Trends of Antimicrobial Susceptibility in Clinically Significant Coagulase-Negative Staphylococci Isolated from Cerebrospinal Fluid Cultures in Neurosurgical Adults: a Nine-Year Analysis.

Coagulase-negative staphylococci (CoNS) are the main pathogens in health care-associated ventriculitis and meningitis (HCAVM). This study aimed to assess antimicrobial susceptibility. Moreover, the treatment and clinical outcome were described. All neurosurgical adults admitted to one of the largest neurosurgical centers in China with clinically significant CoNS isolated from cerebrospinal fluid cultures in 2012 to 2020 were recruited. One episode was defined as one patient with one bacterial strain. Interpretive categories were applied according to the MICs. The clinical outcomes were dichotomized into poor (Glasgow Outcome Scale 1 to 3) and acceptable (Glasgow Outcome Scale 4 to 5). In total, 534 episodes involving 519 patients and 16 bacteria were analyzed. Over the 9 years, eight antimicrobial agents were used in antimicrobial susceptibility tests, including six in over 80% of CoNS. The range of resistance rates was 0.8% to 84.6%. The vancomycin resistance rate was the lowest, whereas the penicillin resistance rate was the highest. The linezolid (a vancomycin replacement) resistance rate was 3.1%. The rate of oxacillin resistance, representing methicillin-resistant staphylococci, was 70.2%. There were no significant trends of antimicrobial susceptibility over the 9 years for any agents analyzed. However, there were some apparent changes. Notably, vancomycin-resistant CoNS appeared in recent years, while linezolid-resistant CoNS appeared early and disappeared in recent years. Vancomycin (or norvancomycin), the most common treatment agent, was used in 528 (98.9%) episodes. Finally, 527 (98.7%) episodes had acceptable outcomes. It will be safe to use vancomycin to treat CoNS-related HCAVM in the immediate future, although continuous monitoring will be needed. IMPORTANCE Coagulase-negative staphylococci are the main pathogens in health care-associated ventriculitis and meningitis. There are three conclusions from the results of this study. First, according to antimicrobial susceptibility, the rates of resistance to primary antimicrobial agents are high and those to high-level agents, including vancomycin, are low. Second, the trends of resistance rates are acceptable, especially for high-level agents, although long-term and continuous monitoring is necessary. Finally, the clinical outcomes of neurosurgical adults with coagulase-negative staphylococci-related health care-associated ventriculitis and meningitis are acceptable after treatment with vancomycin. Therefore, according to the antimicrobial susceptibility and clinical practice, vancomycin will be safe to treat coagulase-negative staphylococci-related health care-associated ventriculitis and meningitis.

Normocellular Community-Acquired Bacterial Meningitis in Adults: A Nationwide Population-Based Case Series.

STUDY OBJECTIVE: This study sought to describe the clinical presentation of normocellular community-acquired bacterial meningitis in adults. METHODS: Using the prospective, nationwide, population-based database of the Danish Study Group of Infections of the Brain, the study identified all adults with normocellular community-acquired bacterial meningitis who were treated at departments of infectious diseases in Denmark from 2015 through 2018. Normocellular community-acquired bacterial meningitis was defined as a cerebrospinal fluid leukocyte count of up to 10×106/L combined with detection of bacteria in the cerebrospinal fluid. Outcome was categorized according to the Glasgow Outcome Scale at discharge. RESULTS: Normocellular cerebrospinal fluid was observed in 12 of 696 (2%) patients with community-acquired bacterial meningitis. The median age was 70 years (range 17 to 92 years), and 8 of 12 (67%) patients were male. All patients had symptoms suggestive of community-acquired bacterial meningitis and pathogens identified by culture (Streptococcus pneumoniae, n=10; Staphylococcus aureus, n=1) or polymerase chain reaction (Neisseria meningitidis; n=1) of the cerebrospinal fluid. Bacteremia was found in 9 of 12 (75%) patients, and 1 of 12 (8%) presented with septic shock. None of the patients had serious underlying immunocompromising conditions. The median times from admission to lumbar puncture and meningitis treatment were 2.5 hours (interquartile range 1.1 to 3.9 hours) and 2.6 hours (interquartile range 0.9 to 22.8 hours). In 3 of 11 (27%) patients, empiric treatment for community-acquired bacterial meningitis was interrupted by a normal cerebrospinal fluid cell count. The overall case-fatality rate was 3 of 12 (25%); meningitis treatment was interrupted in 1 of these patients, and 8 of 12 (67%) had a Glasgow Outcome Scale score of 1 to 4 at discharge. CONCLUSION: Normocellular community-acquired bacterial meningitis is not very common, but it is important to consider and may be associated with a pneumococcal cause.

