Use of Monte Carlo simulation to optimize antibiotic selection for bloodstream infections caused by Enterobacteriaceae in Shandong Province, China.

The increasing rates of resistance to ß-lactams have made it more challenging for clinicians to select appropriate antibiotic treatment for bloodstream infections (BSIs) caused by suspected Enterobacteriaceae. The objective of this analysis was to determine the optimal dosage regimens of ß-lactams for treatment of BSIs based on analysis of 19,334 Enterobacteriaceae collected from blood specimens. Monte Carlo simulation using pharmacokinetic parameters of infected patients was performed to determine the probability of overall pharmacokinetic/pharmacodynamic (PK/PD) target attainment (OPTA). E. coli, K. pneumoniae, and E. cloacae were the 3 most common species. Nine of the 16 tested regimens had optimal OPTAs (>90%) for Enterobacteriaceae overall (meropenem 2g q8h, 3 h infusion; meropenem 2g q8h, 0.5h; meropenem 1g q8h, 0.5h; piperacillin/tazobactam 4.5g q8h, 3h; ceftazidime 2g q8h, 3h; imipenem 0.5g q6h, 0.5h; imipenem 1g q8h, 0.5h; piperacillin/tazobactam 3.375g q6h, 0.5h; ceftazidime 2g q8h, 0.5h). Four other regimens had sub-optimal OPTAs of 80 to 90% (piperacillin/tazobactam 4.5g q8h, 0.5h; ceftazidime 1g q8h, 0.5h; cefepime 2g q12h, 3h; and cefepime 2g q12h, 0.5h). Although there are high antibiotic MICs among Enterobacteriaceae in Shandong Province, carbapenem- , ceftazidime- and piperacillin/tazobactam- based regimens provide the optimal treatment.

Pediatric Febrile Urinary Tract Infection Caused by ESBL Producing Enterobacteriaceae Species.

BACKGROUND: Over the past decade, drug resistance pattern has worsened for many of the uropathogens due to overuse of antibiotics for empiric treatment. The burden of extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae associated urinary tract infections (UTI) has become increasingly more common, limiting treatment options among children presenting with febrile UTI. We investigated the burden and correlates of ESBL producing Enterobacteriaceae associated UTI among children and antibacterial resistance pattern. METHODS: 284 midstream urine specimens were collected using standard aseptic techniques from 284 children who were diagnosed with suspected UTI. Urine culture and bacteria isolation were performed following standard bacteriological techniques. The Kirby-Bauer disk diffusion technique and the double-disc synergy test were used to investigate antibiotic susceptibility and presence of ESBL production. RESULTS: UTI was confirmed using a positive urine culture for a relevant pathogen in 96/284 (33.8%) of the cases. Enterobacteriaceae accounted for 75% (72/96) of etiologies of UTI in children. The most frequent Enterobacteriaceae spp. were E. coli, 44.4% (32/72) and K. pneumonia, 27.8% (20/72). The overall multidrug resistance rate was 86.1% (62/72). ESBL-producers accounted for 41.7% (30/72) of the isolated Enterobacteriaceae. ESBL producing K. pneumonia and E. coli isolates accounted for 70% (14/20) and 37.5% (12/32), respectively. History of UTI in the past 1 year (adjusted odds ratio (AoR) = 0.08, 95%CI (0.01 - 0.57)) and medium family wealth index (AoR = 0.03, 95%CI (0.00 - 0.27)) protected from infection with ESBL-producing Enterobacteriaceae. Conclusion. ESBL production was more common in K. pneumonia and appeared to be a major factor contributing drug resistance UTI in children. The findings call for the need to incorporate ESBL testing in the routine clinical practice. The resistance level to commonly prescribed first-line antibiotics observed within Enterobacteriaceae was alarming calling for strengthened antimicrobial stewardship.

Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients.

