Inhibition of Pro-Inflammatory Microglia with Minocycline Improves Cognitive and Sleep-Wake Dysfunction Under Respiratory Stress in a Sporadic Model for Alzheimer's Disease.

BACKGROUND: Neuroinflammation in Alzheimer's disease (AD) can occur due to excessive activation of microglia in response to the accumulation of amyloid-ß peptide (Aß). Previously, we demonstrated an increased expression of this peptide in the locus coeruleus (LC) in a sporadic model for AD (streptozotocin, STZ; 2 mg/kg, ICV). We hypothesized that the STZ-AD model exhibits neuroinflammation, and treatment with an inhibitor of microglia (minocycline) can reverse the cognitive, respiratory, sleep, and molecular disorders of this model. OBJECTIVE: To evaluate the effect of minocycline treatment in STZ model disorders. METHODS: We treated control and STZ-treated rats for five days with minocycline (30 mg/kg, IP) and evaluated cognitive performance, chemoreflex response to hypercapnia and hypoxia, and total sleep time. Additionally, quantification of Aß, microglia analyses, and relative expression of cytokines in the LC were performed. RESULTS: Minocycline treatment improved learning and memory, which was concomitant with a decrease in microglial cell density and re-establishment of morphological changes induced by STZ in the LC region. Minocycline did not reverse the STZ-induced increase in CO2 sensitivity during wakefulness. However, it restored the daytime sleep-wake cycle in STZ-treated animals to the same levels as those observed in control animals. In the LC, levels of A and expression of Il10, Il1b, and Mcp1 mRNA remained unaffected by minocycline, but we found a strong trend of minocycline effect on Tnf- α. CONCLUSION: Our findings suggest that minocycline effectively reduces microglial recruitment and the inflammatory morphological profile in the LC, while it recovers cognitive performance and restores the sleep-wake pattern impaired by STZ.

Evaluating FMX-101 as a promising therapeutic for the treatment of acne.

INTRODUCTION: Oral minocycline is a mainstay of therapy for moderate-to-severe acne; however, systemic side effects which include hepatotoxicity, lupus-like syndrome, drug hypersensitivity syndrome, autoimmune hepatitis, polyarteritis nodosa, gastrointestinal side effects and skin hyperpigmentation are of concern. Topical antibiotics commonly used in acne, such as erythromycin and clindamycin, present high P. acnes resistance rates which has opened the market for new topical antibiotics. FMX-101 is a novel topical minocycline foam that has shown promising results in phase I, II and III trials for the treatment of moderate-to-severe acne with a better safety profile than oral minocycline. AREAS COVERED: The author provides an overview FMX-101 including its clinical efficacy and safety. The author then provides their expert opinion on this treatment and its potential for the treatment option for acne. EXPERT OPINION: The topical foam formulation of FMX-101 has been shown to reduce both inflammatory and non-inflammatory lesions and to improve IGA scores in patients with moderate-to-severe acne without significant systemic absorption thus limiting associated side effects. Overall, the proven efficacy and safety profile of FMX-101, together with the low systemic absorption, high skin tolerability and cosmetically acceptable foam formulations render this novel therapy an important addition to the acne treatment armamentarium.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Ability of two single-step restorative materials to avoid crown darkening caused by intracanal minocycline paste.

OBJECTIVES: This study aimed to quantitatively assess the ability of two single-step restorative materials to avoid crown darkening caused by the use of minocycline as an intracanal medicament. MATERIALS AND METHODS: After coronal access and instrumentation, 120 maxillary incisors were divided into four groups (n = 30). Two experimental groups according to the restorative material applied to the inner walls of the access cavity: OB, OptiBond All-In-One + minocycline intracanal paste; U200, RelyX U200 + minocycline intracanal paste. Two control groups without restorative materials: MIN, minocycline intracanal paste and SL, saline intracanal. Color determination was performed using a spectrophotometer at five time points, immediately after materials were applied (baseline), and at 7, 14, 21, and 28 days from the baseline. RESULTS: Decrease in the mean values of L* (luminosity) was observed after insertion of minocycline paste in all groups at all time points. Statistically significant differences were absent between the time points (P > .05). After 28 days, MIN showed significantly more darkening (ΔL*) (- 10.6 ± 7.3) than OB (- 5.4 ± 6.2), U200 (- 5.8 ± 3.9) and SL (- 2.3 ± 1.2) (P < .05). CONCLUSIONS: Crown darkening can be minimized by the previous application of RelyX U200 or OptiBond All-In-One to the inner walls of the access cavity before a minocycline-containing paste is applied as an intracanal medication. CLINICAL RELEVANCE: The American Association of Endodontists Clinical Considerations for Regenerative Procedures in necrotic immature teeth suggests the triple antibiotic paste as an intracanal medication (2018). However, discoloration and crown darkening are common unfavorable outcomes. The clinical protocol suggested in this paper has shown to be able to minimize crown darkening, predictably leading to a better patient-centered clinical success.

