Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review

Background

Technologies and life support management have enhanced the survival of preterm infants. The immune system of newborns is immature, which contributes to the occurrence of healthcare-associated infections. The overlap of several conditions with neonatal sepsis and the difficulty of diagnosis and laboratory confirmation during this period result in a tendency to over-treat neonatal sepsis. The use of antimicrobial agents is a risk factor for multidrug-resistant bacterial infections. This work aimed to perform a systematic review of the relationship between inadequate use of antimicrobial agents and increase in neonatal sepsis related to healthcare assistance, due to bacterial resistance.

Characteristics of Enterobacter cloacae prosthetic joint infections

ObjectivesEnterobacter cloacae prosthetic joint infections (PJI) are rare and poorly documented.Patients and methodsWe conducted a retrospective and monocentric study in an orthopedic unit supporting complex bone and joint infections. Between 2012 and 2016 we collected background, clinical, biological, and microbiological data from 20 patients presenting with prosthetic joint infection and positive for E. cloacae, as well as data on their surgical and medical treatment and outcome.ResultsInfections were localized in the hip (n = 14), knee (n = 5), or ankle (n = 1). The median time between arthroplasty and septic revision was three years. Fourteen patients (70%) had undergone at least two surgeries due to previous prosthetic joint infections. The median time between the last surgery and the revision for E. cloacae infection was 31 days. Eleven patients (55%) were infected with ESBL-producing strains. The most frequently used antibiotics were carbapenems (n = 9), cefepime (n = 7), quinolones (n = 7), and fosfomycin (n = 4). The infection was cured in 15 patients (78.9%) after a 24-month follow-up. Five patients had a recurrent infection with another microorganism and four patients had a relapse of E. cloacae infection. The global success rate was 52.7% (58.3% for DAIR and 75% for DAIR + ciprofloxacin).ConclusionProsthetic joint infections due to E. cloacae usually occur early after the last prosthetic surgery, typically in patients with complex surgical and medical histories. The success rate seems to be increased when DAIR is associated with ciprofloxacin.     

The efficacy and safety of tazobactam/ceftolozane in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection

We report efficacy and safety results for a combination of a novel cephalosporin class antibiotic and a β-Lactamase inhibitor, tazobactam/ceftolozane (1:2) at a dose of 1.5 g intravenously every 8 h in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection.This study design was a nonrandomized, multicenter, open-label trial, and the treatment period was 7 days. Of 115 patients enrolled in this study, 114 received tazobactam/ceftolozane, and 90 were included in the efficacy analyses. Ninety-nine isolates (bacterial count ≥10⁵ CFU/mL) were identified by urine culture. The main baseline uropathogens were Escherichia coli (80 isolates), Klebsiella pneumoniae (8 isolates), and Proteus mirabilis (3 isolates). Of these, 13 isolates were ESBL-producers.The favorable per-patient microbiological response rate at 7 days after the final administration of tazobactam/ceftolozane was 80.7% (71/88). The response rate in uncomplicated pyelonephritis was 90.0% (36/40), complicated pyelonephritis 63.6% (14/22), and complicated cystitis 80.8% (21/26). The favorable clinical response rate was 96.6% (86/89), and composite response rate (based on microbiological and clinical response) was 80.7% (71/88). The eradication rate by uropathogen was 83.5% (66/79) in E. coli, 42.9% (3/7) in K. pneumoniae, and 100% (3/3) in P. mirabilis.The incidence of drug-related adverse events was 17.5% (20/114 patients). The most common drug-related adverse events were diarrhea and alanine aminotransferase increased in 5.3% (6/114 patients each). Drug-related serious adverse events and deaths were not observed.These results support the safety and efficacy of tazobactam/ceftolozane and suggest it will be a useful treatment for uncomplicated pyelonephritis and complicated urinary tract infection.     

Enhanced detection of carbapenemase-producing Enterobacteriaceae by an optimized phenol red assay

Screening for the detection of carbapenemase-producing bacteria still encounters issues related to workflow, limit of detection, or qualitative interpretation. We developed a spectrophotometry-based version of the Carba NP phenol red assay (Nordmann et al., 2012) in a microtiter plate format, compatible with low bacterial cell counts. We were able to detect highly active carbapenemases such as KPC and IMP in 30 min. A wider range of carbapenemases including OXA-48 were detected using higher inocula, still being competitive compared with currently available phenol red assays. Validation experiments of our test with a panel of 81 Enterobacteriaceae showed good performance with 93% of sensitivity and 92% of specificity. The compatibility of our routine-friendly protocol with automation offers great perspectives for high throughput screening in outbreak situations and/or in big laboratories.     

