Adjunctive Corticosteroids Research Articles

The ADRENAL study protocol: ADjunctive corticosteroid tREatment iN criticAlly ilL patients with septic shock

The ADRENAL study protocol: ADjunctive corticosteroid tREatment iN criticAlly ilL patients with septic shock

Fluoroquinolone Treatment and Susceptibility of Isolates From Bacterial Keratitis

To analyze the relationship between fluoroquinolone use at presentation and minimum inhibitory concentration in bacterial keratitis. The Steroids for Corneal Ulcers Trial was a randomized, double-masked, placebo-controlled trial assessing the effect of adjunctive topical corticosteroid treatment on outcomes in bacterial keratitis. After presentation, all patients were treated with moxifloxacin hydrochloride, 0.5%. We compare antibiotic use at presentation with minimum inhibitory concentration against moxifloxacin for all isolates. Separate analyses accounted for organism species and fluoroquinolone generation. Topical fluoroquinolone use at presentation was reported in 92 of 480 cases (19.2%). Causative organisms in the 480 cases included Streptococcus pneumoniae (247 cases [51.5%]), Pseudomonas aeruginosa (109 cases [22.7%]), and Nocardia species (55 cases [11.5%]). Isolates from patients who reported fluoroquinolone use at presentation had a 2.01-fold-higher minimum inhibitory concentration (95% CI, 1.39-fold to 2.91-fold; P < .001). Fourth-generation fluoroquinolones were associated with a 3.48-fold-higher minimum inhibitory concentration than those isolates that were not exposed to pretreatment at enrollment (95% CI, 1.99-fold to 6.06-fold; P < .001). This study provides evidence that prior use of fluoroquinolones is associated with antibiotic resistance. clinicaltrials.gov Identifier: NCT00324168.

A Systematic Review on the Role of Adjunctive Corticosteroids in Herpes Simplex Virus Encephalitis: Is Timing Critical for Safety and Efficacy?

Most herpes simplex virus encephalitis (HSVE) patients become disabled despite antiviral therapy. Adjunctive corticosteroid therapy may improve outcomes. This was a systematic review of the literature addressing the use of corticosteroids in HSVE. Data suggesting that steroids decrease the immunological response and enhance viral replication originated from non-neural microenvironments. Early steroid administration might be harmful because initial damage in HSVE is mediated by viral replication. Steroid treatment improves outcomes in animal models by inhibiting the subsequent inflammatory response. Clinical observations support a similar benefit in symptomatic HSVE patients. Cerebrospinal fluid inflammatory markers might guide appropriate timing in future clinical practice. Experimental and clinical observations suggest a benefit from adjunctive steroid therapy in HSVE. Nevertheless, current evidence is not yet sufficient to endorse this approach as a standard of practice.

Adjunctive corticosteroids for all forms of tuberculosis?

Adjunctive corticosteroids for all forms of tuberculosis?

Corticosteroids for pneumonia: Are we there yet?

See article, page 263

Adjunctive Corticosteroid to Counteract Adverse Drug Reactions from First-Line Antituberculous Drugs

Inclusion of H and R in anti-TB drug regimen is critical to highly effective short-duration TB treatment. Completion of antiTB therapy is severely compromised when H or R are removed from treatment regimens. Unfortunately, H or R induces ADRs and physicians may initiate desensitization therapy to promote anti-TB therapy completion. When desensitization therapy does not mitigate the anti-TB ADRs, anti-TB therapy is often delayed. Previous studies suggest that corticosteroid adjust therapy may improve anti-TB drug ADR management. In this study, patients receiving prednisolone to counteract ADRs, despite desensitization therapy, display modest benefits in anti-TB treatment completion.

Diagnosis and management of miliary tuberculosis: current state and future perspectives