Severe and Persistent Thyroid Dysfunction Associated with Tetracycline-Antibiotic Treatment in Youth.

Thyroid dysfunction in adolescents treated with minocycline for acne has been previously described as transient effect and/or associated with autoimmune thyroiditis. We report nonimmune-mediated thyroid dysfunction associated with minocycline/doxycycline in 3 adolescents whose clinical courses suggest an adverse effect that may be more common, serious, and persistent than realized previously.

[Pseudotumor cerebri secondary to consumption of minocycline in a pediatric patient]. / Pseudotumor cerebral secundario al consumo de minociclina en un paciente pediátrico.

Pseudotumor cerebri is a syndrome characterized by an elevated intracranial pressure greater than 20 cmH2O with ventricles and cerebrospinal fluid of normal characteristics. Consumption of minocycline have been described among the causes associated with this syndrome. We present a 13-year old female patient with a history of acne treated with minocycline who began with severe headache, diplopia and blurred vision. The diagnosis of pseudotumor cerebri was made, indicating the immediate antibiotic suspension and the beginning of the treatment with acetazolamide. Although the pathogenesis of pseudotumor cerebri is not fully known, an association with minocycline has been observed. This antibiotic is often used by health professionals for the management of acne, so it is important to consider its complications before being prescribed.

El pseudotumor cerebral se caracteriza por una elevación de la presión intracraneal mayor de 20 cmH2O, con ventrículos y líquido cefalorraquídeo de características normales. El consumo de minociclina es una de las causas asociadas a este síndrome. Presentamos una paciente de 13 años de edad con antecedentes de acné tratado con minociclina. Comenzó con cefalea intensa, diplopía y visión borrosa. Se constató el diagnóstico de pseudotumor cerebral y se indicó la suspensión inmediata del antibiótico y el inicio del tratamiento con acetazolamida. Aunque la patogénesis de pseudotumor cerebral no es totalmente conocida, se ha observado una asociación con el empleo de minociclina. Este antibiótico es de uso frecuente para el manejo del acné, por lo que es importante considerar sus complicaciones antes de ser prescrito.

Pseudotumor cerebral secundario al consumo de minociclina en un paciente pediátrico / Pseudotumor cerebri secondary to consumption of minocycline in a pediatric patient

El pseudotumor cerebral se caracteriza por una elevación de la presión intracraneal mayor de 20 cmH2O, con ventrículos y líquido cefalorraquídeo de características normales. El consumo de minociclina es una de las causas asociadas a este síndrome. Presentamos una paciente de 13 años de edad con antecedentes de acné tratado con minociclina. Comenzó con cefalea intensa, diplopía y visión borrosa. Se constató el diagnóstico de pseudotumor cerebral y se indicó la suspensión inmediata del antibiótico y el inicio del tratamiento con acetazolamida. Aunque la patogénesis de pseudotumor cerebral no es totalmente conocida, se ha observado una asociación con el empleo de minociclina. Este antibiótico es de uso frecuente para el manejo del acné, por lo que es importante considerar sus complicaciones antes de ser prescrito.

