Penicillin-resistant Streptococcus Research Articles

Community-acquired upper respiratory tract infections and the role of third-generation oral cephalosporins

Common community-acquired infections include those of the upper respiratory tract. In the 1990s, the antimicrobial treatment of upper respiratory tract infections focused on penicillin-resistant Streptococcus pneumoniae. However, following the introduction of a pneumococcal conjugate vaccine, a decrease in invasive pneumococcal disease occurred, and in the case of otitis media a shift towards Haemophilus influenzae as the predominant causative pathogen was observed. Future antimicrobial therapy for outpatient upper respiratory tract infections may need to focus on pathogens such as penicillin-susceptible S. pneumoniae, β-lactamase-producing H. influenzae, β-lactamase-negative amoxicillin-resistant H. influenzae and Moraxella catarrhalis. In these circumstances, third-generation oral cephalosporins, such as cefixime and cefdinir, could be increasingly used as an optional first-line therapy in community practice for upper respiratory tract infections suspected to be caused by these key pathogens, as an alternative to amoxicillin–clavulanate.

Population-Level Interventions to Reduce the Development and Transmission of Community-Associated Antimicrobial Resistance: A Perspective from the National Collaborating Centre for Infectious Diseases

Antimicrobial resistance (AMR) in bacteria is the end result of a multitude of factors. Some of the key factors beyond innate resistance include antimicrobial selective pressure (1–5), acquisition of a foreign genetic resistance element(s) (1–5), clonal dissemination (1) and new mutations (2,3,5); factors vary for different species and geographical locations. Increased global antimicrobial use is the foremost reason for the spread of AMR in the community setting (1). Social networks of individuals (households, schools and child care facilities) have served both as a reservoir for these bacteria and as a common route for their transmission. Similarly, hospitals, nursing homes and long-term care facilities have also served as reservoirs for antibiotic-resistant organisms, and the discharge of patients from these facilities contributes to the spread of resistance within communities. In addition, the use of antimicrobials in food animals has been an important contributing cause (1).

急性中耳炎に対するＴｅｂｉｐｅｎｅｍ ｐｉｖｏｘｉｌの有用性―スコアリング・システムを用いた重症度評価とその臨床効果―

In recent years, high prevalence penicillin-resistant Streptococcus pnenumoniae (PRSP) strains and β-lactamase non-producing ampicillin-resistant Haemophilus influenzae (BLNAR) strains have been reported the treatment of acute otitis media (AOM) in children. Between September 2005 and March 2006, we performed a clinical efficacy study on Tebipenem-pivoxil (TBPM-PI) in children with acute otitis media. We assessed the severity of disease by using a scoring system based on symptoms and tympanic membrane changes, and a clinical efficacy study was carried out using the improvement in the score results cross linked in a table together with symptoms and TM findings and the objective grading of the physician in charge. 16 patients were enrolled in this study, ages were from 0 to 5 years old, with a median age of 3.50 years. S. pneumoniae, H. influenzae, and M. catarrhalis were detected as causative bacteria. The doses of TBPM-PI administered to children with AOM were 4 mg/kg b.i.d (10 cases) or 6 mg/kg b.i.d (6 cases) for seven days. The overall efficacy rates of TBPM-PI for AOM according to the clinical efficacy judged by the scoring system and the grading of attending physicians were 90.5% and 100%, respectively. The eradication rate of pathogens at the end of treatment was 4/4. Based on our results, the present study strongly suggested that TBPM-PI would be an effective antimicrobial agent against moderate to severe AOM. Moreover, the scoring system was very useful for the decision making regarding the appropriate treatment regimen of AOM.

