Coexistence of two blaKPC-2 genes in a blaNDM-1-carrying multidrug-resistant ST15 Klebsiella pneumoniae isolate recovered from cerebrospinal fluid in China.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly reported worldwide and has posed a serious challenge for public health. Here we report the complete genome sequence of a multidrug-resistant (MDR) K. pneumoniae carrying one blaNDM-1 and two copies of blaKPC-2 genes isolated from a cerebrospinal fluid specimen in China. METHODS: The minimal inhibitory concentrations (MICs) of 26 antimicrobial agents against K. pneumoniae strain KP46 were measured. The complete genome sequence of KP46 was determined using Illumina and Nanopore platforms. The derived short and long reads were assembled using Unicycler. Multilocus sequence typing (MLST), antimicrobial resistance genes, virulence genes, and plasmid replicons were predicted in silico using the BacWGSTdb server. The phylogenetic relationship between KP46 and 454 ST15 K. pneumoniae strains obtained from NCBI GenBank database was analysed based on a core genome MLST (cgMLST) strategy. RESULTS: K. pneumoniae strain KP46 was resistant to all antimicrobial agents tested, except for tigecycline, colistin, cefiderocol, and fosfomycin. The genome sequence of KP46 belonged to sequence type 15 (ST15), which contained seven circularized contigs comprising 5 674 521 bp, including one chromosome and six plasmids. Serval antimicrobial resistance genes were identified, including a blaNDM-1 gene located in a 53 096 bp IncX3 plasmid, and two copies of blaKPC-2 gene located both in a 103 807 bp IncX6 and an 88 164 bp IncFII plasmid, respectively. The most closely related strain was another ST15 strain also isolated from China with five cgMLST loci differences. CONCLUSION: We reported the first complete genome sequence of a K. pneumoniae ST15 clinical isolate coharbouring blaNDM-1 and two copies of blaKPC-2 in China. This study will provide insight into the antimicrobial resistance mechanisms and phylogeny of carbapenem-resistant ST15 K. pneumoniae.

Klebsiella pneumoniae-related invasive liver abscess syndrome complicated by purulent meningitis: a review of the literature and description of three cases.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) invasive liver abscess syndrome (ILAS) with purulent meningitis was rarely identified the mainland of China. Last winter, we received 3 cases of K. pneumoniae meningitis and all of them died in a short time. We report these cases in order to find the reason of high mortality and discuss effective effort to improve these patients' prognosis. CASE PRESENTATION: Three patients with uncontrolled diabetes developed live abscess and purulent meningitis. Upon admission, the clinical manifestations, laboratory result of blood and cerebrospinal fluid (CSF) and imaging examinations were compatible with K. pneumoniae ILAS which had metastasis infection of meningitis. Even with timely adequate antibiotic therapy and strict glycemic control, all of the patients' condition deteriorated rapidly and died in a short time. CONCLUSION: The reason of patients' poor prognosis might be the absence of liver abscess drainage, high level of CSF protein which indicates severe inflammation and unknown special but stronger virulence factors of K. pneumoniae the patients' living place Zhangjiakou. Strict glycemic control, early drainage of liver abscess and appropriate antibiotic application are recommended for treating this condition, further progress on the pathogenesis and treatment of K. pneumoniae meningitis may help patients gain a better prognosis.

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Efficacy of Ceftaroline Fosamil against Escherichia coli and Klebsiella pneumoniae strains in a rabbit meningitis model.

In this study, the efficacy of ceftaroline fosamil was compared with that of cefepime in an experimental rabbit meningitis model against two Gram-negative strains (Escherichia coli QK-9 and Klebsiella pneumoniae 1173687). The penetration of ceftaroline into inflamed and uninflamed meninges was also investigated. Both regimens were bactericidal, but ceftaroline fosamil was significantly superior to cefepime against K. pneumoniae and E. coli in this experimental rabbit meningitis model (P < 0.0007 against K. pneumoniae and P < 0.0016 against E. coli). The penetration of ceftaroline was approximately 15% into inflamed meninges and approximately 3% into uninflamed meninges.

Clinical characteristics of post-neurosurgical Klebsiella pneumoniae meningitis in adults and a clinical comparison to the spontaneous form in a Taiwanese population.

A total of 46 patients (nine post-neurosurgical, 37 spontaneous) with adult bacterial meningitis (ABM) caused by Klebsiellapneumoniae infection were included in this study. The nine patients in the post-neurosurgical K. pneumoniae ABM group (seven male, two female) had a mean age of 48.9 years. Two patients in this group also had diabetes mellitus (DM) and one had liver disease. The most common presentation of patients in post-neurosurgical K. pneumoniae ABM group was fever (nine patients), followed by altered consciousness (seven patients) and hydrocephalus (six patients). With medical and/or surgical treatment, a mortality of 22.2% (2/9) occurred. Compared to patients who had spontaneous K. pneumoniae ABM, those with the post-neurosurgical form had a lower incidence of community-acquired infection, seizure and DM, but had a higher incidence of leukocytosis, hydrocephalus, cerebrospinal fluid leak and bacterial strains with extended-spectrum beta-lactamase. Univariate analysis found these clinical differences to be statistically significant, however they were not significant on multivariate analysis. This study reveals that there are clinical differences between the post-neurosurgical and spontaneous presentations of K. pneumoniae ABM.