Pseudotumor cerebri is a syndrome characterized by an elevated intracranial pressure greater than 20 cmH2O with ventricles and cerebrospinal fluid of normal characteristics. Consumption of minocycline have been described among the causes associated with this syndrome. We present a 13-year old female patient with a history of acne treated with minocycline who began with severe headache, diplopia and blurred vision. The diagnosis of pseudotumor cerebri was made, indicating the immediate antibiotic suspension and the beginning of the treatment with acetazolamide. Although the pathogenesis of pseudotumor cerebri is not fully known, an association with minocycline has been observed. This antibiotic is often used by health professionals for the management of acne, so it is important to consider its complications before being prescribed.

Tooth discolouration and internal bleaching after the use of triple antibiotic paste.

AIM: To assess the discolouration of teeth with closed and open apices after placement of triple antibiotic paste (TAP, ciprofloxacin, metronidazole and minocycline) in the pulp chamber and whether discolouration could be reversed by internal bleaching procedures. METHODOLOGY: Twenty extracted human mandibular premolars were divided into 2 groups (n = 10): teeth with closed apices (CA) and teeth with open apices (OA). After conventional access, the TAP was sealed in the pulp chamber for 3 weeks. The paste was removed by a rinse with sodium hypochlorite (NaOCl) and a mixture of sodium perborate and distilled water was sealed in the pulp chamber for 1, 2 and 3 weeks. The shade was measured by a spectrophotometer at six time periods: baseline (T0), after 3 weeks of placement of TAP (T1), after removal of TAP with a NaOCl rinse (T2) and after 1 (T3), 2 (T4) and 3 (T5) weeks of internal bleaching with sodium perborate paste. Data were collected based on the CIELAB-CIE1976 (L*a*b*) system and analysed using t-tests and anova. RESULTS: A significant decrease in the mean values of L* (lightness) was observed after treatment with TAP (T1, P < 0.05). Considerable increases in these values after bleaching with sodium perborate (T3 < T4 < T5) were found in both groups. The only significant difference in the intergroup analysis was between T1 and T2, in which ΔE values in the OA group were higher (P = 0.04). CONCLUSIONS: TAP discoloured the tooth structure, but discolouration could be reversed with sodium perborate paste. In general, teeth with closed and open apices had the same rates of discolouration and bleaching.

Utilização de materiais restauradores autocondicionantes na prevenção de descoloração coronária causada por minociclina / Use of self-etching restorative materials to prevent crown discoloration caused by minocycline

O objetivo desse estudo foi comparar a capacidade de dois materiais restauradores em prevenir a descoloração coronária causada pela minociclina como medicação intracanal e propor uma técnica de fácil implementação para encorajar o uso da pasta tri-antibiótica para desinfecção do sistema de canais radiculares durante procedimentos de regeneração pulpar sem perda estética. Cem dentes foram selecionados, seus canais radiculares foram instrumentados e divididos em quatro grupos de acordo com o tratamento dentinário utilizado: Grupo OB- Agente adesivo OptiBond All-In-One (KERR); Grupo U200- Cimento resinoso auto-condicionante e auto adesivo RelyX U200 (3M ESPE); Grupo MIN- Sem revestimento; Grupo CN- Sem revestimento (controle negativo). Em todos os grupos, com exceção do CN, foi utilizada pasta de minociclina como medicação intracanal coberta por uma bolinha de algodão e vedados com restauração provisória. As medições de cor foram realizadas com um espectrofotômetro no início do estudo (T0), e 7(T7), 14 (T14), 21 (T21) e 28 dias (T28) pós-minociclina. Os resultados obtidos foram submetidos à análise estatística. As diferenças de cor (∆E*) foram crescentes nos grupos CN, OB, U200 e MIN, respectivamente. A diferença de luminosidade (∆L*) foi também crescente nos grupos CN, OB, U200 e MIN, respectivamente. Houve diferença significante entre os grupos MIN e CN, e entre os grupos MIN e U200 (p<0,05). O eixo amarelo-azul (∆b*) não apresentou alteração de cor significante (p>0,05). Uma alteração de cor significante no eixo vermelho-verde (∆a*) foi observada no grupo MIN em relação ao grupo CN (p<0,05). Portanto, conclui-se que a técnica foi fácil de ser implementada, ambos materiais reduziram a descoloração da coroa causada pela pasta de minociclina mas foram ineficazes em impedi-la completamente.