Tuberculosis (TB) remains one of the most important causes of death from an infectious disease, and it poses formidable challenges to global health at the public health, scientific, and political level. Miliary TB is a potentially fatal form of TB that results from massive lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli. The epidemiology of miliary TB has been altered by the emergence of the human immunodeficiency virus (HIV) infection and widespread use of immunosuppressive drugs. Diagnosis of miliary TB is a challenge that can perplex even the most experienced clinicians. There are nonspecific clinical symptoms, and the chest radiographs do not always reveal classical miliary changes. Atypical presentations like cryptic miliary TB and acute respiratory distress syndrome often lead to delayed diagnosis. High-resolution computed tomography (HRCT) is relatively more sensitive and shows randomly distributed miliary nodules. In extrapulmonary locations, ultrasonography, CT, and magnetic resonance imaging are useful in discerning the extent of organ involvement by lesions of miliary TB. Recently, positron-emission tomographic CT has been investigated as a promising tool for evaluation of suspected TB. Fundus examination for choroid tubercles, histopathological examination of tissue biopsy specimens, and rapid culture methods for isolation of M. tuberculosis in sputum, body fluids, and other body tissues aid in confirming the diagnosis. Several novel diagnostic tests have recently become available for detecting active TB disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. A high index of clinical suspicion and early diagnosis and timely institution of antituberculosis treatment can be lifesaving. Response to first-line antituberculosis drugs is good, but drug-induced hepatotoxicity and drug–drug interactions in HIV/TB coinfected patients create significant problems during treatment. Data available from randomized controlled trials are insufficient to define the optimum regimen and duration of treatment in patients with drug-sensitive as well as drug-resistant miliary TB, including those with HIV/AIDS, and the role of adjunctive corticosteroid treatment has not been properly studied. Research is going on worldwide in an attempt to provide a more effective vaccine than bacille Calmette–Guérin. This review highlights the epidemiology and clinical manifestation of miliary TB, challenges, recent advances, needs, and opportunities related to TB diagnostics and treatment.

Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: A 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis

In spite of antituberculosis chemotherapy, tuberculous (TB) pericarditis causes death or disability in nearly half of those affected. Attenuation of the inflammatory response in TB pericarditis may improve outcome by reducing cardiac tamponade and pericardial constriction, but there is uncertainty as to whether adjunctive immunomodulation with corticosteroids and Mycobacterium w (M. w) can safely reduce mortality and morbidity. The primary objective of the IMPI Trial is to assess the effectiveness and safety of prednisolone and M. w immunotherapy in reducing the composite outcome of death, constriction, or cardiac tamponade requiring pericardial drainage in 1,400 patients with TB pericardial effusion. The IMPI trial is a multicenter international randomized double-blind placebo-controlled 2 × 2 factorial study. Eligible patients are randomly assigned to receive oral prednisolone or placebo for 6 weeks and M. w injection or placebo for 3 months. Patients are followed up at weeks 2, 4, and 6 and months 3 and 6 during the intervention period and 6-monthly thereafter for up to 4 years. The primary outcome is the first occurrence of death, pericardial constriction, or cardiac tamponade requiring pericardiocentesis. The secondary outcome is safety of immunomodulatory treatment measured by effect on opportunistic infections (eg, herpes zoster) and malignancy (eg, Kaposi sarcoma) and impact on measures of immunosuppression and the incidence of immune reconstitution disease. IMPI is the largest trial yet conducted comparing adjunctive immunotherapy in pericarditis. Its results will define the role of adjunctive corticosteroids and M. w immunotherapy in patients with TB pericardial effusion.

Prior Elicitation and Bayesian Analysis of the Steroids for Corneal Ulcers Trial

Purpose: To elicit expert opinion on the use of adjunctive corticosteroid therapy in bacterial corneal ulcers. To perform a Bayesian analysis of the Steroids for Corneal Ulcers Trial (SCUT), using expert opinion as a prior probability.Methods: The SCUT was a placebo-controlled trial assessing visual outcomes in patients receiving topical corticosteroids or placebo as adjunctive therapy for bacterial keratitis. Questionnaires were conducted at scientific meetings in India and North America to gauge expert consensus on the perceived benefit of corticosteroids as adjunct treatment. Bayesian analysis, using the questionnaire data as a prior probability and the primary outcome of SCUT as a likelihood, was performed. For comparison, an additional Bayesian analysis was performed using the results of the SCUT pilot study as a prior distribution.Results: Indian respondents believed there to be a 1.21 Snellen line improvement, and North American respondents believed there to be a 1.24 line improvement with corticosteroid therapy. The SCUT primary outcome found a non-significant 0.09 Snellen line benefit with corticosteroid treatment. The results of the Bayesian analysis estimated a slightly greater benefit than did the SCUT primary analysis (0.19 lines verses 0.09 lines).Conclusion: Indian and North American experts had similar expectations on the effectiveness of corticosteroids in bacterial corneal ulcers; that corticosteroids would markedly improve visual outcomes. Bayesian analysis produced results very similar to those produced by the SCUT primary analysis. The similarity in result is likely due to the large sample size of SCUT and helps validate the results of SCUT.

