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[A case of refractory tuberculous meningitis markedly improved by intrathecal administration of isoniazid (INH)].

We report a case of refractory tuberculous meningitis which was markedly improved by intrathecal administration of isoniazid (INH). The patient was a 35-year-old woman diagnosed with systemic lupus erythematosus (SLE) at age 25, who was being managed with steroid therapy. She was admitted to another hospital due to miliary tuberculosis at age 34, and after discharge continued with a regimen of 2 anti-tuberculosis drugs (INH. Rifampicin (RFP)). She was admitted to our hospital with severe headache and fever on June 18, 2001. She showed severe meningeal irritation, and cerebrospinal fluid (CSF) examination revealed cell counts of 207/microliter (72% polynuclear cells), protein level of 300 mg/dl, glucose level of 13 mg/dl, chloride (Cl) level of 104 mEq/l, adenosine deaminase (ADA) level of 10.0 IU/l. The CSF culture was negative for Mycobacterium tuberculosis (M. tuberculosis) and direct polymerase chain reaction (PCR) for M. tuberculosis DNA was negative, but nested PCR was positive in preserved CSF samples. Marked leptomeningeal enhancement at the basilar meninges was noted by cranial MRI on gadolinium (Gd)-DTPA enhanced T1-weighted images. We diagnosed her condition as tuberculous meningitis and administered a total of 5 anti-tuberculosis drugs over about 2 months. However, during this period, both her clinical and CSF findings worsened, and she developed severe consciousness disturbance showing marked hydrocephalus on cranial MRI in August 2001. Therefore, we initiated intrathecal administration of INH 100 mg 3 times a week for progressive tuberculous meningitis. After the initiation of intrathecal therapy, both her consciousness disturbance and CSF findings were improved almost immediately. Ventriculo-peritoneal shunt operation was performed for hydrocephalus on September 26, 2001, and her clinical symptoms were further improved. To our knowledge, this is the first reported case of refractory tuberculous meningitis markedly improved by intrathecal administration of INH. Our findings suggested that intrathecal administration of INH was useful for refractory tuberculous meningitis.

Adult↗

[A diagnostic decision rule for managing children with signs of meningeal irritation].

OBJECTIVE: To develop a diagnostic decision rule based on clinical features to predict the risk of bacterial meningitis in children with signs of meningeal irritation. DESIGN: Retrospective and prospective. METHOD: Predictors for bacterial meningitis were identified by collecting clinical data from the records of 360 patients (aged 1 month to 15 years) who consulted the Casualty Department, Sophia Children's Hospital, Rotterdam, the Netherlands, with signs of meningeal irritation during the period 1988-1998. The diagnostic decision rule derived was prospectively validated on 226 similar children who consulted the casualty departments of four hospitals in the Netherlands during the period 1999-2001. RESULTS: Predictors for bacterial meningitis were the main complaint and vomiting (in the history) persisting for a long time, the presence of meningeal irritation, cyanosis, petechiae, disturbed consciousness (during physical examination), and a high serum concentration of C-reactive protein. Liquor analysis parameters with an added diagnostic value were the total polymorphonuclear cell count in the liquor and the liquor/blood glucose ratio. The use of these patient characteristics in a decision rule accurately predicted the chance of bacterial meningitis. The rule can also be used to refine the indication for lumbar puncture and empirical antibiotic treatment.

Adolescent↗

MR imaging of meningeal carcinomatosis by systemic malignancy.

