Changing epidemiology of bacterial meningitis

Immunization against the most common meningeal pathogens is the leading factor associated with decreased incidence of bacterial meningitis in countries where routine vaccination is available. This is most dramatically illustrated by the reduction in the incidence of Haemophilus influenzae type b meningitis. The incidence of bacterial meningitis has decreased by 55% since the introduction of the H. influenzae type b conjugate vaccine in 1990. H. influenzae occurred primarily in children younger than 5 years of age, and so the median age of patients with bacterial meningitis has now increased to 39 years of age in the United States, and the leading pathogen is currently Streptococcus pneumoniae. Three other control measures (ie, universal screening and antibiotic prophylaxis of pregnant women for Group B streptococci and the implementation and availability of the S. pneumoniae and Neisseria meningitidis conjugate vaccines) have likely further decreased the incidence of these meningeal pathogens. Lastly, the worldwide emergence of multidrug-resistant pneumococci has complicated the empiric therapy of bacterial meningitis.     

Cerebrospinal Fluid Glucose Levels and Sensorineural Hearing Loss in Bacterial Meningitis

Background: Low cerebrospinal fluid (CSF) glucose levels have been associated with sensorineural hearing loss (SNHL) in bacterial meningitis but systematic investigations are lacking.Patients and Methods: A retrospective case control study was conducted comparing CSF glucose levels in 47 cases with and 145 controls without SNHL following bacterial meningitis.Results: The mean CSF glucose level (standard deviation [SD]) was 1.3 mmol/l (1.2) in cases and 2.5 mmol/l (1.6) in controls (p < 0.001). The difference between the groups was significant for Streptococcus pneumoniae and Haemophilus influenzae but not for Neisseria meningitidis infection. It was independent of the delay of treatment if this was greater than 12 h. This delay was significantly longer in cases compared to controls.Conclusion: In bacterial meningitis other than that caused by N. meningitidis and independent of the duration of symptoms prior to diagnosis, CSF glucose levels were significantly lower in patients developing a SNHL compared to controls.     

Bacterial Meningitis in an Urban Area: Etiologic Study and Prognostic Factors

Abstract Objectives: The study of clinical features, diagnostic methods and prognostic factors of bacterial meningitis, in an urban area. Patients and Methods: All patients admitted between June 2001 and July 2004 in the emergency departments of a few hospitals, with the diagnosis of bacterial meningitis were included. CSF and blood cultures were performed in every case. Phenotypic characterization of strains of Streptococcus pneumoniae and Neisseria meningitidis identified by culture were performed. In order to detect the three most common agents it was done a PCR assay in culture negative CSF samples. Results: Bacterial meningitis was diagnosed in 201 patients. Etiologic definition was based on culture in 142 patients (70.6%), done by CSF PCR assay in 33 (16.4%) other patients and exclusively by latex agglutination test results in two cases. Thus, an etiologic diagnosis was established in 177 (88%) cases. Antigenic characterization showed a slight prevalence of N. meningitidis phenotype C:2b:P1; the S. pneumoniae serotype characterization showed that 43.8% of identified serotypes are not included in any of the available vaccines. Eighteen patients died (8.9%). The statistic analysis found that factors associated with an adverse outcome were age older than 50 years (OR 7.07; IC 95% 1.1–27.4), the presence of comorbidities (OR 3.3; IC 95% 1.1–9.6) and the occurrence of systemic complications (OR 5.8; IC 95% 2.1–16.0). Conclusions: This epidemiologic pattern is similar to that found in other countries after the introduction of Haemophilus influenzae b conjugated vaccine. The association of culture and noncultural methods of diagnosis had a better performance in defining the etiology. Comparing to other series, in-patients mortality rate was lower (8.9%) than usually referred to, being considered unfavourable prognostic factors the age more than 50 years, the presence of comorbidities and of systemic complications.     

Cerebrospinal fluid penetration of cefmenoxime in children with bacterial meningitis

Summary Blood and cerebrospinal fluid (CSF) concentrations of cefmenoxime were determined either microbiologically or by means of HPLC in 20 children with proven or suspected bacterial meningitis. Sixteen children suffered from bacterial meningitis: causative organisms wereHaemophilus influenzae type b (n=10),Streptococcus pneumoniae (n=4) andNeisseria meningitidis (n=2). In these patients the cefmenoxime concentration in the CSF ranged from 0.9 to 12.2 mg/l, with a mean concentration of 4.63 mg/l 1.5–3 h after the last intravenous cefmenoxime application and 24–48 h after initiating therapy with 200 mg cefmenoxime/kg/d in four doses. In eight cases the bactericidal titers of the CSF were examined during therapy. Titers between 1:64 and 1:2,048, exceeding the minimal bactericidal concentration, were found. After five doses of cefmenoxime 50 mg/kg, two CSF cultures showed bacterial growth: oneH. influenzae (bactericidal titer in CSF 1:256) and oneS. pneumoniae.

