Tuesday, December 30, 2008

Daptomycin: rationale and role in the management of skin and soft tissue infections.

Daptomycin: rationale and role in the management of skin and soft tissue infections.
J Antimicrob Chemother. 2008 Nov

Seaton RA.
Department of Infectious Diseases and General Medicine, Brownlee Centre, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, Scotland, UK.

The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide tolerance in S. aureus has underlined the importance of the newer anti-MRSA agents, particularly in the management of complicated skin and soft tissue infections (cSSTIs). The novel cyclic lipopeptide antibiotic daptomycin shows marked in vitro cidality against MRSA compared with both vancomycin and linezolid. Although comparative studies in cSSTIs have demonstrated non-inferiority with vancomycin and semi-synthetic penicillins, data from both clinical trials and observational studies suggest in vivo cidality as evidenced by rapid resolution of clinical signs of local inflammation and reduced duration of therapy. Overall success in SSTI post-marketing studies is >90%, and >88% in MRSA-infected patients, with no difference in the outcome observed between those with complicated versus uncomplicated infections. When used at licensed doses (4-6 mg/kg), daptomycin is safe and effective in SSTIs with significant muscle toxicity occurring in only 0.4% to 2.5% of patients. Clinical failure in daptomycin-treated SSTIs is associated with severity of infection (creatinine clearance <30>

Journal of Antimicrorbial Chemotherapy

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine.

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine.
Spine J. 2008 Dec 26

Burdette SD.
Department of Medicine, Wright State University Boonshoft School of Medicine, Dayton, OH 45409, USA.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is increasingly common. Treatment with vancomycin-based therapy is often unsuccessful. Daptomycin is a relatively new lipopeptide antibiotic with potent activity against MRSA.

PURPOSE: To describe the successful management of MRSA infection involving the spine.

STUDY DESIGN: Two case reports of MRSA infection, one involving epidural and lumbar subdural abscesses, the other with osteomyelitis and discitis.

METHODS: Two cases are described, one with lumbar epidural and subdural abscesses and the other with osteomyelitis and discitis of the spine. Switching from vancomycin to daptomycin plus rifampin-based therapy resulted in patient improvement that allowed discharge from the hospital.

RESULTS: Both patients recovered fully from their infection.

CONCLUSIONS: Daptomycin is a safe and effective option for the treatment of MRSA infection involving the spine.

PMID: 19112049 [PubMed - as supplied by publisher]

Friday, November 28, 2008

Antibiotic choices by paediatric residents and recently graduated paediatricians for typical infectious disease problems in children.

Antibiotic choices by paediatric residents and recently graduated paediatricians for typical infectious disease problems in children.

Paediatr Child Health. 2006 Dec

Smart K, Lemay JF, Kellner JD.
Pediatric Emergency Medicine.

OBJECTIVE: To evaluate antibiotic choices and recommendations for duration of therapy made by paediatric residents (PRs) and recently graduated paediatricians (RGPs) in several typical infectious disease conditions.

METHODS: In autumn 2002, a two-page questionnaire was sent to 276 core PRs in Canadian residency programs and to a random selection of 276 RGPs from across Canada. The questionnaire described 10 scenarios: otitis media, pharyngitis, sinusitis, bronchopneumonia, lobar pneumonia, meningitis, pyelonephritis, osteomyelitis, cellulitis, and fever and neutropenia. The participants were asked primarily about initial antibiotic selection and duration of treatment for each scenario.

RESULTS: There were 251 participants (overall response rate of 45%). The two most common antibiotic recommendations constituted 85% or more of the total for all scenarios except acute otitis media, sinusitis, cellulitis, and fever and neutropenia. There was a twofold or more difference in the range of recommended duration of treatment for all scenarios and a threefold or more difference for sinusitis, meningitis and osteomyelitis. PRs were more likely than RGPs to use broader spectrum cephalosporins for pneumococcal pneumonia (33% versus 15%, respectively; P=0.001) and to treat sinusitis for just five to 10 days (39% versus 22%, respectively; P=0.01). Also, 33% of all participants recommended amoxicillin/clavulanate or a cephalosporin rather than amoxicillin for sinusitis.

