External ventriculostomy-associated infection reduction after updating a care bundle.

BACKGROUND: Despite the clinical benefits of external ventricular drains (EVD), these devices can lead to EVD-related infections (EVDRI). The drainage insertion technique and standardized guidelines can significantly reduce the risk of infection, mainly caused by gram-positive bacteria. However, gram-negative microorganisms are the most frequent causative microorganisms of EVDRI in our hospital. We aimed to determine whether a new bundle of measures for the insertion and maintenance of a drain could reduce the incidence of EVDRI. This cohort study of consecutive patients requiring EVD from 01/01/2015 to 12/31/2018 compared the patients' characteristics before and after introducing an updated protocol (UP) for EVD insertion and maintenance in 2017. RESULTS: From 204 consecutive patients, 198 requiring EVD insertion were included (54% females, mean age 55 ± 15 years). The before-UP protocol included 87 patients, and the after-UP protocol included 111 patients. Subarachnoid (42%) and intracerebral (24%) hemorrhage were the main diagnoses at admission. The incidence of EVDRI fell from 13.4 to 2.5 episodes per 1000 days of catheter use. Gram-negative bacteria were the most frequent causative microorganisms. Previous craniotomy remained the only independent risk factor for EVDRI. EVDRI patients had increased mechanical ventilation durations, hospital and ICU stays, and percutaneous tracheostomy requirements. CONCLUSIONS: A care bundle focusing on fewer catheter sampling and more accurate antiseptic measures can significantly decrease the incidence of EVDRI. After implementing the management protocol, a decreased incidence of infections caused by gram-negative and gram-positive bacteria and reduced ICU and hospital lengths of stay were observed.

Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

A Care Bundle Intervention to Prevent Surgical Site Infections After a Craniotomy.

BACKGROUND: Although surgical site infections after a craniotomy (SSI-CRANs) are a serious problem that involves significant morbidity and costs, information on their prevention is scarce. We aimed to determine whether the implementation of a care bundle was effective in preventing SSI-CRANs. METHODS: A historical control study was used to evaluate the care bundle, which included a preoperative shower with 4% chlorhexidine soap, appropriate hair removal, adequate preoperative systemic antibiotic prophylaxis, the administration of 1 g of vancomycin powder into the subgaleal space before closing, and a postoperative dressing of the incisional surgical wound with a sterile absorbent cover. Patients were divided into 2 groups: preintervention (January 2013 to December 2015) and intervention (January 2016 to December 2017). The primary study end point was the incidence of SSI-CRANs within 1 year postsurgery. Propensity score matching was performed, and differences between the 2 study periods were assessed using Cox regression models. RESULTS: A total of 595 and 422 patients were included in the preintervention and intervention periods, respectively. The incidence of SSI-CRANs was lower in the intervention period (15.3% vs 3.5%; P < .001). Using a propensity score model, 421 pairs of patients were matched. The care bundle intervention was independently associated with a reduced incidence of SSI-CRANs (adjusted odds ratio, 0.23; 95% confidence interval, .13-.40; P < .001). CONCLUSIONS: The care bundle intervention was effective in reducing SSI-CRAN rates. The implementation of this multimodal preventive strategy should be considered in centers with high SSI-CRAN incidences.

Impact of pre-hospital antibiotic therapy on mortality in invasive meningococcal disease: a propensity score study.

The role of pre-hospital antibiotic therapy in invasive meningococcal diseases remains unclear with contradictory data. The aim was to determine this role in the outcome of invasive meningococcal disease. Observational cohort study of patients with/without pre-hospital antibiotic therapy in invasive meningococcal disease attended at the Hospital Universitari de Bellvitge (Barcelona) during the period 1977-2013. Univariate and multivariate analyses of mortality, corrected by propensity score used as a covariate to adjust for potential confounding, were performed. Patients with pre-hospital antibiotic therapy were also analyzed according to whether they had received oral (group A) or parenteral antibiotics (early therapy) (group B). Five hundred twenty-seven cases of invasive meningococcal disease were recorded and 125 (24%) of them received pre-hospital antibiotic therapy. Shock and age were the risk factors independently related to mortality. Mortality differed between patients with/without pre-hospital antibiotic therapy (0.8% vs. 8%, p = 0.003). Pre-hospital antibiotic therapy seemed to be a protective factor in the multivariate analysis of mortality (p = 0.038; OR, 0.188; 95% CI, 0.013-0.882). However, it was no longer protective when the propensity score was included in the analysis (p = 0.103; OR, 0.173; 95% CI, 0.021-1.423). Analysis of the oral and parenteral pre-hospital antibiotic groups revealed that there were no deaths in early therapy group. Patients able to receive oral antibiotics had less severe symptoms than those who did not receive pre-hospital antibiotics. Age and shock were the factors independently related to mortality. Early parenteral therapy was not associated with death. Oral antibiotic therapy in patients able to take it was associated with a beneficial effect in the prognosis of invasive meningococcal disease.