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Liquorspiegel von Cefmenoxim bei Kindern mit bakterieller Meningitis

Zusammenfassung Bei zwanzig Kindern wurden Serum- und Liquorspiegel von Cefmenoxim mittels HPLC oder aber mikroskopisch bestimmt. Sechzehn Kinder litten an bakterieller Meningitis:Haemophilus influenzae Typ b (n=10),Streptococcus pneumoniae (n=4),Neisseria meningitidis (n=2). Die Proben wurden 24–48 h nach Behandlungsbeginn (200 mg cefmenoxim/kg/die) in vier Einzeldosen 1,5–3 h nach der letzten Gabe entnommen. Die Liquorspiegel bei den Kindern mit entzündeten Meningen lagen zwischen 0,9 bis 12,2 mg/l, im Mittel 4,63 mg/l. In acht Fällen wurde die Liquorbakterizidie bestimmt. Die Titer lagen zwischen 1:64 bis 1:2048. Zwei Liquorkulturen nach fünf Dosen 50 mg/kg zeigten bakterielles Wachstum. Einmal fand sichH. influenzae (Liquorbakterizidie 1:256) und einmalS. pneumoniae.

     

Changing epidemiology of bacterial meningitis in the United States

Bacterial meningitis is an important cause of morbidity and mortality in the United States and throughout the world. Over the past 20 years, there have been significant changes in the epidemiology of bacterial meningitis. The most important change is the decrease in the frequency of Haemophilus influenzae type b as the most common etiologic agent of bacterial meningitis, since the H. influenzae type b conjugate vaccine was introduced. Streptococcccus pneumoniae is now the major cause of bacterial meningitis in the US and bacterial meningitis is now a disease predominantly of adults, rather than of infants and children. Emergence of antimicrobial resistance in S. pneumoniae has also altered the approach to antimicrobial therapy in patients with pneumococcal meningitis, indicating the need to use preventive strategies to reduce the frequency of this serious infection. Recent licensure of the heptavalent pneumococcal conjugate vaccine will likely decrease the overall incidence of pneumococcal meningitis.     

Carrier state of Haemophilus influenzae type b (Hib), Streptococcus pneumoniae,Streptococcus pyogenes,Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara,Nepal

ObjectiveTo determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae), Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children.MethodsSpecimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 102 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures.ResultsPotential pathogens isolated in our study were S. pneumoniae (14.7%), Staphylococcus aureus (12.7%), Corynebacterium diphtheriae (3.9%), Streptococcus pyogenes (3.9%) and Haemophilus influenzae (1.9%). Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73%) and resistance of Staphylococcus aureus to oxacillin (23%).ConclusionsPharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.     

Etiology of central nervous system infections in the Philippines and the role of serum C-reactive protein in excluding acute bacterial meningitis

Objectives: The value of measurements of serum C-reactive protein (CRP) in differentiating central nervous system (CNS) infections of varying etiologies in the Philippines was investigated.Methods: A wide array of bacteriologic and virologic methods as well as computed tomography, typical clinical presentation, and autopsy were used for etiologic diagnosis.Results: Among 103 patients with CNS infection, etiology was identified in 60 (58%) cases. Bacteria were found in 19 (including 7 Streptococcus pneumoniae, 5 Haemophilus influenzae, 3 Neisseria meningitidis), tuberculosis in 4, viruses in 38 (including 20 coxsackievirus, 8 measles, 4 adenovirus, and 4 poliovirus infections), and brain abscess in 3 patients. C-reactive protein was elevated on admission in all 18 cases of bacterial meningitis tested, exceeding 50 mg/L in 17 (94%), and was not affected by prior antibacterial treatment. The mean CRP was significantly higher in the bacterial group than in the viral group (207 ± 111 mg/L vs. 39 ± 34 mg/L; P < 0.001). In the viral group one third had CRP above 50 mg/L. In patients with tuberculous meningitis, brain abscess, or cryptococcal meningitis, CRP was moderately to highly elevated.Conclusions: In the presence of a normal CRP concentration (below 10 mg/mL) acute bacterial meningitis is excluded even in a developing country setting and antimicrobial therapy is not warranted.     

