minocycline and Pneumonia

The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Drug Therapy, Combination; Hospitals; Humans; Minocycline; Pneumonia; Prognosis; Tigecycline

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).. Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Pneumonia; Polymyxin B; Polymyxins; Tigecycline; Treatment Outcome; Urinary Tract Infections

Myasthenic crisis is a rare, yet serious condition that carries a 3%-8% mortality rate. Although infection is a common cause of decompensation in myasthenia gravis, several antibiotics classes have also been associated with an exacerbation. Selecting antibiotics can be a daunting clinical task and, if chosen inappropriately, can carry significant deleterious consequences. Not only do clinicians have to focus on treating the underlying infection appropriately, but avoiding antibiotics that may potentiate a myasthenic crisis is also vital.. An 85-year-old female with a history of myasthenia gravis presented to the emergency department (ED) with increasing generalized weakness and shortness of breath. Clinical work-up was consistent with a community-acquired pneumonia (CAP) diagnosis. Her medical history included a myasthenia gravis exacerbation shortly after receiving moxifloxacin for CAP. After reviewing the patient's allergies, as well as potential antibiotic triggers, the decision was made to treat with tigecycline. The patient responded well to tigecycline therapy and was deemed stable for discharge on day 4 of hospitalization. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Evaluation of the myasthenia gravis patient frequently originates in the ED. It is important for clinicians to be able to distinguish between an underlying illness and a myasthenic crisis. In the event of an infectious process causing clinical deterioration in a myasthenia patient, optimal antibiotic selection becomes paramount. This patient case highlights the addition of tigecycline to the armamentarium of therapies available to treat myasthenia gravis patients presenting to the emergency department with CAP.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Disease Progression; Female; Fluoroquinolones; Humans; Minocycline; Moxifloxacin; Myasthenia Gravis; Pneumonia; Tigecycline

Tigecycline is an antibiotic agent with a broad spectrum, which has an antibacterial effect against many multidrug-resistant organisms. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is disputed.. In this report, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of tigecycline for the treatment of HAP. The primary outcome was the rate of clinical cure, and the secondary outcomes were mortality and adverse events (AEs).. Four trials involving 1,234 patients were included. The standard-dose tigecycline and comparator groups did not differ significantly in their rates of clinical cure. However, high-dose tigecycline was more effective than standard-dose tigecycline or the comparators for the treatment of HAP. There was no significant difference in mortality between the standard-dose or high-dose regimen and the comparators. Although the safety profile of standard-dose tigecycline was similar to the comparators, the high-dose regimen exhibited more AEs compared with the other groups.. High-dose tigecycline is efficient for the treatment of HAP but is associated with more AEs.

Topics: Anti-Bacterial Agents; Databases, Factual; Female; Half-Life; Hospitals; Humans; Male; Minocycline; Odds Ratio; Pneumonia; Tigecycline

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.. 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.. 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.. 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.

Topics: Adult; Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Cross Infection; Humans; Minocycline; Pneumonia; Respiratory Tract Infections; Tigecycline

As the spread of multidrug-resistant (MDR) and extensive drug-resistant (XDR) organisms constitutes a real threat for patients, new antimicrobials are needed. Tigecycline, the first-in-class glycylcycline, possesses an extended spectrum of antimicrobial activity including MDR and XDR organisms, which holds promise as a treatment option beyond currently approved indications and deserves expanded evaluation of its pharmacokinetics/pharmacodynamics (PK/PD).. This review highlights the areas where our knowledge on PK/PD of tigecycline has been both strengthened and questioned during the recent years. New information has become available on the PK of tigecycline in patients with complicated skin and skin structure infections, complicated intra-abdominal infection, community- and nosocomial-acquired pneumonia. Human PD data from clinical trials linking tigecycline drug exposure to clinical, microbiological and toxicological outcomes are also of great interest.. Tigecycline remains one of our last resorts against MDR pathogens; its clear role has to be re-defined through intense PK/PD applications; dose escalation and exploration of combinations with other antibiotics seem to be the first step towards an expansion of its currently approved indications. The lung remains the most controversial and challenging site regarding the PK/PD standpoint due to the predominance of Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator-associated pneumonia infections, for which tigecycline is mostly used off-label.

Topics: Anti-Infective Agents; Clinical Trials as Topic; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Glycylglycine; Humans; Intraabdominal Infections; Minocycline; Pneumonia; Tigecycline

A 39-year old woman was admitted to our hospital because of cough and abnormal shadows on chest radiographs. She had been treated for 5 months for acne vulgaris with minocycline hydrochloride (MINO). Chest computed tomographic (CT) scans showed multiple ring-shaped opacities in both lungs. Bronchoalveolar lavage disclosed an increase in the total number of cells and a marked increase of lymphocytes. A lung specimen obtained by transbronchial lung biopsy (TBLB) was pathologically diagnosed as bronchiolitis obliterans organizing pneumonia (BOOP). Withdrawal of minocycline led to rapid remission without treatment. The clinical course and histological findings for TBLB suggested that this case was minocycline-induced BOOP. Several cases with minocycline-induced pneumonitis have been reported. However, there are few reported cases of minocycline-induced BOOP, the present case being only the second found in the literature.