Management of Ventriculoperitoneal Shunt Infections in Adults: Analysis of Risk Factors Associated With Treatment Failure.

Background: Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors that predict failure. Methods: Retrospective, observational study of patients aged ≥12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Results: Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. Conclusions: This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity.

The anti-biofilm effect of macrolides in a rat model of S. aureus foreign-body infection: Might it be of clinical relevance?

Using a tissue cage infection rat model, we test the anti-biofilm effect of clarithromycin on the efficacy of daptomycin and a daptomycin + rifampicin combination against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In vitro: kill curves, daptomycin exposure studies and clarithromycin activity against biofilm were studied. In vivo: the efficacies of clarithromycin, daptomycin or daptomycin + clarithromycin, daptomycin + rifampicin and daptomycin + rifampicin + clarithromycin combinations were evaluated. In vitro: the addition of clarithromycin to daptomycin improved its activity only against one MRSA strain. Changes in daptomycin MIC values appeared more quickly in MSSA than in MRSA strain, and this was not modified by clarithromycin. Clarithromycin prevented biofilm formation but did not eradicate it. In vivo: the daptomycin + rifampicin combination was the most effective treatment and was not improved by the addition of clarithromycin. Daptomycin and daptomycin + clarithromycin had similar effectiveness; the combination protected against the appearance of daptomycin resistance only in one MRSA strain. Using a staphylococcal foreign-body infection model, we observed a slight effect with the addition of clarithromycin to daptomycin, which resulted in protection against the appearance of daptomycin-resistant strains. However, efficacy was not improved. Overall, our findings do not support a relevant clinical role for macrolides in treating device-related staphylococcal infections based on their anti-biofilm effect.

Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides.

BACKGROUND: To evaluate in vitro and in vivo efficacies of linezolid, vancomycin, and the combination of linezolid and rifampicin against two Staphylococcus aureus strains with reduced susceptibility to beta-lactams and one of them also to glycopeptides. METHODS: In vitro killing curves and a rabbit model: Meningitis was induced by intracisternal inoculation of 10(8) CFU/ml of each strain. Five hours later (0 h), rabbits were randomly assigned to control or to therapeutic groups. CSF bacterial counts, lactate and protein concentrations, and pharmacokinetic parameters were determined. RESULTS: In vivo: linezolid and its combination with rifampicin reduced bacterial concentrations at 24 h, median cfu/mL 4.85 vs 3.87 (p < 0.05) for linezolid and 5.02 vs 4.21 (p < 0.05) for linezolid + rifampicin, against the glycopeptide intermediate S. aureus (GISA) strain and improved inflammatory parameters. CONCLUSIONS: Despite the need for more experimental data, our results suggest that linezolid and its combinations could be considered as a potential alternative in difficult-to-treat CNS infections and especially in those due to GISA strains and deserve more studies.

A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis.

OBJECTIVES: This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis. METHODS: Data have been prospectively collected for the period1977-2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5-1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin. RESULTS: In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000). CONCLUSIONS: A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.

Seizure prophylaxis in pneumococcal meningitis, cohort study.

OBJECTIVE: Our aim was to assess seizure development as a complication of pneumococcal meningitis and its possible prevention with antiseizure medication prophylaxis. METHODS: Antiseizure medication (ASM) prophylaxis has been practiced for a long time at our center. We assessed all cases of community-acquired pneumococcal meningitis admitted from January 2010 to April 2021 recorded in our prospective database and conducted further retrospective studies. RESULTS: Of the 86 cases recorded, 21 (24.4%) developed acute symptomatic seizures, more than half of which (11/21; 52.4%) before admission. Seizure development increased the need for orotracheal intubation and intensive care unit admission, while also lengthening hospital stays and suggesting more risk of death and disability at discharge [adjusted odds ratio (aOR), 3.13; 95% confidence interval (CI): 1-9.8]. Of the 74 patients eligible for ASM prophylaxis, 64 received it and 10 did not. ASM prophylaxis seemed effective in preventing seizure development, as only six seizure events were recorded in 64 patients with ASM prophylaxis (9.4%) compared with four in the 10 patients without prophylaxis (40%). Its preventive capacity was especially notable when administered within 4 h of admission. Differences in mortality did not reach statistical significance. Adverse effects were rare. SIGNIFICANCE: Seizure development is a common complication in pneumococcal meningitis and is associated with increased risks of Intensive Care Unit admission, orotracheal intubation, and longer hospital stays. ASM prophylaxis may be effective in blocking seizure development in patients with preventable seizures and may be associated with better prognosis. Further studies are now warranted. PLAIN LANGUAGE SUMMARY: Infection of the meninges (the covering of the brain) due to the common bacteria S pneumoniae, used to be a fatal disease before the introduction of antibiotics and corticoids. Thanks to these drugs, more people survive this disease but, due to the frequent complications, they may have several sequelae. Seizures are a common complication. Our study suggests that they might be prevented by using antiseizure drugs which may reduce both severity and hospital stay.

