BACKGROUND: Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis.
OBJECTIVES: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease.
SEARCH METHODS: We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017.
SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS: We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae.
AUTHORS' CONCLUSIONS: We found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.
Background: Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially among infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. This is the latest update of a review first published in 2005 and updated in 2008 and 2014. Objectives: To evaluate treatment of acute bacterial meningitis with differing volumes of initial fluid administration (up to 72 hours after first presentation) and the effects on death and neurological sequelae. Search methods: For this 2016 update we searched the following databases up to March 2016: the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, CINAHL, Global Health, and Web of Science. Selection criteria: Randomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. Data collection and analysis: All four of the original review authors extracted data and assessed trials for quality in the first publication of this review (one author, ROW, has passed away since the original review; see Acknowledgements). The current authors combined data for meta-analysis using risk ratios (RRs) for dichotomous data or mean difference (MD) for continuous data. We used a fixed-effect statistical model. We assessed the overall quality of evidence using the GRADE approach. Main results: We included three trials with a total of 420 children; there were no trials in adult populations. The largest of the three trials was conducted in settings with high mortality rates and was judged to have low risk of bias for all domains, except performance bias which was high risk. The other two smaller trials were not of high quality. The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants; low quality of evidence) or acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants; low quality of evidence). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants). There was very low quality of evidence favouring maintenance fluid over restrictive fluid for chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants). Authors' conclusions: The quality of evidence regarding fluid therapy in children with acute bacterial meningitis is low to very low and more RCTs need to be conducted. There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis.
BACKGROUND: In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
OBJECTIVES: To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.
SEARCH METHODS: We searched CENTRAL (2015, Issue 1), MEDLINE (1966 to January week 4, 2015), EMBASE (1974 to February 2015), Web of Science (2010 to February 2015), CINAHL (2010 to February 2015) and LILACS (2010 to February 2015).
SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS: We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.
MAIN RESULTS: We included 25 studies involving 4121 participants (2511 children and 1517 adults; 93 mixed population). Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. Nine studies were performed in low-income countries and 16 in high-income countries.Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P value = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.
AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.
BACKGROUND: Human soluzioni di albumina vengono utilizzati per una serie di problemi medici e chirurgici. Indicazioni autorizzate sono il trattamento di emergenza dello shock e le altre condizioni in cui il ripristino del volume ematico è urgente, come in ustioni e ipoproteinemia. Soluzioni di albumina umana sono più costosi di altri colloidi e cristalloidi.
OBIETTIVI: Per quantificare l'effetto sulla mortalità umana frazione proteica albumina plasmatica (PPF) l'amministrazione nella gestione dei pazienti critici.
STRATEGIA DI RICERCA: Abbiamo cercato il Gruppo Cochrane Injuries Specializzata Register (ricerca 31 maggio 2011), il Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovidio) (1948 alla settimana 3 maggio 2011) , EMBASE (Ovidio) (1980 alla Settimana 21 2011), CINAHL (EBSCO) (1982 a maggio 2011), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 a maggio 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 a maggio 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (cercato 10 giugno 2011, limite: ultimi 60 giorni). Elenchi di riferimento degli studi e articoli di revisione sono stati controllati, e gli autori delle prove individuate sono stati contattati.
CRITERI DI SELEZIONE: studi randomizzati controllati che hanno confrontato albumina o PPF senza albumina o PPF o con una soluzione di cristalloidi nei pazienti critici con ipovolemia, ustioni o ipoalbuminemia.
RACCOLTA DATI E ANALISI: Abbiamo raccolto i dati sui partecipanti, soluzione di albumina usate, la mortalità alla fine del follow-up, e la qualità di occultamento di assegnazione. L'analisi è stata stratificata in base al tipo di paziente.
PRINCIPALI RISULTATI: Abbiamo trovato 38 studi che soddisfano i criteri di inclusione e la comunicazione la morte come un risultato. Ci sono stati 1.958 morti tra i 10.842 partecipanti alla sperimentazione.
Per ipovolemia, il rischio relativo di morte in seguito a somministrazione di albumina era 1.02 (intervallo di confidenza 95% (CI) 0,92 a 1,13). Tale stima è stato fortemente influenzato dai risultati dello studio SAFE, che ha contribuito 75,2% delle informazioni (sulla base dei pesi nella meta-analisi). Per le ustioni, il rischio relativo era 2,93 (IC 95% 1,28-6,72) e per ipoalbuminemia il rischio relativo era 1,26 (IC 95% 0,84-1,88). Non c'era una sostanziale eterogeneità tra gli studi nelle varie categorie (Chi2 = 26,66, df = 31, P = 0,69). Il rischio relativo di morte con la somministrazione di albumina era 1,05 (IC 95% 0,95-1,16).