Staphylococcal meningitis therapy with linezolid in a young infant: efficacy, CSF levels and side effects.

BACKGROUND: Linezolid is a synthetic antibiotic which is active against most Gram-positive bacteria, especially on Staphylococcus aureus. Its administration can be required when the infection is due to staphylococcus strains, which are resistant to vancomycin. Although mostly well tolerated, some mild to moderate side effects have been reported. CASE PRESENTATION: This case report describes an infant with multiloculated hydrocephalus, staphylococcal meningitis and prolonged linezolid therapy, in which we observed the association between linezolid administration and a lengthened QTc interval at the electrocardiogram (ECG). To rule out toxic levels during the therapy, plasma and cerebro-spinal fluid concentrations of linezolid were measured and reported. CONCLUSIONS: Although generally well tolerated in neonates and infants, linezolid prolonged administration seems be able to cause QTc interval prolongation. Therefore, its administration in such patients should be limited to cases of bacterial resistance to other antibiotics. In addition to well-known close monitoring of the platelet level, we suggest serial ECG controls before and during linezolid administration. In the case we report, linezolid plasma concentrations resulted within the therapeutic range during therapy, while cerebrospinal fluid (CSF) concentrations appeared lower than those considered effective.

Simultaneous Bilateral Orbital Cellulitis With Meningitis Caused by Methicillin-Resistant Staphylococcus aureus in an Immunocompetent Infant.

The authors report a rare case of fulminant bilateral orbital cellulitis caused by methicillin-resistant Staphylococcus aureus associated with meninigitis in a neonate. The clinical, laboratory, photographic, and radiological records are reviewed. A 17-day-old female infant presented with swelling over both upper eyelids and proptosis in both eyes. Computed tomography showed mutli-loculated abscesses within both orbits. Eyelid swelling and proptosis resolved following transcutaneous aspiration of the purulent material. Cerebrospinal fluid examination yielded Gram-positive cocci, which on culture and polymerase chain reaction testing was identified as methicillin-resistant Staphylococcus aureus. The infant received an extended course of antibiotics. At 12 months of follow-up, the infant was systemically normal with normal milestones, complete ocular movements, and no neurological sequelae. This case highlights the need for cerebrospinal fluid analysis in bilateral orbital cellulitis, even in cases not exhibiting central nervous system involvement. Aggressive medical and surgical treatment is needed in bilateral orbital cellulitis. [J Pediatr Ophthalmol Strabismus. 2020;57:e34-e37.].

CSF lactate.

Lactate is produced from anaerobic glycolysis, which occurs in most tissues in the human body. Blood lactate is tested in most physiologically unwell patients in the Emergency Department and helps to guide treatment and prognosis. Cerebrospinal fluid (CSF) lactate, however, is not often measured. Various central nervous system (CNS) conditions lead to a rise in CSF lactate, including acute neurological infection, stroke, seizures and mitochondrial pathologies. This article discusses the utility and limitations of CSF lactate, highlighting specific clinical situations where it can help in the diagnosis of CNS infections and unexplained encephalopathy.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Positive Culture Samples of Infants with Neonatal Infections in a Tertiary Neonatal Center in Isfahan, Iran.