Primary lumbar epidural abscess without spondylodiscitis caused by Fusobacterium necrophorum diagnosed by 16S rRNA PCR.

We report the case of a 71-year-old woman who presented a primary spinal epidural abscess caused by Fusobacterium necrophorum. This is the second report in the medical literature to associate this organism with a primary spinal epidural abscess without spondylodiscitis. After treatment with emergency laminectomy followed by 8 weeks of antibiotic treatment the patient was cured. Oral metronidazole (500 mg every 8 h) was the definitive choice of treatment. F. necrophorum spinal epidural abscess is rare, although samples for anaerobic culture should be collected in order to improve detection of anaerobic spinal infections. PCR amplification and sequencing of the 16S rRNA permits early diagnosis in anaerobic infections.

Economic impact of a care bundle to prevent surgical site infection after craniotomy: a cost-analysis study.

BACKGROUND: Surgical site infections after craniotomy (SSI-CRAN) significantly impact patient outcomes and healthcare costs by increasing length of stay and readmission and reoperation rates. However, to our knowledge, no study has yet analysed the economic impact of a surgical care bundle for preventing SSI-CRAN. The aim is to analyse the hospital cost saving after implementation of a care bundle for the prevention of SSI-CRAN. METHODS: A retrospective cost-analysis was performed, considering two periods: pre-care bundle (2013-2015) and care bundle (2016-2017). A bottom-up approach was used to calculate the costs associated with infection in patients who developed a SSI-CRAN in comparison to those who did not, in both periods and on a patient-by-patient basis. The derived cost of SSI-CRAN was calculated considering: (1) cost of the antibiotic treatment, (2) cost of length of stay in the neurosurgery ward within the 1-year follow up period, (3) cost of the re-intervention, and (4) cost of the implant for cranial reconstruction, when necessary. RESULTS: A total of 595 patients were included in the pre-care bundle period and 422 in the care bundle period. Mean cost of a craniotomy procedure was approximately €8000, rising to €24,000 in the case of SSI-CRAN. Mean yearly hospital costs fell by €502,857 in the care bundle period (€714,886 vs. €212,029). Extra costs between periods were mainly due to increased length of hospital stay (€573,555.3 vs. €183,958.9; difference: €389,596.4), followed by the cost of implant for cranial reconstruction (€69,803.4 vs. €9,936; difference: €59,867.4). Overall, implementation of the care bundle saved the hospital €500,844.3/year. CONCLUSION: The implementation of a care bundle for SSI-CRAN had a significant economic impact. Hospitals should consider the deployment of this multimodal preventive strategy to reduce their SSI-CRAN rates, and also their costs.

Effect of pulsed light treatment on Listeria inactivation, sensory quality and oxidation in two varieties of Spanish dry-cured ham.

The efficacy of pulsed light (PL) for the surface decontamination of ready-to-eat dry-cured ham was studied in two Spanish varieties, Serrano and Iberian. Listeriainnocua was inoculated on the surface of ham slices that were vacuum-packaged and flashed with 2.1, 4.2 and 8.4 J/cm2. Survivors were enumerated immediately after treatment. Peroxide values, sensory analysis and volatile profile were investigated during storage at 4 and 20 °C. Inactivation of Listeria was higher in Iberian (ca. 2 log cfu/cm2) than in Serrano ham (ca. 1 log cfu/cm2) with 8.4 J/cm2. PL did not increase the peroxide values above the usual levels reported in dry-cured ham, and no rancid notes were observed in the sensory analysis. PL-treated samples showed an increase in the concentration of some volatile compounds, such as methional, dimethyl disulfide and 1-octen-3-one, which imparted slight sulfur and metallic notes, although they disappeared during storage.

