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Petrositis is a rare and severe complication of acute otitis media and mastoiditis. Although the extension of the inflammatory process from the petrous apex to the adjacent Meckel cave can lead to trigeminal pain, an irritation of the trigeminal nerve roots resulting in acute or chronic hyperactivity of masticatory muscles has never been reported. We report here the unusual case of an 86-year-old man who presented with a handicapping myofascial pain and dysfunction syndrome of the right temporal muscle as a heralding manifestation of an unusual form of petrositis. The patient progressively developed a retropharyngeal abscess, a right sphenoid sinusitis, and fatal meningitis. This case demonstrated that (1) myofascial pain and dysfunction syndrome that does not respond to conventional treatments may suggest an unusual etiology and warrant further medical investigations and a detailed medical history and that (2) petrositis can manifest itself with atypical clinical symptoms and radiologic signs. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter baumannii is one of major causative agents of severe, life-threatening hospital infections (HIs), especially in intensive care units (ICUs). Our aim was to discover the risk factors associated with the emergence of HIs caused by carbapenem-resistant Acinetobacter baumannii (CRAB), as well as those associated with death in patients who suffer from such infections. Methodology: A prospective cohort study was conducted over a five-year period in the medical-surgical ICU of the Clinical Centre in Kragujevac, Serbia. The study group comprised patients who had HIs caused by CRAB, while the control group comprised patients infected with carbapenem-sensitive Acinetobacter baumannii. Results: In total, 137 patients developed HIs caused by Acinetobacter baumannii. The mean age of the patients was 59.65 ± 16.08 years, and 99 (72.26%) of them were males. In 95 patients (69.35%), the infection was caused by CRAB. There were six independent risk factors for CRAB infections: use of mechanical ventilation, previous stay in another department, stay in ICU for more than a month, and previous use of carbapenems, aminoglycosides, and metronidazole. Three independent risk factors were found for death in patients with HIs caused by CRAB: use of mechanical ventilation, previous stay in another department, and previous use of carbapenems. Conclusions: The results of this study can be helpful when identifying patients with risk of HIs caused by CRAB and in planning preventive measures. Modification of known risk factors and appropriate institutional policy of antibiotic utilization are important measures that may decrease the incidence and mortality of such infections. [ABSTRACT FROM AUTHOR]

Objectives: Colistin remains a last-line treatment for MDR Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against MDR strains. In order to understand the bacterial responses to these antibiotics, we analysed the transcriptome of A. baumannii following exposure to each. Methods: RNA sequencing was employed to determine changes in the transcriptome following treatment with colistin and doripenem, both alone and in combination, using an in vitro pharmacokinetics (PK)/pharmacodynamics model to mimic the PK of both antibiotics in patients. Results: After treatment with colistin (continuous infusion at 2 mg/L), >400 differentially regulated genes were identified, including many associated with outer membrane biogenesis, fatty acid metabolism and phospholipid trafficking. No genes were differentially expressed following treatment with doripenem (Cmax 25 mg/L, t1/2 1.5 h) for 15 min, but 45 genes were identified as differentially expressed after 1 h of growth under this condition. Treatment of A. baumannii with both colistin and doripenem together for 1 h resulted in >450 genes being identified as differentially expressed. More than 70% of these gene expression changes were also observed following colistin treatment alone. Conclusions: These data suggest that colistin causes gross damage to the outer membrane, facilitates lipid exchange between the inner and outer membrane and alters the normal asymmetric outer membrane composition. The transcriptional response to colistin was highly similar to that observed for an LPS-deficient strain, indicating that many of the observed changes are responses to outer membrane instability resulting from LPS loss. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to identify carbapenem-resistant organisms using routinely collected local microbiology data and describe the epidemiology of carbapenem resistance in two London teaching hospitals. Methods: Data on inpatients infected or colonized with Gram-negative organisms between March 2009 and February 2012 were extracted. A computer algorithm was developed incorporating internationally recognized criteria to distinguish carbapenem-resistant organisms. Multivariable analysis was conducted to identify factors associated with infection or colonization with carbapenem-resistant organisms. Binomial regression was performed to detect changes in resistance trends over time. Results: Yearly incidence of carbapenem resistance was observed to be increasing, with significant increasing trends in Acinetobacter baumannii (47.1% in 2009-10 to 77.2% in 2011-12; P<0.001) and Enterobacter spp. (2.2% in 2009-10 to 11.5% in 2011-12; P<0.001). Single-variable and multivariable analysis demonstrated differences in the proportion of carbapenem-resistant isolates across all variables investigated, including age, sex and clinical specialty; in the latter organism-specific niches were identified. Patients in the youngest age group (16-24 years old) had the highest odds of being infected or colonized with carbapenem-resistant isolates of Escherichia coli, Klebsiella spp. or Pseudomonas aeruginosa. Furthermore, proportions of carbapenem-resistant organisms differed between the hospitals. Conclusions: Carbapenem resistance is an emerging problem within the UK inpatient healthcare setting. This is not an issue confined to the Enterobacteriaceae and fine-resolution surveillance is needed to identify at-risk groups. Regular analysis of routinely collected data can provide insight into the evolving carbapenem-resistance threat, with the ability to inform efforts to prevent the spread of resistance. [ABSTRACT FROM AUTHOR]

Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important healthcare-associated pathogen. We evaluated the impact of CRKP strain type and treatment on outcomes of patients with CRKP bacteriuria. Patients and Methods: Physician-diagnosed CRKP urinary tract infection (UTI)--defined as those patients who received directed treatment for CRKP bacteriuria--was studied in the multicentre, prospective Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRaCKle) cohort. Strain typing by repetitive extragenic palindromic PCR (rep-PCR) was performed. Outcomes were classified as failure, indeterminate or success. Univariate and multivariate ordinal analyses to evaluate the associations between outcome, treatment and strain type were followed by binomial analyses. Results: One-hundred-and-fifty-seven patients with physician-diagnosed CRKP UTI were included. After adjustment for CDC/National Healthcare Safety Network (NHSN)-defined UTI, critical illness and receipt of more than one active antibiotic, patients treated with aminoglycosides were less likely to fail therapy [adjusted OR (aOR) for failure 0.34, 95% CI 0.15-0.73, P=0.0049]. In contrast, patients treated with tigecycline were more likely to fail therapy (aOR for failure 2.29, 95% CI 1.03-5.13, P=0.0425). Strain type data were analysed for 55 patients. The predominant clades were ST258A (n=18, 33%) and ST258B (n=26, 47%). After adjustment for CDC/NHSN-defined UTI and use of tigecycline and aminoglycosides, infection with strain type ST258A was associated with clinical outcome in ordinal analysis (P=0.0343). In multivariate binomial models, strain type ST258A was associated with clinical failure (aOR for failure 5.82, 95% CI 1.47-28.50, P=0.0113). Conclusions In this nested cohort study of physician-diagnosed CRKP UTI, both choice of treatment and CRKP strain type appeared to impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives Antimicrobial stewardship programs ( ASPs) promote the judicious use of antimicrobials by limiting inappropriate use. This article evaluates the impact of a prospective-audit-and-feedback ASP implementation on the appropriate utilization of carbapenems in a tertiary pediatrics and obstetrics/gynecology hospital in Singapore ( KKH) after the establishment of an ASP in July 2011. Methods This was a prospective, single-center, pre-post intervention study designed to analyze the appropriate prescribing of carbapenems pre- ASP (October 2009 to June 2011) and post- ASP (July 2011 to December 2013). Utilization of carbapenems was evaluated by daily defined doses ( DDDs), days of therapy ( DOTs), prescriptions, as well as cost per 100 patient-days pre- ASP and post- ASP using a segmented regression of interrupted time series analysis. Results Of 404 prescriptions for carbapenems reviewed post- ASP, 70.3% were appropriate compared with those prescribed pre- ASP (55.9%; p=0.027). Reasons for inappropriate prescribing included inappropriate choice (36.1%) and duration (31.3%). A total of 61.2% of the interventions (213 of 348) were accepted. For pediatrics, there was a significant decrease in DDDs per 100 patient-days by 55.6% from a baseline of 0.9-0.4 (p=0.013) post- ASP and a reduction in DOTs per 100 patient-days by 46.7% from a baseline of 1.5-0.8 (p=0.06) post- ASP without significant changes in prescription rates. Pediatrics utilization cost increased from a pre- ASP mean of $175 per 100 patient-days to a peak of $238 (p<0.001) and decreased significantly post- ASP to a mean of $149 (p=0.01). For obstetrics/gynecology, there were no significant changes in DDDs (0.3 vs 0.3, p=0.99), DOTs (0.2 vs 0.3, p=0.36), prescriptions (0.03 vs 0.04, p=0.38), or cost ($45 vs $52, p=0.63) per 100 patient-days pre- versus post- ASP. Conclusions ASPs improved the appropriateness of carbapenems prescribing overall and reduced utilization in pediatrics. Identification of areas of inappropriate prescribing will be valuable in guiding future ASP efforts. [ABSTRACT FROM AUTHOR]

Objectives To identify the mechanism(s) underlying cefotaxime resistance in 118 of 21 641 (0.55%) non-typhoidal Salmonella enterica isolates collected from humans throughout England and Wales from January 2010 to September 2012. Methods Non-duplicate isolates (n = 118) resistant to cefotaxime (MICs >1 mg/L) were screened by PCR for genes encoding CTX-M extended-spectrum β-lactamases (ESBLs) and associated ISEcp1-like elements, and for genes encoding acquired AmpC, SHV, TEM, VEB, PER and GES β-lactamases. Sequencing was used to identify specific alleles in selected isolates. Carbapenem resistance was sought by ertapenem disc screening. Results Seventy-nine isolates (0.37% of all referred S. enterica) produced ESBLs, 37 isolates (0.17%) produced CMY-type AmpC enzymes, and 1 isolate had both enzyme types; the mechanism of cefotaxime resistance in 3 isolates could not be identified. Group 1 CTX-M genes were identified in 57 isolates belonging to 22 serotypes, with CTX-M-1 (n = 11), -15 (n = 9) and -55/57 (n = 8) the most prevalent alleles among the 29 (51%) investigated. CTX-M-2 (n = 5), -14 (n = 5), -8 (n = 1) and -65 (n = 1) were also identified. TEM-52 was identified in two isolates and SHV-12 in seven isolates. There was no evidence of carbapenem resistance. ESBL and AmpC genes were detected in both domestically acquired and travel-associated salmonellae. Eighty-nine isolates (75%) were multidrug resistant (resistant to at least three antimicrobial classes) and 42 (36%) had decreased susceptibility to ciprofloxacin (MICs 0.25–1 mg/L), with a further 13 (11%) isolates resistant (MICs >1 mg/L). Conclusions The prevalence of CTX-M and acquired AmpC genes in human non-typhoidal S. enterica from England and Wales is still low, but has increased from 0.03% in 2001–03 to 0.49% in 2010–12. Resistance to third-generation cephalosporins requires monitoring as it may reduce therapeutic options. [ABSTRACT FROM PUBLISHER]

