The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000.

The editors of this Festschrift asked us to review the use of antibiotics for the treatment of bacterial conjunctivitis and keratitis over the past 25 years, a period coinciding with the life of the Castroviejo Corneal Society. We believe it is more appropriate to begin our review in the late 1960s. about the time that experimental and clinical studies and algorithms for the clinical care derived from these studies helped shape a more rigorous approach to therapy. Those years saw the introduction of antibiotics that were adapted for ophthalmic use, many of which are still being used today. We will give more weight to our review of keratitis than conjunctivitis.

Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status.

BACKGROUND: It is important to understand the factors affecting strategies to improve the vitamin A status of populations. We reported previously that a 3-d deuterated-retinol-dilution (DRD) procedure might be used to indicate total body stores of vitamin A. OBJECTIVE: We studied the ability of 3-d DRD to detect changes in the body pool size of vitamin A and the effect of vitamin A status on the bioconversion of plant carotenoids to vitamin A. DESIGN: Two separate, unrelated studies were conducted in 7-13-y-old children with poor or marginal serum retinol concentrations (0.32-0.93 micromol/L) by feeding them controlled diets daily for 5 d/wk for 12 wk, after treatment with an anthelmintic drug. In school 1 (n = 27), lunch and 2 snacks that were provided at school contained 2258 retinol equivalents/d (mostly from orange fruit and vegetables) and 5.3 MJ/d from 33 g fat, 37 g protein, and 209 g carbohydrates; in school 2 (n = 25), 2 snacks provided 2.5 MJ/d from 9.4 g fat, 9.6 g protein, and 119 g carbohydrates, but no carotenes. RESULTS: In school 1, mean serum beta-carotene increased from 0.12 to 0.62 micromol/L (P = 0.0001) and serum retinol increased from 0.68 to 1. 06 micromol/L (P = 0.0001). In school 2, serum beta-carotene increased from 0.06 to 0.11 micromol/L (P = 0.0001) and serum retinol increased from 0.66 to 0.86 micromol/L (P = 0.0001). In school 1, but not school 2, improvement in serum retinol varied inversely with baseline retinol (r = -0.38, P = 0.048). In both schools, 3-d DRD showed reductions in the ratio of serum deuterated to nondeuterated retinol (D:H retinol) postintervention, denoting improvements in vitamin A status; the higher D:H retinol (ie, the poorer the status) at baseline, the greater the reduction in D:H retinol postintervention (school 1: r = -0.99, P = 0.0001; school 2: r = -0.89, P = 0.0001). CONCLUSIONS: Three-day DRD can detect changes in the body pool size of vitamin A, although a predictive equation to quantitate total body stores of vitamin A with the use of 3-d data needs to be developed. Bioconversion of plant carotenoids to vitamin A varies inversely with vitamin A status; improvement in status after dietary interventions is strongly influenced by total body stores of vitamin A and is influenced little or not at all by serum retinol.

Meta-analysis of diagnostic tests for acute sinusitis.

To facilitate management of acute sinusitis, we conducted a meta-analysis of published studies comparing diagnostic tests for this disorder. Thirteen studies were identified through literature search. Based on sinus puncture/aspiration (considered most accurate), 49-83% of symptomatic patients had acute sinusitis. Compared with puncture/aspiration, radiography offered moderate ability to diagnose sinusitis (summary receiver operator curve [SROC] area, 0.83). Using sinus opacity or fluid as the criterion for sinusitis, radiography had sensitivity of 0.73 and specificity of 0.80. Studies evaluating ultrasonography revealed substantial variation in test performance. The clinical evaluation, particularly risk scores formally incorporating history and physical examination findings, had moderate ability to identify patients with positive radiographs (SROC area, 0.74). Many studies were of poor quality, with inadequately described test methods and unblinded test interpretation. In conclusion, acute sinusitis is common among symptomatic patients. Radiography and clinical evaluation (especially risk scores) appear to provide useful information for diagnosis of sinusitis.

Effect of macrolides as part of initial empiric therapy on length of stay in patients hospitalized with community-acquired pneumonia.

