brain abscesses arise from a contiguous focus of infection , a direct implantation due to trauma , or a hematogenous spread from a remote site .
it was reported that the direct spread from surgery , trauma , meningitis , frontal sinusitis , and dental karies was seen in 50% of patients , and that the hematogeneous spread from congenital or other heart diseases , lung and abdominal abscesses was found in 32% of patients . however , 18% had abscesses of an unknown origin .
otitis media also was a direct source of infection , and septicemia or chronic bronchitis also were hematogeneous sources of infection .
the majority of cases show some evidence of a systemic infection , such as peripheral leukocytosis , elevated c - reactive protein ( crp ) values , elevated erythrocyte sedimentation rate , and elevated body temperature .
however , these indicators of an infective process are not prominent in the initial stage , and a correct diagnosis is often not considered in the outpatient department or on admission .
only progressive neurological symptoms frequently prompt an urgent referral for investigation with computed tomography ( ct ) scanning .
the difficulties in making an early diagnosis are responsible for the residual high mortality , in spite of the advent of antibiotic treatment .
the best result can only be achieved if the physician remains alert to the possibility of an intracranial abscess .
the current series of 12 patients with brain abscesses retrospectively analyzed the levels and chronological changes of body temperature , leukocyte , and serum crp for the purpose of making an early and reliable initial diagnosis .
furthermore , sources of infection and infecting organisms were also analyzed to find more information about what antibiotics should be initially selected .
twelve patients with brain abscesses treated between 2006 and 2011 were retrospectively analyzed ( table 1 ) .
the patients included 10 males and 2 females whose ages ranged from 33 to 79 years old .
the underlying diseases were diabetes mellitus ( 2 patients ) , chronic glomerulonephritis treated with immunosuppressant ( 1 patient ) , subarachnoid hemorrhage ( 1 patient ) , cardiac failure and pulmonary fibrosis ( 1 patient ) , and acquired immunodeficiency syndrome ( aids , 1 patient ) .
the initial diagnoses in the outpatient department were brain abscess in 6 patients , cerebral infarction in 2 patients , metastatic brain tumor in 1 patient , alcohol intoxication in 1 patient , venous thrombosis in 1 patient , and simple headache in 1 patient ( table 1 ) .
the time from onset to the final diagnosis of brain abscess was 04 days ( mean 0.8 days ) in the correctly diagnosed 6 patients and 215 days ( mean 7.2 days ) in the inaccurately diagnosed 6 patients .
abbreviations : penicillin ( pcg , benzylpenicillin ; abpc , ampicillin ; ampc , amoxicillin ; pipc , piperacillin ) , sbtpc , sultamicillin ; sbt / abpc , sulbactam / ampicillin ; sbt / cpz , sulbactam / cefoperazone ) , cephalosporin ( cez , cefazolin ; ctm , cefotiam ; caz , ceftazidime ; ctrx , ceftriaxone ) , oral cephem ( cftm , cefteram ; cdtr , cefditoren ; cfpm , cefcapene ) , oxacephem ( fmox , flomoxef ) , carbapenem ( papm , panipenem ; ipm , imipenem ; mepm , meropenem ) , aminoglycoside ( tob , tobramycin ; amk , amikacin ) , macrolide ( em , erythromycin ; cam , clarithromycin ; cldm , clindamycin ) , tetracycline ( mino , minocycline ) , other antibiotic ( vcm , vancomycin ; fom , fosfomycin ; cp , chloramphenicol ; s / t , sulfamethoxazole / trimethoprim ) , quinolone ( tflx , tosufloxacin ; lvfx , levofloxacin ; pzfx , pazufloxacin ) .
the frontal lobe was the most common site of the abscess ( 5 cases ) , and the other lesions were in the parietal lobe in 3 cases , basal ganglia in 2 cases , thalamus in 1 case , and cerebellum in 1 case .
a bacteriological culture was performed under an aerobic condition of 35c for 1824 hours with aerobic bacteria , under an anaerobic condition of 35c for 2 days with anaerobic bacteria , and under an aerobic condition of 35c for 3 days with nocardia .
the identification of the bacterial strains was conducted using an identification kit , and the clinical isolates of nocardia were determined with a restriction fragment length polymorphism method using bacterial 16s rdna .