Analysis resistance of Streptococcus pneumoniae of some hospital in Qingdao from 2005 to 2008

Objective To monitor the resistance of Streptococcus pneumoniae following the 2004 in Qingdao area, and to provide a reasonable basis for clinical application of antimicrobial agents. Methods Collecting respiratory tract, blood, cerebrospinal fluid and other specimens from out-patient and in-patients of some hospital in Qingdao from January 2005 to December 2008. According to the recommendation of NCCLS, antibiotic resistance analysis of 11 kinds of antibiotic to the isolated 231 Streptococcus pneumoniae by micro-agar dilution method, and analysis resistance trends and age differences. Results The results showed that the rate of Streptococcus pneumoniae not sensitive to penicillin is 23. 38% (PRSP: 9.52% , PISP: 13. 85% ) , resistant to cefotaxime is 9. 96% (23/231), resistant to amoxicillin is 12. 55% , resistant to erythromycin is 90. 48% (209/231). PRSP rate of patients younger than 14 years of age 27. 91% (12/43), significantly higher than that of the PRSP rate of adults 5. 38% (10/186). Conclusion The rate of resistant to penicillin Streptococcus pneumoniae increased significantly from 2004, and an increasing trend year by year, the resistance of Streptococcus pneumoniae is also a rising trend year by year. For patients infected low penicillin-resistant Streptococcus pneumoniae in this region, cefotaxime, amoxicillin are preferred drugs. Key words: Streptococcus pneumoniae; Drug resistance; Resistant to penicillin Streptococcus pneumoniae

Newer developments in the treatment of Gram-positive infections

Gram-positive organisms are continually a major cause of infection. These organisms are ever-evolving and exhibit resistance to nearly all available agents. Historically, vancomycin was crowned the drug of choice for many of these organisms including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, and penicillin-resistant Enterococcus spp. Many of these organisms have exhibited reduced susceptibility or frank resistance to vancomycin which has resulted in treatment failure. For this reason, new strategies in treating Gram-positive infections are a hot topic. There are two general approaches to waging this war: i) development of new antimicrobial agents; and ii) reinvigorating old antibiotics that still retain appreciable activity against Gram-positives. We review both antibiotic groupings with a focus on S. aureus, S. pneumoniae and Enterococcus spp.

Zakażenia patogenami alarmowymi na Oddziale Otolaryngologicznym Szpitala Dziecięcego im. prof. dr. med. Jana Bogdanowicza w latach 2005–2008

The development of medicine, in this the new techniques and antibiotic therapy enlarged the survivability of patients in hospital. Applying antibiotics caused breakthrough in treatment stepping out in ill's group infections treated in hospital, however enlarging resistance is natural this effect, resulting from: the selection of resistant strains, the formation of new mechanisms of resistance, and/or the spreading of gene of resistance. Multidrug-resistant strains were included to emergence-pathogens group: MRSA, penicillin-resistant Streptococcus pneumoniae, VRE, Gram-negative producing beta-lactamase of type the ESBL and/or resistant to carbapenems. Emergence-pathogens occurrence leads to: therapeutic failures, the use extorts in therapy of dear medicines or with possibility of workings undesirable. The multidrug-resistant strains spread in hospital environment easily, especially on departments about high waste of medicines with the patients' simultaneously large susceptibility on infection, resulting mainly with state of reduced resistance of organism. The control of hospital infections recognize by present hospitality for the most important criterion of quality of work. Analysis of the emergence-pathogens isolated during treatment in hospital in 2005-2008, from special regard the ENT Department. 50586 children treated in this period in hospital in which was executed 39386 bacteriological investigations, in this 6528 (12.9%) children in ENT Department in which was executed 1566 bacteriological investigations (3.98%). The diagnostics were executed according to routine microbiological procedures with qualification of resistance to antibiotics. Emergence-pathogens infection was confirmed at 2369 children's (4.68%) treated in Hospital, in this in ENT Department at 84 children (1.29%). The most frequent emergence-pathogens in ENT Department were Streptococcus pyogenes, Streptococcus pneumoniae penicillin-resistant and average sensitive on penicillin, Staphylococcus aureus methicillin-resistant and Rotavirus. Streptococcus pneumoniae penicillin-resistant and average sensitive to penicillin and Rotavirus infections are the most frequent hospital infections. The systematic microbiological supervision is indispensable in prevention the spreading of infections of the emergence-pathogens in hospital.