Prediction of bacterial meningitis based on cerebrospinal fluid pleocytosis in children

Children with cerebrospinal fluid pleocytosis are frequently treated with parenteral antibiotics, but only a few have bacterial meningitis. Although some clinical prediction rules, such as bacterial meningitis score, are of well-known value, the cerebrospinal fluid white blood cells count can be the initial available information. Our aim was to establish a cutoff point of cerebrospinal fluid white blood cell count that could distinguish bacterial from viral and aseptic meningitis. A retrospective study of children aged 29 days to 17 years who were admitted between January 1st and December 31th, 2009, with cerebrospinal fluid pleocytosis (white blood cell ≥ 7 μL^?1) was conducted. The cases of traumatic lumbar puncture and of antibiotic treatment before lumbar puncture were excluded. There were 295 patients with cerebrospinal fluid pleocytosis, 60.3% females, medium age 5.0 ± 4.3 years distributed as: 12.2% 1–3 months; 10.5% 3–12 months; 29.8% 12 months to 5 years; 47.5% >5 years. Thirty one children (10.5%) were diagnosed with bacterial meningitis, 156 (52.9%) viral meningitis and 108 (36.6%) aseptic meningitis. Bacterial meningitis was caused by Neisseria meningitidis (48.4%), Streptococcus pneumoniae (32.3%), other Streptococcus species (9.7%), and other agents (9.7%). cerebrospinal fluid white blood cell count was significantly higher in patients with bacterial meningitis (mean, 4839 cells/μL) compared to patients with aseptic meningitis (mean, 159 cells/μL, p < 0.001), with those with aseptic meningitis (mean, 577 cells/μL, p < 0.001) and with all non-bacterial meningitis cases together (p < 0.001). A cutoff value of 321 white blood cell/μL showed the best combination of sensitivity (80.6%) and specificity (81.4%) for the diagnosis of bacterial meningitis (area under receiver operating characteristic curve 0.837). Therefore, the value of cerebrospinal fluid white blood cell count was found to be a useful and rapid diagnostic test to distinguish between bacterial and nonbacterial meningitis in children.     

Etiology and Antimicrobial Susceptibility of Middle Ear Fluid Pathogens in Costa Rican Children With Otitis Media Before and After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine in the National Immunization Program: Acute otitis media microbiology in Costa Rican children

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009).This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction).Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction.Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.     

Incidence of childhood Haemophilus influenzae type b meningitis in Sri Lanka

ObjectiveTo demonstrate the burden of Haemophilus influenzae type b (Hib) disease in Sri Lanka and provide information for decision-making in public health planning and vaccine introduction.MethodsThis was a prospective, population-based study carried out in 2004, to describe the epidemiology and calculate the incidence of meningitis caused by Hib in children <5 years of age in the district of Colombo, Sri Lanka. Hib was identified in cerebrospinal fluid (CSF) specimens by culture and antigen detection (latex agglutination test; LAT).ResultsThe lumbar puncture rate in children <5 years of age was 1.9%. A causative bacterial organism was identified in 108 meningitis cases, and in 54 (50%) this was Hib. The LAT increased the Hib detection rate in CSF four-fold. In 2004, the annual incidence of Hib meningitis in Colombo was 20.1 cases per 100 000 children aged <5 years.ConclusionsThis study is the first from Sri Lanka reporting the Hib meningitis incidence rate pre-vaccine introduction. The reported incidence rate is one of the highest from the Asian region, but is likely an underestimation considering the difficulties in the laboratory identification of Hib.     

Bacterial meningitis 1940–79

The treatment of 1871 episodes of bacterial meningitis (excluding leptospiral meningitis) affecting 1855 patients in the Infectious Diseases Unit of the City Hospital, Edinburgh, over the 40-year period 1940–79 has been reviewed. There was a rapid reduction in mortality in the commoner forms of bacterial meningitis after sulphonamides were introduced and a further improvement following the introduction of penicillin and other antibiotics. Benzylpenicillin alone has given excellent results in meningococcal infections. Of the eight fatalities due to meningococcal infection in the past 20 years, seven were due to fulminant meningococcaemia. Likewise, benzylpenicillin alone has been valuable for pneumococcal meningitis, although it results in a lower cure rate than for meningococcal disease, especially in the very young and those over 55 years of age. Chloramphenicol alone has been the most effective drug for Haemophilus influenzae meningitis, especially since ampicillin resistance is increasing. No deaths from H. influenzae meningitis have occurred since 1943 and there have been few sequelae.Outside the neonatal period, a single antibacterial agent is advocated for most forms of bacterial meningitis, except tuberculous, with the use of corticosteroids and other supporting measures only when indicated.     

