Md200179 117.125

Javier Aguilar, MD, Varinia Urday-Cornejo, MD, Susan Donabedian, MPH, Mary Perri, MT, Robert Tibbetts, PhD, and Marcus Zervos, MD Abstract: Staphylococcus aureus meningitis is a challenging disease Abbreviations: agr = accessory gene regulator, CA-MRSA = and little is known about its epidemiology. There are no established community-associated MRSA, CNS = central nervous system, management guidelines. We retrospectively reviewed the clinical infor- CSF = cerebrospinal fluid, MIC = minimum inhibitory concentra- mation, bacteriologic data, and outcomes of all 33 patients with cere- tion, MRSA = methicillin-resistant Staphylococcus aureus, MSSA = brospinal fluid (CSF) cultures positive for S aureus seen at a single methicillin-susceptible Staphylococcus aureus, PCR = polymerase urban teaching hospital from 1999 to 2008. Pulsed-field gel electropho- chain reaction, PFGE = pulsed-field gel electrophoresis, PVL = resis (PFGE) and polymerase chain reaction for staphylococcal cassette Panton-Valentine leukocidin, SCCmec = staphylococcal cassette chromosome mec (SCCmec), accessory gene regulator (agr) typing, chromosome mec, VP = ventriculoperitoneal.
and Panton-Valentine leukocidin (PVL) loci were done on methicillin-resistant S aureus (MRSA) CSF isolates starting in 2005.
S aureus caused 12 (36%) cases of postoperative and 21 (64%) cases of hematogenous meningitis. MRSA isolates were found in 6 (50%)cases of postoperative and 10 (48%) cases of hematogenous meningitis.
Although the frequency of Staphylococcus aureus meningitis is small compared with other causes of acute bacterial men- Twelve (75%) of the 16 MRSA infections occurred in the last 5 years ingitis, its incidence is growing, especially meningitis caused by of the study. Hematogenous meningitis was associated with older age community-associated methicillin-resistant strains of S aureus ( p = 0.04), injection drug use ( p G 0.01), community-acquired infection (CA-MRSA).1,2,26,39 In the United States, S aureus meningitis ( p G 0.01), underlying disease ( p = 0.01), staphylococcal infection accounts for 1%Y3% of cases of meningitis and is associated outside the central nervous system ( p = 0.01), altered mental status with a high mortality rate of about 50% in adults.13,31,34 World- ( p = 0.02), fever ( p = 0.01), septic shock ( p = 0.03), and bacteremia wide, S aureus meningitis constitutes 0.3%Y8.8% of all cases of ( p G 0.01). The analysis of the 9 MRSA isolates showed 3 PFGE types: 3 USA100 (33%), 5 USA300 (56%), and 1 USAnot100-1100 (11%).
S aureus meningitis has 2 distinct pathogenic mechanisms.
For SCCmec typing, there were 2 (22%) type II and 7 (78%) type IV.
In ‘‘postoperative’’ meningitis,10,43 bacteria are introduced dur- All USA300 strains were SCCmec IVa. For agr typing, there were 5 ing neurosurgical procedures, cerebrospinal fluid (CSF) shunt (56%) type I and 4 (44%) type II. Three isolates (33%) were positive device placement, trauma, or spreading from contiguous infec- for the PVL gene and were USA300 strains. Most patients received tion. In the second group, ‘‘hematogenous’’ or ‘‘spontaneous’’ nafcillin or vancomycin with or without rifampin or trimethoprim/ meningitis, S aureus is disseminated systemically, after bacter- sulfamethoxazole for a mean period of 17 days (range, 1Y42 d). Overall emic spread, secondary to staphylococcal infection outside the mortality was 36%, and it was associated with community-acquired in- An increasing number of cases of staphylococcal meningi- Postoperative and hematogenous S aureus meningitis are distinct tis have been reported over the last few years, as well as new clinical syndromes. S aureus hematogenous meningitis has devastating and different approaches and therapeutic options.1Y3,15,19,24,25,36,39 clinical consequences and elevated mortality rates, especially if it is There are no current established guidelines for S aureus men- acquired in the community. The incidence of MRSA meningitis in- ingitis treatment, and optimal management for this infec- creased over the last 5 years of the study. Treatment of choice is nafcillin tion is still unknown. The most commonly used antimicrobial for methicillin-sensitive strains and vancomycin for MRSA strains. The regimens for S aureus meningitis have been nafcillin for addition of trimethoprim/sulfamethoxazole or rifampin to vancomycin is methicillin-susceptible S aureus strains (MSSA) and vancomycin recommended in severe cases and community-acquired MRSA infec- with or without rifampin or trimethoprim/sulfamethoxazole for tions. Linezolid is also a good option due to its good CSF penetration methicillin-resistant strains (MRSA). New antimicrobial agents and favorable case reports. The mortality rate is higher in infections such as linezolid15,17,27 and daptomycin19,42 have been used with good outcomes in the United States and in other countries in Europe and Asia. In the study presented here, we review the epi-demiology, clinical features, response to treatment, and outcomeof 33 cases of staphylococcal meningitis.