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients suffering from carbapenem-resistant Enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical and microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with bloodstream infections (BSIs) was conducted. Forty-one patients that received CAZ-AVI (the CAZ-AVI group) were compared to 36 patients that received antibiotics other than CAZ-AVI (the control group). There was a significant improvement in the Sequential Organ Failure Assessment (SOFA) score on days 4 and 10 in the CAZ-AVI group compared to that in the control group (P = 0.006, and P = 0.003, respectively). Microbiological eradication was accomplished in 33/35 (94.3%) patients in the CAZ-AVI group and 21/31 (67.7%) patients in the control group (P = 0.021), and clinical cure was observed in 33/41 (80.5%) versus 19/36 (52.8%) patients (P = 0.010), respectively. The results were similar in the BSI subgroups for both outcomes (P = 0.038 and P = 0.014, respectively). The 28-day survival was 85.4% in the CAZ-AVI group and 61.1% in the control group (log-rank test = 0.035), while there were 2 and 12 relapses in the CAZ-AVI and control groups, respectively (P = 0.042). A CAZ-AVI-containing regime was an independent predictor of survival and clinical cure (odds ratio [OR] = 5.575 and P = 0.012 and OR = 5.125 and P = 0.004, respectively), as was illness severity. No significant side effects were recorded. In conclusion, a CAZ-AVI-containing regime was more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically ventilated ICU population evaluated.

Cell-length heterogeneity: a population-level solution to growth/virulence trade-offs in the plant pathogen Dickeya dadantii.

Necrotrophic plant pathogens acquire nutrients from dead plant cells, which requires the disintegration of the plant cell wall and tissue structures by the pathogen. Infected plants lose tissue integrity and functional immunity as a result, exposing the nutrient rich, decayed tissues to the environment. One challenge for the necrotrophs to successfully cause secondary infection (infection spread from an initially infected plant to the nearby uninfected plants) is to effectively utilize nutrients released from hosts towards building up a large population before other saprophytes come. In this study, we observed that the necrotrophic pathogen Dickeya dadantii exhibited heterogeneity in bacterial cell length in an isogenic population during infection of potato tuber. While some cells were regular rod-shape (<10µm), the rest elongated into filamentous cells (>10µm). Short cells tended to occur at the interface of healthy and diseased tissues, during the early stage of infection when active attacking and killing is occurring, while filamentous cells tended to form at a later stage of infection. Short cells expressed all necessary virulence factors and motility, whereas filamentous cells did not engage in virulence, were non-mobile and more sensitive to environmental stress. However, compared to the short cells, the filamentous cells displayed upregulated metabolic genes and increased growth, which may benefit the pathogens to build up a large population necessary for the secondary infection. The segregation of the two subpopulations was dependent on differential production of the alarmone guanosine tetraphosphate (ppGpp). When exposed to fresh tuber tissues or freestanding water, filamentous cells quickly transformed to short virulent cells. The pathogen adaptation of cell length heterogeneity identified in this study presents a model for how some necrotrophs balance virulence and vegetative growth to maximize fitness during infection.

In Vivo Pharmacodynamic Study of Cefiderocol, a Novel Parenteral Siderophore Cephalosporin, in Murine Thigh and Lung Infection Models.

The pharmacokinetic (PK) and pharmacodynamic (PD) parameters which correlated with the in vivo efficacy of cefiderocol were evaluated using neutropenic murine thigh and lung infection models in which the infections were caused by a variety of Gram-negative bacilli. The dose fractionation study using the thigh infection model in which the infection was caused by Pseudomonas aeruginosa showed that the cumulative percentage of a 24-h period that the free drug concentration in plasma exceeds the MIC (%fT>MIC) rather than the free peak level divided by the MIC (fCmax/MIC) and the area under the free concentration-time curve over 24 h divided by the MIC (fAUC/MIC) was the PK/PD parameter that best correlated with efficacy. The study with multiple carbapenem-resistant strains revealed that the %fT>MIC determined in iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) better reflected the in vivo efficacy of cefiderocol than the %fT>MIC determined in cation-adjusted Mueller-Hinton broth (CAMHB). The mean %fT>MIC of cefiderocol required for a 1-log10 reduction against 10 strains of Enterobacteriaceae and 3 strains of Pseudomonas aeruginosa in the thigh infection models were 73.3% and 77.2%, respectively. The mean %fT>MIC for Enterobacteriaceae, P. aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia in the lung infection model were 64.4%, 70.3%, 88.1%, and 53.9%, respectively. These results indicate that cefiderocol has potent efficacy against Gram-negative bacilli, including carbapenem-resistant strains, irrespective of the bacterial species, in neutropenic thigh and lung infection models and that the in vivo efficacy correlated with the in vitro MIC under iron-deficient conditions.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins.

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Retrospective analysis of colistin-resistant bacteria in a tertiary care centre in India.