Topics: Adult; Anti-Bacterial Agents; Cryptogenic Organizing Pneumonia; Female; Humans; Minocycline; Pneumonia; Radiography, Thoracic; Tomography, X-Ray Computed

A 24-year-old woman had been treated with minocycline (MINO) for acute upper airway infection. Two days after the start of MINO therapy, she developed fever, cough, dyspnea, and bloody sputum. Her chest X-ray film revealed bilateral pleural effusions and butterfly shadow, and chest computed tomography revealed markedly increased density of pulmonary tissue in the central lung fields. Arterial blood gas analysis demonstrated severe hypoxemia. The characteristics of the pleural effusion were exudative. Based on the history of her illness and the chest X-ray findings, in addition to the laboratory findings of leukocytosis with eosinophilia and increased serum IgE, drug-induced pneumonia was suspected. Once the treatment with MINO was discontinued, her symptoms, laboratory data, and chest X-ray findings improved rapidly. Microscopic examination of a transbronchial lung biopsy specimen showed increased alveolar septal thickness with formation of Masson's bodies. Although the result of a lymphocyte stimulation test was negative for MINO, the skin test was positive for immediate response. Because of her clinical course, the possibility of induction by other drugs was excluded. This patient was therefore diagnosed to have MINO-induced pneumonia. To date, ten cases of MINO-induced pneumonia have been reported, but no previous case was associated with pleurisy.

Topics: Acute Disease; Adult; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Female; Humans; Minocycline; Pleurisy; Pneumonia; Respiratory Tract Infections; Tomography, X-Ray Computed

A previously healthy 40-year-old woman was admitted with severe dyspnea, cough and slight fever. Chest X-ray film revealed bilateral widespread opaque infiltration with ground glass shadows around it. The laboratory examination showed moderate hepatic and muscular injury with disseminated intravascular coagulation. In addition her arterial blood gas showed severe hypoxemia (PaO2: 25 Torr under room air). Moreover, about 1 week prior to admission, 2 baby budgerigars she had been raising for half a year died. Because of this history and multi-organ injuries, this disease was considered to be acute pneumonia owing to fulminant psittacosis causing acute respiratory failure. On the first day of admission, she was intubated and ventilated mechanically with an oxygen concentration (FIO2) of 100%. Subsequently, treatment with intravenous minocycline (400 mg/day), heparin for D.I.C. and corticosteroid were started. Abnormal findings in both chest X-ray and several laboratory parameters improved gradually though fever continued for a week. On the 14th day of her hospital stay, she was weaned from the ventilator successfully and the administration of corticosteroid and heparin tapered. On the 41st day, she was discharged without any symptoms. Results of complement fixation (CF) antibodies against chlamydia on paired sera showed a significant rise from 1:32 to 1:256. Moreover, both IgG and IgM antibodies for Chlamydia psittaci with microplate immunofluorescent antibody technique (MFA) showed an 8 times' rise during 10 days after admission. The definitive diagnosis was made with positive isolation of C. psittaci from both the throat swab of this patient and the spleen and liver of the dead budgerigar by the cell culture method. Psittacosis should always be borne in mind as a possible cause of fulminant pneumonia with acute respiratory failure, and such a situation can be handled successfully if emergency care including mechanical ventilation is available.

Topics: Acute Disease; Adult; Chlamydophila psittaci; Emergencies; Female; Heparin; Humans; Minocycline; Pneumonia; Psittacosis; Respiration, Artificial; Respiratory Insufficiency; Tetracyclines

In a previous phase 3 study, the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin (imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia. This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia. Subjects with hospital-acquired pneumonia were randomized to receive one of two doses of tigecycline (150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection, depending on the randomization regimen. Clinical response, defined as cure, failure of treatment, or indeterminate outcome, was assessed 10 to 21 days after the last day of therapy. In the clinically evaluable population, clinical cure with tigecycline 100 mg (17/20, 85.0%) was numerically higher than with tigecycline 75 mg (16/23, 69.6%) and imipenem/cilastatin (18/24, 75.0%). No new safety signals with the high-dose tigecycline were identified. A numerically higher clinical response was observed with the 100-mg dose of tigecycline. This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary. (The ClinicalTrials.gov identifier for this clinical trial is NCT00707239.).

Topics: Adult; Aged; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Minocycline; Pneumonia; Tigecycline

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Double-Blind Method; Drug Combinations; Hospital Mortality; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Pneumonia; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

Tigecycline is a new-generation of tetracycline (glycylcyclines) and is active in vitro against bacteria that possess any of the classical genes that confer tetracycline resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition in patients with community- or hospital-acquired pneumonia was described using a population pharmacokinetic model. Additionally, the influence of covariates, such as body surface area, severity of illness, and clinical laboratory measures, on tigecycline disposition was evaluated. An intravenous loading dose of 100 mg was followed by 50 mg of tigecycline every 12 h. The final population pharmacokinetic model was a two-compartment model with linear elimination and with a relationship between tigecycline clearance and body surface area and creatinine clearance. The model was parameterized using total clearance (CL), the volume of the central compartment, distributional clearance from the central to the peripheral compartment, and volumes of distribution at steady state. Relationships between body surface area and creatinine clearance were identified as significant predictors of interindividual variability on CL. This model will serve as the basis for estimating tigecycline exposure for pharmacokinetic-pharmacodynamic analyses for efficacy and safety among patients with community- or hospital-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia; Tigecycline; Young Adult