Conclusioni degli autori: Per i pazienti con ipovolemia, non vi è alcuna prova che l'albumina riduca la mortalità rispetto ad alternative più economiche come la soluzione salina. Non ci sono evidenze che l'albumina riduca la mortalità nei pazienti critici con ustioni e ipoalbuminemia. La possibilità che ci possa essere altamente selezionati popolazioni di pazienti in condizioni critiche in cui l'albumina può essere indicato rimane una questione aperta. Tuttavia, in considerazione della mancanza di evidenza di un beneficio sulla mortalità da albumina e il maggior costo di albumina rispetto alle alternative come soluzione salina, sembrerebbe ragionevole che l'albumina deve essere utilizzato solo nel contesto di ben nascosti ed adeguatamente alimentato studi clinici randomizzati controllati .
OBJECTIVES: The aim of this study was to determine trends in antibiotic resistance profiles of invasive clinical Haemophilus influenzae isolates over the last 20 years.
METHODS: Microbiology laboratories throughout England and Wales regularly submit invasive H. influenzae isolates to the Health Protection Agency for serotyping and antimicrobial susceptibility testing. Antimicrobial resistance was defined using the British Society for Antimicrobial Chemotherapy criteria (http://bsac.org.uk). All H. influenzae isolates from blood and cerebrospinal fluid (CSF) cultures between January 1985 and December 2004 were included.
RESULTS: Over the 20 year study period, 6805 H. influenzae isolates from blood (n = 4932, 72.5%) and CSF (n = 1873, 27.5%) were obtained. Over half the isolates (3736/6805, 54.9%) were identified as Hib, 38.9% (n = 2644) as non-capsulated and 6.2% (n = 425) as other capsulated serotypes. Resistance to ampicillin was highest at 16.2%, followed by trimethoprim (7.7%), tetracycline (1.8%) and chloramphenicol (1.2%). All isolates were susceptible to cefotaxime and only four (0.06%) were resistant to rifampicin. When analysing trends, chloramphenicol and tetracycline resistance rates have remained low since the late 1980s. Ampicillin resistance increased slowly until the mid-1990s and then gradually declined to its lowest rate of 11.6% in 2004. Resistance to trimethoprim initially fell from 10% in 1985 to 1.8% in 1989, but has continued to rise since then to 11.9% in 2004. In a logistic regression model, year of isolate (P < 0.001), non-capsulated H. influenzae (P < 0.001) and younger age (P = 0.004) remained independently associated with trimethoprim resistance.
CONCLUSIONS: Rifampicin and cefotaxime remain highly effective against all invasive H. influenzae isolates. Resistance to ampicillin, chloramphenicol and tetracycline has declined over the past 10 years, but trimethoprim resistance continues to increase rapidly. This finding requires further study but may reflect increased use of trimethoprim in the childhood population.
BACKGROUND: La terapia antibiotica per sospetta meningite batterica acuta (ABM) deve essere avviato immediatamente, prima ancora che i risultati di liquido cerebrospinale (CSF) la cultura e la sensibilità agli antibiotici sono disponibili. Inizio immediato di un trattamento efficace per via endovenosa può ridurre morte e invalidità.
OBIETTIVI: L'obiettivo è quello di confrontare l'efficacia e la sicurezza di cefalosporine di terza generazione (ceftriaxone o cefotaxime) con il trattamento convenzionale con penicillina o ampicillina-cloramfenicolo in pazienti con acquisita in comunità ABM.
Metodi di ricerca: Abbiamo cercato il registro centrale Cochrane dei trial controllati (CENTRAL) (The Cochrane Library 2011, Issue 1), che contiene Registrati specializzata del Cochrane Acute Gruppo Respiratory Infections, il MEDLINE (da gennaio 1966 a marzo settimana 4, 2011) e EMBASE ( gennaio 1974 ad aprile 2011). Abbiamo anche consultato l'elenco di riferimento di articoli di revisione e capitoli di libri, e ha contattato esperti per eventuali studi non pubblicati.
CRITERI DI SELEZIONE: Trials randomizzati e controllati (RCT) a confronto cefalosporine di terza generazione (ceftriaxone o cefotaxime) con antibiotici convenzionali (ampicillina, cloramfenicolo combinazione, o cloramfenicolo da solo) come terapia empirica per ABM in adulti e bambini.
Raccolta dati e analisi: Due autori della revisione indipendente ha applicato i criteri di selezione di studio, ha valutato la qualità metodologica ed estratto i dati.