BACKGROUND: The prevalence of microorganisms in the neonatal intensive care unit (NICU) and neonatal internal wards is constantly changing, thus rendering the practice of empiric antibiotic therapy ineffective due to the resistance of these microorganisms. Therefore, the purpose of this study was to determine the relative frequency of positive cultures of Bactec, blood, cerebrospinal fluid (CSF) and urine in infants admitted to the NICU and neonatal internal ward in Al-Zahra hospital in 2011-2017. METHODS: In this cross-sectional descriptive study, we evaluated 466 positive culture samples from 2853 different cultures (blood, urine, CSF, etc) from infants admitted to the NICU and neonatal internal ward with clinical signs of neonatal infection in Al-Zahra hospital. Isfahan in 2011-2017. The samples were evaluated for type of microorganisms and sensitivity to antibiotics. RESULTS: Positive cultures among Bactec, blood, CSF and urine culture samples were reported at 15.5% (95% confidence interval [CI]: 12.8-18.1) 9.3% (95% CI: 6.8-11.7), 6.4% (95% CI: 4.3-8) and 28.6% (95% CI: 25.4-31.7), respectively. Staphylococcus epidermidis was the most common species in Bactec (46.7%; 95% CI: 38.7-54.6), blood (53.1%; 95% CI: 39.1-67), and CSF (37.1%; 95% CI: 21-53.1) cultures while Klebsiella pneumoniae was the most frequent species in urine culture (28%; 95% CI: 22.2-33.7). CONCLUSION: Considering the results of Bactec and blood cultures, it is essential to reduce staphylococcal infections in our settings.

Methicillin-resistant Staphylococcus aureus (MRSA) sepsis complicated by warm autoimmune haemolytic anaemia secondary to antimicrobial therapy.

A 61-year-old Caucasian woman presented to the emergency room complaining of left-sided chest pain and altered mentation for 3 days. Her medical history included liver cirrhosis and coronary artery disease. On admission, she was found to have methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Due to a decline in mental status, a lumbar puncture was performed and cerebrospinal fluid cultures grew MRSA. She was treated initially with vancomycin. Ceftaroline was later added, due to the high burden of disease and difficulty in clearing her infection. After initiation of ceftaroline, bacteraemia cleared and mental status improved, however, she developed haemolytic anaemia. Ceftaroline was stopped and vancomycin continued. Staphylococcal meningitis is a rare occurrence, estimated at a rate of only 1%-10% of all bacterial meningitis cases. Ceftaroline seems to be a suitable option for disseminated MRSA infection, including MRSA meningitis, when the clinical response to vancomycin is inadequate. Further studies are warranted in order to establish adequate dosing while avoiding adverse effects.

Identification of Potential Cerebrospinal Fluid Biomarkers To Discriminate between Infection and Sterile Inflammation in a Rat Model of Staphylococcus epidermidis Catheter Infection.

Staphylococcus epidermidis cerebrospinal fluid (CSF) shunt infection is a common complication of hydrocephalus treatment, creating grave neurological consequences for patients, especially when diagnosis is delayed. The current method of diagnosis relies on microbiological culture; however, awaiting culture results may cause treatment delays, or culture may fail to identify infection altogether, so newer methods are needed. To investigate potential CSF biomarkers of S. epidermidis shunt infection, we developed a rat model allowing for serial CSF sampling. We found elevated levels of interleukin-10 (IL-10), IL-1ß, chemokine ligand 2 (CCL2), and CCL3 in the CSF of animals implanted with S. epidermidis-infected catheters compared to sterile controls at day 1 postinfection. Along with increased chemokine and cytokine expression early in infection, neutrophil influx was significantly increased in the CSF of animals with infected catheters, suggesting that coupling leukocyte counts with inflammatory mediators may differentiate infection from sterile inflammation. Mass spectrometry analysis revealed that the CSF proteome in sterile animals was similar to that in infected animals at day 1; however, by day 5 postinfection, there was an increase in the number of differently expressed proteins in the CSF of infected compared to sterile groups. The expansion of the proteome at day 5 postinfection was interesting, as bacterial burdens began to decline by this point, yet the CSF proteome data indicated that the host response remained active, especially with regard to the complement cascade. Collectively, these results provide potential biomarkers to distinguish S. epidermidis infection from sterile postoperative inflammation.

Patient and Treatment Characteristics by Infecting Organism in Cerebrospinal Fluid Shunt Infection.