Even though Gemella morbillorum infection (GMI) is rare in humans, it may, nevertheless, cause endocarditis, meningitis, brain abscess, pleural empyema, nephritis, mediastinitis, and -occasionally - liver abscess. We are describing the case of a 64-year-old Caucasian male admitted with fever and abdominal pain. Laboratory parameters revealed inflammation signs, and instrumental examinations showed the presence of diverticula in the ascending colon. Abdominal ultrasound (US) and computer tomography (CT) showed two focal lesions in the right liver lobe. One had the characteristics of a simple cyst; the second was hypoechoic with a low density area, possibly containing necrotic material. USguided needle biopsy was found negative for neoplastic cells, showing purulent infiltrate. Pus culture was found positive for GMI. Systemic antibiotic therapy, coupled with repeated USguided needle aspiration, induced the resolution of the hepatic abscess. Few cases have been reported of hepatic abscess caused by GMI in immunocompetent non-cirrhotic subjects. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance in Pseudomonas aeruginosa has been increasing in recent years. The aim of this study was to investigate the relationship between antimicrobial resistance and class I integron in P. aeruginosa isolated from clinical specimens in Yazd city. Materials and Methods: This cross-sectional study was carried out on 144 P. aeruginosa strains from April 2012 to April 2013. All clinical samples were initially identified by the biochemical method and the antibiotic resistance test was performed using the disc diffusion method according to CLSI recommendations. PCR was carried out for the detection of class I integron. Results: Seventy-nine (54.9%) out of 144 patients were male with mean age of 34.9+22.7 years. Resistance rates to various antibiotics were as follows: gentamicin (63.2%), imipenem (62.5%), amikacin (58.3%), ceftazidime (56.9%), ticarcillin (55.6%), tobramycin (55.6%), piperacillin (54.9%) and ciprofloxacin (48.6%) and 75.3% of the isolates were detected as multi-drug resistant. PCR results showed that 119 (82.6%) P. aeruginosa isolates carried class I integron. Conclusion: Class I integrons are commonly found in P. aeruginosa isolated from the clinical samples. Therefore, the transfer of antibiotic resistance genes is often related to these integrons and the contribution of integrons in antibiotic resistance should be evaluated. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a major cause of healthcare-associated infection, often affecting critically ill patients. The purpose of the study was to examine the associations of carbapenem resistance with mortality, length of hospital stay and hospital costs among patients infected with A. baumannii in intensive-care units ( ICUs) in Colombia. A prospective, multicentre cohort study was conducted among 165 patients with A. baumannii infection admitted to ICUs between April 2006 and April 2010. Patients with carbapenem-resistant A. baumannii had higher risk of 30-day mortality than patients with carbapenem-susceptible A. baumannii in the univariate analysis (unadjusted hazard ratio = 2.12; 95% CI 1.14-3.95; p 0.018). However, carbapenem resistance was not significantly associated with risk of mortality (adjusted hazard ratio = 1.45; 95% CI 0.74-2.87; p 0.28) after adjusting for APACHE II score and other confounding factors. We did not find a significant difference in length of stay in ICU after the onset of infection between the two groups in the multivariate analysis (adjusted mean = 13.1 days versus 10.5 days; p 0.14). The average total cost of hospitalization among patients with carbapenem-resistant A. baumannii was significantly higher than that among patients with carbapenem-susceptible A. baumannii in the multivariate analysis (adjusted cost; US$ 11 359 versus US$ 7049; p <0.001). Carbapenem resistance was not significantly associated with mortality, though we are unable to rule out an increased risk due to the limited sample size. Carbapenem resistance was associated with an additional cost of hospitalization. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is arguably the most serious health-related issue of the current time. This is even more so with carbapenem-resistant Enterobacteriaceae, for such microorganisms are resistant to the carbapenems (the 'antibiotics of last resort'). One of the most important considerations is in the detection of bacteria that carry the carbapenem-resistant gene. For this, molecular-based phenotypic and genetic-based polymerase chain reaction (PCR) methods are available. In contrast to phenotypic methods, molecular-genetic techniques, such as PCR, are considered to have the potential for improved detection of carbapenem-resistant genes by virtue of specificity, accuracy and rapidity. The tendency in PCR techniques is to develop towards the real-time systems equipped with multiplexing functionality. However, as shown in our study, standard PCR with electrophoresis detection continues widely to be used for the detection and identification of the carbapenemase gene. Therefore, despite progress in PCR technology, methods deployed for the detection of serious hospital-acquired infections around the world are arguably neither the most accurate nor the most efficient. This issue is of concern for pharmaceutical scientists in relation to the use and development of PCR technology and in relation to new drug development. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the outcome of carbapenem versus non-carbapenem antimicrobial therapy for pediatric urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae. Materials and Methods: From 2006 to 2011, 42 episodes of UTI caused by ESBL-producing Enterobacteriaceae were diagnosed at Seoul National University Children's Hospital. Patients were grouped according to the antimicrobials they received into a carbapenem group and a non-carbapenem group. Medical records were retrospectively reviewed to assess treatment outcome, time to defervescence after initiation of treatment, and relapse rate. Results: There were 36 children with 42 episodes of UTI caused by ESBL-producing Enterobacteriaceae. Twenty-seven cases (64%) had an underlying urologic disease, 28 (67%) cases were caused by Escherichia coil, and 14 (33%) cases were caused by Klebsiella pneumoniae. Four (10%) cases were treated with carbapenem, 23 cases (55%) were treated with non-carbapenem, and 15 (36%) cases were treated by switching from a carbapenem to a non-carbapenem and vice versa. There was no treatment failure at the time of antimicrobial discontinuation. Between the carbapenem and the non-carbapenem treatment groups, there were no significant differences in bacterial etiology (P=0.59), time to defervescence after the initiation of antimicrobials (P=0.28), and relapse rate (P=0.50). In vitro susceptibility to non-carbapenem antimicrobials did not affect the time to defervescence after the initiation of antimicrobial treatment, and the relapse rate in the non-carbapenem group. Conclusions: This study found no significant difference in the treatment outcome between pediatric patients treated with carbapenem and those treated with non-carbapenem antimicrobials for UTI caused by ESBL-producing Enterobacteriaceae. Therefore, the initially administered non-carbapenem can be maintained in UTI patients showing clinical improvement. [ABSTRACT FROM AUTHOR]

