addition, five patients (all exogenous endophthalmitis) received systemic linezolid and had favourable outcomes in 4/5 cases (complete resolution of infection and visual acuity improvement of at least two lines, except in patients whose vision was limited by coexisting pathology such as central retinal vein occlusion, age-related macular degeneration, optic atrophy, etc). Intravitreal quinupristin/dalfopristin (0.4 mg/0.1 mL) was administered in 3/27 patients, with a favourable outcome.

Visual acuity of 20/400 or better at the final follow-up was recorded in 10/26 patients (38.5%, data were not available for one patient). Six patients had enucleation or no light perception and another six patients had only light perception at the last follow-up examination.

DISCUSSION

Among all Gram-positive organisms with reduced vancomycin susceptibility, Staphylococcus was the most frequently isolated organism in the current study. As reported in the EVS,² coagulase-negative staphylococci and Staphylococcus aureus were the most frequently isolated organism. The first case of vancomycin resistant Staphylococcus aureus was reported from Japan in 1997.²⁶ Among Staphylococcus aureus isolates, the incidence of methicillin resistance has gradually increased in a more recent series.²⁷ In a large case series reported in 2010, 41% of Staphylococcus aureus endophthalmitis isolates were found to be methicillin resistant.²⁷ Exposure to fluoroquinolones has been identified as a risk for methicillin-resistant Staphylococcus aureus (MRSA) infection in hospitalised patients by Weber et al²⁸ due to changes in adhesion and favoured colonisation. All of these cases were sensitive to vancomycin, which is used as first line intravitreal antimicrobial therapy in endophthalmitis cases.

Enterococcus species with decreased sensitivity to vancomycin (minimum inhibitory concentration (MIC) >4) was reported as early as 1957.^29,30 In 1988, the first cases of vancomycin resistant Enterococcus faecalis and Enterococcus faecium (MICs ≥32 mg/mL) were reported from England,³¹ 32 France,³³ Germany,³⁴ and the USA.^35,36 In 1993, almost 14% of enterococci isolated from intensive care units (ICU) in the USA were resistant to vancomycin.³⁷ In 1999, a review of respiratory infections reported that 26% of the enterococcal infections seen in ICUs were vancomycin resistant.³⁸ Including severe sepsis and septic shock, mortality rates as high as 60–70% have been reported in patients with vancomycin resistant enterococcal (VRE) infections.³⁹ Among ocular infections the first case of endogenous endophthalmitis reported to be a VRE infection occurred in a 70-year-old immunosuppressed female patient (with acute myelogenous leukaemia) who was managed with multiple drugs but eventually underwent enucleation.²³ Postoperative endophthalmitis caused by Enterococcus species is uncommon (reported in 2–4% of the positive isolates) but all isolates were reported to be sensitive to vancomycin as per studies published in 1996 and 2005.^6,40

Endophthalmitis caused by Bacillus species is a common isolate in open globe injury infections. In an endophthalmitis case series (1990–2007) from the USA,⁴¹ all 22 Bacillus isolates were susceptible to vancomycin. Similarly in a long term (14 year, 2006–2013) study of post-traumatic endophthalmitis cases from India,⁴² 95.1% (98/103) of cases were reported to be susceptible to vancomycin. However, in the current review, 4/27 cases of endophthalmitis with reported reduced vancomycin susceptibility were caused by Bacillus species. Leuconostoc species, well-known to be opportunistic infectious agents with intrinsic resistance to vancomycin,¹⁰ 11 22 were reported in three of 27 cases in the current review. Leuconostoc species are microaerophilic, catalase-negative, Gram-positive cocci with high intrinsic resistance to vancomycin, and are often mistaken for Streptococcus species because of similar biochemical characteristics. Leuconostoc is a rare opportunistic infectious agent, and more often infects immunocompromised people. The current series also included cases caused by Streptococcus species (3/27) with reduced vancomycin susceptibility, and these three patients underwent enucleation/evisceration.⁸