Antibiotic resistance among bacterial pathogens in Central Africa: a review of the published literature between 1955 and 2008

A systematic review of the published literature on bacterial resistance in Central Africa between 1955 and 2008 was performed. Eighty-three publications from seven countries were retrieved, the majority presenting data on enteric and other Gram-negative pathogens. Despite methodological limitations in many studies, alarming resistance rates are noted in nearly all pathogens. Of special concern are multidrug resistance in Shigella and Salmonella spp. and the emergence of meticillin-resistant Staphylococcus aureus, high-level penicillin-resistant Streptococcus pneumoniae and extended-spectrum β-lactamases among Gram-negative pathogens. These findings make clear that the Central African region shares the worldwide trend of increasing antimicrobial resistance and is in urgent need of sound surveillance based on competent and affordable microbiology to provide clear data on antimicrobial resistance. These data could enable redaction of local treatment guidelines and fuel national and regional policies to contain antimicrobial resistance.

Preparation and biodistribution of [131I]linezolid in animal model infection and inflammation

Linezolid is the first of new class of antibiotics, the oxazolidinones, and exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Aim of the study: Linezolid was to label with I-131 and potential of the radiolabeled antibiotic was to investigate in inflamed rats with S. aureus (S. aureus) and sterile inflamed rats with turpentine oil. Linezolid was labeled with I-131 by iodogen method. Biodistribution of [131I]linezolid was carried out in bacterial inflamed and sterile inflamed rats. Radiolabeling yield of [131I]linezolid was determined as 85 ± 1% at pH 2. After injecting of [131I]linezolid into bacterial inflamed and sterile inflamed rats, radiolabeled linezolid was rapidly removed from the circulation via the kidneys. Binding of [131I]linezolid to bacterial inflamed muscle (T/NT = 77.48 at 30 min) was five times higher than binding to sterile inflamed muscle (T/NT = 14.87 at 30 min) of rats. [131I]linezolid showed good localization in bacterial inflamed tissue. It was demonstrated that [131I]linezolid can be used to detect S. aureus inflammation in rats.

Infections due to Gram-Positive Cocci

The gram-positive cocci that produce infection include pneumococci, group A streptococci, non?group A streptococci (including groups B, C, D, G, and nongroupable streptococci), anaerobic streptococci, enterococci, and staphylococci. This chapter discusses the pathogenesis, diagnosis, and treatment of infections associated with each of these gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA). The clinical infections caused by each of these organisms are reviewed. Tables describe the incidence of pneumococcal disease according to age and underlying disease, factors associated with adverse outcomes in pneumococcal pneumonia; medically important streptococci and enterococci; antibiotic treatment for penicillin-resistant Streptococcus pneumoniae, enterococcal infections, and staphylococcal infections; laboratory tests for streptococcal pharyngitis; clinical manifestations and antibiotic treatment for staphylococcal toxic-shock syndrome (TSS); revised Jones criteria for the diagnosis of acute rheumatic fever, and drug treatment of acute rheumatic fever. This review contains 105 references.

