Prevertebral soft tissue swelling after anterior cervical internal fixation at different segments: a retrospective study.

Atlantoaxial segments have not been discussed in existing studies on prevertebral soft tissue (PVST) swelling after cervical operations. This study aimed to investigate the characteristics of PVST swelling after anterior cervical internal fixation at different segments. This retrospective study included patients who underwent transoral atlantoaxial reduction plate (TARP) internal fixation (Group I, n=73), C3/C4 anterior decompression and vertebral fixation (Group II, n=77), or C5/C6 anterior decompression and vertebral fixation (Group III, n=75) at our Hospital. The PVST thickness at C2, C3, and C4 segments was measured before and 3 days after the operation. Time of extubation, number of patients with postoperative re-intubation and dysphagia were collected. Results show that all patients had significant postoperative PVST thickening (all P<0.01). PVST thickening at C2, C3, and C4 was significantly greater in Group I than in Groups II and III (all P<0.01). PVST thickening at C2, C3, and C4 in Group I was 1.87 (14.12mm/7.54mm), 1.82 (12.90mm/7.07mm) and 1.71 (12.09mm/7.07mm) times of that in Group II, respectively. PVST thickening at C2, C3, and C4 in Group I was 2.66 (14.12mm/5.31mm), 1.50 (12.90mm/8.62mm) and 1.32 (12.09mm/9.18mm) times of that in Group III, respectively. The patients in Group I had significantly later postoperative extubation (Both P<0.01) than the patients in Groups II and III. None of the patients had postoperative re-intubation or dysphagia. We conclude that PVST swelling was greater in patients who underwent TARP internal fixation than in patients who underwent anterior C3/C4 or C5/C6 internal fixation. Hence, after TARP internal fixation, patients should be given proper respiratory tract management and monitoring.

Pharmacodynamics of tigecycline alone and in combination with colistin against clinical isolates of multidrug-resistant Acinetobacter baumannii in an in vitro pharmacodynamic model.

The objectives of this study, which were based on the hypothesis of mutant prevention concentration (MPC), were to compare tigecycline and colistin monotherapy and combination therapy against multidrug-resistant Acinetobacter baumannii (MDR-AB) and to identify changes in the susceptibility of the organism using an in vitro pharmacodynamic model. Human free-drug concentration profiles of colistin and tigecycline used alone and in combination were simulated against four clinical MDR-AB isolates over 24 h. Pharmacodynamic activity was measured as log10 CFU/mL and as the area under the bactericidal curve (AUBC). The minimum inhibitory concentration (MIC) for all isolates was determined in triplicate by the broth microdilution method. All isolates grew to control levels in the tigecycline and colistin monotherapy conditions, and the combination of colistin plus tigecycline 100 mg every 12 h (q12h) or 50 mg q12h achieved a greater reduction in bacterial density than colistin alone (-2.65 ± 1.73 or -2.09 ± 1.47 vs. 0.98 ± 0.64 log10 CFU/mL; P <0.01). Likewise, both combinations significantly reduced the AUBC compared with that achieved using colistin alone (106.9 ± 24.5 or 117.7 ± 23.5 vs. 168.1 ± 14.2 log10 CFU⋅h/mL; P <0.05). When tigecycline or colistin monotherapy concentrations were below MPC, tigecycline MICs increased 4-32-fold and colistin MICs increased >16-fold. No loss in susceptibility to tigecycline was found with combination therapy. A combination of tigecycline (high dose) and colistin may be an effective therapy to synergistically prevent the emergence of resistance during treatment of MDR-AB (tigecycline MIC < 2 mg/L) infections.

Evaluation of Trimethoprim/Sulfamethoxazole (SXT), Minocycline, Tigecycline, Moxifloxacin, and Ceftazidime Alone and in Combinations for SXT-Susceptible and SXT-Resistant Stenotrophomonas maltophilia by In Vitro Time-Kill Experiments.