CONCLUSION: PRs and RGPs made similar and reasonable recommendations, largely in line with published guidelines, for most of the infectious disease scenarios presented. For some conditions, a significant minority of respondents unnecessarily recommended broad-spectrum antibiotics. The most variable responses were for duration of treatment, reflecting the lack of certainty in the published evidence base for many conditions.

PMID: 19030247 [PubMed - in process]

Aerosol antibiotics: considerations in pharmacological and clinical evaluation.

Aerosol antibiotics: considerations in pharmacological and clinical evaluation.

Curr Opin Biotechnol. 2008 Nov 24.

Dudley MN, Loutit J, Griffith DC.
Mpex Pharmaceuticals, San Diego, CA 92121, United States.

Increasing antibiotic resistance and lack of R&D productivity of new classes of antimicrobial agents directed against Gram-negative bacteria necessitate new approaches to maximize the efficacy of existing classes of drugs. Direct administration of drugs to the lung via the inhalational route provides for high concentrations at the target site of action in patients with pulmonary infections. The efficacy of aerosol antibiotic administration has been best demonstrated with aerosolized tobramycin in the management of chronic infections because of Pseudomonas aeruginosa in cystic fibrosis (CF) patients. Unfortunately, inconvenient regimens leading to poor patient adherence to therapy, and the increasing frequency of multidrug-resistant strains have necessitated the search for additional agents. Integration of aerosol science, PK-PD and clinical trial designs are important for the development and evaluation of these new aerosol agents in both chronic infections (e.g. CF and chronic obstructive pulmonary disease (COPD)) as well as acute infections (e.g. bacterial pneumonias).

This review outlines important considerations and recent progress in this emerging area.


Saturday, November 22, 2008

Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis.

Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis.

Am J Med. 2008
Madaras-Kelly KJ, Remington RE, Oliphant CM, Sloan KL, Bearden DT.
College of Pharmacy, Idaho State University, Boise, Idaho, USA.

BACKGROUND: Preferred therapy for purulent skin and soft tissue infections is incision and drainage, but many infections cannot be drained. Empiric therapies for these infections are ill-defined in the era of community-acquired methicillin-resistant Staphylococcus aureus.

METHODS: A multicenter retrospective cohort study of outpatients treated for cellulitis was conducted to compare clinical failure rates of oral beta-lactam and non-beta-lactam treatments. Exclusion criteria included purulent infection requiring incision and drainage, complicated skin and soft tissue infection, chronic ulceration, and intravenous antibiotics. Failure rates were compared using logistic regression to adjust for both covariates associated with failure and a propensity score for beta-lactam treatment.

RESULTS: Of 2977 patients, 861 met inclusion criteria and were classified by treatment: beta-lactam (n = 631) or non-beta-lactam therapy (n = 230). Failure rates were 14.7% versus 17.0% (odds ratio [OR] 0.85, 95% confidence interval [CI], 0.56-1.31) for beta-lactam and non-beta-lactam therapy, respectively. Failure was associated with: age (P = .02), acute symptom severity (P = .03), animal bites (P = .03), Charlson score > 3 (P = .02), and histamine-2 receptor antagonist use (P = .09). Relative efficacy of beta-lactam therapy was greater after adjustment for factors associated with failure but remained statistically insignificant (adjusted OR 0.81, 95% CI, 0.53-1.24); adjusted including propensity score covariate (OR 0.71, 95% CI, 0.45-1.13). Discontinuation due to adverse effects differed between beta-lactam (0.5%) and non-beta-lactam (2.2%) therapies (P = .04).

CONCLUSION: There was no significant difference in clinical failure between beta-lactam and non-beta-lactam antibiotics for the treatment of uncomplicated cellulitis. Increased discontinuation due to adverse events with non-beta-lactam therapy was observed.


Providing outpatient antibiotic therapy for cellulitis in primary care.