Considerable evidence has shown that adequate antibiotic therapy is of utmost importance in the critically ill septic patient. However, antibiotic concentration may be insufficient early in infection course. We propose the concept of dose modulation, meaning front-line variability of antibiotic dose, according to patient and microorganism characteristics, followed by its reduction after clinical response and patient recovery. Therefore, dose modulation means concentrating the largest weight of antibiotics at the front-end, when the microbial load is higher and the pharmacokinetic changes poses the highest risk of underdosing and nibbling off antibiotic dose, when the sepsis syndrome is improving, guided by pharmacokinetic and pharmacodynamic data. [ABSTRACT FROM AUTHOR]

Purpose. Results of a study to determine the impact of a clinical pharmacist's temporary absence from a hospital's antimicrobial stewardship team are presented. Methods. A retrospective chart review was conducted to compare the appropriateness of the use of selected antimicrobial medications with and without regular pharmacist involvement on the hospital's antimicrobial stewardship team. The charts of two samples of patients were evaluated: (1) 119 patients who had received prolonged (≥72 hours) imipenem-cilastatin, linezolid, or micafungin therapy over a three-month period during which a clinical pharmacist routinely provided interventions to help ensure the drugs were used according to institutional guidelines and (2) 111 patients treated with one of the three drugs during a three-month period when the clinical pharmacist did not serve on the stewardship team. Results. Relative to the period of active pharmacist involvement in antimicrobial stewardship, rates of inappropriate use of imipenem-cilastatin, linezolid, and micafungin during the pharmacist's absence were deemed to have increased by 27, 39, and 35 percentage points, respectively, with corresponding increases in the average duration of therapy of 0.7, 4.0, and 3.2 days; in addition, the number of cases of Clostridium difficile infection increased more than threefold (from 8 to 25) during the pharmacist's absence. Conclusion. The temporary absence of a pharmacist from the antimicrobial stewardship team was associated with increased rates of inappropriate use of restricted antimicrobial agents and consequent increases in average durations of therapy. [ABSTRACT FROM AUTHOR]

To investigate the correlation between carbapenem consumption and rates of antimicrobial resistance in Acinetobacter baumannii, carbapenem consumption was expressed as defined daily dose based on the World Health Organization (WHO) anatomical therapeutic chemical classification index. Clinical isolates from 2001-2009 were collected and analyzed using WHONET 5.4 software. Results show that the consumption of imipenem/cilastatin, meropenem, and total carbapenem is significantly correlated with imipenem resistance in A baumannii ( r = 0.818, P = .007; r = 0.817, P = .007; r = 0.827, P = .006). Furthermore, total carbapenem consumption is significantly correlated with meropenem resistance in A baumannii ( r = 0.900, P = .037). In addition, consumption of imipenem/cilastatin, meropenem, and total carbapenem is associated with A baumannii resistance to piperacillin-tazobactam, ceftazidime, cefepime, amikacin, and levofloxacin. These drugs are mainly β-lactams, aminoglycosides, and fluoroquinolones. The imipenem and meropenem resistance rates are significantly correlated with resistance rates to numerous antimicrobial drugs (eg, β-lactams, aminoglycosides, and fluoroquinolones) in A baumannii. Therefore, increased consumption of carbapenem may contribute to the development of resistance in A baumannii to imipenem, meropenem, and other antimicrobial drugs. Cross-resistance possibly occurs among imipenem/cilastatin and meropenem, as well as with β-lactams, aminoglycosides, and fluoroquinolones. [ABSTRACT FROM AUTHOR]

Objectives Outbreaks of OXA-48-like carbapenemase producers are increasingly reported in many European countries and are often the result of difficulties in detection, especially for isolates with MICs of carbapenems that remain in the susceptibility range. Methods An in-house real-time quantitative PCR (qPCR) assay using TaqMan chemistry to detect blaOXA-48-like genes was compared with bacterial culturing on ChromID ESBL and SUPERCARBA media of spiked stool samples with several species producing OXA-48 variants. Results qPCR amplification using plasmid DNA was linear over 10 log dilutions (r2 = 0.998 and slope = −3.14), with an amplification efficiency of 1.10, and the detection limit of the assay was reproducibly estimated at 10 plasmid molecules/PCR. No cross-reaction was detected with DNA extracted from several multidrug-resistant bacteria harbouring other β-lactam resistance genes. The blaOXA-48 qPCR assay was capable of detecting 10–50 cfu of OXA-48 producers/100 mg of faeces. ChromID ESBL was capable of detecting OXA-48 producers (1 × 101 to 3 × 102 cfu/100 mg of faeces), as long as the isolates exhibited a high level of resistance to cephalosporins due to an associated extended-spectrum β-lactamase. The SUPERCARBA screening medium was capable of detecting all the OXA-48-like producers (1–3 × 101 cfu/100 mg of faeces), except those producing OXA-163, a variant lacking carbapenem-hydrolysing activity. Conclusions The qPCR is likely to shorten the time for blaOXA-48 detection from 48 to 4 h and will be a valuable tool for outbreak follow-up in order to rapidly isolate colonized patients and assign them to cohorts. [ABSTRACT FROM PUBLISHER]