From Division of Infectious Diseases and Microbiology (JA, VUC, SD,MP, RT, MZ), Henry Ford Hospital, Detroit, Michigan; and Wayne StateUniversity School of Medicine (MZ), Detroit, Michigan.
Dr. Zervos has received grants from Pfizer, Cubist Pharmaceuticals, We performed a retrospective study at Henry Ford Hospital, Ortho-McNeil, and Astellas Pharma, and has served on speaker a 903-bed tertiary teaching institution located in urban Detroit, Reprints: Javier Aguilar, MD, Division of Infectious Diseases, Henry Ford Michigan, serving a population of 1 million people. We reviewed Hospital, 2799 West Grand Boulevard, CFP-304, Detroit, MI 48202 the medical records of all adult patients who were diagnosed with S aureus meningitis between January 1999 and December Copyright * 2010 by Lippincott Williams & Wilkins 2008. Patients were identified from the microbiology laboratory ISSN: 0025-7974DOI: 10.1097/MD.0b013e3181d5453d records. Demographic, clinical, and laboratory information was Medicine & Volume 89, Number 2, March 2010 Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 collected. Clinical information included predisposing factors, determined to be of the same PFGE strain group if their SmaI past medical history, comorbidities, mode of acquisition, source restriction patterns were 80% similar using the Dice coefficient.37 of infection, description of staphylococcal infections outside Multiplex polymerase chain reaction (PCR) was performed to the CNS, as well as therapeutic management, length of determine the staphylococcal cassette chromosome mec (SCCmec) types I, II, III, and IV.28 Accessory gene regulator(agr) typing was performed for all isolates,38 as was detection of the Panton-Valentine leukocidin (PVL) toxin genes, lukS-PV, andlukF-PV.21 A definitive diagnosis of S aureus meningitis was con- firmed by isolation of S aureus in 1 or more CSF cultures; clinicalevidence of meningeal inflammation, such as fever, altered mental status, and meningeal signs; abnormal CSF features in- Continuous variables were compared using the t test.
cluding at least 1 of the following: pleocytosis (9250 leukocytes Dichotomous data were compared using either a chi-square test per KL), increased lactate concentration (93.5 mmol/L), or Fisher exact test when appropriate. A p value of less than decreased glucose ratio (CSF to serum G 0.4) or decreased 0.05 was considered statistically significant. This study was glucose level (G2.5 mmol/L) if no simultaneous serum glucose approved by the Henry Ford Hospital Institutional Review Board was measured.6 Cases were classified by the mode of ac- quisition as either postoperative meningitis or hematogenousmeningitis. Postoperative meningitis included meningitis sec- ondary to neurosurgery, invasive procedures, lumbar punctures,shunt devices, or trauma. Hematogenous meningitis included patients who had no history of neurosurgical procedures or From January 1999 to December 2008, 668 cases of trauma. Health care-associated (nosocomial) meningitis was bacterial meningitis occurred, of which 33 (4.9%) cases were defined as infection not present when the patient was admit- caused by S aureus. Sixteen of the 33 (48%) cases were caused ted to the hospital, incubating at the time of admission and by MRSA and 17 (52%) by MSSA. Among the 33 cases of S no sooner than 48 hours after admission, or meningitis up to aureus meningitis, 12 (36%) cases were postoperative menin- 1 month after discharge from the hospital where the patient had gitis and 21 (64%) cases were hematogenous meningitis. MRSA undergone neurosurgery or an invasive procedure.
isolates were found in 6 (50%) cases of postoperative and 10 CSF samples were initially obtained through lumbar punc- (48%) cases of hematogenous meningitis. The frequency of ture or aspiration of shunt tubing. Laboratory information on presentation varied from 1 to 5 cases per year, with 12 (75%) of initial and follow-up CSF samples included cell count and dif- the 16 infections caused by MRSA seen in the last 5 years of the ferential, protein levels, lactate concentration, glucose ratio (CSF study. No MSSA meningitis infections occurred from 2006 to to serum), and glucose concentration. Results on blood cultures, 2008. Table 1 compares demographic and clinical information echocardiographic imaging (transthoracic and transesophageal), between cases of postoperative and hematogenous meningitis.
and radiographic studies (computed tomography and magneticresonance imaging) at presentation were also collected.
Patients with hematogenous meningitis were older (mean age, 55.9 yr vs. 47 yr; p = 0.04) and had a higher frequency of community-acquired infection (71% vs. 8%; p G 0.01) than Gram staining was performed on all CSF samples. S aureus patients with postoperative meningitis. Patients with hematog- isolates were identified using routine microbiologic methods. In enous meningitis had underlying diseases more frequently than vitro susceptibilities were determined following Clinical and patients with postoperative meningitis (95% vs. 28%; p = 0.01).