Dissecting the immunological, antimicrobial and clinical effects of vitamin D therapy in tuberculosis

Invited Commentary on ‘Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment’, Coussens et al., Proceedings of the National Academy of Sciences of the United States of America, 2012. ‘Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning’, Sir Winston Churchill, 1942. Vitamin D, in the form of cod-liver oil, was first used as a treatment for tuberculosis (TB) over a century ago. The more recent discovery that macrophages (the intracellular niche of M. tuberculosis) can synthesise the biologically active form of vitamin D – 1,25(OH)D3 – from its precursor, the association of vitamin D deficiency with TB disease,1 and the potent effects of 1,25(OH)D3 on mycobacterial killing in vitro through intracellular expression of the anti-microbial peptide LL-37,2 led to clinical trials of vitamin D as an adjunct to antimicrobial treatment of pulmonary TB. The results of the latest and most robust study were mixed, showing increased speed of sputum culture conversion only in the subset of vitamin D-treated patients with the tt genotype of the TaqI polymorphism of the Vitamin D Receptor.3 However, the investigators have now uncovered profound immunomodulatory effects of vitamin D therapy in their cohort.4 By comparing responses in those given anti-tuberculous therapy alone with those given adjunctive vitamin D, the effects of vitamin D on a range of circulating cytokines and chemokines during recovery from TB were compared. Vitamin D hastened the resolution of M. tuberculosis antigen-independent and antigen–dependent hypercytokineaemia in pulmonary TB; these effects were not restricted to patients with the tt TaqI polymorphism, but occurred also in patients with TT and Tt genotypes. Additionally, and in contrast to the original intention-to-treat analysis, an adjusted per-protocol re-analysis of the 96 patients who completed the full course of study medication showed a significant shortening of time to sputum smear conversion in the whole cohort with adjunctive vitamin D. Given the high efficacy of short course antimicrobial chemotherapy for drug-sensitive TB, detection of even a modest incremental effect of vitamin D on clinical endpoints is notable. Given that vitamin D hastened microbiological clearance, the accelerated resolution of inflammatory responses in patients receiving vitamin D is difficult to interpret. During effective anti-TB drug treatment, mycobacterial load and antigen load progressively decline and a range of M. tuberculosis-induced inflammatory responses wane correspondingly. Therefore, it is unclear whether the observed accelerated resolution of inflammatory responses is mediated directly by effects of vitamin D on the adaptive immune system, as concluded by the authors, or indirectly in response to an accelerated decline in bacillary burden and antigen load mediated by enhanced vitamin D-mediated innate intracellular killing of M. tuberculosis. This uncertainty may have clinical implications. If vitamin D directly attenuates inflammatory immune responses during TB treatment, it might have an adjunctive role in limiting immunopathology in certain clinical subtypes of TB, such as TB meningitis. This would be akin to adjunctive immunosuppressive corticosteroids, where net clinical benefit through suppression of immunopathology depends on the host genotype of key innate immune response genes.5 On the other hand, a number of case-series have posited an association between vitamin D therapy and hyper-inflammatory paradoxical ‘upgrading’ reactions during TB treatment.6 Future clinical trials of adjunctive vitamin D therapy should therefore correlate the kinetics of immune responses with clinical complications of immunopathology, such as paradoxical reactions, as well vitamin D receptor genotypes, although achieving the necessary sample size will be challenging. To unmask the full potential of adjunctive vitamin D therapy, future studies should focus on multidrug-resistant TB where the therapeutic effects of antituberculous antibiotics are blunted. Finally, the tantalising potential of vitamin D as preventative therapy, as suggested by a recent pilot study in Mongolia,7 must not be overlooked.

Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial

Intensified antibiotic treatment might improve the outcome of tuberculous meningitis. We assessed pharmacokinetics, safety, and survival benefit of several treatment regimens containing high-dose rifampicin and moxifloxacin in patients with tuberculous meningitis in a hospital setting. In an open-label, phase 2 trial with a factorial design in one hospital in Indonesia, patients (aged >14 years) with tuberculous meningitis were randomly assigned to receive, according to a computer-generated schedule, first rifampicin standard dose (450 mg, about 10 mg/kg) orally or high dose (600 mg, about 13 mg/kg) intravenously, and second oral moxifloxacin 400 mg, moxifloxacin 800 mg, or ethambutol 750 mg once daily. All patients were given standard-dose isoniazid, pyrazinamide, and adjunctive corticosteroids. After 14 days of treatment all patients continued with standard treatment for tuberculosis. Endpoints included pharmacokinetic analyses of the blood and cerebrospinal fluid, adverse events attributable to tuberculosis treatment, and survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01158755. 60 patients were randomly assigned to receive rifampicin standard dose (12 no moxifloxacin, ten moxifloxacin 400 mg, and nine moxifloxacin 800 mg) and high dose (ten no moxifloxacin, nine moxifloxacin 400 mg, and ten moxifloxacin 800 mg). A 33% higher dose of rifampicin, intravenously, led to a three times higher geometric mean area under the time-concentration curve up to 6 h after dose (AUC(0-6); 78·7 mg.h/L [95% CI 71·0-87·3] vs 26·0 mg.h/L [19·0-35·6]), maximum plasma concentrations (C(max); 22·1 mg/L [19·9-24·6] vs 6·3 mg/L [4·9-8·3]), and concentrations in cerebrospinal fluid (0·60 mg/L [0·46-0·78] vs 0·21 mg/L [0·16-0·27]). Doubling the dose of moxifloxacin resulted in a proportional increase in plasma AUC(0-6) (31·5 mg.h/L [24·1-41·1] vs 15·1 mg.h/L [12·8-17·7]), C(max) (7·4 mg/L [5·6-9·6] vs 3·9 mg/L [3·2-4·8]), and drug concentrations in the cerebrospinal fluid (2·43 mg/L [1·81-3·27] vs 1·52 mg/L [1·28-1·82]). Intensified treatment did not result in increased toxicity. 6 month mortality was substantially lower in patients given high-dose rifampicin intravenously (ten [35%] vs 20 [65%]), which could not be explained by HIV status or severity of disease at the time of presentation (adjusted HR 0·42; 95% CI 0·20-0·91; p=0·03). These data suggest that treatment containing a higher dose of rifampicin and standard-dose or high-dose moxifloxacin during the first 2 weeks is safe in patients with tuberculous meningitis, and that high-dose intravenous rifampicin could be associated with a survival benefit in patients with severe disease. Royal Dutch Academy of Arts and Sciences, Netherlands Foundation for Scientific Research, and Padjadjaran University, Bandung, Indonesia.

Steroids Are OK in Meningococcal Meningitis

How best to use adjunctive corticosteroid therapy for adults with bacterial meningitis has not been straightforward. The strongest support for such

Dexamethasone Downregulates the Systemic Cytokine Response in Patients with Community-Acquired Pneumonia

The influence of adjunctive corticosteroids on the cytokine response in community-acquired pneumonia (CAP) is largely unknown. In this study, we analyzed the effect of dexamethasone on the cytokine response in patients with CAP and evaluated whether this effect is dependent on the causative microorganism. We hypothesized that dexamethasone has a larger effect on the cytokine response in patients with pneumococcal pneumonia than in patients with pneumonia caused by an atypical bacterium. A total of 304 hospitalized, nonimmunocompromised patients with CAP were randomized to an adjunctive 4-day course of 5 mg dexamethasone once a day (n = 151) or a placebo (n = 153). Serum concentrations of interleukin-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), macrophage inflammatory protein-1 alpha (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) were measured on days 0, 1, 2, and 4 and at a control visit. Overall, the concentrations of IL-6 (P < 0.01), IL-8 (P < 0.01), MCP-1 (P < 0.01), and TNF-α (P < 0.01) were significantly lower on day 2 in the dexamethasone group than in the placebo group. In patients with pneumococcal pneumonia (n = 72), both treatment groups showed a rapid decrease of cytokine concentrations; only the concentration of TNF-α (P = 0.05) was significantly lower in the dexamethasone group on day 2. In patients with CAP caused by an atypical pathogen (Legionella pneumophila, Chlamydophila species, Coxiella burnetii, or Mycoplasma pneumoniae; n = 58), IL-1Ra (P < 0.01), IL-6 (P < 0.01), and MCP-1 (P = 0.03) decreased more rapidly in the dexamethasone group than in the placebo group. In conclusion, dexamethasone downregulates the cytokine response during CAP. This effect seems to be dependent on the causative microorganism. This study provides insight into which patients with CAP might benefit most from adjunctive dexamethasone.

Corticosteroid Therapy, Vitamin D Status, and Inflammatory Cytokine Profile in the HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P ≤ .02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P ≤ .04) of ART. Vitamin D deficiency (total 25(OH)D <75 nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P = .004) of ART. Severe vitamin D deficiency (total 25(OH)D <25 nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.