BACKGROUND: The choice of antibiotics to treat community-acquired pneumonia (CAP) is primarily empiric, and the effect of this choice on length of stay (LOS) and mortality is largely unknown. OBJECTIVE: To examine the impact of antibiotic choice on these outcomes in general medical patients hospitalized with CAP. METHODS: One hundred patients hospitalized with CAP were prospectively identified. Seventy-six met inclusion criteria and were entered into the study. After hospital discharge, each medical chart was examined by 2 independent physicians who verified the admitting diagnosis and entered the data for antimicrobial regimens, a CAP mortality prediction tool, a social and disposition index, and other health outcomes. Patients were stratified according to the antibiotic received. Simple regression techniques were used to examine the correlation between initial therapy, specifically, ceftriaxone sodium or a macrolide, and LOS and mortality. RESULTS: Patients who received macrolides within the first 24 hours of admission had a markedly shorter LOS (2.8 days) than those not so treated (5.3 days; P = .01). This effect diminished as the interval before administering macrolides increased. Including ceftriaxone as part of the initial therapy did not appear to affect LOS. Patients given a macrolide for initial treatment did not differ significantly from those not treated in terms of mean age, mortality prediction tool score, or Social and Disposition Index score. Eleven of the 12 patients who received macrolides also received a beta-lactam antibiotic. CONCLUSION: Use of macrolides as part of an initial therapeutic regimen appears to be associated with shorter LOS.

Microbiologic yields and complication rates of vitreous needle aspiration versus mechanized vitreous biopsy in the Endophthalmitis Vitrectomy Study.

PURPOSE: To compare the microbiologic yields and complication rates associated with vitreous needle tap and vitreous biopsy in the Endophthalmitis Vitrectomy Study (EVS). METHODS: Of 420 EVS patients with postoperative endophthalmitis, 201 received immediate vitreous tap or biopsy (without pars plana vitrectomy) by random assignment and 193 completed 9-12 months of follow-up. Vitreous specimens were obtained by biopsy with a 20-gauge vitrectomy cutting instrument or by needle tap with a 22-27-gauge needle. If resistance to aspiration by needle tap was noted, a vitreous biopsy was performed. RESULTS: Of 201 patients undergoing tap or biopsy, 70 (35%) had needle tap, 127 (63%) had mechanized biopsy, and 4 (2%) had initial needle tap that was aborted to mechanized biopsy ("abort" eyes). Intraoperative hyphema occurred in 2 tap eyes (3%), 3 biopsy eyes (2%), and 0 (0%) abort eyes. Postoperative retinal detachment developed in 8 (11%) tap eyes, 10 (8%) biopsy eyes, and 0 (0%) abort eyes (not significant). Respective rates of culture and gram stain positivity were 69% and 42% in tap eyes and 66% and 41% in biopsy eyes (not significant). The rate of severe visual loss (final acuity <5/200) was significantly higher in tap eyes (16 eyes, 24%) compared with biopsy eyes (13 eyes, 11%) and abort eyes (0 eyes, 0%; P = 0.043). The difference was largely explained by the greater proportion of virulent organisms in the tap eyes compared with biopsy eyes. When visual acuity outcome was defined by other thresholds (20/40 and 20/100), the difference was not significant. CONCLUSIONS: This study showed no significant differences between mechanized vitreous biopsy and needle tap with respect to microbiologic yield, operative complications, short-term (9-12 months) retinal detachment risk, or visual outcome. Choice of vitreous sampling procedure must depend on the clinical judgment of the surgeon.

Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk.