Laboratory Standards Institute (CLSI) standards (CLSI, Wayne, The most common comorbidities were cardiovascular disease, PA). In vitro susceptibility to vancomycin was initially deter- diabetes mellitus, chronic kidney disease, and liver cirrhosis. In mined by the clinical microbiology laboratory using automated the group with hematogenous meningitis, 11 (52%) of 21 microdilution with Vitek-2 (bio-Merieux, Durham, NC). Induc- patients were intravenous drugs users. There were no intrave- ible clindamycin resistance was determined using the D-zone nous drug users in the postoperative group. The frequency of test as described by the CLSI. In vitro susceptibilities to van- associated staphylococcal infection outside the CNS was higher comycin and daptomycin were determined using the E-test, in patients with hematogenous meningitis compared to patients following the instructions provided by the manufacturer (AB- with postoperative meningitis (71% vs. 25%; p = 0.01).
Biodisk, Solna, Sweden). Isolates were screened for heteroresis- Paraspinal and/or epidural abscesses (n = 5), endocarditis tance to vancomycin using the macrodilution method E-test.44 (n = 5), skin or soft tissue infections (n = 2), and pneumonia Genomic DNA was prepared and digested with SmaI (New (n = 2) accounted for all the infections outside of the CNS in England BioLabs, Beverly, MA) using a previously described method.23 SmaI fragments were separated using a CHEF-DR III Fever (86% vs. 42%; p = 0.01), septic shock (57% vs. 17%; apparatus (Bio-Rad, Hercules, CA) using the following settings: p = 0.03), and altered mental status (76% vs. 33%; p = 0.02) initial switch time, 5 s; final switch time, 35 s; voltage, 6 V/cm; run were found to be more frequent in the hematogenous meningitis time, 21 h; temperature, 14-C. NCTC 8325 was the reference group. Meningeal signs, headaches, and focal neurologic deficits standard used, which was run in lanes 1, 8, and 15 of a 15-well gel.
were more common in the postsurgical group, although the Pulsed-field gel electrophoresis (PFGE) patterns were compared differences were not statistically significant.
using the BioNumerics software program (Applied Maths, Intracranial devices (n = 10; 83%), recent neurosurgery Belgium). All of the MRSA isolates in this study were compared (n = 6; 50%), and CSF leakage (n = 1; 8%) were the most to MRSA strains USA100 to j1100 (Network on Antimicrobial common predisposing conditions for postoperative meningitis.
Resistance in Staphylococcus aureus, Herndon, VA) as described All patients who had obstructive hydrocephalus requiring shunts by the Centers for Disease Control and Prevention.23 Isolates were had ventriculoperitoneal (VP) devices (n = 9; 75%). No other Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 TABLE 1. Comparison of Postoperative Meningitis and Hematogenous Meningitis Laboratory information: analytical features type of CSF shunt was seen. Meningitis was an early complica- nous meningitis had a higher frequency of bacteremia than pa- tion of neurosurgery, occurring within 2 weeks to 1 month after tients with postoperative meningitis (76% vs. 17%; p G 0.01).
placement of VP shunts or intracranial devices. In the 3 patients MRSA isolates were found in 6 (50%) patients with postop- with postoperative meningitis who did not have a VP shunt, the erative meningitis and in 10 (48%) patients with hematogenous infection was evident 2 weeks after intracranial chemotherapy meningitis. Of these 16 patients, 8 (50%) were susceptible to device placement for glioblastoma multiforme, 3 weeks after a trimethoprim/sulfamethoxazole and 4 (25%) of them were also lumbar puncture due to pseudotumor cerebri, and 3 weeks after susceptible to clindamycin. All of these 8 patients presented with arteriovenous malformation repair surgery. respectively. Two a community-acquired infection. Two MRSA-infected patients (17%) patients with obstructive hydrocephalus and VP shunts had vancomycin minimum inhibitory concentrations (MICs) had also a S aureus surgical wound infection.
92 Kg/mL, and 1 of them was susceptible to rifampin. One pa-tient was found to have a vancomycin intermediate resistant S aureus isolate (VISA, Vitek-2, and E-test MIC = 4 Kg/mL), CSF samples were obtained through aspiration of the shunt which was resistant to trimethoprim/sulfamethoxazole and ri- tubing in all 9 cases of shunt-related infection and by lum- fampin, but susceptible to linezolid.
bar puncture in the remaining 24 patients. CSF features were PGFE and PCR for PVL, SCCmec type, and agr were similar in both groups (see Table 1). No statistically significant done on isolates from 9 patients. The analysis of the MRSA differences were found regarding the CSF leukocyte count, isolates showed 3 PFGE types: 3 USA100 (33%), 5 USA300 gram stain, protein concentration, glucose level, CSF to serum (56%), and 1 USAnot100-1100 (11%). For SCCmec typing, glucose ratio, or lactate concentration. Patients with hematoge- there were 2 (22%) type II and 7 (78%) type IV. All USA300 Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 strains were SCCmec IVa. For agr typing, there were 5 (56%) (range, 10Y21 d). Clinical presentation, molecular analysis, type I and 4 (44%) type II. Three isolates (33%) were positive administered treatment, and outcomes are summarized in for the PVL gene and were USA300 strains. All 3 patients Table 2 and Table 3 for MSSA and MRSA cases, respectively.