Providing outpatient antibiotic therapy for cellulitis in primary care.
Br J Community Nurs. 2008 Nov 7

Nazarko L.

Outpatient parenteral antimicrobial therapy (OPAT) is becoming more widespread. OPAT therapy can be used to treat certain patients who have cellulitis. The decision as to which patients to treat at home must be based on local PCT guidelines—not all patients are suitable for OPAT. OPAT improves patient quality of life by delivering care in the patient's home. This is highly skilled work and the community nurse must have appropriate training and support in order to gain the skills required.

PMID: 18981968 [PubMed - as supplied by publisher]

Outpatient parenteral antibiotic therapy with daptomycin: insights from a patient registry

Outpatient parenteral antibiotic therapy with daptomycin: insights from a patient registry

Int J Clin Pract. 2008 Aug

Martone WJ, Lindfield KC, Katz DE.
Cubist Pharmaceuticals, Inc., Lexington, MA 02421, USA.

AIM: To compare and contrast the characteristics and clinical outcomes of patients who have received daptomycin as outpatients and inpatients.

METHODS: The Cubicin Outcomes Registry and Experience (CORE) is a retrospective chart review of patients who have received daptomycin in participating institutions. Patients treated in 2005 were included in this analysis. Demographic characteristics and clinical outcomes (success = cured + improved) were compared among patients who received outpatient parenteral antibiotic therapy (OPAT) and patients who had received inpatient parenteral antibiotic therapy (IPAT).

RESULTS: Of 1172 patients reported by 52 CORE 2005 participating institutions/investigators, 949 (81.0%) patients were evaluable: 539 (56.8%) received OPAT (OPAT patients), and 410 (43.2%) received only IPAT (IPAT patients). Of the 539 OPAT patients, 273 (50.6%) also received some IPAT, usually preceding OPAT therapy. Successful outcomes [no. of successes/(no. of successes + no. of failures)] for OPAT patients vs. IPAT patients were 94.6% and 86.3% respectively (chi-square test, p <>

CONCLUSIONS: Outpatient parenteral antibiotic therapy use was common (539/949 or 56.8%) among patients in CORE 2005. Clinical outcomes among OPAT patients appeared at least as good as or better than IPAT patients. Better outcomes among OPAT patients were most likely because of patient selection for OPAT. Additional studies should focus on clinical characteristics of patients who would be ideal candidates for daptomycin OPAT.

Wiley InterScience

Wednesday, November 12, 2008

Daptomycin in bone and joint infections: a review of the literature.

Daptomycin in bone and joint infections: a review of the literature.

Arch Orthop Trauma Surg. 2008 Nov 7

Rice DA, Mendez-Vigo L.
St. Joseph's/Candler Health System, Savannah, GA, USA.

INTRODUCTION: To review the pharmacology, pharmacokinetics, efficacy, and safety of daptomycin, a novel antibiotic for the treatment of bone and joint infections, a literature search of relevant articles was conducted.

MATERIALS AND METHODS: A PubMed/MEDLINE search (1990-April 2008) to identify relevant English-language literature was conducted. Search terms included bone and joint infection, osteomyelitis, daptomycin, and methicillin-resistant Staphylococcus aureus (MRSA). Additional articles were identified by reviewing the bibliographies of articles cited. Programs and abstracts from infectious disease meetings were searched, and prescribing information of antibiotics indicated for bone and joint infections consulted. All articles identified from data sources published in English were evaluated.

RESULTS: Caused primarily by Gram-positive pathogens such as S. aureus and, to a lesser extent, Enterococcus faecalis, bone and joint infections are difficult to treat successfully. Surgical intervention and prolonged courses of antibiotics are frequently required, and failure of first-line antibiotic therapy is common. The emergence of S. aureus strains with reduced susceptibility to vancomycin, the longstanding gold standard for bone and joint infections, has complicated the clinical scenario. Few randomized trials comparing the efficacy of different antibiotics for bone and joint infections exist. Daptomycin, a novel intravenous lipopeptide antibiotic, has shown potent in vitro activity against a broad spectrum of Gram-positive bacteria, including many resistant pathogens commonly associated with bone and joint infections such as MRSA and vancomycin-resistant E. faecalis. Early clinical investigation of daptomycin in bone and joint infections unresponsive to antibiotics, such as vancomycin, has found a cure rate of approximately 80%, with a low incidence of adverse events and drug resistance.