Ceftaroline

Ceftaroline is a broad-spectrum cephalosporin currently under clinical investigation for the treatment of complicated skin and skin-structure infections (cSSSI), including those caused by meticillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). Ceftaroline has the ability to bind to penicillin-binding protein (PBP)2a, an MRSA-specific PBP that has low affinity for most other beta-lactam antibacterials. The high binding affinity of ceftaroline to PBP2a (median inhibitory concentration 0.90 microg/mL) correlates well with its low minimum inhibitory concentration for MRSA. Ceftaroline is active in vitro against Gram-positive cocci, including MRSA, meticillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant Enterococcus faecalis (not E. faecium). The broad-spectrum activity of ceftaroline includes many Gram-negative pathogens but does not extend to extended-spectrum beta-lactamase-producing or AmpC-derepressed Enterobacteriaceae or most nonfermentative Gram-negative bacilli. Ceftaroline demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. Limited data show that ceftaroline has a low propensity to select for resistant subpopulations. Ceftaroline fosamil (prodrug) is rapidly converted by plasma phosphatases to active ceftaroline. For multiple intravenous doses of 600 mg given over 1 h every 12 hours for 14 days, the maximum plasma concentration was 19.0 microg/mL and 21.0 microg/mL for first and last dose, respectively. Ceftaroline has a volume of distribution of 0.37 L/kg (28.3 L), low protein binding (<20%) and a serum half-life of 2.6 hours. No drug accumulation occurs with multiple doses and elimination occurs primarily through renal excretion (49.6%). Based on Monte Carlo simulations, dosage adjustment is recommended for patients with moderate renal impairment (creatinine clearance 30-50 mL/min); no adjustment is needed for mild renal impairment. Currently, limited clinical trial data are available for ceftaroline. A phase II study randomized 100 patients with cSSSI to intravenous ceftaroline 600 mg every 12 hours or intravenous vancomycin 1 g every 12 hours with or without intravenous aztreonam 1 g every 8 hours (standard therapy) for 7-14 days. Clinical cure rates were 96.7% for ceftaroline compared with 88.9% for standard therapy. Adverse events were similar between groups and generally mild in nature. In a phase III trial, 702 patients with cSSSI were randomized to ceftaroline 600 mg or vancomycin 1 g plus aztreonam 1 g, each administered intravenously every 12 hours for 5-14 days. Ceftaroline was noninferior to vancomycin plus aztreonam in treating cSSSI caused by both Gram-positive and -negative pathogens. Adverse event rates were similar between groups. Ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline is a promising treatment for cSSSI and CAP, and has potential to be used as monotherapy for polymicrobial infections because of its broad-spectrum activity. Further clinical studies are needed to determine the efficacy and safety of ceftaroline, and to define its role in patient care.

Antimicrobial susceptibility of tigecycline and comparators against bacterial isolates collected as part of the TEST study in Europe (2004–2007)

Tigecycline is a broad-spectrum antimicrobial agent that has been approved for the treatment of skin and soft-tissue infections as well as intra-abdominal infections. The Tigecycline Evaluation and Surveillance Trial (TEST) is a global, longitudinal surveillance study established in 2004 to monitor the in vitro activity of tigecycline and comparator agents against key Gram-negative and Gram-positive pathogens. This report examines data obtained for 24 748 isolates collected across 24 European countries between 2004 and 2007. Tigecycline, meropenem and imipenem were the most active antimicrobial agents against most Gram-negative isolates including multidrug-resistant Acinetobacter baumannii (15.7% of the A. baumannii isolates in this study), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (8.5% of E. coli) and ESBL-producing Klebsiella pneumoniae (13.6% of K. pneumoniae). Only amikacin was active against >90% of Pseudomonas aeruginosa isolates (92.8% susceptible). Tigecycline, linezolid and vancomycin were the most active agents against Gram-positive agents across Europe between 2004 and 2007, with tigecycline displaying the lowest MIC 90 values (minimum inhibitory concentration for 90% of the organisms) against meticillin-resistant Staphylococcus aureus (26.5% of the collected S. aureus isolates), vancomycin-resistant Enterococcus faecium (15.7% of the E. faecium strains) and penicillin-resistant Streptococcus pneumoniae (9.3% of the S. pneumoniae strains). Longitudinal analysis showed no increase in tigecycline MIC values over the 4-year study period, whilst increased resistance was noted for several comparator agents.

Ceftobiprole: a novel cephalosporin with activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus (MRSA)

Ceftobiprole is a novel broad-spectrum cephalosporin with activity against a wide range of Gram-positive and Gram-negative bacteria, including several resistant species such as methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Ceftobiprole is administered intravenously as the prodrug ceftobiprole medocaril, which is almost immediately converted to the active form. It is currently under review by the US Food and Drug Administration (FDA) and is approved in Canada under the trade name Zeftera™. The pharmacokinetics of ceftobiprole are non-complex as it displays a two-compartment model, dose proportionality, linear plasma protein binding and negligible accumulation. The volume of distribution is approximately equal to the extracellular fluid volume and it is cleared primarily by glomerular filtration, resulting in a half-life of approximately 3–4 h. Ceftobiprole displays a low plasma protein binding of approximately 22%. The efficacy of ceftobiprole was demonstrated in two pivotal studies in patients with complicated skin and skin-structure infections (cSSSIs) that compared ceftobiprole with vancomycin in Gram-positive infections in one study and ceftobiprole with vancomycin plus ceftazidime in Gram-positive and Gram-negative infections in the other. The clinical cure rates were similar for ceftobiprole vs. comparator treatments: 93.3% vs. 93.5% with vancomycin only and 90.5% vs. 90.2% with vancomycin plus ceftazidime. The pharmacokinetic/pharmacodynamic profile supports the use of ceftobiprole to treat a wide range of cSSSIs.