with USA100 strains had postoperative meningitis and nosoco- The mortality rate was higher in cases of hematogenous mial infection, and 1 of them died. All 5 patients with USA300 meningitis than in cases of postoperative meningitis (43% vs.
strains had hematogenous meningitis, admitted with sepsis, and 25%), but the difference was not statistically significant. Table 4 3 (60%) were acquired in the community. One of them died in gives the main characteristics of the patients who died compared with those who survived. Mortality was more frequent incommunity-acquired infections than in nosocomial infections (p = 0.03). There were no statistical differences in mortality At presentation, 15 (45%) patients received ceftriaxone and regarding mode of acquisition, clinical presentation, underlying vancomycin as empiric therapy for bacterial meningitis, and in 1 diseases, bacteremia, or type of isolate.
of them ampicillin was also administered. In the other 18 (55%)patients, appropriate antibiotic therapy was started an average of24 hours after presentation, when preliminary results of CSF and gram stain were available. Once the diagnosis of S aureus In the current study, S aureus meningitis accounted for meningitis was established, patients with MSSA infections 4.9% (33/668) of the cases of adult culture-proven bacterial received nafcillin (n = 15; mortality rate 27%) and piperacillin/ meningitis. Even though the frequency of S aureus meningitis is tazobactam (n = 1; patient died). One patient was kept on the small compared to other causes of acute bacterial meningitis,32 combination of ceftriaxone and vancomycin and died a few its incidence is growing in the United States13,31,34 and world- hours after admission and before the final identification of the wide.4,9,41 According to current epidemiologic trends, there isolate. Patients with MRSA infections received vancomycin has been a recent shift from methicillin-susceptible strains to alone (n = 11; mortality rate 45%), vancomycin with trimeth- methicillin-resistant strains. Over the last 5 years, an increasing oprim/sulfamethoxazole (n = 3; mortality rate 33%), vancomy- number of cases of meningitis due to CA-MRSA infection have cin and rifampin (n = 2; both patients survived), and the patient been reported, especially in the United States,29 Asia,5,6 and infected by a VISA strain received linezolid (patient survived).
many countries in Europe,1,30,39 with a significant number oc- The length of treatment was a mean of 17 days (range, 1Y42 d) curring in intravenous drug users but also in healthy individuals and was based on the primary infection (for example, epidural as noted by Naesens et al.26 This observation was confirmed in abscess, skin and soft tissue infection, endocarditis). The 2 our study, with more than 75% of all cases of MRSA meningitis patients who had a MIC 92 Kg/mL received vancomycin alone occurring since 2005, and 11 (52%) cases of 21 hematogenous and died. Twenty patients (67%) had 1 or more than 1 follow-up meningitis cases occurring in intravenous drug users.
CSF analysis with sterilization of the cultures in a mean time of Our findings agree with those of earlier studies,6,30 which 7.7 days. Neither steroids nor intrathecal antimicrobial therapy have suggested that hematogenous and postoperative meningitis was used in any patients in this series.
are distinct clinical entities and present differently. In these studies, In patients with VP shunts (n = 9), all components of the major differences in mortality were reported based on age dis- shunt were eventually removed, with externalization performed tribution, clinical features, and presentation,6,30 which were also previously in 8 cases. One patient died before externalization found in the present series. In comparison with postoperative of the shunt. A new shunt device was placed after resolution of meningitis, hematogenous meningitis is usually a community- the infection in an average of 9 days in 8 patients, and treatment acquired infection29 that mainly affects older patients with severe was continued for an additional period of 14 days on average underlying conditions such as a cardiovascular condition, chronickidney disease, or diabetes.30 Recently, there have been manyreports of cases of S aureus meningitis in healthy patients, with nochronic comorbidities.1,2,24,39 Hematogenous CNS infection also TABLE 4. Mortality: Comparison of Patients Who Died and occurs due to dissemination from distant sources such as epidural abscesses, endocarditis, skin and soft tissue infection, or pneu- monia.6,30 The current study confirmed the observations that bac- teremia and extra-CNS infections were seen more frequently in hematogenous than in postoperative meningitis. Cases of menin-gitis due to infection spreading from surrounding structures such as paranasal sinuses and consequent cavernous sinus thrombosis were also described.24 Concordant with the increasing incidence of S aureus bacteremia in intravenous drug users in Detroit,7 in the current study we found that 52% of patients in the hematogenous meningitis group were intravenous drug users, and 33% had chronic liver disease related to hepatitis B and/or C infection.
Hematogenous meningitis patients present with more severe illness compared to patients with postoperative meningitis, with altered mental status, fever, and septic shock.5,6,30 No differences in the frequency of meningeal signs, focal neurologic findings, or seizures between the groups were found in the current study.