OBJECTIVE: To investigate the magnetic resonance (MR) features of meningeal carcinomatosis, and to improve the ability in understanding and diagnosing meningeal carcinomatosis by MR findings. METHODS: Eleven cases with proven meningeal carcinomatosis were studied by conventional and Gd-DTPA enhanced MR imaging. The enhancement patterns and features, as well as the types of meningeal involvement, were retrospectively analyzed. RESULTS: Conventional MR imaging showed no evident meningeal abnormalities. After the administration of Gd-DTPA, abnormal pia mater enhancement was detected in 9 cases, demonstrating as the continuous, thin, and lineal high signal intensity on the brain surface that could descend into the sulci. The abnormal pial enhancement occurred on the cortical surfaces of cerebellum, brainstem, and cerebrum. No abnormal enhancement in the subarachnoid space was found. Abnormal dura-arachnoid enhancement was seen in 3 cases, showing as the continuous, thick, and curvilineal high signal intensity over the convexities or in the tentorium without extension into the cortical sulci. Cerebral dura-arachnoid involvement was found in all 3 cases and one of them also showed abnormal enhancement in cerebellar dura-arachnoid and tentorium. Of the 11 cases, 9 with pial involvement had abnormal cerebrospinal fluid (CSF) results, 2 involving only the dura-arachnoid had normal CSF results. CONCLUSION: Meningeal carcinomatosis could be well demonstrated by Gd-DTPA enhanced MR imaging, and its type could be differentiated by the enhancement features. Combined with the clinical information, Gd-enhanced MR imaging may lead to the diagnosis and guide the therapy of meningeal carcinomatosis.

Adolescent↗

Outbreaks of aseptic meningitis associated with echoviruses 9 and 30 and preliminary surveillance reports on enterovirus activity--United States, 2003.

Aseptic or viral meningitis is the most common type of meningitis and is associated with an estimated 26,000--42,000 hospitalizations each year in the United States. Enteroviruses are the most common cause of aseptic meningitis. Echovirus 9 (E9) and echovirus 30 (E30) have been associated frequently with outbreaks of aseptic meningitis. During March 2003, several state public health departments noted increased reports of aseptic meningitis and, as of August 7, seven states (Arizona, California, Georgia, Idaho, Oregon, South Carolina, and Texas) had reported outbreaks associated with either E9 or E30. This report summarizes the epidemiologic features of the aseptic meningitis outbreaks in five states (Arizona, California, Georgia, Idaho, and South Carolina) and provides an overview of enterovirus activity in the United States during January 1--August 7. Enteroviruses, E9 and E30 in particular, should be considered in the differential diagnosis of persons with aseptic meningitis.

Arizona↗

[Occurrence of Haemophylus influenzae B meningitis after the implementation of a mass vaccination program].

OBJECTIVE: To evaluate the incidence of Hib meningitis before and after the implementation of a vaccination program in the state of Rio Grande do Sul State, southern Brazil, in 1999. METHODS: This retrospective study summarizes all data concerning Hib meningitis recorded by the state of Rio Grande do Sul Department of Health/Acute Communicable Disease Surveillance Agency between 1995 and 2001. All data were analyzed using the chi-square test (statistical significance: p < 0.005). RESULTS: The decline in the number of cases of Hib meningitis was associated with the Hib vaccine coverage in children. From 1995 to 2001 the incidence of Hib meningitis decreased 89% (from 1.35 cases/100,000 people in 1995 to 0.15 cases/100,000 in 2001 (p < 0.01), especially in children younger than 1 year (p < 0.005). In the same period, Hib meningitis lethality decreased from 17.8 to 6.7 % (p < 0.01). CONCLUSIONS: The implementation of an Hib meningitis vaccination program has nearly eliminated Hib meningitis in the state of Rio Grande do Sul. These findings underscore the need to maintain the vaccination in children, with a thorough investigation of suspected cases and reporting of confirmed cases.

Adolescent↗

Characteristics of nosocomial bacterial meningitis in children.

Nosocomial meningitis is uncommon in children. We reviewed the medical records of all children who developed bacterial meningitis at least 72 hours after admission to Mackay Memorial Hospital for the period July 1992 through June 2000. Clinical manifestations, predisposing factors, pathogens, and outcomes were analyzed. Twenty-two cases of nosocomial meningitis were identified, comprising 9.2% (22/239) of all pediatric cases of bacterial meningitis during the study period. The male-to-female ratio was 14:8. All patients were younger than 6 months of age except for one, who was 7 years old. The mean duration between admission and onset of meningitis was 15.3 days (range, 3 to 58 days). Twenty-two organisms were isolated, including 13 Gram-negative bacteria (59%) and 9 Gram-positive bacteria (41%). The most common pathogen was Escherichia coli (5 cases), followed by Enterobacter cloacae (3), Staphylococcus aureus (3), and Chryseobacterium meningosepticum (3). Seventeen patients (77%) had concomitant bacteremia. Predisposing factors for acquisition of nosocomial meningitis included previous treatment with broad-spectrum antibiotics (68%), prematurity with very low birth weight (41%), and total parenteral nutrition (32%). Two patients (9%) had previous neurosurgical intervention. Four patients (18%) died, 3 of whom were low birth weight premature infants. Nine patients (41%) had sequelae, including developmental delay, hydrocephalus, hearing impairment, and epilepsy. Neurosurgery was not a significant risk factor for the development of nosocomial meningitis, while very low birth weight played an important role. Previous intraventricular hemorrhage or hydrocephalus, prematurity with very low birth weight, infection with Gram-negative bacteria, and prior broad-spectrum antibiotic administration were associated with poor outcome.