To evaluate the efficacy of Switch therapy for community-acquired pneumonia, we conducted a prospective randomized controlled study in thirty-two hospitalized patients. These cases corresponded to Fine's risk classes II to IV. Using a table of random numbers, sixteen patients were assigned to a Switch therapy group, and the other sixteen, to a clinical pathway group. Both groups initially received intravenous antimicrobials. Within the Switch therapy group, when all the patients were afebrile for more than sixteen hours, their intravenous antimicrobials were switched to oral, and the patients were discharged on the following day. For all patients in the clinical pathway group, the critical pathway was defined as an eight-day planned hospitalization, with a time-task matrix formatted for disease treatment, laboratory testing, physical examination, oxygen saturation monitoring, ambulation, diet, patient education and clinical outcome. Switch therapy reduced the period of intravenous antimicrobial administration from 7.6 days to 4.0 days (p < 0.0001). The period required to switch to oral antimicrobials decreased from 8.3 days to 4.8 days (p < 0.0001); hospital stay length, from 9.8 days to 6.5 days (p = 0.0001); and medical resource utilization, from 330, 373 to 227,768 Japanese yen (p = 0.0002). No patient from either group required readmission. In conclusion, Switch therapy was more efficient than management with a clinical pathway for mild to moderate community-acquired pneumonia in hospitalized patients.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Critical Pathways; Erythromycin; Female; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Minocycline; Pneumonia; Prospective Studies

Topics: Adenoviridae; Adenoviridae Infections; Bacterial Infections; Clinical Trials as Topic; Humans; Influenza, Human; Lung; Minocycline; Neisseria meningitidis; Orthomyxoviridae; Paramyxoviridae Infections; Pneumonia; Pneumonia, Viral; Respiratory System; Respirovirus; Sputum; Tetracycline; Trachea

Acinetobacter baumannii is a worldwide health issue in terms of its high antibiotic resistance and ability to form biofilms. Nanoparticles (NPs) with high biocompatibility, high penetrating ability, and low medication dose can successfully treat the antibiotic-resistant infections. In this research, the anti-biofilm activity of niosomes containing minocycline and gallium nitrate (GaN) against A. baumannii biofilm was determined. In order to improve their anti-biofilm properties, minocycline and GaN were encapsulated in niosomes as biocompatible drug carriers. The niosomes' size, zeta potential, shape, stability, drug entrapment efficacy, drug release pattern and antibacterial activity were assessed. Several clinical samples were isolated from the lungs of patients hospitalized at Loghman hospital, Tehran, Iran. The biofilm formation of most lethal clinical isolates of A. baumannii was analyzed. The pneumonia model was generated by intranasally administering A. baumannii suspension to anesthetized mice whose immune systems was compromised twice by cyclophosphamide. Lung infection of the mouse with A. baumannii was confirmed using PCR. After treatment, the lungs were excised under sterile conditions and stained with hematoxylin and eosin (H&E) to determine histological symptoms, inflammation and intercellular secretions. The niosomes contained minocycline and GaN had an average size of 230 nm and a zeta potential of -40 mV, respectively. The percentage of drug entrapment and delayed drug release was both high in niosomal formulations. Niosomes containing minocycline and GaN dispersed 1, 3 and 5 day old biofilms. The mice given the combination of two compounds required less time to be treated than the animals given the single medication (minocycline). The minocycline& GaN-loaded niosomes could be considered as promising candidates to treat the infections caused by A. baumannii biofilm.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Gallium; Iran; Liposomes; Mice; Microbial Sensitivity Tests; Minocycline; Nitrates; Pneumonia

The purpose of this study is to assess the incidence and management of co-infections in hospitalized severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) patients. We retrospectively evaluated the microbiological database records of the SFTS patients in the first affiliated hospital of Anhui Medical University from January 1, 2018, to December 1, 2021. According to the obtained results, co-infections including pulmonary infection, bloodstream infection, biliary tract infection, urinary tract infection, and abdominal infection were observed in SFTS patients. The incidence rate of fungal infections was found to be high in SFTS patients. Furthermore, we suggest that old age people should be evaluated for the risk of fungal infection. In comparison to the non-infection group, patients in the co-infection group were more likely to get mechanical ventilation, antibacterial treatment, antifungal treatment, and blood product therapy (p < 0.001), with a significantly longer length of stay (p < 0.05). In SFTS patients, the most prevalent strains were Aspergillus fumigatus, Aspergillus flavus, Candida, Klebsiella pneumonia, and Escherichia coli. In this investigation, 66.2% (106/160) of patients were given antibiotics, most often Piperacillin/tazobactam or minocycline. 15.6% (25/160) of patients were treated with antifungal drugs: 13.1% (21/160) with voriconazole. Patients with SFTS Associated Pulmonary Aspergillosis (SAPA) received active antifungal treatment, but the mortality rate was still 23.5% (8/34). Only 6 of the 11 patients with SFTS Associated Candidiasis were treated with antifungal drugs with no mortality. Due to the high frequency of fungal pulmonary infection in SFTS patients, more standardized fungal detection program should be strengthened.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bunyaviridae Infections; Coinfection; Humans; Microbiota; Minocycline; Phlebovirus; Piperacillin; Pneumonia; Retrospective Studies; Severe Fever with Thrombocytopenia Syndrome; Tazobactam; Voriconazole