Meningitis and shunt infections are the most common nosocomial CNS infections. Almost all cases of nosocomial meningitis develop postoperatively.10 The reported risk factorsfor nosocomial meningitis include postoperative CSF leakage, intraventricular shunt operations, external ventricular drainage, Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 repeated surgery, and emergency surgery,10 and it is described produces. In the present study, mortality was not seen in patients more frequently in young people, without chronic comorbidities treated with the combination of vancomycin and rifampin, and and with obstructive hydrocephalus.30 S aureus and coagulase- was 33% in patients who received the combination of van- negative Staphylococcus are known to be frequent gram-positive comycin and trimethoprim/sulfamethoxazole, compared with pathogens in postoperative nosocomial meningitis, particularly 45% in patients treated with vancomycin alone. Two patients involving intracranial devices.6,18,30 Our results support these who had vancomycin MICs 92 Kg/mL and received vancomy- observations and confirm that those infections occur immedi- cin alone died due to unresolved meningeal infection. Van- ately after surgery or up to 1 month after an invasive procedure.6,30 comycin failures are described and may be attributed to its poor Series of nosocomial meningitis identified mortality risk factors CSF penetration. The CSF to serum ratios are only approxi- in these patients and include the type of microorganism that mately 20% in patients without meningitis and 50% in patients causes meningitis, the underlying brain disease, initial conscious- with meningitis.26 There are sporadic case reports of suc- ness level, low CSF glucose concentration, presence of bacter- cessful treatment of MRSA meningitis with linezolid.15,17,27,35 emia, and inappropriate antibiotic use.10 This may be explained in part by the excellent CSF penetra- CSF analytical characteristics were similar in both groups.
tion of linezolid (CSF to serum ratios of approximately 70%).17 CSF analysis showed a low yield of organisms6,30 when using Naesens et al26 in their literature review described 3 cases of the gram stain with only 25% positive samples in postoperative CA-MRSA infection that received linezolid and had complete meningitis and 14% in hematogenous meningitis. Bacteremia is resolution of the infection. In the current series we also describe common in hematogenous S aureus meningitis and has been 1 case of nosocomial, postoperative meningitis caused by a observed in 64%Y100% of patients.5,6,30 In the current study heterogeneous resistant S aureus strain (VISA, Vitek-2, and bacteremia was significantly more frequent in hematogenous E-test MIC = 4 Kg/mL) that had a complete resolution of the meningitis, and, as described previously, it is primarily a bac- infection. As far as we know, this is the fourth case described teremic dissemination of an extrameningeal staphylococcal in the literature of MRSA meningitis treated successfully with infectionVfor instance, septic shock is more frequent in this linezolid. However, more data on comparative antimicrobial The present study extends the findings of earlier studies by Recently, daptomycin has been shown to be effective in the including molecular analysis of MRSA strains and strains of S treatment of S aureus meningitis.19,42 In a rabbit meningitis model, aureus with reduced in vitro susceptibility to vancomycin. As far daptomycin showed significantly superior bactericidal activity as we know, this is the first S aureus meningitis series in which compared with vancomycin therapy.14,19 There are also reports of molecular analysis is performed. Isolates of S aureus were MRSA meningitis successfully treated with daptomycin.19,42 It available from 9 patients; 5 were MRSA USA300 strains with must be noted that some isolates of USA300 CA-MRSA have SCCmec IVa and agr I. All of these isolates were associated with already been described as nonsusceptible to daptomycin in vitro.
hematogenous meningitis, and 3 of them were positive for PVL.
Other alternative antimicrobial agents used with success include Earlier reports have suggested that PVL-positive strains have dalbavancin8 for MRSA and flucloxacillin for MSSA,33 but these unique epidemiologic and clinical characteristics, including are not available in the United States.