In order to reduce the risk of postoperative endophthalmitis, antibiotics have been used in irrigating fluid perioperatively^43,44 or injecting intracamerally⁴⁵ during cataract surgery. In the Centers for Disease Control and Prevention (CDC) guidelines for appropriate use of vancomycin⁴⁶ and the report by the Rockefeller University Workshop⁴⁷ published in 1994, the prophylactic use of vancomycin was discouraged in view of the risk of increasing the prevalence of VRE and MRSA. Because of the short duration of drug exposure, prophylactic use of vancomycin in irrigating solution was found to be ineffective against the organisms causing endophthalmitis.⁴⁸ In 2007, two postoperative endophthalmitis cases were reported^18,20 with vancomycin resistant Enterococcus species. In 2011, endophthalmitis caused by vancomycin resistant Staphylococcus species was reported for the first time.^13,14

Intravitreal moxifloxacin has been utilised for the management of endophthalmitis with multidrug resistant bacteria.⁴⁹ The possible overuse of antibiotics in medical practice, the emergence of resistant organisms and of newer infections, and the promotion of antibiotics by the pharmaceutical industry may play an important role in the emergence of drug resistant strains. By the selective advantage of resistant strains in this environment, these resistant bacteria may propagate and become a significant medical liability.

The microbiology laboratory plays an important role in the diagnosis of reduced vancomycin susceptibility. Susceptibility tests with maximum accuracy should be used. Agar dilution, disk diffusion, E-test, agar screen plate, Vitek GPS-TA and GPS-101, and Microscan overnight and rapid panels are performed to test for vancomycin susceptibility in enterococci. However, the most reliable and easy screening test for detection of VanA, VanB and VanC is the agar screening method. Agar dilution, broth MIC, E-test MIC, and a few commercial tests (Microscan and Vitek 2) are performed to test for vancomycin susceptibility in Staphylococcus aureus. The agar dilution and broth MIC methods are CLSI (Clinical and Laboratory Standards Institute) approved.^50–52

Systemic treatment is not universally recommended in the treatment of all endophthalmitis categories. In post-cataract surgery endophthalmitis, systemic antibiotics are not generally utilised in most cases. However, in the presence of post-traumatic or endogenous endophthalmitis, systemic antibiotics are often utilised. Vancomycin is often recommended in life threatening or organ threatening infections caused by susceptible organisms. When vancomycin resistant organisms are present, alternative antibiotics may include systemic or intravitreal linezolid, quinupristin/dalfopristin, daptomycin, tigecycline or other antibiotics to which the organism is susceptible on sensitivity testing.

Based on microbiology susceptibility tests, other treatment options include linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline (table 4) in such cases.^50–68 Multidrug resistance is an important consideration in the management of these infections. Table 5 highlights the mechanism of resistance in these organisms.^50,69,70 Organisms labelled as vancomycin resistant should be evaluated by the tests and interpretive criteria mentioned above. For management of severe life threatening infections caused by vancomycin resistant organisms, linezolid and quinupristin/dalfopristin were the only two drugs approved by the FDA in 1999.⁷¹

Table 4.

Treatment options for infections caused by reduced vancomycin susceptibility—listed by generic (and commercial) names