Infections remain common life-threatening complications of bone marrow transplantation. To examine clinical factors that affect infection risk, we retrospectively studied patients who received bone marrow transplants (53 autologous and 51 allogeneic). Over a median of 27 hospital days, 44 patients developed documented infections. Both autologous transplantation and hematopoietic growth factor use were associated with less prolonged neutropenia and decreased occurrence of infection (P < or = .05). In a survival regression model, variables independently associated with infection risk were the log10 of the neutrophil count (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.32-0.75), ciprofloxacin prophylaxis (HR, 0.42; 95% CI, 0.19-0.95), empirical intravenous antibiotic use (HR, 0.09; 95% CI, 0.03-0.32), and an interaction between neutrophil count and intravenous antibiotic use (HR, 1.86; 95% CI, 1.06-3.29). In this model, infection risk increases steeply at low neutrophil counts for patients receiving no antibiotic therapy. Ciprofloxacin prophylaxis and particularly intravenous antibiotic therapy provide substantial protection at low neutrophil counts. These results can be used to model management strategies for transplant recipients.

[Klatskin's tumor]. / Tumora Klatskin.

During the period 1989-1998, 27 patients with primary proximal bile duct cancer were treated (17 females and 10 males with a mean age of 61 years). The main presenting symptoms were: jaundice (96.2%), itching (92.5%), weight loss (74%) and atypical pain (33.3%). All the patients underwent ultrasound (US) examination, 7 patients endoscopic retrograde cholangiopancreatography (ERCP) and 4 patients computed tomography (CT) examination. US examination revealed the tumor in 51% cases; most frequently a dilatation of the intrahepatic bile ducts was diagnosed with all methods. 8 patients underwent resection of the tumor and one a biliary-enteric anastomosis, in 15 cases a stent was inserted. In 3 cases the extension of the malignancy did not allowed any procedure. Three patients died during immediate postoperative period (mortality 11.2%). The mean survival was 13 months after stenting and 22 months after resection of the tumor. The authors recommended an aggressive surgical therapy for Klatskin tumors.

Are amoxycillin and folate inhibitors as effective as other antibiotics for acute sinusitis? A meta-analysis.

OBJECTIVES: To examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors. DESIGN: Meta-analysis of randomised trials. SETTING: Outpatient clinics. SUBJECTS: 2717 patients with acute sinusitis or acute exacerbation of chronic sinusitis from 27 trials. INTERVENTIONS: Any antibiotic versus placebo; amoxycillin or folate inhibitors versus newer, more expensive antibiotics. MAIN OUTCOME MEASUREMENTS: Clinical failures and cures. RESULTS: Compared with placebo, antibiotics decreased the incidence of clinical failures by half (risk ratio 0.54 (95% confidence interval 0.37 to 0.79)). Risk of clinical failure among 1553 randomised patients was not meaningfully decreased with more expensive antibiotics as compared with amoxycillin (risk ratio 0.86 (0.62 to 1.19); risk difference 0.9 fewer failures per 100 patients (1.4 more failures to 3.1 fewer failures per 100 patients)). The results were similar for other antibiotics versus folate inhibitors (risk ratio 1.01 (0.52 to 1.97)), but data were sparse (n=410) and of low quality. CONCLUSIONS: Amoxycillin and folate inhibitors are essentially as effective as more expensive antibiotics for the initial treatment of uncomplicated acute sinusitis. Small differences in efficacy may exist, but are unlikely to be clinically important.

Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis.

PURPOSE: To perform a meta-analysis to estimate the efficacy of quinolone antibiotics in preventing infections, fevers, and deaths among cancer patients neutropenic following chemotherapy. METHODS: We searched MEDLINE to identify randomized trials of quinolone prophylaxis, controlled either with no prophylaxis or trimethoprim/sulfamethoxazole (TMS) prophylaxis. We pooled relative risks for outcomes using a random-effects model. RESULTS: Eighteen trials with 1,408 subjects were included. Compared with no prophylaxis, quinolones significantly reduced the incidence of gram-negative bacterial infections (relative risk, 0.21; 95% confidence interval [CI], 0.12 to 0.37), microbiologically documented infections (0.65; 0.50 to 0.85), total infections (0.54; 0.31 to 0.95), and fevers (0.85; 0.73 to 0.99). Quinolone prophylaxis did not alter the incidence of gram-positive bacterial, fungal, or clinically documented infections, or infection-related deaths. Results were similar for trials that used TMS as the control regimen. Among those who received quinolones, the incidence of infections due to quinolone-resistant organisms was 3.0% (95% CI, 1.7% to 5.2%) for gram-negative species and 9.4% (95% CI, 5.3% to 16.3%) for gram-positive species. Based on limited data, the incidence of quinolone-resistant infections was not higher among quinolone recipients than controls. With fever as outcome, blinded trials found quinolones less efficacious than did unblinded trials. CONCLUSION: Quinolone prophylaxis substantially reduces the incidence of various infection-related outcomes, but not deaths, in these patients. Although this reduction in infections may translate into a decrease in morbidity, the reduction in fevers (and by extension, use of empiric antibiotics) appears small, and blinded trials provided less evidence for benefit than unblinded trials. Quinolone-resistant infections are uncommon, but continued vigilance is warranted.

Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study.

OBJECTIVE: To analyze the data for cultures and Gram stains prospectively collected by protocol in the Endophthalmitis Vitrectomy Study. DESIGN: Cultures of aqueous, undiluted vitreous, and (for patients who underwent vitrectomy) vitrectomy cassette fluid obtained from 420 patients were prepared on chocolate agar, in thioglycolate broth, and on Sabouraud dextrose agar; Gram stains of the aqueous and undiluted vitreous were made. Criteria were devised to distinguish true pathogens (confirmed positive cultures) from contaminants. SETTING: Private and university-based retina-vitreous practices and corresponding microbiology laboratories. RESULTS: Compared with the aqueous, undiluted vitreous produced a higher percentage of confirmed positive cultures and higher colony counts on chocolate agar and was more frequently the only source of a positive culture from the eye. Nevertheless, the aqueous and vitrectomy cassette fluid were the only source of a positive culture from the eye in 4.2% and 8.9% of eyes, respectively. The overall yields of chocolate agar and thioglycolate broth were similar. A positive Gram stain from the aqueous or undiluted vitreous was highly predictive of a positive culture from the eye, but a negative Gram stain had little predictive value for the culture result. The overall rate of laboratory-confirmed infection was not statistically significantly higher in the vitrectomy group than in the tap or biopsy group. CONCLUSIONS: The vitreous was a richer source of positive cultures and high colony counts than was the aqueous, either because it is more supportive of bacterial growth or because a somewhat larger inoculum of the vitreous than of aqueous could be obtained. The result of Gram stain should not determine the choice of antibiotic drugs in the treatment of endophthalmitis. Vitrectomy, with culture of the vitrectomy cassette fluid, did not produce significantly more positive cultures than tap or biopsy material, and the procedure should not be performed to improve the microbiological yield.

The Endophthalmitis Vitrectomy Study. Relationship between clinical presentation and microbiologic spectrum.

PURPOSE: The authors determine if specific features of the clinical presentation of acute postoperative endophthalmitis correlated with the microbiologic culture results. METHODS: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were evaluated as part of a randomized clinical trial. Results of cultures performed on aqueous and vitreous specimens obtained at presentation were categorized as follows: gram-positive coagulase-negative micrococci, "other" gram-positive, gram-negative, and equivocal/no growth. RESULTS: Eleven features of the initial clinical presentation were associated with significant differences in the microbiologic spectrum (P < 0.05). Baseline factors correlating with higher rates of both gram-negative and other gram-positive isolates were: corneal infiltrate, cataract wound abnormalities, afferent pupillary defect, loss of red reflex, initial light perception-only vision, and symptom onset within 2 days of surgery. Gram-negative organisms did not grow in any eyes in which a retinal vessel could be visualized, and 61.9% of these eyes had equivocal or no growth. Diabetes mellitus was associated with a higher yield of gram-positive, coagulase-negative micrococci. Eye pain was not a discriminator for culture results. CONCLUSIONS: The presenting characteristics of acute endophthalmitis after cataract surgery may be helpful in predicting the most likely culture results. Such predictions do not appear sufficiently strong to guide the initial empiric choice of intravitreal antibiotics.