CONCLUSION: Further studies are warranted to determine if limited clinical evidence, described in individual case reports and a daptomycin-specific retrospective registry, suggests daptomycin is a promising option for patients with bone and joint infections such as MRSA osteomyelitis.


Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: A randomized controlled trial.

Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: A randomized controlled trial.

Scand J Prim Health Care. 2008 Nov

Bjerrum L, Gahrn-Hansen B, Grinsted P.
Research Unit for General Practice, University of Southern Denmark.


To investigate whether short-term treatment with pivmecillinam was more effective than sulfamethizole in patients with acute uncomplicated urinary tract infection (UTI). Design. Randomized controlled trial. Setting. General practice, Denmark.


Patients (n =167) with uncomplicated UTI confirmed by positive urine phase-contrast microscopy. Main outcome measures. Drug efficacy based on clinical and bacteriological cure.


Urinary symptoms disappeared first in patients treated with pivmecillinam, but after five days there was no significant difference in clinical cure rate between the two antibiotics. At the follow-up visit 7-10 days after initiation of treatment, 95.4% of patients treated with pivmecillinam and 92.6% of patients treated with sulfamethizole had no persistent cystitis symptoms (difference 2.8%, CI -4.5%; 10.0%).

Bacteriological cure was observed in 68.8% of patients randomized to pivmecillinam and in 77.9% randomized to sulfamethizole (difference -9.2%, CI -24.7%; 6.3%). Some 26.8% of patients randomized to pivmecillinam experienced a new UTI within 6 months after treatment compared with 18.4% of patients randomized to sulfamethizole (difference 8.4%, CI -4.5%;21.4%). No patients developed septicaemia with urinary pathogens within one year after initial treatment.


Patients treated with a three-day regime of pivmecillinam experienced faster relief of symptoms compared with patients treated with a three-day regime of sulfamethizole. Five days after initiation of treatment there was no significant difference in clinical and bacteriological cure between the two antibiotic regimes.


Tuesday, November 04, 2008

Do we still need the aminoglycosides?

Do we still need the aminoglycosides?

Int J Antimicrob Agents. 2008 Oct 29

Durante-Mangoni E, Grammatikos A, Utili R, Falagas ME.
Unit of Infectious & Transplant Medicine, 2nd University of Naples, Monaldi Hospital, Naples, Italy.

Since the introduction into clinical practice of the aminoglycoside class of antibiotics, a number of other antimicrobial agents with improved safety profile have entered the market. Studies have failed to demonstrate the superiority of aminoglycoside-containing regimens in a number of infection settings. This has raised doubts regarding the actual clinical utility of aminoglycosides. However, the recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reconsider these 'old' antibacterial agents. This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Although some of the aminoglycosides retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world, the relatively frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatment make physicians reluctant to use these compounds in everyday practice. We believe that recent advances in the understanding of the effect of various dosage schedules of aminoglycosides on toxicity combined with the retained (to a considerable degree) activity against the majority of Gram-negative bacterial isolates make this class of antibiotics still valuable in today's clinical practice.

PMID: 18976888 [PubMed - as supplied by publisher]

Rational antibiotic therapy of urinary tract infections

Rational antibiotic therapy of urinary tract infections

Med Monatsschr Pharm. 2008 Oct

Wagenlehner FM, Naber KG, Weidner W.
Klinik und Poliklinik für Urologie und Kinderurologie, Justus-Liebig-Universität Giessen, Rudolf-Buchheim-Str. 7, 35385 Giessen.