Background: Pseudomonas aeruginosa is the most important bacterium isolated from burn wounds, and its resistance to imipenem due to metallo-beta-lactamases is increasing. This study was designed to detect vim1, vim2, ipml and ipm2 metallo-beta-lactamases genes between Pseudomonas aeruginosa isolates isolated from Shahid Motahari Burns Hospital, Iran. Methods: To that end, we isolated 483 nonduplicate consecutive isolates of P. aeruginosa from burn infections; and after biochemical confirmation, we examined the imipenem susceptibility via the Kirby-Bauer method. All the imipenem-resistant and imipenem-intermediate isolates were screened for vim1, vim2, ipml and ipm2 genes through the PCR method. Results: From the 483 isolates, 272 (56%) and 63 (13%) isolates had resistant and intermediate zones in their imipenem antibiogram pattern, respectively. Fifty-four (16.1%), 7 (2.1%), 22 (6.6%), and 11 (3.3%) of the resistant and intermediate isolates had vim1, vim2, ipml and ipm2 genes in their PCR results, respectively. Conclusion: MBL-mediated imipenem resistance in P. aeruginosa is a cause for concern in the treatment of infective burn patients. The rate of imipenem resistance due to MBL was increased dramatically and newer versions of MBL families were detected for the first time. These results suggest that an effective method should be provided to fight MBL production in clinical isolates [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 61-66 Abstract Nine isolates of Klebsiella pneumoniae were isolated from a renal transplant patient suffering from recurrent urosepsis over a period of 4 months. Imipenem resistance was detected after imipenem-ertapenem therapy. When treatment was switched to tigecycline the K. pneumoniae developed resistance to tigecycline (MIC = 8 mg/L). The nine isolates were tested by determination of agar dilution MICs, phenotypic carbapenemase, extended-spectrum beta-lactamases and metallo-beta-lactamase (MBL) testing and pulsed-field gel electrophoresis. Polymerase chain reaction and sequencing analysis were employed for identification of bla genes and mapping of the integron carrying the MBL gene. The nine isolates were clonally related and all produced the SHV-12 enzyme. Five MBL-producing isolates showed imipenem MICs ranging from 2 to 64 mg/L and all were detected by testing with imipenem and EDTA. The five isolates harboured the blaVIM-1 gene. Three isolates showed increased tigecycline MICs (4-8 mg/L). Serial blood cultures obtained on the same day resulted in a VIM-positive/tigecycline-susceptible and a VIM-negative/tigecycline-resistant K. pneumoniae isolate. No isolate developed concurrent imipenem and tigecycline resistance. The patient had a persistent urinary tract infection and recurrent bacteraemia caused by a mixed population of Klebesiella pneumoniae isolates adapting to the selective pressure of antimicrobial therapy at the time. The present study is a worrisome example of what could happen when an immunocompromised host is subjected to the pressures of antimicrobial therapy. In addition, we report the first treatment-emergent MIC increase of tigecycline from 0.5 to 8 mg/L in K. pneumoniae. [ABSTRACT FROM AUTHOR]

Class D β-lactamases with carbapenemase activity are emerging as carbapenem-resistance determinants in Gram-negative bacterial pathogens, mostly Acinetobacter baumannii and Klebsiella pneumoniae. Carbapenemase activity is an unusual feature among class D β-lactamases, and the structural elements responsible for this activity remain unclear. Based on structural and molecular dynamics data, we previously hypothesized a potential role of the residues located in the short-loop connecting strands β5 and β6 (the β5-β6 loop) in conferring the carbapenemase activity of the OXA-48 enzyme. In this work, the narrow-spectrum OXA-10 class D β-lactamase, which is unable to hydrolyze carbapenems, was used as a model to investigate the possibility of evolving carbapenemase activity by replacement of the β5-β6 loop with those present in three different lineages of class D carbapenemases (OXA-23, OXA-24, and OXA-48). Biological assays and kinetic measurements showed that all three OXA-10-derived hybrids acquired significant carbapenemase activity. Structural analysis of the OXA-10loop24 and OXA-10loop48 hybrids revealed no significant changes in the molecular fold of the enzyme, except for the orientation of the substituted β5-β6 loops, which was reminiscent of that found in their parental enzymes. These results demonstrate the crucial role of the β5-β6 loop in the carbapenemase activity of class D β-lactamases, and provide previously unexplored insights into the mechanism by which these enzymes can evolve carbapenemase activity. [ABSTRACT FROM AUTHOR]

Purpose. Selected i.v. antimicrobials were evaluated against Pseudomonas aeruginosa isolates collected from U.S. hospitals to predict the likelihood of achieving maximal bactericidal activity. Methods. The pharmacodynamic profiles of ceftazidime, doripenem, imipenem-cilastatin, levofloxacin, meropenem, and piperacillin.tazobactam were simulated for 5000 adult patients using pharmacokinetic data from infected patients with the minimum inhibitory concentrations of 6142 P. aeruginosa isolates in U.S. hospitals collected during 2009. The probability of achieving bactericidal activity in this population, referred to as the cumulative fraction of response (CFR), was calculated for each antimicrobial. An optimal regimen was defined as achieving a CFR of .90%. Results. The majority of isolates were collected from male inpatients who were not in an intensive care unit (ICU) and were over age 65 years. Standard dosing for all antimicrobials failed to achieve optimal CFRs, regardless of hospital location. While high-dose prolonged infusions improved the CFRs for the β-lactams, optimal exposures were only attained by doripenem (2 g every 8 hours infused over 1 hour; 0.5-2 g every 8 hours infused over 4 hours) and meropenem (2 g every 8 hours infused over 0.5 and 3 hours) for all isolates. Non-ICU isolates had approximately 5-10% higher CFRs compared with those collected in the ICU. Lower-respiratory-tract isolates had a lower predicted CFR than did isolates from the blood and skin or wounds. Conclusion. Simulated pharmacodynamic profiles of i.v. antimicrobials commonly used to treat P. aeruginosa indicated that higher dosages and prolonged infusion times are needed to achieve optimal exposure for bactericidal activity. [ABSTRACT FROM AUTHOR]