Risultati principali: Diciannove studi che hanno coinvolto 1.496 pazienti sono stati inclusi nell'analisi. Non c'era eterogeneità dei risultati tra gli studi a qualsiasi risultato, tranne la diarrea. Non c'era alcuna differenza statisticamente significativa tra i due gruppi nel rischio di morte (differenza di rischio (RD) 0%, intervallo di confidenza 95% (CI) -3% al 2%), il rischio di sordità (-4% RD, 95% CI -9% a 1%) o rischio di fallimento del trattamento (RD -1%, IC 95% -4% al 2%). Tuttavia, ci sono stati rischi significativamente diminuiti di positività cultura della CSF dopo 10 o 48 ore (RD -6%, IC 95% -11% a 0%) e gli aumenti statisticamente significativi del rischio di diarrea tra i gruppi (RD 8%; 95% CI 3% al 13%) con le cefalosporine di terza generazione. Il rischio di neutropenia e rash cutanei non erano significativamente differenti tra i due gruppi. Tuttavia, a causa di un aumento della resistenza agli antibiotici dal 1980, la constatazione di questo esame dovrebbero essere letti con cautela.
Conclusioni degli autori: La revisione mostra alcuna differenza clinicamente importante tra cefalosporine di terza generazione (cefotaxime o ceftriaxone) e antibiotici convenzionali (ampicillina, cloramfenicolo combinazione, o cloramfenicolo da solo). Pertanto la scelta dell'antibiotico dipende costo e la disponibilità. Il modello di resistenza antimicrobica contro diversi antibiotici deve essere attentamente monitorata in basso a medio reddito così come paesi ad alto reddito.
OBIETTIVO: Per esaminare le prove di efficacia del trattamento con antibiotici prima del ricovero in reducing mortalità da meningite meningococcica.
DESIGN: revisione sistematica.
FONTI DI DATI: register Cochrane di studi e revisioni sistematiche, database di abstract di recensioni di efficacia, valutazione della tecnologia sanitaria, della ricerca e nazionale registro Inghilterra e Galles, Medline, Embase, CAB e salute.
Studi inclusi: studi che descrivono i risultati vitale di almeno 10 casi di malattia meningococcica classificati o meno gli antibiotici sono stati dati prima del ricovero in ospedale.
RISULTATI: 14 studi osservazionali ha incontrato i criteri di revisione. Trattamento antibiotico orale dato prima del ricovero è stata associata ad una riduzione della mortalità tra i casi (risk ratio combinato 0,17, intervallo di confidenza al 95% ,07-0,44). In sette studi in cui sono stati osservati tutti i pazienti inclusi nelle cure primarie, l'associazione tra antibiotici per via parenterale prima del ricovero e il risultato è stato incoerente (Chi2 per eterogeneità 11,02, P = 0,09). Dopo aggiustamento per la percentuale di assunzione di antibiotici per via parenterale prima del ricovero, non c'era eterogeneità residua. Una percentuale maggiore di pazienti trattati con antibiotici per via parenterale prima del ricovero è stata associata ad una riduzione della mortalità dopo il trattamento tale e viceversa (P = 0,04).
CONCLUSIONE: confondimento in base alla gravità è la spiegazione più probabile sia per l'effetto benefico di antibiotici per via orale e l'effetto nocivo osservato in alcuni studi di antibiotici per via parenterale. Non possiamo concludere o meno dato antibiotici prima del ricovero avere un effetto sulla mortalità. I dati sono coerenti con beneficio quando una parte sostanziale dei casi vengono trattati.
Microbiological tests for diagnosis of acute meningococcal disease are important for the clinical management of patients with this often-fatal illness, but cultures are frequently negative after antibiotics have been administered. Retrospective studies suggest that examination of skin biopsies may aid a rapid diagnosis and that cultures of skin biopsies are often positive even after antimicrobial treatment has commenced. This prospective controlled study aimed to assess the diagnostic value of skin biopsy compared with investigations of blood and cerebrospinal fluid (CSF) in patients with skin lesions and presumed meningococcal disease. A total of 43 patients, 31 with suspected acute meningococcal infection and 12 controls, were included. All skin biopsies were investigated by Gram stain and routine microbiological culture. In 25 patients, meningococcal infection was diagnosed microbiologically. The clinical diagnosis was meningococcal meningitis in 8 patients, meningococcal sepsis in 11 patients, and a combination of both in 6 patients. The sensitivity of cultures of blood, CSF, and skin biopsies was 56%, 50%, and 36%, respectively. When culture and Gram stain were combined, positive results were obtained in 56%, 64%, and 56%, respectively. There was no correlation between the diagnostic yield of skin biopsies and previous antibiotic treatment. In 14 patients, the diagnosis was based exclusively on one positive sample: CSF in 7 (28%) patients, blood in 4 (16%) patients, and skin biopsy in 3 (12%) patients. The sensitivity of skin biopsies was highest in patients with the least extensive skin lesions. Specificity was 100%. Microbiological investigation of skin biopsies increased the diagnostic yield and could be considered a component of the routine diagnostic work-up in patients with suspected meningococcal infection, even after the initiation of antimicrobial treatment.