more metastatic disease.1 Three of the 5 patients with CA- The empiric treatment for meningitis is still vancomycin MRSA infections presented with sepsis, and 1 of them died with and ceftriaxone. Then, after cultures and susceptibilities are septic shock. Postoperative meningitis and nosocomial disease finalized, we recommend a high dose of beta-lactamase-resistant were caused by USA100 strains in 3 patients, concordant with penicillin (oxacillin or nafcillin) for MSSA infections and van- findings in previous molecular studies.7 One patient had an comycin for MRSA infections. In the present series, the numbers MRSA USAnot100-1100 strain and corresponded to a postop- of MRSA-infected patients treated with each regimen was too erative meningitis case. The later 4 strains contained agr II and small to draw a statistical conclusion; however, based on our mortality rates, we recommend using the combination of van- The objective of initial empiric antibiotic therapy is to comycin with either rifampin or trimethoprim/sulfamethoxazole, achieve adequate therapeutic levels in CSF, in addition to or switching to linezolid after further susceptibility testing is providing activity against possible pathogens. When CSF culture performed, especially when dealing with severe MRSA infec- reveals a particular bacterial pathogen, treatment should be directed toward the specific pathogen depending on the results The optimal duration of treatment is not known. Some studies of in vitro susceptibility. The therapy of S aureus meningitis is support the use of a 3-week course of antibiotic therapy.11 In the challenging because of the limited therapeutic options in the current study, sterilization of CSF cultures occurred after a mean setting of increasing antimicrobial resistance, the difficulty in period of 7.7 days. The length of treatment should be based on the achieving therapeutic drug concentrations in the CSF, and the lack primary infection in all cases with a simultaneous infection outside of established management guidelines. The concentration reached the CNS (for example, epidural abscess, skin and soft tissue in- in compartments with low immune defense such as the CSF is an fection, endocarditis). In cases of postoperative meningitis, appro- important factor for treatment success, and it depends on its priate antibiotic therapy should be initiated, followed by removal physicochemical properties and the degree of absorption through of the shunt or infected intracranial device as soon as possible and continuation of therapy until the infection clears. Once that Semisynthetic beta-lactamase-resistant penicillins are con- goal is achieved, placement of a new shunt should be followed sidered the therapy of choice for MSSA meningitis, with nafcillin by continuation of antibiotic therapy for at least 14 days. Ad- and oxacillin the most commonly used drugs. In our study, juvant steroid therapy shows no benefit in the treatment of mortality in patients who received nafcillin alone was 27%. The staphylococcal meningitis20 and could potentially reduce CSF optimal therapy for MRSA meningitis has not been established, penetration of antimicrobial agents. Other studies have also but generally has been vancomycin with or without rifampin or assessed the benefit of intrathecal antibiotic therapy, with dif- trimethoprim/sulfamethoxazole. Vancomycin should also be used in patients with penicillin allergy. CA-MRSA presents a unique Mortality associated with S aureus meningitis is high challenge due to its pathogenicity and the severity of disease it (14%Y77%), and usually higher in hematogenous meningitis Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 (19%Y71%) than in postoperative meningitis (11%Y28%).30 In infections caused by methicillin-resistant and methicillin-sensitive the current series the overall mortality was 36%, and it was strains. Infection. 2001;29:245Y250.
different in the 2 groups: 43% for hematogenous meningitis and 7. Chua T, Moore CL, Perri MB, Donabedian SM, Masch W, Vager D, 25% for postoperative meningitis, but with no statistical dif- Davis SL, Lulek K, Zimnicki B, Zervos MJ. Molecular epidemiology ference. In our series, infections acquired in the community were of methicillin-resistant Staphylococcus aureus bloodstream significantly associated with mortality, a finding that has a great isolates in urban Detroit. J Clin Microbiol. 2008;46:2345Y2352.
impact in the management of these patients. No differences were 8. Drew RH. Emerging options for treatment of invasive, found regarding age, the presence of severe underlying diseases, multidrug-resistant Staphylococcus aureus infections.
altered mental status, bacteremia, septic shock, or the antimi- crobial susceptibility of the strain when we compared mortality 9. Dzupova O, Rozsypal H, Prochazka B, Benes J. Acute bacterial among hematogenous and postoperative meningitis. The limita- meningitis in adults: predictors of outcome. Scand J Infect Dis.
tions of this study include its retrospective design and the fact that it was performed in a single center study. Its strengths are 10. Erdem I, Hakan T, Ceran N, Metin F, Akcay SS, Kucukercan M, the number of cases collected over a period of 10 years and Berkman MZ, Goktas P. Clinical features, laboratory data, management the addition of molecular analysis to the evaluation of MRSA and the risk factors that affect the mortality in patients with postoperative meningitis. Neurol India. 2008;56:433Y437.
In conclusion, S aureus meningitis is a relatively uncommon but serious type of acute bacterial meningitis that is progressively 11. Fong IW, Ranalli P. Staphylococcus aureus meningitis. Q J Med.
increasing in incidence and experiencing a shift from methicillin- sensitive strains to methicillin-resistant strains. Postoperative and 12. Fuglsang-Damgaard D, Pedersen G, Schonheyder HC. Positive blood hematogenous meningitis are 2 different clinical syndromes with cultures and diagnosis of bacterial meningitis in cases with negative distinct pathogenic mechanisms. Hematogenous meningitis is culture of cerebrospinal fluid. Scand J Infect Dis. 2008;40:229Y233.
usually caused by bacteremia from an infection outside the CNS, 13. Gendelman HE, Persidsky Y. Infections of the nervous system.
and is usually severe. When CA-MRSA is the etiologic agent, the strains are more frequently USA300 with SCCmec IVa and agr I, 14. Gerber P, Stucki A, Acosta F, Cottagnoud M, Cottagnoud P. Daptomycin with or without PVL. Postoperative meningitis is a nosocomial is more efficacious than vancomycin against a methicillin-susceptible infection usually associated with CSF shunt devices, and is Staphylococcus aureus in experimental meningitis. J Antimicrob clinically less severe. Infections caused by nosocomial MRSA are more frequently associated with USA100 SCCmec II agr II strains 15. Higa T, Tasaka T, Kubo Y, Nakagiri I, Sano F, Matsuhashi Y, Fukai Y, without PVL. Further susceptibilities and molecular analysis Wada H, Tohyama K, Sugihara T. Successful treatment of should be performed for better management of these infections.