Prevalence of Haemophilus influenzae type b infection in Chinese children: a systematic review and meta-analysis

Background

Haemophilus influenzae type b is an important cause of invasive bacterial disease in children worldwide. The establishment of epidemiological estimates is an essential first step towards the introduction of H influenzae type b vaccine into the Chinese national immunisation programme. We therefore undertook a systematic review and meta-analysis to estimate the prevalence of H influenzae type b in Chinese children.

Bacterial etiology and pneumococcal urinary antigen in moderate exacerbation of chronic obstructive pulmonary disease

BackgroundThis study aimed to establish nationwide data for the distributions of typical and atypical bacterial pathogens in Korean patients with moderate acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and evaluate the clinical usefulness of a urinary antigen test (UAT) to detect Streptococcus pneumoniae.MethodsThis study was a post hoc analysis of a randomized controlled trial designed to compare oral zabofloxacin with moxifloxacin for treating outpatients with moderate AECOPD. From clinics across South Korea, 342 subjects with AECOPD were enrolled, and their blood, sputum, and urine samples were collected at baseline. A serologic test, sputum culture and polymerase chain reaction (PCR), and UAT were performed to identify bacterial pathogens. Bacterial prevalence and regional distributions were analyzed. The patients’ characteristics and clinical response between UAT-positive and UAT-negative groups were compared, as were the Streptococcus pneumoniae detection rates using conventional sputum culture and PCR versus UAT.ResultsThe most commonly isolated pathogen was Haemophilus influenzae (30.3%), followed by Streptococcus pneumoniae (24.7%) and Pseudomonas aeruginosa (14.0%), with no significant regional differences in bacterial distribution. Patients with positive UAT for Streptococcus pneumoniae showed no clinical failure when treated with respiratory quinolone (0.0%), whereas 11.8% of patients with negative UAT showed clinical failure (P=0.037). UAT showed moderate agreement with sputum culture by kappa coefficient (κ=0.476).ConclusionsThe bacterial prevalence in patients with moderate AECOPD in South Korea showed correlations with the global prevalence, without significant regional differences. In outpatient settings, UAT has the potential to be used as a supplemental tool with sputum culture as a guide for determining the suspicion of bacterial exacerbation.     

"Bacterial Meningitis in children and adolescents: an observational study based on the national surveillance system"

Background  

Bacterial meningitis is a group of life threatening infections that mostly affect children and adolescents, and may be the cause of severe neurological sequelae. Cuba has implemented massive vaccination programmes against both Neisseria meningitidis (serogroup C in 1979 and B in 1987), and Haemophilus influenzae type b (1999), two of the main causal pathogens. We described and discussed some epidemiological aspects of the current status of bacterial meningitis to learn from the Cuban experience.     

Intravenous plus intraventricular tigecycline-amikacin therapy for the treatment of carbapenem-resistant Klebsiella pneumoniae ventriculitis: A case report

Rationale:Central nervous system infections (CNSIs) are one of the most serious complications after neurosurgery, especially carbapenem-resistant bacterial meningitis. Owing to the poor blood-brain barrier permeability of most antibiotics, the treatment of CNSIs by intraventricular (IVT) administration is becoming a hot topic in clinical research. Currently, the treatment of CNSIs caused by carbapenem-resistant Klebsiella pneumoniae is mainly based on intraventricular injection of an antibiotic combined with one or more other systemic intravenous (IV) antibiotics, whereas there are few case reports of intraventricular injection of 2 antibiotics.Patient concerns:A 57-year-old man with an open craniocerebral injury presented with dyspnea, high fever, and seizures associated with surgery.Diagnosis:Intracranial infection caused by carbapenem-resistant K. pneumoniae was diagnosed.Interventions:On the advice of a clinical pharmacist, the patient was given tigecycline (100 mg IV + 3 mg IVT q12h) combined with amikacin (0.8 g IV + 30 mg IVT qd) antiinfective therapy. Ultimately, the pathogens in the cerebrospinal fluid were eradicated after 7 days, and the CNSIs were completely cured after 14 days.Outcomes:The patient recovered and was discharged from the hospital without adverse reactions.Lessons:A series of in vitro and in vivo synergy tests of carbapenem-resistant K. pneumoniae showed that tigecycline combined with aminoglycosides had good synergistic effects and effectively suppressed bacterial resistance selection. Intravenous plus intraventricular tigecycline-amikacin seems to be a safe and effective treatment option for carbapenem-resistant K. pneumoniae CNSIs.     