Asplenia congénita y purpura fulminans neumocóccico en paciente pediátrico: Reporte de caso con necropsia y revisión del tema

Absent or defective splenic function is associated with a high risk of fulminant bacterial infections, especially due to encapsulated bacteria. Not knowing this condition may delay medical treatment. Streptococcus pneumoniae is the leading cause of sepsis in these patients. Asplenic patients are at high risk for septic shock and eventually purpura fulminans, a life-threatening condition. We report the case of a 3 years oíd girl, with mitral stenosis and recurrent pneumonía that was admitted due to fever but in the next few hours presented hypotension, purpura and livedo reticularis. Laboratory test showed leucopenia (3.400/mm(3)), bandemia (43% of immature forms), thrombocytopenia, hypoprothombinemia and severe lactic acidosis (ph: 7.0 and lactic acid 11 mmol/1). The patient developed septic shock and multiorganic failure. Mechanical ventilation, volume resuscitation, vasoactive drugs and antibiotic therapy was initiated. Ultrasound was performed on the second day, demostrating asplenia. Peripheral blood smear showed Howell-Jolly bodies. Patient had a positive blood culture for penicillin-resistant Streptococcus pneumoniae (serotype 19F). Patient died of intracerebral hemorrhage after 8 days of admission. Necropsy confirmed asplenia and bilateral suprarenal haemorrhage. Absence of spleen can lead to life threatening infections, it is important to recognize it because vaccination and antibiotic prophylaxis can provide life-saving protection. This case provides a reminder to pursue asplenia as a potential underlying mechanism for invasive bacterial infection in children.

In vitro activity of the investigational ketolide cethromycin against macrolide- and penicillin-resistant Streptococcus pneumoniae: review of the 1998 to 2006 Canadian Respiratory Organism Susceptibility Study (CROSS)

In vitro activity of the investigational ketolide cethromycin against macrolide- and penicillin-resistant Streptococcus pneumoniae: review of the 1998 to 2006 Canadian Respiratory Organism Susceptibility Study (CROSS)

Hospital-Based Study of the Prognostic Factors in Adult Patients with Acute Community-Acquired Bacterial Meningitis in Tokyo, Japan

Prognostic factors related to community-acquired bacterial meningitis (BM) in adult patients have been evaluated using multivariate analysis in The Netherlands, where the rate of antibiotic resistance was low. However, an evaluation of these factors in countries with a high rate of antibiotic resistance has not yet been done. Thus, we studied the prognostic factors in adults with community-acquired BM in our hospitals, which are located in Tokyo, Japan, where the rate of antibiotic resistance is high. We selected 71 consecutive adult patients with community-acquired BM in which the pathogens were identified and then classified the patients into two groups based on the Glasgow Outcome Scale: a favorable outcome group (n=48), and an unfavorable outcome group (n=23). Their clinical and laboratory variables were analyzed using single logistic regression analysis followed by multiple logistic regression analysis. The overall mortality rate was 23%. The rate of antibiotic resistance was 54.9%. The most common resistant bacteria were penicillin-resistant Streptococcus pneumoniae, followed by methicillin-resistant Staphylococcus aureus. The Glasgow Coma Scale score (GCS) at the initiation of antibiotic therapy and a low thrombocyte count were identified as significant unfavorable prognostic factors (GCS: p=0.020, odds ratio=0.528, 95%CI=0.309-0.902; thrombocyte count: p=0.037, odds ratio=0.802, 95%CI=0.652-0.987). The presence of antibiotic-resistant bacteria was not identified as a prognostic factor. Patients with a low GCS at the initiation of antibiotic therapy and low thrombocyte counts had unfavorable outcomes. With appropriate antibiotic administration, the antibiotic-resistant bacteria were not identified as an unfavorable prognostic factor, even in an area with a high rate of antibiotic resistance.