Purpose. A case of persistent multidrug-resistant (MDR) Acinetobacter baumannii ventriculitis successfully treated with a prolonged and novel combination of antimicrobials is reported. Summary. A 38-year-old, 84-kg Caucasian woman with a recent history of craniotomy was admitted with nausea, fever, headache, photophobia, and drainage from her craniotomy incision. She underwent a repeat craniotomy on hospital day 4 with abscess debridement and repair of a cerebrospinal fluid leak. Cultures grew MDR A. baumannii, coagulase-negative Staphylococcus species, and methicillin-resistant Staphylococcus aureus. Based on the limited published pharmacokinetic and pharmacodynamic data for colistin, we determined a favorable outcome with i.v. colistin monotherapy was unlikely and decided to treat the patient with simultaneous i.v. and intraventricular colistin, as well as intraventricular tobramycin and i.v. rifampin. She was treated with a total of 36 days of intraventricular colistin, 40 days of intraventricular tobramycin, 51 days of i.v. colistin and rifampin, and 56 days i.v. vancomycin for infection that persisted despite multiple debridements. The patient had subsequent improvement in clinical manifestations and eradication of infection. She was subsequently discharged to an acute rehabilitation facility on hospital day 77 with posttreatment sequelae including mental impairment and renal failure requiring hemodialysis. Follow-up visits revealed significant improvement in her mental status, speech, and strength on the side not affected by the stroke. Conclusion. Prolonged combination therapy with intraventricular colistin and tobramycin plus i.v. colistin, rifampin, and vancomycin led to the resolution of a persistent central nervous system infection caused by MDR A. baumannii. [ABSTRACT FROM AUTHOR]

Background: The laboratory detection of Pseudomonas aeruginosa that produce metallo-ββ-lactamases (MBLs) is not well defined in regions with a low prevalence of these enzymes. We report a study that developed ethylenediaminetetraacetic acid (EDTA) disk screen tests using doripenem, imipenem and meropenem and investigated the prevalence of these enzymes among clinical isolates of imipenem-resistant P. aeruginosa in Rotterdam during 2008--2009. Methods: Using strains with well-characterized ββ-lactamases and the Clinical and Laboratory Standards Institute (CLSI) disk methodology similar to extended-spectrum ββ-lactamase (ESBL) detection, inhibition zone diameters were determined in tests with doripenem, imipenem, and meropenem, alone and in combination with 370 μμg of EDTA. These tests were compared with the MBL E-test. A positive test was a ≥≥5 mm increase in zone diameter in the presence of EDTA. Results: The imipenem EDTA disk screen test showed a sensitivity of 100% and a specificity of 90% in 96 recent clinical isolates. Imipenem in combination with doripenem performed better than imipenem alone, meropenem, and the MBL E-test (sensitivity of 100%; specificity of 95%). The majority of clinical isolates were isolated from patient respiratory specimens. Of the 96 imipenem-resistant P. aeruginosa isolated, 35 (36%) were positive for blaVIM genes. Conclusions: The EDTA imipenem/doripenem disk test showed accurate and reproducible results with excellent sensitivity and specificity. It is simple to perform and interpret and can be easily introduced into the workflow of a clinical laboratory to screen for MBLs in imipenem-resistant P. aeruginosa. Due to its high specificity the test is also suitable for regions with a low prevalence of these enzymes. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are a problem frequently encountered by paediatric healthcare providers. Recent data suggest that extended-spectrum ββ-lactamase (ESBL)-producing bacteria are an emerging cause of UTIs in non-hospitalized patients. We report our experience of ertapenem use in 50 patients with complicated UTIs, mainly pyelonephritis, caused by ESBL-producing organisms. Methods: Fifty patients aged <16 y who had a complicated UTI caused by ESBL-producing organisms and who were treated with ertapenem at our hospital from 1 January 2009 to 31 December 2009, were included in the study. Results: There were 20 (40%) males and 30 (60%) females with a mean ±± standard deviation age of 38.6 ±± 36.9 months (range 6--156 months). Twenty-eight patients had no urological abnormality. In 40 patients ertapenem was initiated after results of microbiological cultures became available. Ertapenem was initiated empirically for 10 patients known to be colonized with ESBL-producing bacteria. Urine cultures were negative at 3.3 ±± 0.7 days (range 2--5 days) after starting ertapenem treatment. The mean duration of ertapenem treatment was 7.8 ±± 1.2 days (range 7--14 days). No laboratory or clinical side effects were observed. Conclusions: Ertapenem is promising for the culture-guided treatment of ESBL-producing Gram-negative complicated UTIs. Well-designed prospective studies are needed to define the role of ertapenem in treating complicated paediatric UTIs, especially upper UTIs. [ABSTRACT FROM AUTHOR]