. minimum inhibitory concentration ( mic ) was measured with dry plate ( eiken chemical co. , ltd . ,
the initial therapy was conducted with intravenous infusion of antibiotics or antimicrobials ( table 1 ) .
the secondary intravenous antibiotics or antimicrobials were administered according to the results of the microbial sensitivity test .
excision of abscess was performed in 6 cases , and aspiration of abscess with / without decompressive craniotomy or ventricular drainage was performed in 4 cases .
three patients developed ventriculitis and/or meningitis ( ventriculitis group ) and 9 cases did not ( non - ventriculitis group ) .
the inflammatory indices of body temperature , leukocyte counts , and crp levels were analyzed and compared within each group .
the mean leukocyte count on admission was 9,694/mm in the non - ventriculitis group and 14,477/mm in the ventriculitis group ( fig .
the maximum leukocyte count was 12,708/mm in the non - ventriculitis group and 20,747/mm in the ventriculitis group .
the leukocyte count increased significantly after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.028 ) .
the mean serum crp level on admission was 2.72 mg / dl in the non - ventriculitis group and 10.68 mg / dl in the ventriculitis group ( fig .
the maximum crp was 10.47 mg / dl in the non - ventriculitis group and 31.95 mg / dl in the ventriculitis group .
the crp in the non - ventriculitis group increased significantly after admission ( wilcoxon signed - ranks test , p=0.028 ) .
the maximum crp was significantly higher in the ventriculitis group in comparison to the non - ventriculitis group ( welch s t test , p=0.001 ) .
the mean temperature on admission was 37.3c in the non - ventriculitis group and 37.9c in the ventriculitis group ( fig .
the maximum temperature was 38.6c in the non - ventriculitis group and 39c in the ventriculitis group .
the temperature significantly increased after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.011 ) . for leukocytes ,
the mean time for each of the indicators of infection to reach their maximum values was 10.8 days from the onset in the non - ventriculitis group and 6.7 days in the ventriculitis group .
the respective values for crp were 12.6 days in the non - ventriculitis group and 6.7 days in the ventriculitis group .
in respect to body temperature , the values were 17.1 days in the non - ventriculitis group and 7 days in the ventriculitis group ( no significant differences between each groups , fig .
these were analyzed separately in patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
the leukocyte count increased significantly ( * ) after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.028 ) .
levels of crp at the initial stage and their maximum levels . these were analyzed separately in patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
the crp in the non - ventriculitis group increased significantly ( * ) after admission ( wilcoxon signed - ranks test , p=0.028 ) .
the maximum crp was significantly ( * ) higher in the ventriculitis group in comparison to the non - ventriculitis group ( welch s t test , p=0.001 ) .
levels of body temperature at the initial stage and their maximum levels . these were analyzed separately in patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
the temperature significantly ( * ) increased after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.011 ) .
time ( days ) for each inflammatory index to reach their maximum values in the patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
a hematogenous spread from a remote site was the most common cause of an abscess ( 11 cases ) .
dental caries were found in 4 cases , and the other lesions were lung and retroperitoneal abscess in 1 case and gluteal abscess in 1 case .
although the source of the infection was not recognized , hematogenous spread was suspected in another 5 cases .
an abscess occurred following the infection of a ventriculoperitoneal shunt in one case of subarachnoid hemorrhage .
the primary causative organisms were streptococcus viridians ( 2 cases ) , streptococcus milleri ( 1 case ) , and fusobacterium nucleatum ( 1 case ) in 4 cases of abscesses arising from dental caries .
the causative organism was nocardia farcinica in 1 case of retroperitoneal and lung abscess , and nocardia sp . in 1 case of gluteal abscess .
toxoplasma infection was suggested by the mri findings in the patient with aids , although no immunoserological test was performed .
carbapenem , tetracycline , and quinolone were generally effective for many types of bacteria , including nocardia ( fig .
2 ) . penicillin , cephalosporin , sultamicillin and macrolide were effective for many kinds of bacteria other than nocardia .
imipenem was ineffective for propionibacterium sp . , and benzylpenicillin was ineffective for prevotella sp .
abbreviations : mic , minimum inhibitory concentration ; penicillin ( pcg , benzylpenicillin ; abpc , ampicillin ; ampc , amoxicillin ; pipc;piperacillin ) , sbtpc , sultamicillin ; cephalosporin ( cez , cefazolin ; ctm , cefotiam ; ctx , cefotaxime ; caz , ceftazidime ; ctrx , ceftriaxone ) , oral cephem ( cftm , cefteram ; cdtr , cefditoren ; cfpm , cefcapene ) , oxacephem ( fmox , flomoxef ) , carbapenem ( papm , panipenem ; ipm , imipenem ; mepm , meropenem ) , aminoglycoside ( tob , tobramycin ; amk , amikacin ) , macrolide ( em , erythromycin ; cam , clarithromycin ; cldm , clindamycin ) , tetracycline ( mino , minocycline ) , other antibiotic ( vcm , vancomycin ; fom , fosfomycin ; cp , chloramphenicol ) , quinolone ( tflx , tosufloxacin ; lvfx , levofloxacin ; pzfx , pazufloxacin ) .