Delayed Cerebral Vasculopathy in Pneumococcal Meningitis: Epidemiology and Clinical Outcome. A Cohort Study.

BACKGROUND: To describe the prevalence, clinical characteristics, impact of systemic steroids exposure and outcomes of delayed cerebral vasculopathy (DCV) in a cohort of adult patients with pneumococcal meningitis (PM). METHODS: Observational retrospective multicenter study including all episodes of PM from January 2002 to December 2015. DCV was defined as proven/probable/possible based upon clinical criteria and pathological-radiological findings. DCV-patients and non-DCV-patients were compared by univariate analysis. RESULTS: 162 PM episodes were included. Seventeen (10.5%) DCV-patients were identified (15 possible, 2 probable). At admission, DCV-patients had a longer duration of symptoms (>2 days in 58% vs. 25.5% (p 0.04)), more coma (52.9% vs. 21.4% (p 0.03)), lower median CSF WBC-count (243 cells/uL vs. 2673 cells/uL (p 0.001)) and a higher proportion of positive CSF Gram stain (94.1% vs. 71% (p 0.07)). Median length of stay was 49 vs. 15 days (p 0.001), ICU admission was 85.7% vs. 49.5% (p 0.01) and unfavorable outcome was found in 70.6% vs. 23.8% (p 0.001). DCV appeared 1-8 days after having completed adjunctive dexamethasone treatment (median 2,5, IQR=1.5-5). CONCLUSIONS: One tenth of the PM developed DCV. DCV-patients had a longer duration of illness, were more severely ill, had a higher bacterial load at admission and had a more complicated course. Less than one third of cases recovered without disabilities. The role of corticosteroids in DCV remains to be established.

Linezolid for therapy of Staphylococcus aureus meningitis: a cohort study of 26 patients.

BACKGROUND: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection. METHODS: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015). RESULTS: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient. CONCLUSIONS: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.

Invasive Meningococcal Disease: What We Should Know, Before It Comes Back.

BACKGROUND: Invasive meningococcal disease (IMD), sepsis and/or meningitis continues to be a public health problem, with mortality rates ranging from 5% to 16%. The aim of our study was to further knowledge about IMD with a large series of cases occurring over a long period of time, in a cohort with a high percentage of adult patients. METHODS: Observational cohort study of patients with IMD between 1977 hand 2013 at our hospital, comparing patients with only sepsis and those with meningitis and several degrees of sepsis. The impact of dexamethasone and prophylactic phenytoin was determined, and an analysis of cutaneous and neurological sequelae was performed. RESULTS: A total of 527 episodes of IMD were recorded, comprising 57 cases of sepsis (11%) and 470 of meningitis with or without sepsis (89%). The number of episodes of IMD decreased from 352 of 527 (67%) in the first to 20 of 527 (4%) in the last quarter (P < .001). Thirty-three patients died (6%): 8 with sepsis (14%) and 25 with meningitis (5%) (P = .02). Cutaneous and neurological sequelae were present in 3% and 5% of survivors of sepsis and meningitis, respectively. The use of dexamethasone was safe and resulted in less arthritis, and patients given prophylactic phenytoin avoided seizures. CONCLUSIONS: The frequency of IMD has decreased sharply since 1977. Patients with sepsis only have the highest mortality and complication rates, dexamethasone use is safe and can prevent some arthritis episodes, and prophylactic phenytoin might be useful in a selected population. A rapid response and antibiotic therapy may help improve the prognosis.

Risk factors for surgical site infection after craniotomy: a prospective cohort study.

Background: Although surgical site infection after craniotomy (SSI-CRAN) is a serious complication, risk factors for its development have not been well defined. We aim to identify the risk factors for developing SSI-CRAN in a large prospective cohort of adult patients undergoing craniotomy. Methods: A series of consecutive patients who underwent craniotomy at a university hospital from January 2013 to December 2015 were prospectively assessed. Demographic, epidemiological, surgical, clinical and microbiological data were collected. Patients were followed up in an active post-discharge surveillance programm e for up to one year after surgery. Multivariate analysis was carried out to identify independent risk factors for SSI-CRAN. Results: Among the 595 patients who underwent craniotomy, 91 (15.3%) episodes of SSI-CRAN were recorded, 67 (73.6%) of which were organ/space. Baseline demographic characteristics were similar among patients who developed SSI-CRAN and those who did not. The most frequent causative Gram-positive organisms were Cutibacterium acnes (23.1%) and Staphylococcus epidermidis (23.1%), whereas Enterobacter cloacae (12.1%) was the most commonly isolated Gram-negative agent. In the univariate analysis the factors associated with SSI-CRAN were ASA score > 2 (48.4% vs. 35.5% in SSI-CRAN and no SSI-CRAN respectively, p = 0.025), extrinsic tumour (28.6% vs. 19.2%, p = 0.05), and re-intervention (4.4% vs. 1.4%, p = < 0.001). In the multivariate analysis, ASA score > 2 (AOR: 2.26, 95% CI: 1.32-3.87; p = .003) and re-intervention (OR: 8.93, 95% CI: 5.33-14.96; p < 0.001) were the only factors independently associated with SSI-CRAN. Conclusion: The risk factors and causative agents of SSI-CRAN identified in this study should be considered in the design of preventive strategies aimed to reduce the incidence of this serious complication.