Topics: Humans; Minocycline; Pneumonia; Sputum; Tigecycline

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline

Topics: Acinetobacter baumannii; Animals; Cyclophosphamide; Male; Minocycline; Pneumonia; Rats; Rats, Sprague-Dawley

Topics: Clindamycin; Combined Modality Therapy; Doxycycline; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Pneumonia; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients' 30-day mortality.A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients.A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96-142.29; P < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05-4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52-5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37-5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27-1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Survival Rate; Taiwan; Tigecycline; Treatment Outcome

We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Prospective Studies; Soft Tissue Infections; Tigecycline; Urinary Tract Infections

Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of minocycline in combination with colistin for the treatment of minocycline-resistant A. baumannii may warrant further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Biofilms; Cefepime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gentamicins; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Taiwan; Thienamycins

Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 μg/ml versus 3 μg/ml [P < 0.05] and 2 μg/ml versus 3.4 μg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Colistin; Enzyme-Linked Immunosorbent Assay; Imipenem; Interleukin-10; Lysophosphatidylcholines; Mice; Microbial Sensitivity Tests; Minocycline; Pneumonia; Sepsis; Tigecycline; Tumor Necrosis Factor-alpha

Bordetella bronchiseptica is a bacterial pathogen usually isolated from animals and rarely causes human infections. There are, however, some reports that B. bronchiseptica causes human respiratory infections in immunocompromised patients or those with underlying respiratory diseases, although there is a lack of treatment guidelines. An 80-year-old woman was admitted to our hospital to treat anti-neutrophil cytoplasmic antibodies-associated vasculitis. On the 16th day after admission, she complained of a productive cough with right pleuritic pain and had low-grade fever. After chest CT scans, we diagnosed pneumonia. Gram stain of her sputum revealed moderate levels of gram-negative coccobacilli, which was later identified as B. bronchiseptica by mass spectrometry. According to the result of minimum inhibitory concentration, we successfully treated the pneumonia with minocycline. This case suggests that B. bronchiseptica pneumonia can be treated by minocycline if the minimum inhibitory concentration is less than 0.25 μg/mL.

Topics: Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Bordetella bronchiseptica; Bordetella Infections; Female; Humans; Minocycline; Pneumonia; Respiratory Tract Infections; Vasculitis

The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Blood Coagulation Tests; Female; Fibrinogen; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Partial Thromboplastin Time; Pneumonia; Prothrombin Time; Thrombin Time; Tigecycline; Young Adult

Antimicrobial resistance among Acinetobacter baumannii is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of A. baumannii. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 μg/ml). Time-kill studies were performed over 24 h using approximately 10(6) CFU/ml of each strain with clinically relevant minocycline concentrations (2 μg/ml and 8 μg/ml), with and without polymyxin B (0.5 μg/ml). The in vivo efficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥ 4×) was observed in the presence of PAβN. The intracellular concentration and in vitro bactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Mice; Microbial Sensitivity Tests; Minocycline; Pneumonia; Polymyxin B

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S. maltophilia.. A total of 102 strains of S. maltophilia were isolated from sputum and bronchoalveolar lavage (BAL) specimens of patients with HAP in our institution. The minimum inhibitory concentration (MIC) values of minocycline, tigecycline, moxifloxacin, and levofloxacin were determined by the agar dilution method. Based on the MICs and the population pharmacokinetic parameters of the investigated antimicrobials, a Monte Carlo simulation was performed to simulate the pharmacokinetic/pharmacodynamic (PK/PD) indices of different regimens. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens.. The susceptibility rates to minocycline, tigecycline, moxifloxacin, and levofloxacin were 96.1%, 80.4%, 74.5%, and 69.6%, respectively. The estimated CFRs were 96.2% for minocycline 100 mg twice daily; 50.8%/67.1%/75.4% for tigecycline 50/75/100 mg twice daily; 34.3%/48.0%/56.6% for levofloxacin 500/750/1000 mg once daily; and 45.7% for moxifloxacin 400 mg once daily.. The simulation results suggest that minocycline may be a proper choice for treatment of HAP caused by S. maltophilia, while tigecycline, moxifloxacin, and levofloxacin may not be optimal as monotherapy.

Topics: Adult; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cross Infection; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Minocycline; Monte Carlo Method; Moxifloxacin; Pneumonia; Sputum; Stenotrophomonas maltophilia; Tigecycline

In this study, we describe a patient in whom tigecycline-induced drug fever and leukemoid reaction (LR) after 3 weeks of therapy for pneumonia.A 62-year-old man developed aspiration pneumonia on February 1, 2015. He had received multiple antibiotics at another hospital, but did not respond well. Disease rapidly progressed, and he was referred to our department on February 14. We adjusted the antibiotic therapy to tigecycline + vancomycin, and added voriconazole to empiric antifungal therapy. Pneumonia largely improved, and we discontinued vancomycin and voriconazole on February 28. With tigecycline monotherapy, his clinical status remained stable.On March 7, he developed high fever and LR (white blood cell count: 38.25 × 10(9)/L). Erythrocyte sedimentation rate and C-reactive protein were elevated, and CD8+ T cells had been abnormally activated. After a careful physical examination and laboratory investigation, we confirmed that primary infection did not progress and no other cause was evident. So we figured fever and LR might be induced by tigecycline. After discontinuing tigecycline and adding low-dose steroid, fever and LR totally resolved in 3 days, which further confirmed our diagnosis.According to this case and literature review, drug-induced hypersensitivity should be considered in the differential diagnosis of fever and LR when the therapeutic duration of tetracycline approximates 3 weeks. Monitoring T-cell subsets may facilitate early diagnosis. When necessary, we should discontinue the suspected drug to confirm diagnosis.