nine patients had an independent gait at discharge , but one required assistance with walking ( table 1 ) .
one patient was transferred to another hospital and required a wheelchair . the patient with aids
three of the 6 incorrectly - diagnosed patients at discharge required help with walking , needed a wheelchair , or had consciousness disturbance ( table 2 ) .
in contrast , all 6 correctly - diagnosed patients could move about independently at discharge ( p=0.046 , chi - square for independence test ) .
the condition at discharge in patients with correct or incorrect initial diagnosis the initial incorrect diagnosis resulted in a significantly poor patient outcome .
the mean leukocyte count on admission was 9,694/mm in the non - ventriculitis group and 14,477/mm in the ventriculitis group ( fig .
the maximum leukocyte count was 12,708/mm in the non - ventriculitis group and 20,747/mm in the ventriculitis group .
the leukocyte count increased significantly after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.028 ) .
the mean serum crp level on admission was 2.72 mg / dl in the non - ventriculitis group and 10.68 mg / dl in the ventriculitis group ( fig .
the maximum crp was 10.47 mg / dl in the non - ventriculitis group and 31.95 mg / dl in the ventriculitis group .
the crp in the non - ventriculitis group increased significantly after admission ( wilcoxon signed - ranks test , p=0.028 ) .
the maximum crp was significantly higher in the ventriculitis group in comparison to the non - ventriculitis group ( welch s t test , p=0.001 ) .
the mean temperature on admission was 37.3c in the non - ventriculitis group and 37.9c in the ventriculitis group ( fig .
the maximum temperature was 38.6c in the non - ventriculitis group and 39c in the ventriculitis group .
the temperature significantly increased after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.011 ) . for leukocytes ,
the mean time for each of the indicators of infection to reach their maximum values was 10.8 days from the onset in the non - ventriculitis group and 6.7 days in the ventriculitis group .
the respective values for crp were 12.6 days in the non - ventriculitis group and 6.7 days in the ventriculitis group .
in respect to body temperature , the values were 17.1 days in the non - ventriculitis group and 7 days in the ventriculitis group ( no significant differences between each groups , fig .
these were analyzed separately in patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
the leukocyte count increased significantly ( * ) after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.028 ) .
levels of crp at the initial stage and their maximum levels . these were analyzed separately in patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
the crp in the non - ventriculitis group increased significantly ( * ) after admission ( wilcoxon signed - ranks test , p=0.028 ) .
the maximum crp was significantly ( * ) higher in the ventriculitis group in comparison to the non - ventriculitis group ( welch s t test , p=0.001 ) .
levels of body temperature at the initial stage and their maximum levels . these were analyzed separately in patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
the temperature significantly ( * ) increased after admission in the non - ventriculitis group ( wilcoxon signed - ranks test , p=0.011 ) .
time ( days ) for each inflammatory index to reach their maximum values in the patients with ventriculitis and/or meningitis ( ventriculitis group ) and in cases without ventriculitis and meningitis ( non - ventriculitis group ) .
a hematogenous spread from a remote site was the most common cause of an abscess ( 11 cases ) .
dental caries were found in 4 cases , and the other lesions were lung and retroperitoneal abscess in 1 case and gluteal abscess in 1 case .
although the source of the infection was not recognized , hematogenous spread was suspected in another 5 cases .
an abscess occurred following the infection of a ventriculoperitoneal shunt in one case of subarachnoid hemorrhage .
the primary causative organisms were streptococcus viridians ( 2 cases ) , streptococcus milleri ( 1 case ) , and fusobacterium nucleatum ( 1 case ) in 4 cases of abscesses arising from dental caries .
the causative organism was nocardia farcinica in 1 case of retroperitoneal and lung abscess , and nocardia sp . in 1 case of gluteal abscess .
toxoplasma infection was suggested by the mri findings in the patient with aids , although no immunoserological test was performed .
carbapenem , tetracycline , and quinolone were generally effective for many types of bacteria , including nocardia ( fig .