The incidence of carbapenem-resistant Enterobacteriaceae has been steadily rising. The morbidity, mortality and financial implications of such patients are significant. We did a retrospective analysis of the case records of 11 patients who had culture report positive for pan drug-resistant (PDR) organisms. There were total 15 isolates of PDR organisms in 11 patients. These were associated with catheter-associated urinary tract infections (7), tracheitis (4), bacteraemia (2), meningitis (1) and soft-tissue infection (1). Average APACHE II score was 23.72 (range 7-36) indicating patients with multiple co-morbidities and organ dysfunction. The average length of hospital stay was 60.72 (25-123) days. The overall mortality rate was 81.81 per cent, while PDR infection-related mortality was 18.18 per cent. Strict implementation of antibiotic stewardship programme is essential to limit use and prevent abuse of colistin.

Selection of an appropriate empiric antibiotic regimen in hematogenous vertebral osteomyelitis.

BACKGROUND: Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO. METHOD: We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. RESULTS: In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). CONCLUSIONS: Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.

Bloodstream infections in hospitalized adults with dengue fever: Clinical characteristics and recommended empirical therapy.

BACKGROUND: Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed. METHODS: Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected. RESULTS: Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week. CONCLUSIONS: BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Pectobacterium and Dickeya Responsible for Potato Blackleg Disease in New York State in 2016.

Beginning in 2014, outbreaks of blackleg disease compromised potato (Solanum tuberosum) production in the northeastern United States. Disease severity was atypical for plantings with certified seed. During 2016, 43 samples with blackleg symptoms were analyzed, originating from more than 20 farms operating in New York State. A combination of techniques was employed to identify the blackleg pathogens: isolation in vitro, diagnostic PCR assays for Pectobacterium and Dickeya sp., pathogenicity assays, and DNA sequencing. Twenty-three bacterial isolates were obtained, the majority of which were designated D. dianthicola or P. parmentieri; two of the isolates were designated P. atrosepticum. All isolates were pathogenic in stem lesion and tuber soft rot assays and exhibited pectin degrading activity (pitting) in crystal violet pectate agar medium. Phylogenetic analyses of dnaX gene sequences placed all but one of the isolates into clades corresponding to D. dianthicola, P. parmentieri, or P. atrosepticum. One atypical isolate clustered with P. carotovorum subspecies. Data are consistent with the hypothesis that D. dianthicola from New York and the northeast are part of a single clade, and at least three different soft rot bacteria were associated with blackleg during 2016 in New York.

Re-exploring the value of surveillance cultures in predicting pathogens of late onset neonatal sepsis in a tertiary care hospital in southern Sri Lanka.

OBJECTIVE: To identify the validity of surveillance cultures in predicting causative organism(s) of late onset neonatal sepsis. RESULTS: Prospective analytical study was conducted from January to April 2011 at the Neonatal Intensive Care Unit, Teaching Hospital, Karapitiya, Galle, Sri Lanka. Fifty neonates were screened on admission and weekly thereafter for colonization with potential pathogens. On suspicion of infection, relevant samples were cultured and tested for antibiotic sensitivity. There were 55 episodes of clinically suspected infections including 33 nosocomial infections. One-third (17/55) of all clinically suspected infections were culture positive. Out of 55, only 33 episodes were clinically suspected nosocomial infections. Clinically suspected nosocomial infection rate was 50/1000 patient-days. Culture proven nosocomial infection rate was 13.61/1000 patient-days. Coliforms were the commonest clinical isolate (76%) and 2/3 of them produced extended spectrum ß lactamase. More than 80% of the isolates causing late onset sepsis were sensitive to carbapenems and aminoglycosides. Sensitivity, specificity, positive predictive value and negative predictive value of surveillance cultures were 77.8, 37.5, 31.8 and 81.8%, respectively. Surveillance samples can be used to predict pathogens of late-onset sepsis. Broad-spectrum antibiotics (carbapenems, aminoglycosides) are recommended as empirical therapy for late-onset neonatal sepsis.

Soft Rot Enterobacteriaceae Are Carried by a Large Range of Insect Species in Potato Fields.