Advances in the management of bacterial septic arthritis

The acute hot, swollen joint is a common medical presentation. It has a broad differential diagnosis, the most serious of which is bacterial septic arthritis. This article will discuss the epidemiology and pathogenesis of bacterial septic arthritis. The emergence of newer pathogenic organisms with changing antibiotic sensitivities will also be reviewed. The role that experimental animal models have played in clarifying some of the pathogenetic pathways of disease, as well as providing potential targets for novel therapies, will be presented. The clinical criteria for diagnosis will be discussed as well as the role of serum and synovial investigations to aid diagnosis. A guideline for antibiotic therapy will be shown as well as evidence suggesting that therapies, such as adjunctive corticosteroids, bisphosphonates and cytokine therapies, could improve the prognosis of septic arthritis. This article emphasizes that the diagnosis of septic arthritis rests principally on maintaining a high level of clinical suspicion. Early diagnosis with prompt and appropriate investigation and treatment is the mainstay of reducing the morbidity and mortality associated with the disease.

Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)‐infected and HIV‐uninfected persons

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP. We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP. Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P=0.01) and received appropriate antibiotics later in the course of hospitalization (5.2days vs. 1.1days, P<0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P=0.39) and 90-day mortality (41% vs. 28%, P=0.20) were detected. Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.

Corticosteroids as primary therapy in Kawasaki disease

Coronary artery aneurysms affect a substantial proportion of patients with Kawasaki disease, especially when standard therapy fails. Adjunctive primary corticosteroid treatment reduces inflammation and might reduce the incidence of coronary artery disease in a subset of patients at high risk of this comorbidity, but reliably identifying such individuals is a challenge.

Usefulness of corticosteroid therapy during chronic disseminated candidiasis: case reports and literature review

Chronic disseminated candidiasis (CDC) is a disseminated fungal infection that is frequently seen in patients undergoing intensive treatment of haematological malignancies. The first signs of CDC appear during neutrophil recovery. Clinical and physiopathological characteristics of CDC suggest it belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome (IRIS). We report five cases of CDC treated with antifungal therapy and adjuvant corticosteroids to decrease the exacerbated inflammatory response. We conducted a retrospective study in the Haematology Department of the University Hospital of Tours, France. The five reported cases were treated for CDC with antifungal therapy and adjuvant corticosteroids. Of the five cases of CDC, one was proven and four were possible, according to the 2008 European Organization for Research and Treatment of Cancer (EORTC) classification. All patients were being treated for acute leukaemia. In all cases, symptoms disappeared 2.8 days (range, 1-7) after the beginning of adjunctive corticosteroid therapy. Corticosteroids were administered on average for 146 days (range, 4 weeks-1 year) and antifungal therapy was administered for the duration of chemotherapy consolidation. There was no exacerbation of CDC symptoms during the next round of chemotherapy or bone marrow transplantation. One patient died from relapse of leukaemia. Within the framework of IRIS, adjuvant corticosteroid therapy could rapidly improve CDC symptoms and allow continued chemotherapy without delay and without compromising the haematological prognosis.

Is adjunctive corticosteroid beneficial in pneumococcal meningitis in a region with high rates of resistance to penicillin and ceftriaxone?

The role of adjunctive corticosteroids remains controversial in meningitis by penicillin-resistant pneumococci. We determined the effect of adjunctive corticosteroids in adults with pneumococcal meningitis in a region with a high rate of penicillin resistance. A multicenter, retrospective cohort study was conducted between 1998 and 2008 in Korea. The mortality and neurological sequelae were evaluated. Among 93 patients with pneumococcal meningitis, adequate adjunctive corticosteroids were given in 45.2%. The penicillin resistance rate was 60.0%, and 42.1% were nonsusceptible to ceftriaxone. The 30-day mortality rates in the group receiving adequate corticosteroid therapy, the group in which corticosteroid was not given, and that inadequately given were 24.3, 31.6, and 27.3%, respectively, and there was no difference between the groups. The rates of development of neurological sequelae were 34.3, 33.3, and 43.5%, respectively. Multivariate analysis showed that adequate corticosteroids did not reduce mortality (HR 0.773, 95% CI 0.293-2.040) and neurologic sequelae (HR 0.604, CI 0.262-1.393). Propensity-adjusted analysis showed that adjunctive corticosteroid was not associated with time to death (HR 0.949, CI 0.374-2.408), however, a decreasing tendency was shown in neurologic sequelae in the adequate corticosteroid group (HR 0.479, CI 0.207-1.110). In conclusion, adjunctive corticosteroids did not affect mortality in adults with pneumococcal meningitis in a region with high rates of resistance to penicillin and ceftriaxone; however, the patients receiving adequate corticosteroid therapy tended to develop neurologic sequelae less frequently.

Corticosteroids for Bacterial Keratitis

To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation. Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (-0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, -0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, -0.31 to -0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (-0.37 to -0.04; P = .02). We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. clinicaltrials.gov Identifier: NCT00324168.