BACKGROUND: Previous studies of cerebrospinal fluid (CSF) shunt infection treatment have been limited in size and unable to compare patient and treatment characteristics by infecting organism. Our objective was to describe variation in patient and treatment characteristics for children with first CSF shunt infection, stratified by infecting organism subgroups outlined in the 2017 Infectious Disease Society of America's (IDSA) guidelines. METHODS: We studied a prospective cohort of children <18 years of age undergoing treatment for first CSF shunt infection at one of 7 Hydrocephalus Clinical Research Network hospitals from April 2008 to December 2012. Differences between infecting organism subgroups were described using univariate analyses and Fisher's exact tests. RESULTS: There were 145 children whose infections were diagnosed by CSF culture and addressed by IDSA guidelines, including 47 with Staphylococcus aureus, 52 with coagulase-negative Staphylococcus, 37 with Gram-negative bacilli, and 9 with Propionibacterium acnes. No differences in many patient and treatment characteristics were seen between infecting organism subgroups, including age at initial shunt, gender, race, insurance, indication for shunt, gastrostomy, tracheostomy, ultrasound, and/or endoscope use at all surgeries before infection, or numbers of revisions before infection. A larger proportion of infections were caused by Gram-negative bacilli when antibiotic-impregnated catheters were used at initial shunt placement (12 of 23, 52%) and/or subsequent revisions (11 of 23, 48%) compared with all other infections (9 of 68 [13%] and 13 of 68 [19%], respectively). No differences in reinfection were observed between infecting organism subgroups. CONCLUSIONS: The organism profile encountered at infection differs when antibiotic-impregnated catheters are used, with a higher proportion of Gram-negative bacilli. This warrants further investigation given increasing adoption of antibiotic-impregnated catheters.

Coagulase-negative staphylococci are associated to the mild inflammatory pattern of healthcare-associated meningitis: a retrospective study.

The epidemiology of healthcare-associated meningitis (HAM) is dominated by commensal bacteria from the skin, as coagulase-negative staphylococci (CoNS). We hypothesized that the pauci-symptomatic and mild inflammatory patterns of HAM are related to the low pathogenic state of CoNS. Our aim was to describe clinical and biological features of CoNS HAM, compared to other HAM. All consecutive patients with HAM admitted in our hospital were retrospectively included from 2007 to 2014. HAM due to CoNS were compared to HAM caused by other bacteria (controls) for clinical and laboratory patterns. Seventy-one cases of HAM were included, comprising 18 CoNS and 53 controls. Patients were not different in terms of baseline characteristics. CoNS HAM occurred later after the last surgery than controls (17 vs. 12 days, p = 0.029) and had higher Glasgow Coma Scale (GCS) score (14 vs. 13, p = 0.038). Cerebrospinal fluid (CSF) analysis revealed a lower pleocytosis (25 vs. 1340/mm3, p < 0.001), a higher glucose level (3.75 vs. 0.8 mmol/L, p < 0.001), and a lower protein level (744 vs. 1751 mg/L, p < 0.001) in the CoNS group than in the control group, respectively. HAM due to CoNS was significantly less symptomatic and less inflammatory than HAM due to other bacteria.

Rapid Time to Positivity of Cerebrospinal Fluid Culture with Coagulase-Negative Staphylococcus Is More Likely to Reflect a True Infection Than Contamination.

OBJECTIVE: Cerebrospinal fluid (CSF) culture is the gold standard for diagnosing postoperative central nervous system infection. The time to positivity (TTP) of an automated continuous blood culture system may indicate the original concentration of the organism. Coagulase-negative Staphylococcus (CoNS), the common organism recovered in CSF, poses difficulty in differentiating infection from contamination. This study investigated the TTP of CSF culture with CoNS and its relationship to clinical parameters and prognosis. METHODS: Adult neurosurgical patients with CoNS who recovered via the use of CSF culture in BacT/ALERT Pediatric FAN blood culture bottles and were admitted from September 2013 to July 2015 were enrolled. The demographics, clinical and microbiological data, and treatment were reviewed, and the TTP of each culture was retrieved. RESULTS: Thirty-nine adult patients with CoNS recovered from CSF culture were included. The TTP ranged from 7.68 to 57.36 hours. A univariate logistic regression analysis indicated patients with rapid TTP (<21.5 hours) compared with those with longer TTP were more likely to be female, show an effective response to antibiotic therapy within 7 days, have clean-contaminated surgical incisions, and show CSF leak. A multivariate logistic regression analysis indicated that being female, an effective antibiotic therapy within 7 days, and clean-contaminated surgical incisions were independent predictors of rapid TTP. CONCLUSIONS: Targeted antibiotic therapy was more likely to be beneficial to patients with a rapid TTP within 7 days, which suggested that CoNS with a rapid TTP represents the pathogen of central nervous system infection rather than contamination in neurosurgical patients.