Topics: Anti-Bacterial Agents; Fever; Humans; Leukemoid Reaction; Male; Middle Aged; Minocycline; Pneumonia; Tigecycline

To investigate the spectrum and antimicrobial resistance of major pathogensthat causing nosocomial infections in China, 2013.. Nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 13 teaching hospital around China were collected. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The CLSI M100-S23 criteria were used for interpretation.. Of all cases, 1 022 cases were from BSI, 683 from HAP and 674 from IAI.Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI while Acinetobacter baumanii (34.6%) and Pseudomonas aeruginosa were dominated in HAP. Tigecycline, imipenem and meropenem exhibited high potency against Enterobacteriaceae and the susceptibilities rates were 95.6%, 94.2%and 95.2% respectively. Enterobacteriaceae demonstrated high resistance against cephalosporins (52.3%) and fluoroquinolones (38.9%) but were susceptible to β-lactam+inhibitor. Of all the Enterobacteriaceae, 30.5% were ESBLs positive and 4.3% were carbapenem resistant. Acinetobacter baumanii showed low susceptibilities to the microbial agents except for tigecycline (90.5%) and colistin (100%). The rate of carbapenem resistant Acinetobacter baumanii was 76.6%. Amikacin, ciprofloxacin, cefepime and piperacillin/tazobactam showed high antibacterial activity against Pseudomonas aeruginosa with susceptible rate 88.5%, 77.6%, 72.7% and 64.5% respectively. The resistant rate to imipenem and meropenem were 42.1% and 32.2%. All Staphylococcus aureus (166 strains) were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. MRSA accounted for 46.9% of all the Staphylococcus aureus. The prevalence of MRSA in IAI (55.2%) and HAP (54.4%) were higher that that in BSI (35.0%). No Enterococcus strains were found resistant to tigecycline, linezolid and daptomycin. VRE was found in Enterococcus faecium, accounting for 1.9% of all Enterococcus faecium strains.. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are the most common pathogens causing nosocomial infections. Nosocomial pathogens showed high susceptibilities against tigecycline. For ESBLs-producing Enterobacteriaceae strains, β-lactam+Inhibitor show high antibacterial activities. Vancomycin, teicoplanin and linezolid exhibit high potency to Staphylococcus aureus and Enterococcus.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefepime; Cephalosporins; China; Cross Infection; Hospitals, Teaching; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline; Vancomycin

Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking.. The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009-2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups.. A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% - 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81).. Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Taiwan; Tigecycline

Topics: Anti-Bacterial Agents; Eosinophilia; Hepatitis, Autoimmune; Humans; Lupus Erythematosus, Systemic; Minocycline; Nephritis; Pneumonia

Chemical pleurodesis is an effective treatment for persistent air leakage and secondary pneumothorax. We report the case of a 57-year-old man who presented with pneumothorax and was treated by tube thoracostomy. Because of malpositioning of the chest tube, the minocycline that was administered for pleurodesis was injected into the lung parenchyma instead, which induced chemical pneumonitis. A review of literature indicated that this is the first report of minocycline-associated chemical pneumonitis and its successful treatment.

Topics: Anti-Bacterial Agents; Chest Tubes; Humans; Male; Middle Aged; Minocycline; Pneumonia; Radiography, Thoracic

We describe an immunocompromised patient with disseminated Legionella pneumophila infection. A chronic leg ulcer was probably the port of entry for the infection. Treatment required several operations and prolonged antimicrobial treatment. To our knowledge, this is the first case report of Legionella soft tissue infection and pneumonia treated with tigecycline.

Topics: Anti-Bacterial Agents; Humans; Immunocompromised Host; Leg Ulcer; Legionella pneumophila; Legionnaires' Disease; Male; Middle Aged; Minocycline; Pneumonia; Soft Tissue Infections; Tigecycline

When evaluating the pharmacodynamics of antimicrobials, assumptions are often made relative to their pharmacokinetics. One example of this is applying tissue penetration results of uninfected hosts to those displaying a targeted illness. As tigecycline evolves into a potential treatment option for pneumonia, we determined whether the presence of a lung infection affected the penetration of the drug into the epithelial lining fluid (ELF).. Single doses of tigecycline 50 and 25 mg/kg were administered to neutropenic ICR mice with or without the presence of an Acinetobacter baumannii lung infection. Serum samples were gathered at 0.5-24 h after tigecycline administration; bronchoalveolar lavage was conducted at 1, 1.5, 4 and 8 h. Tigecycline concentrations were determined by HPLC. Comparisons of ELF penetration in infected and uninfected lungs were based on the ratios of the AUC(0-8) in ELF and the free AUC(0-8) in serum. AUCs were calculated by the trapezoidal rule.. The group without pulmonary infection displayed an ELF penetration ratio of 8.1 and 6.2 for the 50 and 25 mg/kg doses, respectively. The respective penetration ratios in the infected lungs were 23.3 and 12.9.. While tigecycline exhibits excellent ELF penetration in healthy and infected murine lungs, the presence of infection greatly enhances penetration. Moreover, increased systemic exposures of tigecycline result in greater ELF penetration, regardless of infection status. When future tigecycline clinical trials for the treatment of pneumonia are considered, escalated doses may reap greater than expected benefits towards achieving adequate pharmacodynamic indexes within the lungs.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Humans; Lung; Mice; Mice, Inbred ICR; Minocycline; Pneumonia; Serum; Tigecycline