Bacterial Infections↗

[Mumps meningitis: a case mix in a Neurology Department].

INTRODUCTION: Parotiditis is a viral infection that produces a non-suppurative inflammation of the parotid glands, although it may affect other salivary glands, the testicles, meninges and the pancreas. Clinical meningitis appears in 1-10% of cases, normally between the 4th and the 10th day after infection of the parotid glands. In this study, we analyse the clinical and analytic characteristics of the patients admitted to our Neurology Department over the last 12 years. CASE REPORTS: A retrospective study was conducted by analysing the hospital discharge reports. The eligibility criterion was the existence of an acute meningeal syndrome linked to the presence of positive IgM titres for the parotiditis virus. In all, 13 cases were found, with a mean age of 16.5 years, and most of them were males (92.3%). Parotiditis preceded meningitis in all our patients with an average of 8.3 days, while orchiepididymitis, when it occurred, appeared at the same time or after meningitis. Analysis of the cerebrospinal fluid showed a lymphocyte profile with glycorrhachia above 40%, except in two cases that showed a non-persistent neutrophilic profile. There was a transient 30.7% reduction in prothrombin time in the patients. No sequelae were observed. CONCLUSIONS: Vaccination campaigns have drastically reduced the number of cases of meningitis due to this germ since the second half of the 90s. This virus must be borne in mind in cases of meningitis in young males who come from underdeveloped countries.

Adolescent↗

Clinical characteristics of adult Escherichia coli meningitis.

The clinical characteristics and therapeutic outcomes of adult meningitis due to Escherichia coli alone have not been examined adequately. In this study, we analyzed the clinical and laboratory data of 15 adult patients with monomicrobial E. coli meningitis. The 15 patients, collected over a period of 18 years (January 1986-December 2003), included 7 men and 8 women, aged 45-77 years. They accounted for 5% (15/306) of our adult bacterial meningitis with single pathogen infection. This study also revealed that a post-neurosurgical state is the most important factor predisposing adult patients to develop E. coli meningitis. In this study, all of the tested E. coli strains showed their susceptibility to imipenem and/or meropenem, however, E. coli strains that are not susceptible to third-generation cephalosporin have emerged since 2001. As to the therapeutic results of these 15 cases, all 4 patients without appropriate antibiotic treatment died and the other 11 patients with appropriate antibiotic treatment showed a mortality rate of 27%. The emergence of third-generation cephalosporin non-susceptible E. coli strains in adult bacterial meningitis, as shown in this study, has caused a therapeutic challenge in choosing initial empirical antibiotics for treating adult patients with post-neurosurgical meningitis. Our results emphasize that the timely use of appropriate antibiotics is essential for the management of this potentially fatal central nervous system infection. However, it should be noted that the number of cases examined in this study is too small to reach a therapeutic conclusion regarding adult E. coli meningitis, and further large-scale studies will be needed for this purpose.

Adult↗

Haemophilus influenzae type B meningitis among children in Hanoi, Vietnam: epidemiologic patterns and estimates of H. Influenzae type B disease burden.