Pathogenic soft rot Enterobacteriaceae (SRE) belonging to the genera Pectobacterium and Dickeya cause diseases in potato and numerous other crops. Seed potatoes are the most important source of infection, but how pathogen-free tubers initially become infected remains an enigma. Since the 1920s, insects have been hypothesized to contribute to SRE transmission. To validate this hypothesis and to map the insect species potentially involved in SRE dispersal, we have analyzed the occurrence of SRE in insects recovered from potato fields over a period of 2 years. Twenty-eight yellow sticky traps were set up in 10 potato fields throughout Norway to attract and trap insects. Total DNA recovered from over 2,000 randomly chosen trapped insects was tested for SRE, using a specific quantitative PCR (qPCR) TaqMan assay, and insects that tested positive were identified by DNA barcoding. Although the occurrence of SRE-carrying insects varied, they were found in all the tested fields. While Delia species were dominant among the insects that carried the largest amount of SRE, more than 80 other SRE-carrying insect species were identified, and they had different levels of abundance. Additionally, the occurrence of SRE in three laboratory-reared insect species was analyzed, and this suggested that SRE are natural members of some insect microbiomes, with herbivorous Delia floralis carrying more SRE than the cabbage moth (Plutella xylostella) and carnivorous green lacewing larvae (Chrysoperla carnea). In summary, the high proportion, variety, and ubiquity of insects that carried SRE show the need to address this source of the pathogens to reduce the initial infection of seed material.IMPORTANCE Soft rot Enterobacteriaceae are among the most important pathogens of a wide range of vegetables and fruits. The bacteria cause severe rots in the field and in storage, leading to considerable harvest losses. In potato, efforts to understand how soft rot bacteria infect and spread between healthy plants have been made for over a century. Early on, fly larvae were implicated in the transmission of these bacteria. This work aimed at investigating the occurrence of soft rot bacteria in insects present in potato fields and at identifying the species of these insects to better understand the potential of this suspected source of transmission. In all tested potato fields, a large proportion of insects were found to carry soft rot bacteria. This suggests a need to give more weight to the role of insects in soft rot ecology and epidemiology to design more effective pest management strategies that integrate this factor.

Pterostilbene, a Potential MCR-1 Inhibitor That Enhances the Efficacy of Polymyxin B.

We characterized the synergistic effect produced between pterostilbene and polymyxin B (fractional inhibitory concentration [FIC] index = 0.156 or 0.188) against MCR-producing Escherichia coli strains of both human and animal origins. The time-killing assays showed that either pterostilbene or polymyxin B failed to eradicate the mcr-1- and NDM-positive E. coli strain ZJ487, but the combination eliminated the strain by 1 h postinoculation. The survival rate of mice after intraperitoneal infections was significantly enhanced from 0% to 60% in the group in which combination therapy was applied.

Sieving through gut models of colonization resistance.

The development of innovative high-throughput genomics and metabolomics technologies has considerably expanded our understanding of the commensal microorganisms residing within the human body, collectively termed the microbiota. In recent years, the microbiota has been reported to have important roles in multiple aspects of human health, pathology and host-pathogen interactions. One function of commensals that has attracted particular interest is their role in protection against pathogens and pathobionts, a concept known as colonization resistance. However, pathogens are also able to sense and exploit the microbiota during infection. Therefore, obtaining a holistic understanding of colonization resistance mechanisms is essential for the development of microbiome-based and microbiome-targeting therapies for humans and animals. Achieving this is dependent on utilizing physiologically relevant animal models. In this Perspective, we discuss the colonization resistance functions of the gut microbiota and sieve through the advantages and limitations of murine models commonly used to study such mechanisms within the context of enteric bacterial infection.

Interplay of classic Exp and specific Vfm quorum sensing systems on the phenotypic features of Dickeya solani strains exhibiting different virulence levels.

Bacteria from the genus Dickeya cause severe symptoms on numerous economically important plants. Dickeya solani is the Dickeya species most frequently found on infected potato plants in Europe. D. solani strains from different countries show high genetic homogeneity, but significant differences in their virulence level. Dickeya species possess two quorum sensing (QS) mechanisms: the Exp system based on classic N-acyl-homoserine lactone (AHL) signals and a specific system depending on the production and perception of a molecule of unknown structure, Virulence Factor Modulating (VFM). To study the interplay between these two QS systems, five D. solani strains exhibiting different virulence levels were selected. Mutants were constructed by inactivating genes coding for each QS system. Double mutants were obtained by simultaneous inactivation of genes coding for both QS systems. Most of the D. solani mutants showed an attenuation of chicory maceration and a decreased production of plant cell wall-degrading enzymes (PCWDEs) and motility, but to different degrees depending on the strain. The VFM-QS system seems to regulate virulence in both D. solani and Dickeya dadantii, but the AHL-QS system has greater effects in D. solani than in D. dadantii. The inactivation of both QS systems in D. solani did not reveal any additive effect on the tested features. The inactivation of vfm genes generally has a more dominant effect relative to that of exp genes. Thus, VFM- and AHL-QS systems do not work in synergy to modulate the production of diverse virulence factors and the ability to macerate plant tissue.