BACKGROUND: The optimal therapy for infections caused by Stenotrophomonas maltophilia (S. maltophilia) has not yet been established. The objective of our study was to evaluate the efficacy of trimethoprim/sulfamethoxazole (SXT), minocycline, tigecycline, moxifloxacin, levofloxacin, ticarcillin-clavulanate, polymyxin E, chloramphenicol, and ceftazidime against clinical isolated S. maltophilia strains by susceptibility testing and carried out time-kill experiments in potential antimicrobials. METHODS: The agar dilution method was used to test susceptibility of nine candidate antimicrobials, and time-killing experiments were carried out to evaluate the efficacy of SXT, minocycline, tigecycline, moxifloxacin, levofloxacin, and ceftazidime both alone and in combinations at clinically relevant antimicrobial concentrations. RESULTS: The susceptibility to SXT, minocycline, tigecycline, moxifloxacin, levofloxacin, ticarcillin-clavulanate, chloramphenicol, polymyxin E, and ceftazidime were 93.8%, 95.0%, 83.8%, 80.0%, 76.3%, 76.3%, 37.5%, 22.5%, and 20.0% against 80 clinical consecutively isolated strains, respectively. Minocycline and tigecycline showed consistent active against 22 SXT-resistant strains. However, resistance rates were high in the remaining antimicrobial agents against SXT-resistant strains. In time-kill experiments, there were no synergisms in most drug combinations in time-kill experiments. SXT plus moxifloxacin displayed synergism when strains with low moxifloxacin MICs. Moxifloxacin plus Minocycline and moxifloxacin plus tigecycline displayed synergism in few strains. No antagonisms were found in these combinations. Overall, compared with single drug, the drug combinations demonstrated lower bacterial concentrations. Some combinations showed bactericidal activity. CONCLUSIONS: In S. maltophilia infections, susceptibility testing suggests that minocycline and SXT may be considered first-line therapeutic choices while tigecycline, moxifloxacin, levofloxacin, and ticarcillin-clavulanate may serve as second-line choices. Ceftazidime, colistin, and chloramphenicol show poor active against S. maltophilia. However, monotherapy is inadequate in infection management, especially in case of immunocompromised patients. Combination therapy, especially SXT plus moxifloxacin, may benefit than monotherapy in inhibiting or killing S. maltophilia.

A Monte Carlo pharmacokinetic/pharmacodynamic simulation to evaluate the efficacy of minocycline, tigecycline, moxifloxacin, and levofloxacin in the treatment of hospital-acquired pneumonia caused by Stenotrophomonas maltophilia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis

In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned "old antibiotics", polymyxins, have been reintroduced to the clinic. To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I2 method was used for heterogeneity. Nineteen controlled and six single-arm cohort studies comprising 1086 patients met the inclusion criteria. For controlled studies, no significant difference was noted for overall mortality (OR, 0.79; 95% CI, 0.58-1.08; p = 0.15), clinical response rate (OR, 1.24; 95% CI, 0.61-2.54; p = 0.55), or microbiolog- ical response rate (OR, 0.59; 95% CI, 0.26-1.36; p = 0.22) between polymyxin-treated groups and the control groups. Subgroup analyses showed that 28-day or 30-day mortality was lower in patients who received polymyxin combination therapy than in those who received monotherapy (OR, 0.36; 95% CI, 0.19-0.68; p < 0.01) and the control groups (OR, 0.49; 95% CI, 0.31-0.75; p < 0.01). The results of the six single-arm studies were in accordance with the findings of controlled studies. One controlled and two single-arm studies that evaluated the occurrence of nephrotoxicity reported a pooled incidence rate of 19.2%. Our results suggest that polymyxins may be as efficacious as other antimicrobial therapies for the treatment of carbapenem-resistant Enterobacteriaceae infection. Compared to polymyxin monotherapy, combination regimens may achieve lower 28-day or 30-day mortality. Future large-volume, well-designed randomized control trials are required to determine the role of polymyxins in treating carbapenem-resistant Enterobacteriaceae infections.

Prophylactic use of macrolide antibiotics for the prevention of chronic obstructive pulmonary disease exacerbation: a meta-analysis.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs. METHODS: We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year. RESULTS: Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01). Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049). CONCLUSIONS: Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.

Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis.

In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned "old antibiotics", polymyxins, have been reintroduced to the clinic. To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I(2) method was used for heterogeneity. Nineteen controlled and six single-arm cohort studies comprising 1086 patients met the inclusion criteria. For controlled studies, no significant difference was noted for overall mortality (OR, 0.79; 95% CI, 0.58-1.08; p=0.15), clinical response rate (OR, 1.24; 95% CI, 0.61-2.54; p=0.55), or microbiological response rate (OR, 0.59; 95% CI, 0.26-1.36; p=0.22) between polymyxin-treated groups and the control groups. Subgroup analyses showed that 28-day or 30-day mortality was lower in patients who received polymyxin combination therapy than in those who received monotherapy (OR, 0.36; 95% CI, 0.19-0.68; p<0.01) and the control groups (OR, 0.49; 95% CI, 0.31-0.75; p<0.01). The results of the six single-arm studies were in accordance with the findings of controlled studies. One controlled and two single-arm studies that evaluated the occurrence of nephrotoxicity reported a pooled incidence rate of 19.2%. Our results suggest that polymyxins may be as efficacious as other antimicrobial therapies for the treatment of carbapenem-resistant Enterobacteriaceae infection. Compared to polymyxin monotherapy, combination regimens may achieve lower 28-day or 30-day mortality. Future large-volume, well-designed randomized control trials are required to determine the role of polymyxins in treating carbapenem-resistant Enterobacteriaceae infections.