	Linezolid (Zyvox)50–54	Quinupristine/dalfopristine (Synercid)55–57	Daptomycin (Cubicin)58–62	Tigecycline (Tygacil)63–68
Class	Oxazolidinone (fermentation byproduct of Streptomyces roseosporus)	Streptogramin (isolated from Streptomyces pristinaespiralis)	Cyclic lipopeptide	Glycylcycline (a derivative of minocycline)
Mechanism of action	Inhibits initiation of protein synthesis by binding 23S rRNA of the 50S subunit of bacterial ribosome	Inhibits bacterial protein synthesis by interfering with function of 23S RNA (quinidine: dalfopristine=3:7)	Terminates bacterial DNA, RNA and protein synthesis and cell death by forming transmembrane channels in cell membrane and depolarisation of membrane potential	Inhibits bacterial protein synthesis by irreversibly binding to 30 S ribosomal unit
Route and dose	Oral—600 mg twice daily Intravenous—600 mg twice daily Intravitreal—300 mg/0.1 mL (rabbits) Topical—2 mg/mL (rabbits)	Intravenous—7.5 mg/kg 8 hourly Intravitreal—0.4 mg/0.1 mL In vitro—MIC90 0.5–2 mg/L	Intravenous—4–6 mg/kg per day Intravitreal—200 mg/0.05 mL (rabbits) Topical—1% (rabbits)	Intravenous—100 mg/100 ml over 30–60 min followed by 50 mg twice daily Intravitreal—0.5–1 mg/0.1 mL (rabbits) Topical—10–50 mg/mL (rabbits)
Side effects with systemic dose	Reversible myelosuppression, irreversible peripheral neuropathy, optic neuropathy (when used for >14 days)	Arthralgia, myalgia, pain and Periphlebitis at injection site	Not significant Minor gastrointestinal disturbances	Hypersensitivity-like reaction
Spectrum of activity	GPO, MRSA, VRSA, VISA, VRE, CNS, GNO, mycobacteria	MRSA, VISA, VRSA, Streptococcus species, CNS	VRSA, VRE, Staphylococcus, Streptococcus, Enterococcus species	MSSA, MRSA, VISA, VRE, Escherichia coli and Klebsiella pneumonia
Others	First pharmacologically active oxazolidinone (fermentation byproduct of Streptomyces roseosporus). Good intraocular availability after intravenous and oral administration	First intravitreal (0.4 mg/0.1 mL) use of quinupristin/dalfopristin acute postoperative endophthalmitis in 2011	Pharmacokinetics are linear at dose of 4–12 mg/kg/day. Available only in intravenous formulation	Minimum inhibitory concentration 90 (MIC90) of MDR bacteria range from 0.12–4 μg/mL

CNS, coagulase-negative staphylococci; FDA, US Food and Drug Administration; GNO, Gram-negative organism; GPO, Gram-positive organisms; MDR, multidrug resistant bacteria; MRSA, methicillin-resistant Staphylococcus aureus; VISA, vancomycin intermediate sensitive Staphylococcus aureus; VRE, vancomycin resistant Enterococcus; VRSA, vancomycin-resistant Staphylococcus aureus.

Table 5.

Mechanisms of reduced vancomycin susceptibility or vancomycin resistance among various strains of Enterococcus and Staphylococcus species

Organisms	Mechanism of reduced vancomycin susceptibility
Enterococci	By acquisition of following genotypes: VanA/VanB/VanC/VanD/VanE
Staphylococci  Fully resistant strains  Strains with reduced vancomycin susceptibility ►Vancomycin intermediate Staphylococcus aureus ►Heterogeneous VISA (hVISA)	By acquisition of VanA gene from vancomycin resistant enterococci (VRE) By having mutations in either graRS/vraSR/walKR operon leading ultimately to cell wall thickening, decreased autolysis, reduced protein A production, increased capsule expression, increased D-alanylation of teichoic acid, and reduced accessory gene regulator (agr) activity. These are the vancomycin susceptible Staphylococcus aureus strains which upon subculture produce subcolonies with vancomycin resistance

As reported by the CDC in 2013,⁷² every year two million people in the USA become infected with bacteria that are antibiotic resistant. Every year antibiotic resistance adds $20 billion (£13 billion, €18.5 billion) in excess direct healthcare costs, with additional costs to society for lost productivity as high as $35 billion (£23 billion, €32 billion) a year. To combat and halt resistance, the CDC recommends various measures for the prevention of infection and spread of resistance. These measures include immunisation, infection control actions in healthcare settings, safe food preparation and handling, general hand washing, tracking clinical data on antibiotic-resistant infections, causes of infections, root cause analysis, and antibiotic stewardship programmes.⁷³

CONCLUSIONS

Vancomycin is an important first line antibiotic for the management of Gram-positive organisms causing endophthalmitis. In the current review of the literature, Enterococcus, Staphylococcus and Streptococcus species were the most common isolates with reduced susceptibility and/or vancomycin resistance. A significant limitation of the current review is that the various laboratory test methods used to detect drug resistance in different reports were not uniform. The cost and access to testing can be a barrier to the detection of reduced vancomycin susceptibility. In endophthalmitis patients with reduced vancomycin susceptibility and/or vancomycin resistance, visual acuity outcomes were generally poor.