2 ) . penicillin , cephalosporin , sultamicillin and macrolide were effective for many kinds of bacteria other than nocardia .
imipenem was ineffective for propionibacterium sp . , and benzylpenicillin was ineffective for prevotella sp .
abbreviations : mic , minimum inhibitory concentration ; penicillin ( pcg , benzylpenicillin ; abpc , ampicillin ; ampc , amoxicillin ; pipc;piperacillin ) , sbtpc , sultamicillin ; cephalosporin ( cez , cefazolin ; ctm , cefotiam ; ctx , cefotaxime ; caz , ceftazidime ; ctrx , ceftriaxone ) , oral cephem ( cftm , cefteram ; cdtr , cefditoren ; cfpm , cefcapene ) , oxacephem ( fmox , flomoxef ) , carbapenem ( papm , panipenem ; ipm , imipenem ; mepm , meropenem ) , aminoglycoside ( tob , tobramycin ; amk , amikacin ) , macrolide ( em , erythromycin ; cam , clarithromycin ; cldm , clindamycin ) , tetracycline ( mino , minocycline ) , other antibiotic ( vcm , vancomycin ; fom , fosfomycin ; cp , chloramphenicol ) , quinolone ( tflx , tosufloxacin ; lvfx , levofloxacin ; pzfx , pazufloxacin ) .
nine patients had an independent gait at discharge , but one required assistance with walking ( table 1 ) .
three of the 6 incorrectly - diagnosed patients at discharge required help with walking , needed a wheelchair , or had consciousness disturbance ( table 2 ) .
in contrast , all 6 correctly - diagnosed patients could move about independently at discharge ( p=0.046 , chi - square for independence test ) .
the condition at discharge in patients with correct or incorrect initial diagnosis the initial incorrect diagnosis resulted in a significantly poor patient outcome .
headache , vomiting , drowsiness and focal symptoms , sometimes accompanied by focal or generalized seizures , are the classic symptoms of brain abscess . in addition , papilledema is commonly found in drowsy patients that appear ill .
however , many individuals frequently fail to show all of these symptoms . in such people ,
half of the patients in the current series were diagnosed inaccurately in the initial stage , and it took 7.2 days to achieve the final diagnosis of brain abscess for the misdiagnosed patients .
bibliographically , the average time between the onset of the symptoms and confirmed diagnosis was 9.6 days .
it was reported that patients with brain abscess usually show high leukocyte counts ( 12,40032,300/mm ) at the time of admission .
the crp was elevated to a high level ( 221.6 mg / dl ) in 69.271.4% of patients on admission , and 25.650% of abscess patients were febrile ( 37.839.8c ) at the time of admission . however , the value of these inflammatory indices were generally lower than the ones reported in the non - ventriculitis group of the current series .
the mean leukocyte count , crp level and body temperature on admission were 9,694/mm , 2.72 mg / dl , and 37.3c , respectively .
this tendency made the initial diagnosis of brain abscess more difficult in the patients without ventriculitis .
body temperature is known to be associated with cytokine levels in serum and cerebrospinal fluid . in the current series , therefore
, the inflammatory reaction was considered to be less prominent in the non - ventriculitis group than in the ventriculitis group .
microbial infection stimulates the production of cytokines , such as interleukin-1,6,8 and tnf - alpha , in the macrophage , dendrite cells , and glial cells .
interleukin-6 causes a biphasic neutrophilia , wherein the first peak results from the mobilization of polymorphonuclear leukocytes into the circulating pool from the marginated pool , and the second peak results from an accelerated bone marrow release of polymorphonuclear leukocytes .
interleukin-1 stimulates the production of crp in hepatocytes , and cytokines such as interleukin-1,6 and tnf - alpha act on the preoptic area of the hypothalamic thermoregulatory center and regulate body temperature . in the current series , the change of inflammatory indices began with increased leukocyte counts , followed by elevation of crp and body temperature .
the mean time for each infectious indicator to reach its maximum value in the non - ventriculitis group was 10.8 days for leukocytes , 12.6 days for crp , and 17.1 days for body temperature . in an experiment with rabbit in which the endogeneous pyrogen was injected in to the cerebroventricular region , these inflammatory indices changed chronologically in the order of body temperature , leukocyte count , and crp . in the current series ,
the pattern of chronological change of the inflammatory indices was different from that of the rabbit experiment , but our results will help us diagnose patients correctly .
the causative organisms were reported to be eventually identified in 5881% of cases . the majority of them were gram - positive bacteria .
anaerobes were present in 23% of patients , and methicillin - resistant staphylococcus aureus or nocardia were also identified in some patients .
it was reported that the primary causative organisms were streptococcus milleri , staphylococcus aureus and bacterioides in dental caries , streptococcus milleri , b - haemolytic streptococcus , staphylococcus aureus and bacterioides in sinusitis , streptococcus and proteus mirabilis in otitis media , haemophillus influenza in chronic bronchitis , and streptococcus milleri and staphylococcus epidermidis in infections of an unknown origin . in the current series ,
the primary causative organisms from dental caries were streptococcus viridians , streptococcus milleri , or fusobacterium nucleatum .