Background The emergence of carbapenemases in Enterobacteriaceae is driving a search for therapeutic alternatives. We tested ACHN-490, a sisomicin derivative that evades all plasmid-mediated aminoglycoside-modifying enzymes, against 82 carbapenem-resistant Enterobacteriaceae isolates. Comparators included internationally and locally available aminoglycosides. Methods The isolates variously had KPC (n = 12), SME-1 (n = 1), IMP (n = 13), VIM (n = 5), NDM (n = 17) or OXA-48 (n = 19) carbapenemases, or had combinations of impermeability with AmpC (n = 5) or extended-spectrum β-lactamases (n = 10). They included 53 Klebsiella spp., 19 Enterobacter spp., 6 Escherichia coli and 4 others; most were multiresistant. Genes were identified by PCR and sequencing; MICs were measured by CLSI agar dilution. Results ACHN-490 was active at ≤2 mg/L against all 65 isolates with carbapenem resistance mechanisms other than NDM enzyme, mostly with MICs of 0.12–0.5 mg/L; isepamicin was active against 63/65 at ≤8 mg/L. In contrast, 35% were resistant to gentamicin at 4 mg/L, 61% to tobramycin at 4 mg/L and 20% to amikacin at 16 mg/L. However, 16 of the 17 isolates with NDM-1 enzyme were resistant to ACHN-490, with MICs ≥64 mg/L, and these were cross-resistant to all other human-use aminoglycosides tested. Their behaviour was associated with ArmA and RmtC 16S rRNA methylases. Apramycin (a veterinary aminoglycoside) retained its full activity, with MICs of 4–8 mg/L versus strains with armA or rmtC, though resistance was seen in one Klebsiella pneumoniae with AAC(3)-IV (MIC ≥256 mg/L). Conclusions ACHN-490 has potent activity versus carbapenem-resistant isolates, except those also harbouring 16S rRNA methylases; isepamicin is also widely active, though less potent than ACHN-490. Evasion of 16S rRNA methylases by apramycin is noteworthy and may provide a starting point for future aminoglycoside development. [ABSTRACT FROM PUBLISHER]

Purpose. The chemistry, pharmacology, antimicrobial activity, pharmacokinetics, pharmacodynamics, efficacy and safety in humans, and formulary considerations of doripenem are reviewed. Summary. Doripenem, a member of the β-lactam class of antibiotics, is the newest addition to the carbapenems. It exhibits concentration-independent bactericidal activity against gram-positive bacteria; enteric and nonenteric gram-negative bacteria, including extended-spectrum β-lactamase-producing strains; and anaerobic pathogens. Doripenem was found to be noninferior to meropenem in the treatment of complicated intraabdominal infections and noninferior to levofloxacin in the treatment of complicated urinary tract infections including pyelonephritis and was granted marketing approval by the Food and Drug Administration for these two indications. Doripenem was also found to be noninferior to imipenem in the treatment of ventilator-associated pneumonia and noninferior to piperacillin--tazobactam in the treatment of hospital-acquired pneumonia. It has a favorable safety profile, with gastrointestinal complaints and headache being the most common adverse effects and allergic reactions the most serious adverse effects. Doripenem has a relatively low potential to induce seizures. The only known clinically relevant drug interaction is that coadministration with valproic acid may result in reductions of valproic acid serum concentrations. As with most renally eliminated antibiotics, the dose of doripenem should be adjusted according to kidney function. Conclusion. Doripenem is an injectable carbapenem antibiotic with a spectrum of activity comparable to that of imipenem and meropenem. Its safety is similar to that of other carbapenems. [ABSTRACT FROM AUTHOR]

The incidence, clinical characteristics, risk factors, antimicrobial susceptibility, and outcomes of nosocomial imipenem-resistant A. baumannii (IRAB) infections during a 5-y period (2003–2007) were retrospectively analyzed. A total of 720 patients with 925 episodes of A. baumannii infection were included in the study. A. baumannii infections were seen mostly in intensive care units. The incidence was 6.2 per 1000 admissions. The most common infections were pneumonias and bloodstream infections. Imipenem resistance among Acinetobacter strains increased significantly each y of the study (from 43.3% to 72.9%). Mortality was related to the presence of imipenem resistance, stay in intensive care unit, female gender, old age, and pneumonia. Haemodialysis, malignancy, and mechanical ventilation were significant risk factors for IRAB infections. Imipenem resistance was higher in strains isolated from patients with pneumonia. IRAB strains showed higher resistance rates to other antibiotics than imipenem-susceptible strains. The most active antimicrobial agents against A. baumannii were cefoperazone–sulbactam and netilmicin. The incidence of A. baumannii infections and imipenem resistance increased during the study period. IRAB infections should be considered in patients on mechanical ventilation and haemodialysis and in patients with malignancies. [ABSTRACT FROM AUTHOR]

Nine Klebsiella pneumoniae isolates showing non-susceptibility to carbapenems were collected from three centres in the north-eastern region of Hungary. The minimum inhibitory concentrations (MICs) of antibiotics were determined by Etest. The putative production of a carbapenemase was tested by the modified Hodge test. The presence of blaKPC genes was verified by polymerase chain reaction (PCR) and sequencing. Furthermore, molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All isolates showed extensively drug-resistant (XDR) phenotype, and of these, eight isolates were highly resistant to colistin. The isolates carried blaKPC-2, blaSHV-12, blaTEM-1 and blaSHV-11. PFGE analysis of the nine KPC-2-producing Hungarian ST258 K. pneumoniae isolates, two KPC-2-producing Norwegian ST258 isolates and 33 CTX-M-15-producing ST11 isolates revealed the existence of one genetic cluster at an 88% similarity level. The overall results of the PFGE clustering, MLST and the presence of SHV-11 in both ST11 and ST258 suggest that this is the first hyperepidemic clonal complex of multidrug-resistant K. pneumoniae, probably CC258/CC340, possibly undergoing worldwide spread. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis or hydatid disease is a zoonotic parasitic infection caused by larval stage of cestode Echinococcus spp. Humans are an accidental intermediate host and present with the involvement of different organs, the liver being the most common while kidney is the rarest site. Here, authors are reporting a case of a 55-year-old woman who presented with renal failure and was found to have a right-sided intrarenal hydatid cyst, diagnosed and treated with nephroscopy without sacrificing the kidney. She had an uneventful postoperative course and her renal function improved dramatically. She is now on oral albendazole therapy and doing well on follow-up. To the best of our knowledge, renal failure has never been reported in the literature as clinical manifestation of intrarenal hydatid cyst in adult population. [ABSTRACT FROM AUTHOR]