meningoencephalitis caused by methicillin-resistant Staphylococcus MSSA strains may cause both types of meningitis, with poorer aureus with intravenous linezolid in an allogeneic cord blood outcomes seen in hematogenous infection cases. Treatment of stem cell transplant recipient. Scand J Infect Dis. 2008;40:990Y992.
choice is nafcillin for MSSA strains and vancomycin for MRSA 16. Jourdan C, Convert J, Peloux A, Boussaid O, Grando J, Tigaud S.
strains. The addition of trimethoprim/sulfamethoxazole or rifam- EAdequate intrathecal diffusion of teicoplanin after failure of pin to vancomycin is recommended in severe cases and in vancomycin, administered in continuous infusion in three cases infections caused by CA-MRSA. Linezolid is also a good option of shunt associated meningitis^. Pathol Biol (Paris). 1996;44:389Y392.
due to its good CSF penetration and favorable case reports. The 17. Kessler AT, Kourtis AP. Treatment of meningitis caused by mortality rate is higher in infections acquired in the community methicillin-resistant Staphylococcus aureus with linezolid. Infection.
18. Laguna-Del Estal P, Castaneda-Pastor A, Gil-Navarro M, Garcia-Madero R, Lopez-Cano Gomez M, Agud-Fernandez M.
EComparative study of meningitis due to Staphylococcus aureus and 1. Aspiroz C, Martin I, Lozano C, Torres C. EFirst case in Spain of coagulase-negative Staphylococci in adults^. Rev Neurol. 2009;48:2Y6.
meningitis caused by community-acquired methicillin-resistant 19. Lee DH, Palermo B, Chowdhury M. Successful treatment of Staphylococcus aureus ST88 producing Panton-Valentine methicillin-resistant Staphylococcus aureus meningitis with leucocidin.^. Enferm Infecc Microbiol Clin. 2009;Apr 29.
daptomycin. Clin Infect Dis. 2008;47:588Y590.
20. Lerche A, Rasmussen N, Wandall JH, Bohr VA. Staphylococcus 2. Brouwer MC, Keizerweerd GD, De Gans J, Spanjaard L, Van De Beek aureus meningitis: a review of 28 consecutive community-acquired D. Community acquired Staphylococcus aureus meningitis in adults.
cases. Scand J Infect Dis. 1995;27:569Y573.
Scand J Infect Dis. 2009;41:375Y377.
21. Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, 3. Cabellos C, Verdaguer R, Olmo M, Fernandez-Sabe N, Cisnal M, Ariza Vandenesch F, Etienne J. Involvement of Panton-Valentine J, Gudiol F, Viladrich PF. Community-acquired bacterial meningitis in leukocidin-producing Staphylococcus aureus in primary skin elderly patients: experience over 30 years. Medicine (Baltimore).
infections and pneumonia. Clin Infect Dis. 1999;29:1128Y1132.
22. Matsubara H, Makimoto A, Higa T, Kawamoto H, Kanda Y, Kami M, 4. Chang WN, Lu CH. Diagnosis and management of adult bacterial Tanosaki R, Mineishi S, Ohira M, Takaue Y. Successful treatment of meningitis. Acta Neurol Taiwan. 2009;18:3Y13.
meningoencephalitis caused by methicillin-resistant Staphylococcus 5. Chang WN, Lu CH, Huang CR, Chuang YC, Tsai NW, Chen SF, aureus with intrathecal vancomycin in an allogeneic peripheral blood Chang CC, Wang HC, Chien CC, Wu JJ. Epidemiology of adult stem cell transplant recipient. Bone Marrow Transplant. 2003;31:65Y67.
staphylococcal meningitis in southern Taiwan: a clinical comparison 23. McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, of Staphylococcus aureus infection and coagulase-negative Tenover FC. Pulsed-field gel electrophoresis typing of staphylococcal infection. Jpn J Infect Dis. 2007;60:262Y266.
oxacillin-resistant Staphylococcus aureus isolates from the United 6. Chang WN, Lu CH, Wu JJ, Chang HW, Tsai YC, Chen FT, Chien CC.
States: establishing a national database. J Clin Microbiol.
Staphylococcus aureus meningitis in adults: a clinical comparison of Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.
Medicine & Volume 89, Number 2, March 2010 24. Munckhof WJ, Krishnan A, Kruger P, Looke D. Cavernous sinus 35. Sabbatani S, Manfredi R, Frank G, Chiodo F. Linezolid in the treatment thrombosis and meningitis from community-acquired of severe central nervous system infections resistant to recommended methicillin-resistant Staphylococcus aureus infection. Intern Med J.
antimicrobial compounds. Infez Med. 2005;13:112Y119.