Telavancin: A new lipoglycopeptide for Gram-positive infections

Telavancin is a lipoglycopeptide derivative of vancomycin. Similar to vancomycin, it demonstrates activity in vitro against a variety of Gram-positive pathogens, including but not limited to methicillin-resistant Staphylococccus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Modifications to vancomycin's structure expanded telavancin's spectrum of activity in vitro to include organisms such as glycopeptide-intermediate S. aureus (GISA), vancomycin-resistant S. aureus (VRSA) and vancomycin-resistant enterococci (VRE). However, the clinical implications of this are currently unknown. Similar to other glycopeptides, televancin binds to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus in Gram-positive organisms, resulting in inhibition of bacterial cell wall synthesis. In addition, telavancin causes depolarization of the bacterial cell membrane and increased membrane permeability. The resulting activity in vitro is rapidly bactericidal and concentration dependent, with the ratio of area under the time concentration curve to minimum inhibitory concentration (AUC/MIC) as the best predictor of activity in animal models to date. In humans, telavancin exhibits a pharmacokinetic profile that permits once-daily intravenous administration. Doses of 7.5 and 10 mg/kg/day have been studied in clinical trials. The need for dosage adjustments based on age, gender and obesity appear unnecessary. In addition, moderate hepatic impairment does not appreciably alter the pharmacokinetics of the drug. Because telavancin is extensively cleared by the kidneys, dosage adjustments will be required in patients with moderate to severe renal impairment. Published phase II and III clinical trials have shown telavancin to be comparable to standard therapy for the treatment of complicated skin and soft tissue infections. Clinical trials in the treatment of S. aureus bacteremia and hospital-acquired pneumonia are under way. Adverse effects overall appear to be mild and reversible, with taste disturbance, foamy urine, headache, procedural site pain, nausea and vomiting being the most commonly reported. However, renal toxicity was reported more frequently with telavancin than with vancomycin in two phase III clinical trials (3% versus 1%). Prolongation of the corrected QT (QTc) interval has been more common with telavancin than comparator agents, but no clinically significant electrocardiogram (ECG) changes or cardiac abnormalities have been observed to date. Although human pregnancy data is not currently available, animal data revealed limb malformations that were possibly related to telavancin therapy. Therefore, the potential teratogenicity of this agent must be considered in women who are pregnant or may become pregnant.

Pneumococcal Osteomyelitis: Report of One Case

Acute osteomyelitis is uncommon in pediatric patients, affecting one in five thousand children younger than the age of thirteen. Bone infection caused by Streptococcus pneumoniae is extremely rare, accounting for only 1.3% of acute osteomyelitis in children. We report a case of penicillin-resistant Streptococcus pneumoniae-induced acute osteomyelitis in a 7-month-old male infant who was treated successfully with intravenous vancomycin and oral clindamycin.

Serotonin Toxicity as a Consequence of Linezolid Use in Revision Hip Arthroplasty

Linezolid is the first in a new group of antibiotics called oxazolidinones. As a potent antimicrobial, it has activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, penicillin-resistant Streptococcus pneumoniae, and macrolide-resistant streptococci. There are several documented case reports of serotonin toxicity when used with selective serotonin reuptake inhibitors. The symptoms of serotonin syndrome are alteration of mental state, autonomic dysfunction, and neuromuscular disorders. This article presents a case of an interaction of the serotonin reuptake inhibitor venlafaxine and linezolid and the possible diagnostic problems that can occur. A 58-year-old woman presented with signs of systemic infection. Her medical history included bladder resection for transitional cell carcinoma, bilateral total hip arthroplasty (THA), and depression, for which she was on venlafaxine. Serological and imaging investigations revealed MRSA infection of the bilateral THA. The patient was started on vancomycin and rifampicin intravenously. As intravenous access was becoming problematic and long-term antibiotics were needed, treatment was changed to oral linezolid and oral rifampicin. Four days after the commencement of linezolid, the patient was acutely disorientated with generalized cerebellar signs and no autonomic dysfunction. A computed tomography scan of the head and lumbar puncture revealed no abnormal findings. A diagnosis of serotonin toxicity was made. The patient recovered when linezolid and venlafaxine were discontinued and supportive measures were provided. Linezolid is a popular choice of antibiotic, especially for the treatment of orthopedic-related MRSA infections. Patients who commonly require linezolid as an antimicrobial are those with complex infections where other antibiotic treatment has failed. It is therefore important to be vigilant with linezolid use. Physicians should be aware of the nonspecific presentation of serotonin symptoms and the treatment.