Diagnostic value of the serum galactomannan and (1, 3)-ß-D-glucan assays for invasive pulmonary aspergillosis in non-neutropenic patients.

OBJECTIVE: Galactomannan (GM) and (1, 3)-ß-D-glucan (BG) are considered useful seromarkers for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with neutropenia. However, there is still limited data on these seromarkers for testing non-neutropenic patients who are at the risk of IPA. The aim of this study was to evaluate the value of these two serum antigen assays for the early diagnosis of IPA in patients without neutropenia. METHODS: Between January 2011 and December 2012, 97 patients with suspected IPA admitted to the department of respiratory diseases and the respiratory intensive care unit were prospectively monitored. Serum GM and BG assays were performed before the patients received antifungal therapy. RESULTS: Patients were classified as proven IPA (n=11), probable IPA (n=16), possible IPA (n=4), or non-IPA (n=66). The most common underlying disease of patients with IPA was chronic obstructive pulmonary disease (18.5%), and 22.2% patients with IPA had no known diseases. The sensitivities, specificities, and positive and negative predictive values of the GM and BG assays and at least one positive on both assays were 40.7%/89.4%/61.1%/78.7%, 48.1%/78.8%/48.1%/78.8%, and 70.4%/75.8%/54.3%/86.2%, respectively. CONCLUSION: Compared with the testing of neutropenic patients, the serum GM or BG assay alone was less useful for the diagnosis of IPA in non-neutropenic patients. However, at least one positive result of the two serum assays appeared to be useful in the diagnosis of IPA in non-neutropenic patients.

Effect of proton pump inhibitors on in vitro activity of tigecycline against several common clinical pathogens.

In this study, we evaluated the effect of proton pump inhibitors (PPIs) on in vitro antimicrobial activity of tigecycline against several species of clinical pathogens. Clinical non-duplicate isolates of Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis and three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia and Enterobacter cloacae) were collected from a tertiary hospital and their MICs of tigecycline alone and in combination with PPIs (omeprazole, lansoprazole and pantoprazole) were determined. With one randomly selected isolate of each bacterial species, an in vitro time-kill study was performed for the confirmation of the effect of PPIs on tigecycline activity. The MIC changes after PPIs addition correlated with the PPIs concentrations in the test media. Compared with tigecycline alone, the addition of 5 mg/L PPIs could increase the MICs of tigecycline by 0 to 2-fold and the addition of 50 mg/L PPIs could increase the MICs of tigecycline by 4 to >128-fold. The time-kill study confirmed that the addition of PPIs could affect the in vitro activity of tigecycline. Even at low concentration (5 mg/L) of omeprazole and pantoprazole, antagonistic effect could be observed in E. cloacae and E. faecalis strains. We conclude that In vitro activity of tigecycline can be influenced by the presence of PPIs in a concentration-dependent manner.

In vitro effects of tigecycline in combination with colistin (polymyxin E) and sulbactam against multidrug-resistant Acinetobacter baumannii.

The lack of active antimicrobial agents against multidrug-resistant (MDR) Acinetobacter baumannii has posed great threat to the public health. Combination therapies with antibiotics owning different antimicrobial mechanisms have been proposed as good options for treating MDR A. baumannii infections. This study was aimed to investigate the in vitro effects of tigecycline in combination with colistin and sulbactam against MDR A. baumannii. A total of 70 strains from two hospitals in China were examined in the study. The checkerboard method was used for determining synergistic activity of different antibiotic combinations. Tigecycline/colistin combination displayed synergistic and partial synergistic activity in 24.3% of the isolates, whereas the tigecycline/sulbactam combination showed synergistic and partial synergistic activity in 64.3% of the isolates. Neither of the combinations showed antagonism in this study. In addition, for evaluating the ability of combinations on resistance prevention, mutant prevention concentrations (MPCs) of tigecycline, colistin, sulbactam alone and tigecycline in combination with colistin and sulbactam were studied against MDR A. baumannii. Compared with tigecycline used alone, combination therapies could achieve lower MPCs of tigecycline. However, when the MPCs of dual-drug therapy were in conjunction with clinical pharmacokinetic profiles, combinations may not strictly curb the occurrence of resistance at current dosage regimen. In summary, this study suggested that combination therapy was a good option for treating MDR A. baumannii infections. But the finding that combination with these drugs at current dosage regimen may not prevent emergence of resistance warranted further studies on dosage of combined antibiotics required for achieving resistance prevention.