Rational antibiotic therapy of urinary tract infections Urinary tract infections (UTI) are frequent infections in the outpatient and nosocomial setting. Generally UTI can be stratified into uncomplicated and complicated infections with respect to treatment options. Uncomplicated UTI are mainly caused by E. coli, whereas complicated UTI exhibit a broader bacterial spectrum with a higher rate of multiresistant uropathogens. On the other hand increasing resistance rates are also found in uncomplicated UTI, e.g. against aminopenicillins, Co-trimoxazol and increasingly also fluoroquinolones. This fact has to be considered in the empirical therapy. Recurrent UTI are frequently found in young, sexually active women, and postmenopausal women. In complicated UTI the complicating factors have to be diagnosed and treated additionally to the antibiotic treatment. If not treated, a severe UTI and urosepsis can develop.

PMID: 18972869 [PubMed - in process]

Sunday, October 26, 2008



Trans R Soc Trop Med Hyg. 2008 Oct 21

Davidson RN, den Boer M, Ritmeijer K.
Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ, UK.

Paromomycin is an aminoglycoside that is active against Gram-negative and many Gram-positive bacteria as well as some protozoa and cestodes. It is out of use as an antibiotic but was licensed in 2007 in India as an effective, well tolerated and affordable treatment for visceral leishmaniasis (VL) at a dose of 11mg/kg (base) for 21 days. Currently, the non-profit group Drugs for Neglected Diseases Initiative is conducting studies on paromomycin (as monotherapy and in combination) in VL in Africa, and the Institute for OneWorld Health is conducting a Phase IV study in India. Paromomycin in combination with sodium stibogluconate has proven to be effective in African and Indian VL and improves survival in African VL. To prevent the emergence of drug-resistant leishmaniasis in areas of anthroponotic transmission (India and Africa), paromomycin should be used as part of combination therapy for VL. Further trials testing different combinations are much needed. In addition, the distribution of paromomycin (like other drugs for leishmaniasis) should be well regulated and preferably restricted to the public sector. These strategies should ensure the longevity of paromomycin as a useful drug for VL


Friday, August 15, 2008

Isolation, Structure, and Antibacterial Activity of Philipimycin

Isolation, Structure, and Antibacterial Activity of Philipimycin, A Thiazolyl Peptide Discovered from Actinoplanes philippinensis MA7347.

J Am Chem Soc. 2008 Aug

Zhang C, Occi J, Masurekar P, Barrett JF, Zink DL, Smith S, Onishi R, Ha S, Salazar O, Genilloud O, Basilio A, Vicente F, Gill C, Hickey EJ, Dorso K, Motyl M, Singh SB.

Bacterial resistance to antibiotics, particularly to multiple drug resistant antibiotics, is becoming cause for significant concern. The only really viable course of action is to discover new antibiotics with novel mode of actions. Thiazolyl peptides are a class of natural products that are architecturally complex potent antibiotics but generally suffer from poor solubility and pharmaceutical properties. To discover new thiazolyl peptides potentially with better desired properties, we designed a highly specific assay with a pair of thiazomycin sensitive and resistant strains of Staphylococcus aureus, which led to the discovery of philipimycin, a new thiazolyl peptide glycoside. It was isolated along with an acid-catalyzed degradation product by bioassay-guided fractionation. Structure of both compounds was elucidated by extensive application of 2D NMR, 1D TOCSY, and HRESIFT-MS/MS. Both compounds showed strong antibacterial activities against Gram-positive bacteria including MRSA and exhibited MIC values ranging from 0.015 to 1 mug/mL. Philipimycin was significantly more potent than the degradation product. Both compounds showed selective inhibition of protein synthesis, indicating that they targeted the ribosome. Philipimycin was effective in vivo in a mouse model of S. aureus infection exhibiting an ED 50 value of 8.4 mg/kg. The docking studies of philipimycin suggested that a part of the molecule interacts with the ribosome and another part with Pro 23, Pro 22, and Pro 26 of L11 protein, which helped in explaining the differential of activities between the sensitive and resistant strains. The design and execution of the bioassay, the isolation, structure, in vitro and in vivo antibacterial activity, and docking studies of philipimycin and its degradation product are described.