Contribution of capsular and clonal types and beta-lactam resistance to the severity of experimental pneumococcal meningitis.

We used a rabbit model to assess the effects of capsular serotype, genetic background and beta-lactam resistance on the course and severity of experimental meningitis. Meningitis was induced by five pneumococcal strains belonging to five different clones with known invasive potential: two serotype 3 strains (ST260(3) and Netherlands(3)-31 clones) and three serotype 23F strains with different beta-lactam susceptibility patterns (Spain(23F)-1 clone, Tennessee(23F)-4 clone and a double locus variant of the Tennessee(23F)-4 clone). Major differences in secondary bacteremia and mortality rates were observed between serotypes 3 and 23F, as were divergences in the CSF lactate, protein and lipoteichoic-teichoic acid concentrations. Minor differences in the CSF-induced inflammatory response were found among strains belonging to the same serotype. Our results suggest that capsular serotype might be the main factor determining the course and severity of pneumococcal meningitis and genetic background contributes to a lesser extent. The acquisition of beta-lactam resistance does not reduce the virulence of the invasive clones. Since five strains belonging to two serotypes were studied, our findings have to be confirmed with other pneumococcal serotypes.

Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa.

To compare the efficacy of meropenem, ceftazidime, tobramycin and ceftazidime+tobramycin in a guinea-pig model of P. aeruginosa meningitis. After anesthesia, the atlanto-occipital membrane was punctured with a butterfly needle and 100 microl of a solution containing 10(6)CFU/ml of P. aeruginosa were injected directly into the cisterna magna. Four h later, therapy was initiated with saline or antibiotics given im for 48 h in doses that obtained CSF levels as in human meningitis: ceftazidime 200 mg/kg/8h, meropenem 200 mg/kg/8h, tobramycin 30 mg/kg/24h. Tobramycin was also given intracisternally. Animals were sacrificed at different time points. CSF and blood samples were collected and a meningeal swab was performed. Four hours after inoculation, bacterial concentration in CSF was 4 to 5log10CFU and mean WBC was 16,000/-l. All control animals died in 24h with a 12% increase in cerebral edema. All blood-cultures were negative. Ceftazidime, ceftazidime+tobramycin and meropenem reduced the CSF bacterial concentration at 8h by 2.5log10. At 48 h all CSF cultures were sterile but meningeal swab cultures remained positive in 30%. Our results suggest that meropenem may be at least as effective as ceftazidime and that the addition of tobramycin to ceftazidime may improve its efficacy.

Invasive meningococcal disease: Impact of short course therapy. A DOOR/RADAR study.

BACKGROUND: Invasive meningococcal disease is a severe infection. The appropriate duration of antibiotic therapy is not well established. METHODS: Two hundred and sixty-three consecutive patients with invasive meningococcal disease treated with 4 days' antibiotic therapy were compared with 264 consecutive patients treated previously at the same center with 7 days' antibiotic therapy. A Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) study was also performed. RESULTS: No relapses were recorded in any patient. Patients on the 4-day course were 63% female, with a median age of 23 years old (IQR 16-54) and patients on the 7-day course were 61% female, with a median age of 17 years old (IQR 12-43). Case fatality rate was 7% in the 4-d patients and 6% in the 7-d patients (p = 0.582). Neurological sequelae were recorded in 6% of the 4-d group and in 7% of the 7-d group ((p = 0.509) and cutaneous sequelae in 3% in both groups. There were no statistical significant differences between the groups in terms of clinical characteristics, laboratory findings or complications. The probability that a patient had a randomly chosen DOOR better with the 4-day regimen than with the 7-day regimen was 80.4% [95% CI 80.1-80.7%]. CONCLUSION: Invasive meningococcal disease may be successfully treated with a four-day course of antibiotic therapy without relapses.