Tigecycline (TGC) is an extended-spectrum antibiotic with activity against Staphylococcus aureus, including methicillin (meticillin)-resistant S. aureus strains, which are well-recognized pathogens in nosocomial pneumonia. The objective of this study was to characterize the exposure-response relationship for TGC against S. aureus in an immunocompromised BALB/c murine pneumonia model. Six S. aureus isolates were studied, and the TGC MICs for those isolates ranged from 0.125 to 0.5 mg/liter. The pharmacokinetics (PK) of TGC in serum and bronchoalveolar lavage (BAL) fluid were evaluated, as was the level of protein binding of the compound in this murine species. Administration of TGC at 1.56 to 150 mg/kg of body weight/day in single or two to three divided doses was used in the efficacy studies. TGC displayed linear PK and had a mean half-life of 10.9 +/- 2.5 h. Efficacy was highly correlated with the area under the free concentration-time curve (fAUC)/MIC (r(2) = 0.93). The 80% and 50% effective exposure indexes and the stasis exposure index were similar between the isolates (means +/- standard deviations, 3.04 +/- 1.12, 1.84 +/- 1.3, and 1.9 +/- 1.5, respectively). Maximal efficacy was predicted at a 2.85-log(10)-CFU reduction. TGC appeared to accumulate in the interstitial space, as the ratios of the fAUC from 0 to 8 h of epithelial lining fluid to plasma were 7.02, 15.11, and 23.95 for doses of 12.5, 25, and 50 mg/kg, respectively. TGC was highly effective in this murine pneumonia model. In light of current MIC distributions, the fAUC/MIC targets that we defined against S. aureus are readily achievable in humans given conventional doses of TGC.

Topics: Animals; Anti-Bacterial Agents; Female; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Minocycline; Pneumonia; Staphylococcal Infections; Tigecycline

We present 6 cases of multidrug-resistant (MDR) Acinetobacter baumannii pneumonia in lung transplant recipients. All cases were treated with imipenem and/or non-traditional antibiotics, such as tigecycline and colistimethate, and had different microbiologic and clinical outcomes. Prior treatment with broad-spectrum anti-microbial therapy was the single most likely risk factor for the development of infection due to MDR Acinetobacter baumannii. Ideal preventive and therapeutic strategies for this pathogen in lung transplant recipients require further study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Lung Transplantation; Male; Minocycline; Pneumonia; Risk Factors; Tigecycline; Treatment Outcome

The in vitro activity of tigecycline was evaluated against baseline pathogens isolated from patients enrolled in phase 3 clinical trials for community-acquired pneumonia conducted in 29 countries worldwide. Tigecycline was active against the most prevalent pathogens, including Streptococcus pneumoniae (MIC(90) 0.06 mg/L), Staphylococcus aureus (MIC(90) 0.25 mg/L), Haemophilus influenzae (MIC(90) 0.5 mg/L) and Klebsiella pneumoniae (MIC(90) 1 mg/L). Twelve isolates of S. pneumoniae expressing tet(M) and two isolates of K. pneumoniae producing extended-spectrum beta-lactamases isolated during the study were susceptible to tigecycline. The excellent in vitro activity of tigecycline against these clinical isolates confirmed its potential utility against pathogens associated with community-acquired pneumonia.

Topics: Anti-Bacterial Agents; Bacteria; Clinical Trials as Topic; Community-Acquired Infections; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tetracycline Resistance; Tigecycline

A pharmacodynamic model was used to generate supportive data comparing tigecycline with other broad-spectrum agents against pathogens implicated in hospital-acquired pneumonia (HAP). A 5000 patient Monte Carlo simulation determined the probability of target attainment (PTA) of tigecycline (+/- ceftazidime) compared with imipenem, levofloxacin, and piperacillin/tazobactam (+/- vancomycin). PTA was calculated over MICs of current Gram-positive and Gram-negative bacteria collected from worldwide surveillance and weighted by the expected prevalence of these pathogens causing HAP. For monotherapy, the weighted PTA was imipenem (78.2%), piperacillin/tazobactam (73.3%), tigecycline (62.9%), and levofloxacin (62.5%). By pathogen PTA was greatest for tigecycline against Gram-positives, and ceftazidime or imipenem against Gram-negatives. Combination therapy increased PTA to 88.6%, 85.5%, 80.6%, and 69.8% for tigecycline, imipenem, piperacillin/tazobactam, and levofloxacin, respectively. Based on contemporary resistance data, tigecycline plus ceftazidime is predicted to achieve its pharmacodynamic targets similarly to combination therapy with imipenem plus vancomycin for the treatment of patients with HAP.