PMID: 18698773 [PubMed - as supplied by publisher]

Thursday, August 07, 2008

Tobramycin-induced hepatotoxicity

Tobramycin-induced hepatotoxicity

Ann Pharmacother. 2007 Dec

Nisly SA, Ray SM, Moye RA.
College of Pharmacy and Health Sciences, Butler University, Indianapolis, IN, USA.

OBJECTIVE: To report a case of tobramycin-induced hepatotoxicity.

CASE SUMMARY: A 20-year-old female was hospitalized for treatment of Pseudomonas aeruginosa bacteremia and osteomyelitis. Empiric intravenous antibiotic therapy with piperacillin/tazobactam, vancomycin, and ciprofloxacin was started, and based on the results of culture and sensitivity testing, was changed to intravenous ceftazidime and tobramycin 70 mg every 8 hours on hospital day 3. Liver enzyme levels then increased over days 3-6. Tests for hepatitis A, B, and C were all nonreactive, and HIV testing was negative. On day 8, therapy was changed from ceftazidime to piperacillin/tazobactam and the tobramycin dose was increased to 100 mg every 8 hours. Due to a continued increase in total bilirubin, aspartate aminotransferase, and alanine aminotransferase, piperacillin/tazobactam was discontinued and aztreonam was started on day 10. All antibiotics were stopped on day 12 and the elevated liver parameters began to decrease. Aztreonam and ciprofloxacin were restarted on day 16, and most laboratory test results returned to baseline levels by day 19; total bilirubin and alkaline phosphatase decreased to lower than baseline values.

DISCUSSION: This case illustrates a possible occurrence of tobramycin-induced hepatotoxicity. Liver enzymes rose when tobramycin therapy was initiated, markedly increased when the tobramycin dose was increased, then resolved upon discontinuation of therapy. Other medication-related causes were ruled out by temporal relationship or rechallenge (aztreonam). Use of the Naranjo probability scale indicated a possible relationship between hepatotoxicity and tobramycin therapy. Other adverse reaction scales specific for evaluation of drug-induced liver disease were also used. Both the Council for International Organizations of Medical Sciences and Maria and Victorino scales indicated a probable likelihood of tobramycin-induced hepatotoxicity. This patient was not rechallenged with tobramycin due to the highly suggestive timeline present, lack of specific symptoms, and unnecessary risk to the patient.

CONCLUSIONS: Although no other case reports on this interaction have been published through October 9, 2007, historical data from tertiary sources reveal the possibility of aminoglycoside-induced hepatotoxicity; therefore, tobramycin-induced hepatotoxicity cannot be ruled out in this patient. Clinicians should be aware of this adverse event.

Annals of Pharmacotherapy

Neuralgic Amyotrophy Associated with Antibiotic Therapy

Neuralgic Amyotrophy Associated with Antibiotic Therapy

Ann Pharmacother. 2008 Aug

Finstad K, Guajardo JR, Scoville C.
Department of Child Health, University Hospital and Clinics, Columbia, MO.

OBJECTIVE: To report a case of neuralgic amyotrophy associated with antibiotic therapy.

CASE SUMMARY: A 22-year-old male with cystic fibrosis had been nonadherent to treatment for 4 years; when he returned to the clinic with symptoms, his forced expiratory volume in 1 second dropped from 84% predicted to 43% predicted. He was admitted to the hospital for treatment after failing to improve on oral ciprofloxacin and inhaled tobramycin. Treatment was initiated with intravenous tobramycin 560 mg daily and piperacillin/tazobactam 4.5 g infused every 6 hours. He continued inhaled tobramycin 300 mg twice daily, his home doses of pancreatic replacement enzymes and vitamins, albuterol 2.5 mg by high flow nebulizer (HFN) 4 times daily, and dornase alpha 2.5 by HFN daily. Sputum cultures were positive for methicillin-resistant Staphylococcus aureus, and intravenous vancomycin 1 g every 8 hours was added to the treatment regimen on hospital day 7. The patient developed bilateral shoulder pain followed by decreased function of his upper extremities 2 days later. He was treated with oral ibuprofen 600 mg every 6 h and oral cyclobenzaprine 5 mg daily, which improved his pain, but the shoulder stiffness remained throughout his hospital stay and persisted for 2 months following discharge. These symptoms resolved but recurred rapidly (within 24 h) and were more debilitating following a second exposure to the same antibiotics at the same doses 8 months later when the patient was readmitted for treatment of another cystic fibrosis-related pulmonary exacerbation.