From March 2000 to February 2002, a population-based study of Haemophilus influenzae type b (Hib) meningitis was conducted among children less than five years of age in Hanoi, Vietnam. Children with suspected bacterial meningitis were referred to hospitals and each patient underwent standardized clinical examination and microbiologic testing. In Hanoi, 580 children were evaluated for bacterial meningitis and 23 (4%) had confirmed or probable Hib meningitis. The incidence of all Hib meningitis was 12/100,000 child-years less than five years of age and 26/100,000 child-years less than two years of age. Nationally, an estimated 1,005 children less than five years of age are hospitalized for Hib meningitis and 5,107 are hospitalized for Hib pneumonia. Among children with Hib meningitis, at least 100 will develop severe neurologic sequelae and 40 will die. These data suggest there is a substantial burden of Hib disease in Vietnam. National leaders will be provided with these data to facilitate development of national vaccination policies for children in Vietnam.

Child, Preschool↗

[A case of aseptic meningitis caused by relapsing polychondritis].

We report a patient of relapsing polychondritis (RP) with antecedent aseptic meningitis. A 65-year-old man has developed headache and fever. Neurological examination showed meningeal signs, and cerebrospinal fluid (CSF) examination revealed meningeal inflammation which contained 450 polymorphonuclear cells/microl, 302 mononuclear cells/microl, and 0 red cells/microl, with 79 mg protein/dl. Serologic testing for autoimmune disease as well as the culture and cytology of CSF were negative. He admitted our hospital as having aseptic meningitis and experienced antibiotic therapy. However, his pyrexia continued and he developed repeating visual and hearing impairment reacting to steroid. Three months later, he became behaviorally deaf, and bilateral auricular chondritis occurred with nonerosive seronegative inflammatory polyarthritis. The result of condral biopsy was consistent with the diagnosis of RP showing cartilage surrounded by an intense inflammatory cell response with a decreased number of chondrocytes. A clinical diagnosis was made and prednisolone 60 mg/day was begun with the result of resolution of the auricular chondritis, and slight improvement of his deafness. Aseptic meningitis is a rare complication of RP. Only one report detailed RP patient who had preceding meningitis. RP is a potentially lethal disease resulting from suffocation by airway collapse, the complications of a cardiac large vessel, and so on. For improvement of a life prognosis, an early diagnosis and treatment are indispensable. Although RP is a rare discovery, it is necessary that RP should be taken into consideration and be differentiated as a cause of relapsing aseptic meningitis.

Aged↗

[Assessment of psychomotor development in preschool and early preschool children, as a long term outcome of neonatal bacterial meningitis].

Disorder of the cognitive function and psychomotor retardation in the preschool and early preschool children is a result of neonatal bacterial meningitis in most cases. We have investigated 142 patients after neonatal bacterial meningitis and bacterial sepsis. We followed these children during 7 years (1998-2005). The whole contingency was divided into three groups: I group - bacterial meningitis (64 cases), II group - bacterial meningitis and sepsis (56 cases) and III (control) group - 22 patients with bacterial sepsis of different degrees. With the purpose of estimation of the psychomotor development, we have applied: Bayley screening test of infant developmental test (0 -2 y); Denver developmental screening test, and Denver-2 (0-6 y); Raven progressive matrices (5-11 y); Wechsler Intelligence scale for children (6-15 y). We have determined that the results of neonatal bacterial meningitis are predictors of severe long-term outcome of the disease. Analysis of the obtained data enables us to conclude that outcome of neonatal bacterial meningitis and sepsis in combination with bacterial meningitis is more severe than of bacterial sepsis.

Child↗

Corticosteroids and bacterial meningitis.

Despite timely and appropriate antimicrobial therapy of bacterial meningitis, neurologic sequelae still occur in some children. This also remains true for the third generation cephalosporins such as ceftriaxone and cefotaxime despite their extraordinary high bactericidal titers in the cerebrospinal fluid of children with bacterial meningitis. The most effective way to prevent neurologic damage in these patients is to prevent the infection from developing in the first place. This may be achievable in the very near future for meningitis due to Haemophilus influenzae type b, the most common organism causing meningitis in children in many parts of the world. Unfortunately, even though such means of prevention may be available or under development, ensuring that all children receive these immunizations is very difficult to accomplish. Furthermore, some forms of bacterial meningitis are not likely to be preventable by immunization or other methods and thus efforts to develop new means to minimize the neurologic damage due to meningitis remain important. One such effort involves the use of antiinflammatory agents in addition to antimicrobial therapy for the treatment of this infection. This review will focus on the role of one such antiinflammatory agent, corticosteroids, as adjunctive therapy for bacterial meningitis.