Prevention and Treatment of Penicillin-Resistant Streptococcus pneumoniae Meningitis After Intracraniofacial Surgery With Distraction Osteogenesis

The prevalence of penicillin-resistant Streptococcus pneumoniae (PRSP) meningitis has increased worldwide, particularly in East Asia and the United States. We recently experienced a case of PRSP meningitis that developed during frontofacial distraction. The patient was a 7-year-old girl with Crouzon disease who was treated by frontofacial monobloc/Le Fort IV minus glabellar osteotomy with quadruple internal distraction devices. Penicillin-resistant Streptococcus pneumoniae meningitis was diagnosed after surgery and treated successfully with meropenem (a carbapenem) at 120 mg kg d every 8 hours, ceftriaxone (a third-generation cephalosporin) at 100 mg kg d every 12 hours, and vancomycin (a glycopeptide) at 45 mg kg d every 6 hours. This case indicates that severe and fatal bacterial meningitis may occur as a postoperative complication due to multidrug-resistant bacteria indigenous to the nasal cavity after simultaneous osteotomy of the cranium and facial bone in intracraniofacial surgery, such as that for syndromic craniosynostosis and hypertelorbitism. In such cases, preventive strategies should include preoperative administration of pneumococcal vaccine, preoperative screening of nasal bacterial flora by nasal culture test, and prior administration of a carbapenem with good cerebrospinal fluid transfer or a third- or fourth-generation cephem covering PRSP. Postoperatively, suspected meningitis may be treated with a combination of the 3 drugs used in our case, in parallel with emergency cephalic contrast computed tomography and culture tests of blood and cerebrospinal fluid. Our experience suggests that these measures will facilitate a successful outcome in frontofacial distraction osteogenesis.

In vivo efficacy and pharmacokinetics of tomopenem (CS-023), a novel carbapenem, against Pseudomonas aeruginosa in a murine chronic respiratory tract infection model

Tomopenem (CS-023) is a novel parenteral carbapenem with broad-spectrum activity against Gram-positive and -negative bacteria, as well as potent activity against drug-resistant pathogens, including penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. We compared the in vivo activity of tomopenem and that of meropenem in a chronic lower respiratory infection mouse model of P. aeruginosa. Mice with chronic airway infection by P. aeruginosa were treated with saline (as the control, twice daily), tomopenem (100 mg/kg, twice daily) or meropenem (100 mg/kg, twice daily) for 7 days. After treatment, the number of viable bacteria in lungs and histopathological findings were analysed. The pharmacokinetics of tomopenem and meropenem were also analysed after initial treatment. The number of viable bacteria in lungs treated with saline, tomopenem or meropenem was 4.21 +/- 1.28, 2.91 +/- 0.87 and 3.01 +/- 1.00 log(10) cfu/lung (mean +/- SEM), respectively (P < 0.05, control versus tomopenem- or meropenem-treated groups). In the histopathological examination of lung specimens, the control group had the features of chronic bronchial infection; however, tomopenem- and meropenem-treated groups had fewer inflammatory cells compared with the control group. The pharmacokinetic parameter of % time above MIC for tomopenem and meropenem was 16% and 17% in sera and 15% and 18% in lungs, respectively. Tomopenem significantly reduced the number of viable bacteria in a murine model of chronic airway infection by P. aeruginosa, compared with the control. Considering the longer half-life of tomopenem in humans compared with most other carbapenems, tomopenem treatment of chronic airway infection with P. aeruginosa is expected to be efficacious.