Infections are a significant cause of morbidity and mortality in patients with sickle cell disease. Loss of splenic function in these patients makes them highly susceptible to some bacterial infections. Non-tuberculous mycobacterial infections in patients with sickle cell disease are extremely rare and only two cases have been reported previously. We describe a case of sepsis caused by non-tuberculous mycobacterium, Mycobacterium terrae complex in a patient with febrile sickle cell disease. M terrae complex is a rare clinical pathogen and this is the first reported case of sepsis secondary to this organism in a patient with sickle cell disease. The patient responded to imipenem and amikacin therapy. [ABSTRACT FROM AUTHOR]

Background: In this study, it is aimed to determine in-vitro susceptibility of some antibiotics against extended spectrum beta-lactamase (ESBL) positive and quinolone resistant E. coli strains isolated from patients with urinary tract infections. Methods: A total of 98 E. coli strains which were ESBL positive and resistant to quinolones were included to the study. ESBL test were performed by double-disc synergy test and antibiotic susceptibility were determined by Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute criteria. Results: The susceptibility rate of the isolates against imipenem, piperacillin-tazobactam and cefoperazone-sulbactam were found 96.9%, 68.4%, and 75.5% respectively. Conclusion: It was found that imipenem is the most effective antibiotic in urinary tract infections caused by resistant isolates. [ABSTRACT FROM AUTHOR]

The article presents abstracts related to infectious diseases including one on tigecycline versus imipenem/cilastatin for hospital acquired pneumonia, one on pre-exposure prophylaxis to prevent HIV and one on cranberry juice and recurrent urinary tract infections.

Background Carbapenems are a frequent firstline therapy in complicated intra-abdominal infections (cIAIs). We examined the microbiology, epidemiology, and outcomes among patients hospitalized in the United States with culture-positive cIAIs in the context of their exposure to empiric carbapenem treatment (ECT). Methods We performed a multicenter retrospective cohort study of Premier database of ~180 hospitals, 2013–2017. Using an International Classification of Diseases (ICD)-9/10-based algorithm, we identified all culture-positive adult patients hospitalized with cIAI and examined their microbiology, epidemiology, and outcomes. Results Among 4453 patients with cIAIs, 3771 (84.7%) had a gram-negative (GN) and 1782 (40.0%) a gram-positive organism; 1185 (26.6%) received ECT. Compared with those on non-ECT, patients on ECT were less frequently admitted from home (82.5% vs 86.0%) or emergently (76.0% vs 81.4%; P <.05 for each); E. coli were less frequent, whereas P. aeruginosa and Enterococcus spp. were more prevalent and resistance to third-generation cephalosporins (C3R; 10.1% vs 5.1%; P <.001) and carbapenems (CR; 3.6% vs 1.2%; P <.001) was more common. In adjusted analyses, ECT was associated with no rise in mortality, shorter postinfection length of stay (–0.59 days; 95% confidence interval [CI], –1.15 to –0.03), but higher postinfection costs ($3844; 95% CI, $1921 to $5767) and risk of Clostridioides difficile (odds ratio, 2.15; 95% CI, 1.02 to 4.50). Conclusions Among patients hospitalized with cIAI, the majority were gram-negative. Despite a 10% prevalence of C3R, fully one-quarter of all empiric regimens contained a carbapenem. ECT was a marker for slightly lower postinfection length of stay, but higher costs and risk of hospital complications. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 61-year-old male patient who had the diagnosis of diffuse large B-cell lymphoma 6 years ago. Topics discussed include hospitalization of patient for high fever, fatigue, acute renal failure, and bibasilar crepitant rales, blood count measurement with a Beckman Coulter LH 780 hematology analyzer and evidence of high fasting glucose, blood urea nitrogen, creatinine, alkaline phosphatase, lactate dehydrogenase revealed via biochemical analysis.

A letter to the editor is presented which discusses metabolic alkalosis' occurrence after taking imipenem-cilastatin.

The article focuses on infection prevention and control issues. A move to publish observed hand hygiene compliance rates is finding more support as a means of improving quality of care and ensuring transparency and accountability. There are many contaminated laptops and phones since a report sponsored by The Co-operative Pharmacy reveals that 1 in 20 technology addicts uses these while in the toilet. To prevent transmission of airborne viral infections in hospital waiting rooms, waiting times and the number of susceptible patients should be minimized.

A response from the authors of the article "Metabolic alkalosis: A less appreciated side effect of imipenem-cilastin use" in the previous issue is presented.

A letter to the editor is presented in response to the article "Metabolic alkalosis: A less appreciated side effect of Imipenem-cilastin use" by P. S. Panda and colleagues in the July-August 2013 issue.

The article discusses potentially severe drug interactions which have been reported in patients who take carbapenem antibiotics and the drug sodium valproate at the same time.