Cerebrospinal Fluid Infection Associated with Silver-Impregnated External Ventricular Drain Catheters.

OBJECTIVE: Silver-impregnated external ventricular drains (EVDs) have reduced the number of cases of ventriculitis. Risk factors for developing ventriculitis associated with plain EVD catheters have been well documented and incorporated into clinical practice, but risk factors in association with silver EVDs are unknown. Therefore, we sought to determine the risk factors for developing ventriculitis in patients with a silver EVD. METHODS: Prospectively collected data on consecutive patients undergoing insertion of a silver-impregnated EVD between October 2011 and September 2013 were analyzed. Cerebrospinal fluid (CSF) infection was defined as positive CSF microbiologic culture. Univariate and multivariate regression was performed to identify independent risk factors for CSF infection. RESULTS: There were 362 EVDs placed in 263 patients (142 women; median age 52 years; interquartile range, 40-62 years). There were 15 infections (6.4 per 1000 days of EVD drainage) recorded. Gram-negative organisms (8 of 15) were most commonly observed, although Staphylococcus was the most common genus (7 of 15; 46%) identified. Univariate analysis indicated that patients requiring EVD replacement (P < 0.0001), patients requiring bilateral EVDs (P < 0.0001), and patients with a CSF leak (P < 0.0001) were at increased risk of infection. Only need for EVD replacement remained significant on multivariate analysis (P < 0.0001, odds ratio = 15.9, confidence interval = 4.5-55.9). CONCLUSIONS: We identified an infection rate of 5.2% in this large contemporary series of patients undergoing silver EVD insertion according to a set protocol. These data suggest that targeting strategies to reduce Staphylococcus species is important, and increased vigilance for an increased incidence of gram-negative organisms is needed. Decreasing the need for EVD replacement is important in reducing infection rates further.

Evaluation of posttraumatic recurrent bacterial meningitis in adults.

BACKGROUND: Acute bacterial meningitis may develop as a complication after head trauma. The aim of this study was to present the demographic, clinical, microbiological and radiological characteristics of adult patients who presented with recurrent bacterial meningitis attacks after trauma. METHODS: Using a retrospective approach, the medical records of patients with acute recurrent bacterial meningitis (RBM) were reviewed, and those who had a history of trauma were included into the study. RBM was diagnosed based on clinical, bacteriologic and laboratory results. Demographic characteristics, clinical course, laboratory test results including cerebrospinal fluid analysis (CSF), radiological images, and the applied treatments were evaluated. RESULTS: A total of two hundred and twelve patients with acute bacterial meningitis were included into the study. RBM was diagnosed in twenty-five patients (11.8%), and in 18 of these patients (8.5%), the attacks had occurred subsequent to a trauma. In the CSF cultures of four patients, S. pneumoniae growth was observed. CT cisternography indicated CSF leaks in eleven patients. Moreover, bone fractures were observed in the CT images of ten patients. Ceftriaxone therapy was prescribed to 83% of the patients. Eight patients had a history of a fall in childhood, and five were involved in traffic accidents before acute bacterial meningitis. Four of the patients developed epilepsy and one developed deafness as sequelae. CONCLUSION: Since RBM attacks are frequently observed following trauma, in patients with a history of trauma who present with meningitis, the risk of recurrence should be considered.

Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety of meropenem for adult bacterial meningitis in Japan.

The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 µg/ml up to 8.47 h and was over 1 µg/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens.

Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU.