Topics: Anti-Bacterial Agents; Cross Infection; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Ofloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Tigecycline

A 51-year-old man was admitted to our hospital with fever, dry cough and dyspnea. He had taken minocycline for 11 days because of urinary tract infection. Chest X-ray on admission showed diffuse reticular shadows in bilateral lung fields with bilateral pleural effusion. Cessation of minocycline led to spontaneous improvement of symptoms and radiographic findings. The lymphocyte stimulation test for minocycline with peripheral blood and pleural effusion were negative. After provocation test with minocycline, he developed fever and dry cough and bilateral ground glass opacity appeared on his chest X-ray. He was diagnosed as minocycline-induced pneumonitis and recovered rapidly following corticosteroid therapy.

Topics: Anti-Bacterial Agents; Bronchial Provocation Tests; Humans; Lymphocyte Activation; Male; Methylprednisolone; Middle Aged; Minocycline; Pleural Effusion; Pneumonia; Radiography, Thoracic; Treatment Outcome

An 80-year-old man was admitted because of dyspnea on effort. We suspected an acute exacerbation of chronic heart failure and idiopathic interstitial pneumonia caused by right-sided pneumonia. A nodular shadow in right upper lobe spread and consolidated into the airspace, and it failed to improve despite administration of meropenem trihydrate, vancomycin hydrochloride and clindamycin. A definitive diagnosis of Legionella micdadei pneumonia was made on the basis of this organism being isolated in culture from bronchial lavage fluid and subsequent identification of Legionella micdadei using DNA-DNA hybridization. The airspace consolidation gradually improved following treatment with intravenous erythromycin and minocycline hydrochloride.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteriological Techniques; Bronchoalveolar Lavage Fluid; DNA, Bacterial; Erythromycin; Humans; Legionella; Legionellosis; Male; Minocycline; Nucleic Acid Hybridization; Pneumonia; Treatment Outcome

A 30-year-old woman who had been receiving minocycline for 11 days to treat a skin burn presented with high fever and progressive dyspnea. Chest radiography demonstrated bilateral pulmonary infiltrates with ground glass opacities. She was admitted to our hospital under a tentative diagnosis of minocycline-induced pneumonia. Minocycline therapy was discontinued at hospital admission, which led to dramatic clinical and radiographic improvement. Bronchoalveolar lavage fluid (BALF) analysis three days after the onset of the pneumonia showed increased numbers of total cells (7.68 x 10(5)/ml), neutrophils (33%) and eosinophils (14%). An increased number of peripheral blood neutrophils was also noted at the time of hospital admission. Follow-up evaluations of BALF 10 days and 34 days after the onset showed rapidly declining numbers of neutrophils and eosinophils. We also measured the levels of several cytokines in BALF, suggesting that TNF-alpha and IL-8 contributed to the accumulation of neutrophils, whereas IL-5 contributed to the accumulation of eosinophils. In summary, we report here the temporal change in the inflammatory cell and cytokine profile in BALF, serum, or both, in a case of drug-induced pneumonia.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cytokines; Eosinophils; Female; Humans; Leukocyte Count; Minocycline; Neutrophils; Pneumonia

Topics: Anti-Bacterial Agents; Female; Humans; Instillation, Drug; Kidney Diseases, Cystic; Middle Aged; Minocycline; Pneumonia

Pneumonitis with eosinophilia is one of the less common and severe adverse effects of minocycline. The disease evolves in days or weeks from the beginning of treatment, and is usually characterized by dyspnea, fever and bilateral infiltrates in the chest X-ray. With cessation of the antibiotic, and sometimes adding cortico-steroids, clinical and roentgenological resolution follow. We present a case given minocycline for folliculitis and 3 weeks later fever, cough and shortness of breath developed. The clinical and roentgenological course was consistent with minocycline pneumonitis accompanied by eosinophilia.

Topics: Adult; Anti-Bacterial Agents; Eosinophilia; Folliculitis; Humans; Male; Minocycline; Pneumonia

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Fatal Outcome; Humans; Male; Minocycline; Niacinamide; Pemphigoid, Bullous; Pneumonia; Skin

We report a case of minocycline-induced pneumonitis. A 30-year-old woman was treated with minocycline for mycoplasma pneumonia of the right upper lobe. About 15 days after starting treatment, she developed a productive cough, stridor, and dyspnea. The chest X-ray film showed pulmonary infiltration in the left middle lung field. Based on the clinical history and the detection of eosinophilia in the bronchoalveolar fluid, drug-induced pneumonitis was suspected. Treatment with minocycline was discontinued and prednisolone (20 mg/day) was started, after which her symptoms subsided and there was marked regression of the pulmonary infiltrates on chest X-ray films. The lymphocyte stimulation test for minocycline was negative, but the diagnosis was confirmed by a positive oral provocation test.