A model of the transmission of antibiotic-resistant bacteria in the intensive care unit.

Antibiotic resistance is a growing problem, affecting microorganisms found both in hospitals and in the community. In most patients, resistant organisms arise by transmission of already resistant microorganisms from another person, rather than arising by mutation in the index patient. Antibiotic resistance genes are often borne on plasmids or transposons on which they may be spread rapidly to other organisms in the same species or in other species. Plasmids and transposons readily pick up genes for resistance to other antibiotics or nonantibiotic agents ("linked resistance"). Control of the spread of antibiotic resistance may require limitation of the usage of other agents with linked resistance as well as of the antibiotics of primary interest. A model is described for the analysis of the transmission of antibiotic-resistant enteric bacteria in the ICU. The model deals with the baseline level of antibiotic resistance in the "source" patient, the effect of antibiotics in augmenting the concentration of resistant organisms in that patient, the role of patient-to-patient contact, and factors which may influence the "colonizability" of the recipient patient. Possible measures to reduce the spread of antibiotic resistance are discussed. It is hoped that the model may serve to focus discussion on some key ingredients of the transmission cycle.

Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study.

PURPOSE: To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. METHODS: Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. RESULTS: Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%). Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase-negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species. All gram-positive isolates tested were susceptible to vancomycin. Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). CONCLUSIONS: Gram-positive, coagulase-negative micrococci predominated in this series. Vancomycin was active against all gram-positive isolates tested. Amikacin and ceftazidime showed equivalent activity against gram-negative isolates. Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci.

Optimal management of postoperative endophthalmitis and results of the Endophthalmitis Vitrectomy Study.

The Endophthalmitis Vitrectomy Study was a multicenter randomized clinical trial. A total of 420 patients who had developed acute endophthalmitis after cataract surgery were randomly assigned to undergo vitrectomy or tap and biopsy and to receive either systemic antibiotics (ceftazidime and amikacin) or no systemic antibiotics. At 9 months patients were assessed for final visual acuity and media clarity. There was no difference in final visual acuity or media clarity whether or not systemic antibiotics were used. Patients who presented with hand motion acuity or better did not show a benefit from immediate vitrectomy. However, patients who presented with light-perception-only visual acuity had substantial benefit over immediate vitrectomy, with a threefold (33% vs 11%) increased frequency of achieving 20/40 vision or better, double the frequency of achieving 20/100, and a decrease by half in the frequency of severe visual loss to less than 5/200. These differences were statistically significant.

Single or multiple daily doses of aminoglycosides: a meta-analysis.

OBJECTIVE: To assess relative efficacy and toxicity of aminoglycosides given by single daily dose compared with multiple daily doses. DESIGN: Meta-analysis of 21 randomised trials identified through MEDLARS (1966 to January 1995). Data were overviewed with fixed effects and random effects models and with meta-regression analysis. SUBJECTS: Total of 3091 patients with bacterial infection, most without pre-existing renal disease. INTERVENTIONS: Patients were randomized to receive aminoglycosides once daily or multiple times daily with similar total daily dose. MAIN OUTCOME MEASURES: Clinical failure of treatment, nephrotoxicity, ototoxicity, and mortality. RESULTS: Single daily dose regimen produced a non-significant decrease in risk of antibiotic failures (random effects risk ratio 0.83 (95% confidence interval 0.57 to 1.21)). Benefit of once daily dosing was greater when the percentage of pseudomonas isolates in a trial was larger. Once daily administration reduced risk of nephrotoxicity (fixed effects risk ratio 0.74 (0.54 to 1.00)). Similar trends were noted for patients with febrile neutropenia and for children. There was no significant difference in ototoxicity between the two dosing regimens, but the power of the pooled trials to detect a meaningful difference was low. There was no significant difference in mortality. CONCLUSIONS: Once daily administration of aminoglycosides in patients without pre-existing renal impairment is as effective as multiple daily dosing, has a lower risk of nephrotoxicity, and no greater risk of ototoxicity. Given the additional convenience and reduced cost, once daily dosing should be the preferred mode of administration.