36. Sayana S, Khanlou H. Meningitis due to hematogenous dissemination of 25. Murray MJ, Fawi NM, Barter DA. Staphylococcus aureus meningitis community-associated methicillin-resistant Staphylococcus aureus secondary to occult spinal extradural abscess. Eur J Pediatr. 2008;167: (MRSA) in a patient with AIDS. J Int Assoc Physicians AIDS Care 26. Naesens R, Ronsyn M, Druwe P, Denis O, Ieven M, Jeurissen A. Central 37. Singh A, Goering RV, Simjee S, Foley SL, Zervos MJ. Application nervous system invasion by community-acquired meticillin-resistant of molecular techniques to the study of hospital infection. Clin Staphylococcus aureus. J Med Microbiol. 2009;58:1247Y1251.
38. Strommenger B, Cuny C, Werner G, Witte W. Obvious lack of 27. Ntziora F, Falagas ME. Linezolid for the treatment of patients with association between dynamics of epidemic methicillin-resistant central nervous system infection. Ann Pharmacother. 2007;41:296Y308.
Staphylococcus aureus in central Europe and agr specificity groups.
28. Okuma K, Iwakawa K, Turnidge JD, Grubb WB, Bell JM, O_Brien FG, Eur J Clin Microbiol Infect Dis. 2004;23:15Y19.
Coombs GW, Pearman JW, Tenover FC, Kapi M, Tiensasitorn C, 39. Valentini P, Parisi G, Monaco M, Crea F, Spanu T, Ranno O, Tronci M, Ito T, Hiramatsu K. Dissemination of new methicillin-resistant Pantosti A. An uncommon presentation for a severe invasive infection Staphylococcus aureus clones in the community. J Clin Microbiol.
due to methicillin-resistant Staphylococcus aureus clone USA300 in Italy: a case report. Ann Clin Microbiol Antimicrob. 2008;7:11.
29. Pedersen M, Benfield TL, Skinhoej P, Jensen AG. Haematogenous 40. Van Bambeke F, Tulkens PM. EPharmacodynamics of antibiotics in Staphylococcus aureus meningitis. A 10-year nationwide study of 96 CSF: principles and consequences (predictive factors of efficacy).^.
consecutive cases. BMC Infect Dis. 2006;6:49.
Med Mal Infect. 2009;39:483Y492. EEpub 2009 Jun 4.^ 30. Pintado V, Meseguer MA, Fortun J, Cobo J, Navas E, Quereda C, Corral 41. Varon E. EEpidemiology of acute bacterial meningitis in adult patients in I, Moreno S. Clinical study of 44 cases of Staphylococcus aureus France.^. Med Mal Infect. 2009;39:432Y444. EEpub 2009 Apr 22.^ meningitis. Eur J Clin Microbiol Infect Dis. 2002;21:864Y868.
42. Wallace MR, Sander AW, Licitra C, Rosenberg M, Giles D, Okorie ON.
31. Pizon AF, Bonner MR, Wang HE, Kaplan RM. Ten years of clinical Methicillin-resistant Staphylococcus aureus meningitis successfully experience with adult meningitis at an urban academic medical center.
treated with daptomycin. Infect Dis Clin Pract. 2009;17:69Y70.
43. Wang KW, Chang WN, Huang CR, Tsai NW, Tsui HW, Wang HC, 32. Revest M, Michelet C. EPredisposing factors of community acquired Su TM, Rau CS, Cheng BC, Chang CS, Chuang YC, Liliang PC, bacterial meningitis (excluding neonates).^. Med Mal Infect. 2009;39: Tsai YD, Lu CH. Post-neurosurgical nosocomial bacterial meningitis in adults: microbiology, clinical features, and outcomes. J Clin 33. Ritchie SR, Rupali P, Roberts SA, Thomas MG. Flucloxacillin treatment of Staphylococcus aureus meningitis. Eur J Clin Microbiol Infect Dis.
44. Wootton M, MacGowan AP, Walsh TR, Howe RA. A multicenter study evaluating the current strategies for isolating Staphylococcus aureus 34. Roos KL. Acute bacterial meningitis. Semin Neurol. 2000;20: strains with reduced susceptibility to glycopeptides. J Clin Microbiol.
Copyright @ 2010 Lippincott Wil iams & Wilkins. Unauthorized reproduction of this article is prohibited.



WIRKSTOFF BEZEICHNUNG (MARKEN NAME) Abacavir (Ziagen®) Abacavir + lamivudine,zidovudine (Trizivir®) Acetazolamide (Diamox®) Acitretin (Soriatane®) Albuterol (Ventolin®, Proventil®) Albuterol + ipratropium (Combivent®) Ammonium chloride Amphotericin B (Amphocin®, Fungizone®) Amphotericin B lipid formulations (IV) (Abelcet®) Amprenavir (Agenerase) Anidulafungin (Eraxis®) Ari


MIMS Full Prescribing Information Periactin Company Aspen Primary Section: Cardiovascular System - Antimigraine preparations MIMS revision date: 01 Dec 2010 Composition Cyproheptadine hydrochloride. Excipients Maize starch, calcium hydrogen phosphate, lactose, magnesium stearate. Description Chemical name: the sesquihydrate of 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-me

Copyright © 2010 Health Drug Pdf