nocardia farcinica or nocardia sp . were involved when the abscess originated from other infections .
the primary causative organisms were streptococcus milleri and propionibacterium sp . when the source of infection was unrecognized .
antibiotics must be selected during the initial stage before the bacteria are identified in a laboratory culture .
these tendencies of this disease revealed in the current series will help us in the selection of appropriate antibiotics .
optimal management of brain abscesses requires intensive antibiotic therapy , for which the selection of an appropriate antibiotic is crucial .
the treatment has usually been performed with penicillin ( benzylpenicillin ) or cephalosporin ( cefotaxime or ceftriaxone ) in combination with vancomycin or metronidazole .
although metronidazole is stable in abscesses and a high concentration of it can be obtained from cerebrospinal fluid , its usage is not covered by japanese national medical insurance .
cure was obtained in 100% of the patients with imipenem therapy , in contrast with 86.7% of patients with the conventional chemotherapy , including penicillin and metronidazole .
another report also mentioned the efficacy of carbapenems ( imipenem or meropenem ) versus standard chemotherapy ( cefotaxime and metronidazole ) .
cure was obtained in 81.8% of those on imipenem , and 96.0% of those on meropenem , in contrast with 66.7% of those cured on standard chemotherapy . the microbial sensitivity test in the current series also showed that carbapenem therapy is a reasonable therapeutic choice for treatment of bacterial brain abscesses , including nocardia infection .
another antibiotic can be selected if there is little possibility that nocardia is the cause .
penicillin , cephalosporin , sultamicillin , and macrolide were effective for many types of bacteria other than nocardia in the current series .
nocardiosis is an opportunistic infection that has been frequently noted in patients with malignancies , systemic lupus erythematosis , long - term steroid usage , transplantation , and hiv infection .
however , recent data demonstrated that central nervous system nocardiosis was common or more prevalent in patients with normal immune systems , as shown in our patient number 6 . at any rate ,
nocardial brain abscesses remain a clinical challenge associated with high mortality and morbidity rates , because nocardia is resistant to many antibiotics .
the recommended treatment is usually imipenem with amikacin , ceftriaxone with amikacin , amoxicillin - clavulanate , minocycline , sulfamethoxazole / trimethoprim , sulfisoxazole , ciprofloxacin , clindamycin , linezolid , or vancomycin . in the current series , carbapenem ( imipenem ) , tetracycline ( minocycline ) , and quinolone ( levofloxacin , pazufloxacin ) proved effective for nocardia .
a brain abscess has a lethal nature despite recent advances in its diagnosis and treatment .
poor prognostic factors were prominent consciousness disturbance at admission , an age below 2 years , and multiple abscesses .
fungus and aerobic bacteria were related to poor outcomes . in the current series , initial incorrect diagnoses resulted in significantly poor outcomes .
the delay in making a diagnosis allows time for the rapid enlargement of the brain abscess and causes consciousness disturbance .
therefore , the early diagnosis of brain abscess , proper estimation of causative organisms from the source of infection , and appropriate usage of antibiotics are mandatory .
 abstractthis study retrospectively analyzed 12 patients with brain abscesses . 
 half of the patients were diagnosed inaccurately in the initial stage , and 7.2 days were required to achieve the final diagnosis of brain abscess . 
 the patients presented only with a moderately elevated leukocyte count , serum crp levels , or body temperatures during the initial stage . 
 these markers changed , first with an increase in the leukocyte count , followed by the crp and body temperature . 
 the degree of elevation tended to be less prominent , and the time for each inflammatory index to reach its maximum value tended to be longer in the patients without ventriculitis than in those with it.the causative organisms of a brain abscess were detected in 10 cases . 
 the primary causative organisms from dental caries were streptococcus viridians or milleri , and fusobacterium nucleatum . 
 nocardia sp . or farcinica were common when the abscess was found in other regions . 
 the primary causative organisms of unrecognized sources of infection were streptococcus milleri and prolionibacterium sp . 
 nocardia is resistant to many antibiotics . 
 however , carbapenem , tetracycline and quinolone were effective for nocardia as well as many other kinds of bacteria.in summary , the brain abscesses presented with only mildly elevated inflammatory markers of body temperature , leukocyte and crp . 
 these inflammatory markers were less obvious in the patients without ventriculitis and/or meningitis . 
 the source of infection tended to suggest some specific primary causative organism . 
 it was reasonable to initiate therapy with carbapenem . 