Topical Antibiotic Prophylaxis for Preventing Surgical Site Infections of Clean Wounds: A Systematic Review and Meta-Analysis.

Background: Topical antibiotic agents are not generally indicated for preventing of surgical site infections (SSIs) in clean incisions, and the drug concentrations that should be delivered to local incision sites remain uncertain. The aim of this study was to critically assess the efficacy of topical antibiotic agents in comparison with non-antibiotic agents for preventing SSIs in clean incisions by performing a systematic review and meta-analysis. Methods: We conducted a search of literature in PubMed, Embase, and Cochrane Databases and included randomized controlled trials (RCTs) on topical antibiotic use for patients with clean post-surgical incisions. The primary outcome was the incidence of SSI, presented as the event rate. Eleven RCTs were included. Results: Using random-effects modeling, the pooled risk ratio (RR) of developing a post-surgical incisions infection was 0.83 (95% confidence interval [CI], 0.61-1.16; I2, 0%). In subgroup analyses, no reductions in SSI were observed when topical antibiotic agents were used to treat incisions due to spinal (RR, 0.75; 95% CI, 0.40-1.38; I2, 0%), orthopedic (RR, 0.69; 95% CI, 0.37-1.29; I2, 0%), dermatologic (RR, 0.77; 95% CI, 0.39-1.55; I2, 65%), or cardiothoracic surgeries (RR, 1.31; 95% CI, 0.83-2.06; I2: 0%). The incidence of SSI across different operative phases did not differ for the application of topical antibiotic agents compared with non-antibiotic agents (RR, 0.80; 95% CI, 0.56-1.14; I2, 0%). Conclusions: The results of this meta-analysis show that topical antibiotic agents provide no clinical benefit for preventing SSI in clean incisions.

Molecular characteristics and in vitro effects of antimicrobial combinations on planktonic and biofilm forms of Elizabethkingia anophelis.

OBJECTIVES: To investigate the in vitro activity of antibiotics against clinical Elizabethkingia anophelis isolates and to find a suitable antibiotic combination with synergistic effects to combat antibiotic-resistant E. anophelis and its associated biofilm. METHODS: E. anophelis isolates were identified by 16S rRNA sequencing; 30 strains with different pulsotypes were identified and the MIC, antibiotic resistance mechanism, antibiotic combination activity and killing effects of antimicrobial agents on biofilms of these strains were determined. RESULTS: All E. anophelis isolates were susceptible to minocycline and cefoperazone/sulbactam (1:1). More than 90% of clinical isolates were susceptible to cefoperazone/sulbactam (1:0.5), piperacillin/tazobactam and rifampicin. Some novel mutations, such as gyrA G81D, parE D585N and parC P134T, that have never been reported before, were identified. The synergistic effect was most prominent for the combination of minocycline and rifampicin, with 93.3% of their FIC index values ≤0.5, and no antagonism was observed using the chequerboard method. This synergistic effect between minocycline and rifampicin was also observed using time-killing methods for clinical E. anophelis isolates at both normal inoculum and high inoculum. Twenty-nine isolates tested positive for biofilm formation. Minocycline remained active against biofilm-embedded and biofilm-released planktonic E. anophelis cells; however, the enhanced effect of minocycline by adding rifampicin was only observed at 24 h (not at 72 and 120 h). CONCLUSIONS: Although E. anophelis was resistant to many antibiotics and could exhibit biofilm formation, minocycline showed potent in vitro activity against this pathogen and its associated biofilm.

The impact of inoculum size on the activity of cefoperazone-sulbactam against multidrug resistant organisms.

OBJECTIVES: This study aims to assess the in vitro activity of cefoperazone alone and different cefoperazone-sulbactam ratios against different inoculum sizes of multidrug resistant organisms. METHODS: Minimum inhibitory concentrations (MICs) of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1:1 and 2:1 against a normal inoculum size of 5 × 105 CFU/ml and a high inoculum size of 5 × 107 CFU/ml were measured. RESULTS: Each 33 isolates of extended-spectrum ß-lactamases (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were collected. After the addition of sulbactam at a 1:1 ratio, most MIC50 and MIC90 values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio (all P < 0.05). For ESBL-producing E. coli, the susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 97.0 to 87.9% and 90.9 to 60.6%, for normal to high inoculum, respectively. For ESBL-producing K. pneumoniae, both susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 75.8%, and 63.6% at normal inoculum to 51.5% and 42.4% at high inoculum. CONCLUSIONS: Cefoperazone-sulbactam at a 1:1 ratio has greater in vitro activity against most multidrug resistant organisms than cefoperazone-sulbactam at a 2:1 ratio. Such combinations were not influenced by the inoculum size of ESBL-producing E. coli and K. pneumoniae and could be a therapeutic option for treating severe infections.