Determination of Pathogens in Postoperative Wound Infection After Surgically Reduced Calcaneal Fractures and Implications for Prophylaxis and Treatment.

High rates of postoperative wound infection (POWI) have been reported after surgery for calcaneal fractures. This is a retrospective cohort study to determine the causative pathogens of these infections and subsequent treatment strategies. In addition, microbacterial growth from superficial wound swabs and deep fluid or tissue cultures were compared. Patients with a unilateral surgically treated calcaneal fracture during a 15-year period were included. Patient, fracture, and surgical characteristics were collected from the electronic medical records. An infection was categorized as deep or superficial using the Centers for Disease Control and Prevention criteria. Secondary outcomes were wound edge necrosis and wound dehiscence. The collection of culture swabs, their results, and treatment strategies were documented. Of 357 patients, 92 (26%) developed a POWI; 55 (60%) deep and 37 (40%) superficial. The most frequent causative pathogens were Enterobacteriaceae and Staphylococcus aureus. Of the 55 patients with deep infection, 31 (56%) were treated with intravenous antibiotics and surgical debridement, 2 (4%) with intravenous antibiotics, and 22 (40%) with implant removal. In 33 of 92 patients (36%) with a POWI, both superficial and deep cultures were obtained, with a microorganism not cultured from the superficial swab 13 (39%) times. In conclusion, we found that one quarter of patients with operative calcaneal fracture treatment developed a POWI, mainly caused by Enterobacteriaceae or S. aureus. Physicians should not rely on the results of superficially obtained cultures for adequate treatment of deep infection. Because the spectrum of sensitivity profiles varies greatly between hospitals and countries, we recommend empiric antibiotic treatment of both gram-positive and gram-negative microorganisms on suspicion of deep infection.

Effectiveness of Chinese Herbal Medicine Combined with Antibiotics for Extensively Drug-Resistant Enterobacteria and Nonfermentative Bacteria Infection: Real-Life Experience in a Retrospective Cohort.

Chinese herbal medicines (CHMs) have been successfully used in the treatment of infectious diseases, yet the effectiveness of CHMs for extensively drug-resistant enterobacteria (XDRE) infection remains unclear. Herein we developed a retrospective multicenter study including 766 patients with XDRE and nonfermentative bacteria (NFB) infection to investigate the effectiveness of CHMs combined with antibiotics in the treatment of XDRE infections in clinical daily practice in a cohort of patients and compared the regular antibiotics monotherapy. After 14-day treatment, the 547 patients accepted CHMs combined with antibiotics therapy indicating a more desirable effectiveness compared to the 219 patients treated with antibiotics monotherapy. The primary evaluation indexes included white blood cell count (WBC) and percentage of neutrophil (N%) in blood test. Secondary evaluation indexes consisted of body temperature, breath, heart rate, platelets, hemoglobin, red blood cell, albumin, creatinine, glucose, and 28-day survival rates. Briefly speaking, in our experience, CHMs combined with antibiotics therapy achieved more desirable effectiveness in treating XDRE infections compared with antibiotics monotherapy, and CHMs might be a potential huge resource in the field of XDRE infection management and enlighten the new antibiotics research and development. This trial is registered with ChiCTR-ORC-17011760.

Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Ceftazidime-avibactam is a novel cephalosporin-beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.

Use of tigecycline in pediatric clinical practice.

INTRODUCTION: Tigecycline, a derivative of minocycline, is an extended-spectrum antimicrobial agent. It has a restricted approval field in children and the experience of its adoption in clinical practice is reserved for cases of challenging infections. The aim of this review was to summarize evidence regarding the use of tigecycline in infants and children, focusing on the drug's clinical efficacy data and tolerability profile. Areas covered: We have conducted a literature search of the Cochrane Library, EMBASE, and MEDLINE databases, from their inception through 5 January 2017, using the following terms: tigecycline, newborn, infant, child, pediatrics, adolescent, human, clinical trial, and case report. Articles were excluded if they were redundant or not pertinent. Bibliographies of all relevant articles were also evaluated. Seventeen publications were included: 1 pharmacokinetic study, 16 case reports. In the selected publications, the patients' mean age was 4.45 years, 38.7% of children was <3 years old and favorable clinical response was achieved in 74.2% of cases. Expert commentary: Tigecycline may be a considerable option in life-threatening infections in pediatric patients. Its administration is well tolerated and has demonstrated a good clinical response in nonbacteremic patients. However, the available clinical records are limited and more studies are needed.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.