OBJECTIVE: To report the difficulty in achieving and maintaining target antibiotic exposure in critically ill patients with deep-seeded infections. CASE SUMMARY: We present a case of a 36-year-old man who was admitted to the intensive care unit with diffuse central nervous system and peripheral methicillin-sensitive Staphylococcus aureus infection (minimum inhibitory concentration; MIC, 1 µg/mL). Owing to the complicated nature of the infection, sequential concentrations of free flucloxacillin were measured in plasma and cerebrospinal fluid (CSF) and used to direct antibiotic dosing. Unsurprisingly, the trough plasma concentrations of flucloxacillin were below the MIC (0.2-0.4 µg/mL), and the corresponding CSF concentrations were undetectable (<0.1 µg/mL) with standard intermittent bolus dosing of 2 g every 4 hours. By administering flucloxacillin by continuous infusion (CI) and increasing the dose to 20 g daily, the plasma (2.2-5.7 µg/mL) and CSF (0.1 µg/mL) levels were increased, albeit lower than the predefined targets (plasma, 40 µg/mL; CSF, 4 µg/mL). DISCUSSION: The presence of physiological changes associated with critical illness-namely, hypoalbuminemia and augmented renal clearance-may significantly alter antibiotic pharmacokinetics, and this phenomenon may lead to suboptimal antibiotic exposure if they are not accounted for. This case also highlights the value of applying CI in such patient groups and demonstrates the significance of monitoring plasma and CSF drug concentrations in optimizing antibiotic delivery. CONCLUSIONS: Future research should aim to evaluate the utility of such drug monitoring with regard to patient outcomes and cost-effectiveness.

The causes and treatment outcomes of 91 patients with adult nosocomial meningitis.

BACKGROUND/AIMS: Frequent pathogens of nosocomial meningitis were investigated and the adequacy of empiric antibiotic therapy was assessed. Outcomes of nosocomial meningitis were also evaluated. METHODS: Ninety-one patients, who were diagnosed and treated for nosocomial meningitis at a single tertiary hospital in Daegu, Korea for 10 years, were included. Medical record and electronic laboratory data on the causative pathogens, antibiotics used, and outcomes were retrospectively investigated. RESULTS: Coagulase-negative Staphylococcus (40.9%) was the most common pathogen, followed by Acinetobacter (32.5%). Both were cultured as a single organism in cerebrospinal fluid (CSF). Seventy-eight patients (85.7%) had infections related to external ventricular drains (EVD). The most common empirical antibiotics were extended-spectrum beta-lactam antibiotics plus vancomycin (35/91, 38.6%). Of the 27 patients who had cultured Acinetobacter in CSF, 10 (37%) were given the wrong empirical antibiotic treatment. Seven of the 27 patients (26.9%) with cultured Acinetobacter died, and overall mortality of the 91 patients was 16.5%. In the multivariate analysis, the presence of combined septic shock (p < 0.001) and a persistent EVD state (p = 0.021) were associated with a poor prognosis. CONCLUSIONS: Acinetobacter is one of the leading pathogens of nosocomial meningitis and may lead to inadequate coverage of empiric antibiotic therapy due to increasing resistance. An EVD should be removed early in cases of suspected nosocomial meningitis, and carbapenem might be required for the poor treatment response.

[Pharmacodynamics of antibiotics in CSF: principles and consequences (predictive factors of efficacy)]. / Pharmacodynamie des antibiotiques dans le LCR : principes et conséquences (facteurs prédictifs d'efficacité).

The rational selection of antibiotics for the treatment of meningitis must take into account several criteria, among which their intrinsic activity against the causative bacteria, and their pharmacokinetic and pharmacodynamic properties. The intrinsic activity is evaluated by the Minimal Inhibitory Concentration (MIC), which, however, does not give any information on the bactericidal potency of the drug (important property for infections localized in compartments with low immune defense such as the CSF). The capacity of the antibiotic to reach the infected compartment depends on its physicochemical properties (molecular weight, lipophilicity) and its protein binding capacity, but also on the properties of the blood-CSF barrier (permeability modulated by inflammation and activity of active transporters). Pharmacodynamics correlate intrinsic activity to pharmacokinetics by determining the optimal value of the ratio between MIC and time of exposure, area under the curve, or peak concentration. On these bases, beta-lactams appear as first-line antibiotics, if used with large and repeated doses (or even as a continuous infusion), because of their time-dependent activity. The choice of the molecule is based on the susceptibility of the bacterium. Potential alternatives include chloramphenicol (limited however by its toxicity), moxifloxacin (showing high bactericidal effect, a low MIC, and appropriate penetration) but little clinically documented, linezolid and vancomycin for Methicillin-Resistant Staphylococcus aureus (MRSA), and vancomycin for penicillin non-susceptible pneumococci. Other molecules in clinical development are being evaluated for this indication.