Topics: Adult; Asthma; Drug Hypersensitivity; Female; Humans; Minocycline; Pneumonia; Respiratory Hypersensitivity

A 76-year-old man who was admitted to the hospital because of chronic renal insufficiency and chronic hepatitis died of Corynebacterium group JK pneumonia, after showing a slight improvement by treatment of Staphylococcus aureus with sulbactam/cefoperazone and minocycline. Transtracheal aspiration (TTA) just before his death revealed numerous gram-positive bacilli phagocytized by many neutrophils and more than 10(8) colony forming units (CFU)/ml of Corynebacterium group JK. A drug susceptibility test showed Corynebacterium group JK was resistant to many antibiotics, with the exception of vancomycin and amikacin.

Topics: Aged; Cefoperazone; Corynebacterium; Corynebacterium Infections; Disease Susceptibility; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Immunocompromised Host; Kidney Failure, Chronic; Male; Minocycline; Opportunistic Infections; Pneumonia; Pneumonia, Staphylococcal; Sulbactam

Topics: Adult; Antigens, Bacterial; Chlamydia Infections; Chlamydophila psittaci; Complement Fixation Tests; Doxycycline; Erythromycin; Female; Humans; Minocycline; Pneumonia; Psittacosis; Tetracycline

All three patients complained of cough, fever and dyspnea. Their chest X-ray films revealed interstitial changes such as Kerley B lines. The results of lymphocyte stimulation tests were all negative for Minocycline (MINO), whereas the provocation tests were all positive in three cases. The onsets of symptoms appeared 7, 12 and 9 hours after administration of MINO respectively, which suggested type III allergy in terms of the latency period. In cases No. 1 and No. 3, lung tissue specimens obtained by transbronchial biopsy showed findings of mild acute eosinophilic pneumonia. The bronchoalveolar lavage fluid of case No. 3 showed eosinophilia. On diagnosing MINO-induced pneumonitis, the lymphocyte stimulation test is not always beneficial, whereas the provocation test is supposed to be a safe and sure method.

Topics: Adult; Aged; Bronchi; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Eosinophilia; Humans; Lymphocyte Activation; Male; Minocycline; Pneumonia

We treated three patients of chlamydial pneumonia with OFLX, two patients were diagnosed as psittacosis and one as pneumonia associated with TWAR strain by serologic test. Three hundred mg of OFLX was orally administered three times per day and the duration of treatment was from seven to fourteen days, and we compared the clinical effectiveness of OFLX in three cases (mild: 1, moderate: 2) with that of MINO in eleven cases (mild: 3, moderate: 8), who were administered two hundred mg of MINO two times per day orally or intravenously. We isolated C. psittaci from three pet birds including case 2 and the in vitro activity of OFLX and MINO against three strains of C. psittaci was determined. Clinical effectiveness were observed and obtained results were as follows. 1) In OFLX group, three patients judged as "Good", and in MINO, one patient as "Excellent", ten as "Good". 2) The duration of pneumonic shadow was 9.33 +/- 3.21 in OFLX group, 10.3 +/- 3.50 in MINO group, and there was no significant difference between both groups. 3) The in vitro activity of OFLX and MINO against 3 strains was 0.78-1.56 micrograms/ml and 0.025 microgram/ml, respectively. From these results, it was concluded that OFLX was considered to be a useful antichlamydial agent in the treatment of mild or moderate cases of chlamydial pneumonia.

Topics: Adolescent; Adult; Child; Chlamydophila psittaci; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Minocycline; Ofloxacin; Pneumonia; Psittacosis

Topics: Child; Female; Humans; Minocycline; Nocardia Infections; Pneumonia; Rifampin

Topics: Adolescent; Female; Humans; Minocycline; Pneumonia; Tetracyclines

Topics: Female; Humans; Middle Aged; Minocycline; Pneumonia; Pulmonary Fibrosis; Tetracyclines

Topics: Adult; Aged; Burns; Escherichia coli; Female; Humans; Infusions, Parenteral; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Penicillins; Pneumonia; Tetracyclines; Urinary Tract Infections

Topics: Animals; Bacterial Infections; Guinea Pigs; Legionnaires' Disease; Minocycline; Pneumonia; Tetracyclines

Two patients had community-acquired Acinetobacter calcoaceticus var anitratus pneumonia. Both patients were alcoholic and one was cirrhotic. One patient died and the other received two weeks of gentamicin therapy and survived. Misinterpretation of the sputum Gram stain delayed diagnosis and institution of proper therapy in both cases. In addition to organisms sensitive to penicillins such as Neisseria or Haemophilus, Acinetobacter must be considered in the differential diagnosis of community-acquired Gram-negative coccobacillary pneumonia.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Alcoholism; Amikacin; Diagnostic Errors; Drug Resistance, Microbial; Female; Gentamicins; Humans; Liver Cirrhosis; Male; Middle Aged; Minocycline; Pneumonia; Sputum; Staining and Labeling; Tobramycin

Topics: Bronchitis; Bronchopneumonia; Child; Child, Preschool; Female; Humans; Infusions, Parenteral; Male; Minocycline; Pneumonia; Tetracyclines

Topics: Chloramphenicol; Doxycycline; Erythromycin; Humans; Leg; Lincomycin; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Penicillin Resistance; Penicillins; Pneumonia; Sepsis; Streptococcus pneumoniae; Tetracycline; Thrombophlebitis

Topics: Carrier State; Cross Infection; Demeclocycline; Doxycycline; Drug Resistance, Microbial; Humans; Lincomycin; Microbial Sensitivity Tests; Minocycline; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tetracycline