Dynamic changes of matrix metalloproteinase-9 in patients with Klebsiella pneumoniae meningitis.

To quantitate cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase 9 (MMP-9) in adult patients with Klebsiella pneumoniae meningitis and to correlate levels of MMP-9 with parameters of intrathecal inflammation and analyze the kinetic changes of MMP-9. In a prospective cohort study, levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP-1) concentrations were measured in the CSF of six adult patients with meningitis and 11 controls. MMP-9 and TIMP-1 were detected in all of the six patients at presentation and follow up lumbar puncture. CSF levels of MMP-9 (6.71+/-7.29 ng/ml) and TIMP-1(454.3+/-242.9 ng/ml) were higher in patients than in the control group (0.07+/-0.11 ng/ml and 27.14+/-39.34 ng/ml, respectively). Levels of MMP-9 correlated with CSF concentrations of protein, cell count and lactate. Repeated lumbar punctures showed that levels of MMP-9 decrease during clinical recovery, although the levels of MMP-9 in the CSF are variable because of the small number of cases. The relative change in gelatin zymography is comparable to the changes of MMP-9 levels found in ELISA. MMP-9 levels in CSF may be a useful tool in follow-up in patients with K. pneumoniae meningitis.

Investigation of the clonal dissemination of Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases in a neonatal ward, Sousse, Tunisia.

This study was designed to investigate the spread of extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-Kp) strains in Sousse hospital, during 7-month period by using phenotypic and genotypic markers. A total of 57 clinical isolates of ESBL-Kp, 22 strains recovered from seriously infected neonates and 35 strains recovered from colonized neonates and hospitalized in the neonatal ward of Sousse hospital, Tunisia, was subjected to 99 carbon source utilization tests, ribotyping and pulse-field gel electrophoresis (PFGE) profiles of total genomic DNA. Biotyping, ribotyping and PFGE typing showed that four different clones circulated in the neonatal ward between January and July 1997 and suggested that the epidemic strain belonged to the same biotype, ribotype and PFGE pattern, and was represented by 18 isolates from infected neonates and 28 isolates from colonized neonates. Biotyping, ribotyping and PFGE typing appeared to be reliable methods for distinguishing K. pneumoniae strains. Biotyping, which has the advantage of simplicity and rapidity, may be used as a first screening method.

Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis.

CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinal fluid (CSF) of patients with culture-proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32) and compared these results with levels of other CXC-chemokines, CXCL8- (interleukin-8) and CXCL1-related oncogene (growth-related oncogene (GRO)-alpha). Patients with bacterial meningitis had profoundly elevated CSF concentrations of all three chemokines. CXCL5 was not detectable in patients with aseptic meningitis or control subjects. CSF from patients with bacterial meningitis exerted chemotactic activity towards neutrophils, which was partially inhibited by neutralizing antibodies against CXCL5 and CXCL8, but not CXCL1. CSF from controls exerted minor chemotactic activity, which could be strongly enhanced by the addition of recombinant CXCL5, CXCL8 or CXCL1. During bacterial meningitis, CXCL5 is elevated in CSF, where it is involved in the recruitment of neutrophils to the central nervous system.

Klebsiella meningitis in adults: clinical features, prognostic factors and therapeutic outcomes.

Sixty adult Klebsiella meningitis patients have been identified at Kaohsiung Chang Gung Memorial Hospital in a period of 13 years. Most cases were associated with debilitating diseases, and devastating metastatic septic abscesses are common in diabetic patients with K. pneumoniae meningitis. Although the mortality rate has been significantly reduced in recent years, there has been an increase in nosocomial infections and the emergence of multi-antibiotic resistant strains. Significant prognostic factors include appropriate antibiotic therapy, the presence of septic shock, disseminated intravascular coagulation, and high cerebrospinal fluid protein levels and white blood cell counts. Initial empiric therapy with a third generation cephalosporin should be considered for community-acquired meningitis while antibiotics such as carbapenems should be considered as initial empiric therapy for patients with postneurosurgical meningitis. Early diagnosis and the use of appropriate antibiotics are of crucial importance.

Neonatal meningitis.