Adrenal Cortex Hormones↗

[Epidemiologic studies of various forms of meningitis based on public health reports in West Berlin from 1981 to 1985].

In the Federal Republic of Germany, four types of meningitis must be reported since 1980 instead of the previous two categories (i.e. meningococcal disease and other forms of meningitis). Consequently, various forms of purulent meningitis can be differentiated from viral meningitis. A retrospective study, considering the population of West Berlin, carried out between the years 1981 and 1985, shows the influence of age, nationality and living areas on morbidity and mortality rate. A critical evaluation was undertaken, considering possible changes in management efficiency of public health authorities since the introduction of the new reporting system. Population at high risk, predisposed to develop meningococcal meningitis, are mainly Turkish children living in areas of high population density and poor social structure. The activities of the public health administration seem inadequate. The reported meningitis cases were partly filed wrongly and thus were transmitted wrongly to the Federal Office of Statistics (Statistisches Bundesamt). No substantial scientific epidemiological analysis was performed. The most frequent reaction of public health authorities was disinfection of apartments, day-care centres and schools, as done for example in 67% of the reported meningococcal meningitis cases, although it is well known that there is no reason for room disinfection in droplet-transmitted infection of the nasopharyngeal mucosa. As shown by our results, the differentiation of the reporting system in use since 1980 did not prove advantageous considering the health policy and epidemiological research of prevention in our study area. Disinfection measures are obsolete.

Bacterial Infections↗

Approach to diagnosis of meningitis. Cerebrospinal fluid evaluation.

CSF evaluation is the single most important aspect of the laboratory diagnosis of meningitis. Analysis of the CSF abnormalities produced by bacterial, mycobacterial, and fungal infections may greatly facilitate diagnosis and direct initial therapy. Basic studies of CSF that should be performed in all patients with meningitis include measurement of pressure, cell count and white cell differential; determination of glucose and protein levels; Gram's stain; and culture. In bacterial meningitis, Limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis. Where there is strong suspicion of tuberculous or fungal meningitis, CSF should also be submitted for acid-fast stain, India ink preparation, and cryptococcal antigen; unless contraindicated by increased intracranial pressure, large volumes (up to 40-50 mL) should be obtained for culture. If a history of residence in the Southwest is elicited, complement-fixing antibodies to Coccidioides immitis should also be ordered. Newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers. Despite the great value of lumbar puncture in the diagnosis of meningitis, injudicious use of the procedure may result in death from brain herniation. Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension. Institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure.

Cerebrospinal Fluid↗

Itraconazole therapy for cryptococcal meningitis and cryptococcosis.

We studied the efficacy of itraconazole, a new oral triazole, in 33 patients (32 were immunocompromised) with cryptococcosis. Diagnoses included cryptococcal meningitis (24 patients), cryptococcemia (19 patients), cryptococcuria (4 patients), osteomyelitis (1 patient), pulmonary cryptococcosis (1 patient), and soft-tissue cryptococcosis (2 patients). Twenty-six patients had the acquired immunodeficiency syndrome, and 4 were transplant recipients. Therapy (200 mg two times per day) was monitored by clinical response, culture, and cryptococcal antigen testing. Cryptococcemia was abolished in 10 (100%) of 10 assessable patients; clinical abnormalities also cleared. Thirteen (65%) of 20 assessable patients with cryptococcal meningitis had complete responses (clinical resolution and negative cultures), 5 (25%) had partial responses, and therapy failed in 2 (10%). Ten (71%) of 14 patients with the acquired immunodeficiency syndrome who had meningitis and were treated with itraconazole as their sole therapy had complete responses, 3 (21%) had partial responses, and therapy failed in 1 (7%). Partial responses or failures were all associated with the failure of previous therapy, severe disease, low serum itraconazole concentrations, or a resistant organism. Noncompliance was associated with relapse (4 patients). Meningitis recrudesced in 3 (20%) of 15 patients who responded to therapy. All 4 patients with pulmonary cryptococcosis, soft-tissue cryptococcosis, or osteomyelitis responded to therapy (100%). Cryptococcuria was abolished in 3 (60%) of 5 assessable patients. The median survival of the 20 patients with the acquired immunodeficiency syndrome who had meningitis exceeded 10.5 months at this writing. Overall results compare favorably with amphotericin B therapy with or without flucytosine. Forty of 44 isolates of Cryptococcus neoformans were susceptible in vitro to itraconazole (minimum inhibitory concentration less than or equal to 3.13 mg/L), 3 were borderline (minimum inhibitory concentration, 6.25 mg/L), and 1 was resistant (minimum inhibitory concentration, 12.5 mg/L). As itraconazole does not penetrate cerebrospinal fluid, the meningitis results are noteworthy and suggest that meningeal and parenchymal penetration is critical. Itraconazole is promising for the treatment of cryptococcosis in patients with and without the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