Use of the QuantiFERON-TB Gold In-Tube Test in the Diagnosis and Monitoring of Treatment Efficacy in Active Pulmonary Tuberculosis.

The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.

The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development.

Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

Clinical Significance of Community- and Healthcare-Acquired Carbapenem-Resistant Enterobacteriaceae Isolates.

This study was conducted to investigate the clinical significance, manifestations, microbiological characteristics and outcomes of carbapenem-resistant Enterobacteriaceae (CRE) isolates, and compare the clinical features of community- and healthcare-acquired CRE isolates. A total of 78 patients were identified to have CRE. Klebsiella pneumoniae was the most common pathogens (n = 42, 53.8%), followed by Enterobacter cloacae (n = 24, 30.8%), and Escherichia coli (n = 11, 14.1%). Most of the patients acquired CRE from healthcare settings (n = 55, 70.5%), and other cases got CRE from community settings (n = 23, 29.5%). Nine cases (11.5%) were classified as CRE colonization. Among the remaining 69 cases of CRE infections, pneumonia (n = 28, 40.6%) was the most common type of infections, followed by urinary tract infection (n = 24, 34.8%), and intra-abdominal infection (n = 16, 23.2%). The patients acquired CRE from community settings were more likely to be elderly, female, and had more urinary tract infections than from healthcare settings. In contrast, the patients acquired CRE from healthcare settings had more intra-abdominal infections, intra-abdominal surgery, and presence of indwelling device than from community settings. In conclusion, community-acquired CRE are not rare, and their associated clinical presentations are different from healthcare-acquired CRE.

Correlation between antibiotic consumption and carbapenem-resistant Acinetobacter baumannii causing health care-associated infections at a hospital from 2005 to 2010.

BACKGROUND/PURPOSE: This study investigated the correlation between antibiotic consumption and the incidence of health care-associated infections (HCAIs) caused by imipenem-resistant Acinetobacter baumannii (IRAB) at a hospital in Taiwan from 2005 to 2010. METHODS: Data on annual consumption (defined daily dose per 1000 patient-days) of extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, carbapenems, aminoglycosides, and fluoroquinolones from 2005 to 2010 were analyzed. Yearly aggregated data on the number of nonduplicate clinical IRAB isolates causing HCAI were collected. The incidence rates of HCAI caused by IRAB were defined as the number of patients infected with IRAB per 1000 inpatient-days. RESULTS: The trend of total consumption (defined daily dose per 1000 patient-days) of extended-spectrum cephalosporins, carbapenems, and fluoroquinolones was significantly increased, but the use of aminoglycosides decreased during 2005 to 2010. During the same period, the incidence of HCAI caused by IRAB gradually increased. The consumptions of carbapenems and fluoroquinolones were positively correlated with the incidence of HCAI caused by IRAB. There was no significant association between the use of extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, and aminoglycosides and the incidence of HCAI caused by IRAB. CONCLUSION: The increasing use of carbapenems and fluoroquinolones was associated with the increasing incidence of HCAI caused by IRAB.

The impact of inadequate terminal disinfection on an outbreak of imipenem-resistant Acinetobacter baumannii in an intensive care unit.

BACKGROUND: This study was conducted to investigate an outbreak caused by imipenem-resistant Acinetobacter baumannii (IRAB) in a medical intensive care unit (ICU) in a regional hospital. METHODS: In response to an IRAB outbreak from October 2012 to February 2013, we developed several infection control measures, including an extensive review process of environmental cleaning and disinfection, and used molecular methods to identify each clinical and environmental IRAB isolate. RESULTS: During this five-month period, 22 patients were colonized with IRAB and 18 patients had IRAB infections. The in-hospital mortality rate was significantly higher among patients with infections rather than colonizations (44.4% vs 9.1%, p = 0.028). Additionally, nine environmental specimens, including five specimens collected after terminal disinfection, were positive for IRAB. 12 environmental isolates and 28 of 36 available clinical isolates belonged to one unique pulsotype A, which was confirmed by molecular methods. We found the concentration of disinfectant, 0.08% sodium hypochlorite, was inadequate. After correcting the environmental cleansing methods, the surveillance study showed no further IRAB isolates on the control panel surfaces of the medical equipment or in patients in the ICU. Additionally, an in vitro study of IRAB immersed in different concentrations of sodium hypochlorite showed that 0.5% sodium hypochlorite eradicates IRAB after 30 seconds of inoculation, but 0.08% sodium hypochlorite only reduces the bacterial load. CONCLUSIONS: This study highlights the importance of the preparation of disinfectants to adequately achieve environmental disinfection in the control of IRAB outbreaks in the ICU.