The aim of this work was to assess the ability of two restorative materials to prevent crown discoloration caused by topic use of minocycline as an intracanal medicament and to propose an easy to implement technique to encourage the use of the tri-antibiotic paste to disinfect the root canal system during pulp regeneration procedures without aesthetic depletion. One hundred teeth were divided into four groups after access and instrumentation by the dentinary treatment: Group OB- Self etching bonding agent OptiBond All-In-One (KERR); Group U200- Self etching resin cement RelyX U200 (3M ESPE); Group MIN- Without restorative material; Group CN- Without restorative material. All groups, except CN, received minocycline as intracanal medicament covered by cotton pellet and sealed with provisional restoration. Color determination were performed with an spectrophotometer at the beginning of the study (T0), 7 days (T7), 14 days (T14), 21 days (T21) and 28 days (T28) after intracanal placement of the minocycline paste. The results were statistically analyzed. Overall color difference (∆E*) increased from Grupo CN, Grupo OB, Grupo U200 and Grupo MIN respectively. There was significant difference between groups MIN and CN, and between groups MIN and U200 (p<0,05). Luminosity difference (∆L*) increased from Groupo CN, Groupo OB, Grupo U200 and Grupo MIN respectively. There was significant difference between groups CN and MIN, between groups MIN and OB, and between groups MIN and U200 (p<0,05). Color variance in the blue-yellow axis (∆b*) showed no statistical difference (p>0,05). Color variance in the red-green axis (∆a*) was significant between groups MIN and CN (p<0,05). We concluded that the technique was indeed easy to implement, both materials reduced the crown discoloration caused by the minocycline paste but were unable to prevent it completely.

Evaluación de la eficacia y seguridad de tigeciclina en el tratamiento de infecciones del tracto respiratorio: Revisión sistemática de la literatura científica / Evaluation of the efficacy and safety of tigecycline for treatment of respiratory tract infections: Systematic review of literature

Background: Tigecycline is indicated for the treatment of complicated skin infections, soft tissue and intraabdominal infections. Its use could be extended to community-acquired pneumonia (CAP) and hospital pneumonia (HN). The objective was to evaluate the efficacy and safety of tigecycline in the treatment of respiratory infections. Methods: systematic review (2012). Databases used were MEDLINE, EMBASE, Cochrane Library, CRD and WOK. We identified clinical trials of adults with respiratory infection, treated with tigecycline. The quality of the studies was assessed using CASPe checklist. Results: We selected four clinical trials of high-moderate quality. Three studies with patients with CAP and a trial with HN patients. In patients with CAP, efficacy of tigecycline (88.6 to 90.6%) was higher than levofloxacin (85.3 to 87.2%). The non inferiority testing was statistically significant (p < 0.001). In the study of patients with HN tigecycline showed an efficiency of 67.9% versus 78.2% for imipenem/cilastatin. Main adverse effects were gastrointestinal. Conclusions: The efficacy of tigecycline is non inferior than levofloxacin in patients with CAP, but less than imipenem in patients with HN. Tigecycline demonstrates noninferiority versus others tested antibiotics, and it shows a good safety profile.

Introducción: Tigeciclina está indicada en el tratamiento de infecciones complicadas de piel, tejidos blandos e intra-abdominales. Su utilización podría extenderse para neumonías adquiridas en la comunidad (NAC) y neumonías hospitalarias (NH). El objetivo ha sido evaluar la eficacia y seguridad de tigeciclina en el tratamiento de infecciones respiratorias. Material y Métodos: Revisión sistemática (2012). Se realizaron búsquedas en MedLine, Embase, Cochrane Library, CRD y WOK. Se localizaron ensayos clínicos de adultos con infección respiratoria, tratados mediante tigeciclina. La calidad de los estudios se valoró mediante los criterios CASPe. Resultados: Se seleccionaron cuatro ensayos clínicos de calidad alta-moderada. Tres estudios incluyeron pacientes con NAC y un estudio a pacientes con NH. En pacientes con NAC la eficacia de tigeciclina (88,6-90,6%) fue no inferior a la de levofloxacina (85,3-87,2%). El "test de no inferioridad" fue estadísticamente significativo (p < 0,001). En el estudio de pacientes con NH, tigeciclina presentó una eficacia de 67,9% frente a 78,2% de imipenem/cilastatina. Los principales efectos adversos fueron gastrointestinales. Conclusiones: la eficacia de tigeciclina es no inferior a la de levofloxacina en pacientes con NAC, pero inferior a imipenem en pacientes con NH. Tigeciclina ha demostrado no inferioridad frente a los otros antimicrobianos testados. Tigeciclina demuestra tener un buen perfil de seguridad.

Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil.

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. RESULTS: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies had shown, no treatment was stopped due to side effects. Nevertheless, patient follow-up and studies with bigger samples are necessary to guarantee the efficacy and safety of the alternative regimen as a second-line scheme in multi-drug therapy.

Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil / Efeitos adversos das drogas (minociclina, ofloxacina e clofazimina) utilizadas no esquema alternativo para pacientes com hanseníase multibacilar, em unidade de referência, Manaus, Amazonas, Brasil

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. Results: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies ...

FUNDAMENTOS: Após introdução do esquema poliquimioterápico padrão, houve declínio nos coeficientes de prevalência e detecção de casos novos; entretanto, os registros de resistência medicamentosa e recidivas representam ameaça para o controle da hanseníase. Dessa forma, a proposição de novos esquemas alternativos e a necessidade de monitorar efeitos adversos são importantes para evitar o abandono do tratamento. OBJETIVO: Descrever efeitos adversos do esquema alternativo contendo clofazimina, ofloxacina e minociclina em pacientes com hanseníase multibacilar. MÉTODOS: Estudo prospectivo, descritivo e observacional de casos multibacilares, incluindo recidivas ou intolerância à poliquimioterapia padrão, realizado na Fundação Alfredo da Matta, Manaus, Amazonas, de abril de 2010 a janeiro de 2012. Os indivíduos receberam a terapia composta de doses diárias auto-administradas de 100mg de minociclina, 400mg de ofloxacina e 50mg de clofazimina e mensais supervisionadas de 300mg de clofazimina por seis meses, seguidas de 18 meses de doses diárias de ofloxacina 400mg, clofazimina 50 mg e supervisionadas mensais de clofazimina 300mg. Resultados: 21 pacientes foram incluídos. Efeitos adversos leves e transitórios foram observados em 33,3% dos pacientes; 45,9% foram atribuídos à ofloxacina, como dor abdominal, náuseas, vômitos, cefaléia e insônia; 21,6% foram associados à clofazimina, com relatos e observação em 100% dos pacientes de hiperpigmentação cutânea. O tempo médio de desenvolvimento das reações adversas a partir do início do esquema foi de 15,2 dias. ...

[Evaluation of the efficacy and safety of tigecycline for treatment of respiratory tract infections: systematic review of literature]. / Evaluación de la eficacia y seguridad de tigeciclina en el tratamiento de infecciones del tracto respiratorio: Revisión sistemática de la literatura científica.

BACKGROUND: Tigecycline is indicated for the treatment of complicated skin infections, soft tissue and intraabdominal infections. Its use could be extended to community-acquired pneumonia (CAP) and hospital pneumonia (HN). The objective was to evaluate the efficacy and safety of tigecycline in the treatment of respiratory infections. METHODS: systematic review (2012). Databases used were MEDLINE, EMBASE, Cochrane Library, CRD and WOK. We identified clinical trials of adults with respiratory infection, treated with tigecycline. The quality of the studies was assessed using CASPe checklist. RESULTS: We selected four clinical trials of high-moderate quality. Three studies with patients with CAP and a trial with HN patients. In patients with CAP, efficacy of tigecycline (88.6 to 90.6%) was higher than levofloxacin (85.3 to 87.2%). The non inferiority testing was statistically significant (p < 0.001). In the study of patients with HN tigecycline showed an efficiency of 67.9% versus 78.2% for imipenem/cilastatin. Main adverse effects were gastrointestinal. CONCLUSIONS: The efficacy of tigecycline is non inferior than levofloxacin in patients with CAP, but less than imipenem in patients with HN. Tigecycline demonstrates noninferiority versus others tested antibiotics, and it shows a good safety profile.