泌尿系感染产超广谱β-内酰胺酶大肠埃希菌的检测与耐药性

目的：了解产超广谱β-内酰胺酶（ESBL）大肠埃希菌在泌尿系感染中流行情况与耐药性,为临床合理用药提供依据。方法：采用K-B纸片扩散法,测定166株大肠埃希菌对12种抗菌药物耐药性,同时使用E-test方法确定ESBL阳性菌株。结果：166株大肠埃希菌共检出ESBL阳性菌70株（42.2%）。亚胺培南对ESBL大肠埃希菌抗菌活性最好（100%）,其次为阿米卡星（81.3%）。结论：产ESBL大肠埃希菌多重耐药严重,治疗该菌泌尿系感染,亚胺培南应作为首选药物。     

Comparative genetic analysis of the antimicrobial susceptibilities and virulence of hypermucoviscous and non-hypermucoviscous ESBL-producing Klebsiella pneumoniae in Japan

BackgroundHypermucoviscous (HMV) Klebsiella pneumoniae produces large amounts of capsular polysaccharides, leading to high mortality. Since extended spectrum beta-lactamase (ESBL)-producing HMV K. pneumoniae strains have increased in Japan, we investigated and compared the antimicrobial susceptibilities and genetic characteristics of HMV and non-HMV ESBL-producing K. pneumoniae.MethodsWe investigated 291 ESBL-producing K. pneumoniae collected between 2012 and 2018, and in them 54 HMV strains were identified and comparable 53 non-HMV strains were selected. Then, ESBL gene detection, plasmid replicon typing, and virulence gene detection were done by PCR amplification.ResultsAlmost all of the HMV K. pneumoniae strains possessed uge (98.1%), wabG (96.3%), rmpA (94.4%), iucA (79.6%), fimH (70.4%), iroB (70.4%), and peg-344 (70.4%). These genes were found less frequently in non-HMV strains (uge 20.8%, wabG 83.0%, rmpA 7.5%, iucA 3.8%, fimH 9.4%, iroB 5.7%, and peg-344 1.9%). K2 capsule type (40.7%) was most common in HMV strains. HMV strains showed higher resistance to cefepime (p = 0.001) and piperacillin/tazobactam (p = 0.005) than non-HMV strains. CTX-M-15 (75.9%, 60.4%) was the dominant ESBL type in both HMV and non-HMV strains, and the most common plasmid replicon type was IncFII (52.1%) in CTX-M-15-producing strains.ConclusionsWe found that HMV strains had more virulence genes and showed higher resistance to antibiotics than non-HMV strains. The most common capsule type was K2. CTX-M-15 was the most common type of ESBL gene in both HMV and non-HMV strains in Japan. The FII plasmid might be related to the spread of CTX-M-15 among K. pneumoniae strains.     

Assessment of prevalence and changing epidemiology of extended-spectrum β-lactamase–producing Enterobacteriaceae fecal carriers using a chromogenic medium

Five hundred fecal samples from 462 patients (68.4% ambulatory) (February–April, 2007) from Madrid (Spain) were screened for extended-spectrum β-lactamase (ESBL) producers using ceftazidime and cefotaxime (1 mg/L) MacConkey (MAC) agar plates and a chromogenic media (chromID ESBL; bioMérieux, Marcy-l'Etoile, France). bla_ESBL, qnr, aac(6′)Ib-cr, and 16S rRNA methylase genes were assessed. A prevalence of 8.2% of ESBL fecal carriers was observed (8.9% hospitalized, 7.9% nonhospitalized patients), higher than that previously observed (1991, 0.6%; 2003, 7.0%). Sensitivity, specificity, and positive and negative predicted values were 100%, 94.8%, 63%, and 100% for chromID ESBL and 87.8%, 89.8%, 43.4%, and 98.9% for MAC, respectively. ESBL distribution was as follows: CTX-M-9-group, 40% (mainly CTX-M-14); CTX-M-1-group, 26.6% (mainly CTX-M-15); SHV-type, 29% (mainly SHV-12); and TEM-type, 4.4%. These enzymes were found in pulsed-field gel electrophoresis nonclonally related Escherichia coli and Klebsiella pneumoniae isolates. Transferable quinolone resistance was confirmed in CTX-M-9 (qnrS1), CTX-M-15 [aac(6′)Ib-cr, qnrS1], and SHV-12 (qnrB7, qnrS1) producers but not 16S rRNA methylase genes. The chromID ESBL medium was reliable to screen ESBL fecal carriers with a general decrease in the laboratory workload. Time-to-time monitoring of ESBL fecal carriers is useful to ascertain current trend of ESBL epidemiology.