[Is Mollaret's meningitis caused by herpes simplex virus type 2?].

Mollaret's meningitis is characterised by recurrent, brief episodes of serous meningitis with symptom-free intervals. Although viral etiology has been suspected, no pathogenic agent has hitherto been found. Using the immunoblot technique, we found IgG antibodies of intrathecal origin against the HSV-2-specific protein, gG2, in a patient with Mollaret's meningitis. Since being put on prophylactic acyclovir treatment twelve months ago, the patient has had no further episodes of meningitis. Because of the similarities between Mollaret's meningitis, recurrent HSV-2 meningitis, and the findings in the case reported here, HSV-2 is suggested as a possible cause of Mollaret's meningitis in general.

Adult↗

Cerebrospinal fluid C-reactive protein in the diagnosis of meningitis in children.

The mortality rate of bacterial meningitis in infants and children is still high (40-50%). Such a mortality rate can be reduced by establishing a prompt and accurate diagnosis. Until now the diagnosis of meningitis is still an important clinical problem. The examination of cerebrospinal fluid C-reactive protein had been done in 44 clinical meningitis patients in the Paediatrics Department, Dr. Sardjito General Hospital qualitatively by means of latex agglutination slide test. Cerebrospinal fluid C-reactive protein was positive in 90% (18/20) of bacterial meningitis patients compared to 8.3% (2/24) of non bacterial meningitis patients. The sensitivity and specificity of cerebrospinal fluid C-reactive protein were 90% and 91.7% respectively and these values were more sensitive and specific than those of white cell count, absolute polymorphonuclear, glucose and protein levels and the cerebrospinal fluid smear (50-80% and 80-91% respectively) which had been performed in the diagnosis of meningitis. It can be concluded that the examination of cerebrospinal fluid C-reactive protein can be used as a diagnostic tool of bacterial meningitis.

Bacterial Infections↗

Bacteriological efficacy of nafcillin and vancomycin alone or combined with rifampicin or amikacin in experimental meningitis due to methicillin-susceptible or -resistant Staphylococcus aureus.

The pharmacokinetics and bacteriological efficacy of nafcillin (NFPC), vancomycin (VCM), amikacin (AMK) and rifampicin (RFP) alone and in VCM combinations were evaluated in the experimental rabbit meningitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA). The mean concentrations of NFPC, VCM, AMK and RFP in cerebrospinal fluid (CSF) with MSSA meningitis exceeded the minimal bactericidal concentrations of MSSA during 8 hours therapy period. The mean CSF penetration rates of the 4 drugs during therapy were from 1% to 26% which are comparable to those observed in humans with meningitis. The median CSF bactericidal titers of RFP, VCM plus RFP, AMK, VCM plus AMK regimens were larger than 1:8 during therapy of MSSA meningitis study. In experimental MRSA meningitis, RFP and VCM plus RFP achieved titers greater than 1: 16 during therapy and at 24 hours. No statistically significant reduction in the CSF bacterial colony count was obtained with any of the antibiotic regimens in MSSA meningitis. By contrast, in 8 hours MRSA meningitis model, significant reductions in the number of MRSA were observed in animals treated for 8 hours with VCM plus RFP (P less than 0.01), RFP (P less than 0.05), and NFPC plus RFP (P less than 0.01).

Amikacin↗