Acid aspiration provokes the pneumonia caused by multidrug-resistant Acinetobacter baumannii in BALB/c mice.

OBJECTIVE: To determine whether acid aspiration provokes the development of multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia in its host. METHODS: Groups of mice were inoculated intratracheally (IT) with 50 µl of 0.1N HCl and 1 × 10(8) colony-forming units (CFU) Ab396 (A+Ab group), or 50 µl of 0.1N HCl and 20 µl of 0.9% saline (A+S group), or 20 µl of 0.9% saline and 1 × 10(8) CFU of Ab396 (S+Ab group), or 50 µl of 0.9% saline and 20 µl of 0.9% saline (S+S group). Cytokines, bacterial loads in the bronchoalveolar lavage fluid (BALF), lung permeability, histopathology of the lungs, and survival rates were evaluated. RESULTS: Only the A+Ab mice developed extensive Ab396 pneumonia and had significantly elevated bacterial loads, increased lung leakage, and lower levels of tumor necrosis factor alpha (TNF-α) compared with the other three groups (p<0.05, Mann-Whitney U-test). Moreover, a strong synergistic effect (p<0.05, two-way analysis of variance) was observed between the acid induction and Ab396 infection, resulting in lung injury and an unfavorable survival outcome. CONCLUSIONS: Lung injury caused by acid aspiration provoked secondary MDRAB pneumonia; also synergistic effects between acid aspiration and Ab396 infection resulted in a detrimental outcome in the infected mice.

Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.

BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.

In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus.

BACKGROUND AND PURPOSE: Little is known about the possible synergism of baicalein, a bioactive flavone of Scutellariae radix (a Chinese herb), when used in conjunction with other antimicrobial agents against vancomycin-resistant Enterococcus (VRE). This in vitro study examined the possible synergism of the combination of baicalein and gentamicin against VRE. METHODS: Minimal inhibitory concentrations (MICs) of baicalein as well as gentamicin were determined against 39 clinical isolates of VRE by the agar dilution method. Synergistic activities were determined using the checkerboard method based on the fractional inhibitory concentration indices and also the time-kill method. Further time-kill studies were conducted with these two agents against one randomly chosen clinical isolate, VRE-096. RESULTS: Minimal concentrations inhibiting 50% (MIC(50)) and 90% (MIC(90)) of isolates for baicalein and gentamicin were all >256 microg/mL. Synergism between baicalein and gentamicin was demonstrated against four clinical isolates of VRE (VRE-70, VRE-940, VRE-096 and VRE-721). When approximately 5 x 10(5) colony-forming units/mL of VRE-096 was incubated with both baicalein at a concentration of 32 microg/mL (1/8 x MIC) and gentamicin at a concentration of 128 microg/mL (1/2 x MIC), there was an inhibitory effect against VRE that persisted for 48 h. At 48 h, the combination of baicalein and gentamicin at these respective concentrations resulted in a reduction of growth by approximately 2 orders of magnitude compared to that for the starting inoculum and by 3 orders of magnitude compared to that for baicalein alone, the more active single agent. CONCLUSION: This study demonstrated that baicalein and gentamicin can act synergistically in inhibiting VRE in vitro.

Opportunistic infections in adults with acquired immunodeficiency syndrome: a comparison of clinical and autopsy findings.

BACKGROUND AND PURPOSE: Many opportunistic infections causing death in acquired immunodeficiency syndrome (AIDS) patients are often not diagnosed prior to death. The objective of this study was to compare the premortem and postmortem diagnoses of opportunistic infections and tumors among 15 AIDS patients treated in a hospital in southern Taiwan. METHODS: Total autopsy (brain, chest and abdominal cavity) was performed in 2 patients, and partial autopsy in 13. RESULTS: Pneumocystis carinii pneumonia, candidiasis, lymphoma, Kaposi's sarcoma, toxoplasmosis and salmonellosis were more commonly diagnosed before death than at autopsy. By contrast, cytomegalovirus (CMV) infections and herpes simplex virus or varicella-zoster virus infections were more frequently diagnosed at postmortem examinations than prior to death. CONCLUSIONS: In conclusion, this study found substantial discrepancies between autopsy findings and premortem clinical diagnoses in AIDS patients, especially for CMV infection.