Bacterial Meningitis in Young Adults in Southern Taiwan: Clinical Characteristics and Therapeutic Outcomes

Abstract Background: To delineate the epidemiologic trend, clinical characteristics and therapeutic outcomes of bacterial meningitis in young adults in southern Taiwan. Patients and Methods: Over a period of 18 years, 329 cases of culture-proven adult bacterial meningitis were identified at our hospital. Among these 329 cases, 62 were identified as young adults (≤ 40 years) and their clinical features, laboratory data and therapeutic outcomes were reviewed. The prognostic factors between fatal and non-fatal groups were compared. Results: The 62 young adults were 48 men and 14 women, aged 17–40 years. Thirty of the 62 patients belonged to nosocomial infection, and the other 32 belonged to community-acquired infection. A total of 74% (46/62) of the patients had a postneurosurgical state as the underlying condition. Alcoholism (n = 8) was the most common underlying condition of the other 16 patients with spontaneous meningitis. Of these 62 patients, Klebsiella pneumoniae (12) and Pseudomonas aeruginosa (9) were the most common implicated gram-negative pathogens. During the late study period, there was an increase in coagulase-negative staphylococcus and Staphylococcus aureus infections. The therapeutic results of this group of patients are as follows: 13 patients died, 18 had full recovery and 31 had varying degrees of neurologic deficits. Impaired consciousness and thrombocytopenia were significant prognostic factors. Conclusion: A postneurosurgical state is an important preceding event for young adults to develop bacterial meningitis. Of the implicated gram-negative pathogens, K. pneumoniae and P. aeruginosa are common; however, there has been an increase in staphylococcal infection in recent years. Therapeutic results of this specific group of patients showed that 20% (13/62) of the patients died, and 50% (31/61) of the patients in this study had neurologic deficits. However, the small case number and possible bias of case selection has limited the analytical conclusions of this study. Further large-scale studies are needed to delineate the clinical characteristics and therapeutic outcomes of bacterial meningitis in this specific group of patients.     

Recurrent Posttraumatic Meningitis due to Nontypable <Emphasis Type="Italic">Haemophilus influenzae</Emphasis>: Case Report and Review of the Literature

Abstract We report a case of relapsing Haemophilus influenzae meningitis in a boy at the age of nearly 3 years and 4.2 years who had been successfully vaccinated against H. influenzae serotype b (Hib). The pathogen was a nonencapsulated (nontypable) H. influenzae strain of biotypes III and VI, respectively. A rhinobasal impalement injury with development of a posttraumatic encephalocele is considered to be the predisposing condition. Review of the literature reveals that in patients systemically infected by nonencapsulated H. influenzae strains predisposing factors such as cerebrospinal fluid-shunts, implants and traumas are often found. To obtain further information on potential new disease patterns H. influenzae isolates from cerebrospinal fluid should be examined for capsule production and, if relevant, further characterized by capsular typing.     

Cefoperazone therapy of bacterial meningitis: A clinical trial

Summary Sixteen hospitalized patients, aged between 10 and 76 years (mean: 34.3 years), with bacterial meningitis were treated i.v. with cefoperazone at daily doses of 4.5 g to 9 g. In two cases ampicillin was given in combination with cefoperazone during the last four days and the first five days of treatment, respectively. The following organisms were isolated:Neisseria meningitidis (n=9),Haemophilus influenzae (n=3),Escherichia coli (n=2),Streptococcus pneumoniae (n=2). Fourteen patients completely recovered from infection and the pathogens were eradicated; the treatment failed in only two patients and both were cured with alternative treatment. Furthermore, in 11 patients cefoperazone serum and CSF levels were determined four times during the first week of treatment (1st, 3rd, 5th and 7th days). No important side effects were recorded.

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Cefoperazon in der Therapie der bakteriellen Meningitis

Zusammenfassung 16 stationäre Patienten mit bakterieller Meningitis im Alter von 10 bis 76 (im Mittel 34,4) Jahren wurden mit Cefoperazon i.v. in einer Dosierung von 4,5 bis 9 g täglich behandelt. Ampicillin wurde in einem Fall zusätzlich während der letzten vier Therapietage gegeben, in einem Fall in den ersten fünf Tagen. Als Erreger wurden in neun FällenNeisseria meningitidis, in drei FällenHaemophilus influenzae und in je zwei FällenEscherichia coli undStreptococcus pneumoniae identifiziert. In 14 Fällen trat vollständige Heilung ein, die Erreger wurden eliminiert. Zwei Patienten konnten nach Versagen der Ersttherapie mit einer Alternativtherapie geheilt werden. Bei 11 Patienten wurden während der ersten Therapiewoche (am 1., 3., 5. und 7. Tag) die Spiegel von Cefoperazon in Serum und Liquor bestimmt. Gravierende Nebenwirkungen wurden nicht beobachtet.