OBJECTIVE: To determine the prevalent bacterial agents of neonatal meningitis and their antibiotic susceptibility in a referral intensive care unit in Assir Central Hospital, Saudi Arabia, during the years 1993-1998. METHODS: Records of newborn infants with positive cerebrospinal fluid culture during the period were retrospectively studied. RESULTS: There were 1473 nursery admissions, of which 32 episodes of meningitis occurred amongst 31 neonates. Klebsiella pneumoniae (31%) and Serratia marcescens (21%) were the main pathogens. The incidence of concurrent septicemia among these infants was 58%. Klebsiella pneumoniae appears to dominate in both early and late onset infections. The sex incidence was equal and the mortality rate was 48%. CONCLUSION: The survey identifies Klebsiella pneumoniae and Serratia sp. as the leading bacterial agents of neonatal meningitis in our environment. The relatively high frequency of Serratia infection in the present survey appears unique as this organism is comparatively rare in other reports across the globe. No Group B Streptococcus was isolated, which is in contrast to reports obtained in Europe, America and Australia where it is the predominant organism of neonatal sepsis or meningitis. Antibiogram identified imipenem and cefotaxime as the empirical antibiotics in infants with a clinical diagnosis of neonatal sepsis in our hospital; no more conventional use of ampicillin. In view of the changing bacterial pattern of infant infection with time even in the same environment, a periodic review of this subject is advocated.

Klebsiella meningitis in Taiwan: an overview.

Klebsiella infection has been considered to be an uncommon cause of meningitis. To determine its incidence and clinical features, we reviewed the microbiologic records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted between 1981 and 1995. Klebsiella meningitis was diagnosed in 79 patients with 83 episodes. All patients had klebsiella isolated from CSF and/or blood and typical symptoms and signs of acute bacterial meningitis. Of these, 74 were over 16 years of age and 2 of the 5 children were infants. There was an increased prevalence rate of klebsiella meningitis after 1986. Of the 83 episodes, only 9 occurred between 1981 and 1986, accounting for 7.8% of 115 cases with CSF and/or blood culture-proven acute bacterial meningitis, whereas in 1987-95, there were 74 episodes accounting for 17.7% of 419 bacteriologically proven cases. K. pneumoniae accounted for 69 episodes, K. oxytoca, 11 episodes and K. ozaenae, 3 episodes. Male gender, diabetes mellitus and liver cirrhosis were commonly associated with K. pneumoniae meningitis. Neurosurgical procedures were frequently associated with K. oxytoca meningitis. All three patients with K. ozaenae meningitis had a primary disease of the nasopharyngeal pathway. The mortality rate due to K. pneumoniae was 48.5%, K. oxytoca, 10% and K. ozaenae, 0%. In patients with K. pneumoniae meningitis, poor prognostic factors included age over 60 years, diabetes mellitus, bacteremia and severe neurological deficits on the first day of treatment.

Ventriculitis caused by Klebsiella pneumoniae successfully treated with pefloxacin in a neonate.

Pefloxacin was applied to a newborn suffering from ventriculitis caused by Klebsiella pneumoniae after failure of routine antibiotics. Treatment was successful. Blood and CSF levels were high, thus documenting good CSF penetration. In addition to this case report, a review of the literature regarding seven neonates with CNS infection treated with fluoroquinolones and from whom CSF levels were obtained, is presented. In conclusion, due to their excellent activity against gram-negative microorganisms, fluoroquinolones may be considered in the treatment of neonatal CNS infections if the pathogen is resistant to routinely used antibiotics. Only limited experience is available with fluoroquinolones in pediatric patients given their potential for cartilage toxicity in young animals.

Intracranial extradural hydatid cysts: report of three cases.

Intracranial extradural hydatid cysts are a rare occurrence with unclear pathogenesis. Three different cases are reported and the postoperative courses are discussed. Of the 11 cases found in the literature, all eight cases whose sex and age were reported are men, and seven of the eight are clustered in between the second and fourth decades.

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase.

We evaluated the pharmacokinetics and therapeutic efficacies of piperacillin and tazobactam, a beta-lactamase inhibitor, given either alone or in different combinations (80:10, 200:10, and 80:25 mg/kg/h), in experimental meningitis due to a strain of Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase. Treatment was administered intravenously as a 7-h constant infusion preceded by a bolus of 20% of the total dose. The mean (+/- standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 +/- 3.9% for piperacillin given alone and 36.3 +/- 21.9% for tazobactam given alone. Combination treatment significantly magnified the concentration of either drug in CSF. Concentrations of bacteria in CSF increased throughout therapy in animals given either drug alone, even at high dosages. In animals given the combination at dosages of 80:10 and 200/10 mg/kg/h, only a suboptimal reduction of CSF bacterial titers was obtained in vivo, i.e. -0.49 +/- 0.34 and -0.73 +/- 0.49 log CFU/ml/h, respectively. An increase in the tazobactam dosage within the combination (80:25 mg/kg/h) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0.97 +/- 0.35 log CFU/ml/h). The study shows that tazobactam is able to provide effective protection against piperacillin hydrolysis by the TEM-3 enzyme within the CSF. Appropriate dosage regimens of various beta-lactam-tazobactam combinations may deserve comparative studies in experimental meningitis caused by organisms producing extended-spectrum beta-lactamases.

[Klebsiella pneumoniae capsular type 48 isolated for the first time in Turkey]. / Türkiye'de ilk defa izole edilen Klebsiella pneumoniae kapsül tip 48 susu.

Capsule type 48 Klebsiella pneumoniae strains were isolated from cerebrospinal fluid and blood specimens of 4 days old baby. This type of Klebsiella were the first observation in Turkey.