DISCUSSION: To our knowledge, this is the first case report illustrating neuralgic amyotrophy triggered by exposure to the antibiotics vancomycin, tobramycin, and piperacillin/tazobactam. After analysis of the case, ruling out other possibilities and using the Naranjo probability scale, we found that there is a highly probable likelihood that the symptoms presented by our patient were secondary to his drug therapy. Neuralgic amyotrophy is a rare condition of unknown etiology that has never before been associated with administration of these antibiotics, individually or in combination. Because of the specifics of the clinical history, we were unable to ascertain whether this complication was due to a single antibiotic or to the combination. It is quite possible that vancomycin was the only culprit, but impossible to ensure with the available evidence.

CONCLUSIONS: Clinicians should be aware of this adverse reaction when facing similar complex neurologic symptoms in patients who are receiving the antibiotic treatment described here, especially vancomycin.

PMID: 18682542 [PubMed - as supplied by publisher]

Wednesday, August 06, 2008

Tigecycline: a critical update.

Tigecycline: a critical update.
J Chemother. 2008 Jul

Shakil S, Akram M, Khan AU.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, India.

Tigecycline is the first Food and Drug Administration (FDA) approved glycylcycline antibiotic. It has shown remarkable in vitro activity against a wide variety of gram-positive, gram-negative and anaerobic bacteria including many multidrug resistant (MDR) strains. However, it has minimal activity against Pseudomonas aeruginosa and Proteus spp. To date, little resistance to tigecycline has been reported. Clinical trials studying complicated skin and skin-structure infections (cSSSIs) demonstrated that tigecycline has equivalent efficacy and safety compared with the combination of vancomycin and aztreonam. For complicated intra-abdominal infections (cIAIs), tigecycline was found to be as effective as imipenem/cilastatin. Adverse events related to tigecycline therapy, i.e. nausea and vomiting, were tolerable. Currently available data suggest that tigecycline may play an important role in the future as a monotherapy alternative to older broad-spectrum antibiotics, such as advanced generation cephalosporins, carbapenems, fluoroquinolones, piperacillin/tazobactam, and gram-positive directed agents (e.g. daptomycin, linezolid and quinupristin/dalfopristin) for which resistance is being increasingly reported from all parts of the world.

PMID: 18676218 [PubMed - in process]

Monday, August 04, 2008

Daptomycin, a lipopeptide antibiotic in clinical practice.

Daptomycin, a lipopeptide antibiotic in clinical practice.
Curr Opin Investig Drugs. 2008 Aug

Weis F, Beiras-Fernandez A, Schelling G.
Department of Anesthesiology, University Hospital Grosshader, Marchioninistrasse 15, 81377, Munich, Germany.

Gram-positive cocci are one of the leading causes of infections in clinical medicine. Since the invention of antibiotic substances, multidrug resistance is a major problem in the treatment of such infections. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for 60% of nosocomial infections in the US. The first-choice drug used in these cases is the glycopeptide vancomycin; however, vancomycin is associated with a significant number of adverse side effects, such as nephro- and ototoxicity. Thus, the discovery of new drugs against MRSA and other multidrug-resistant cocci is of utmost interest. Daptomycin, a lipopeptide, is one of these new drugs and has been successfully used in the treatment of complicated skin and skin-structure infections and right-sided endocarditis. Because of its potency and pharmacological profile, it is increasingly used for new indications not yet approved by the FDA. The purpose of this article is to provide an overview of daptomycin, with particular emphasis on potential new indications for which it could be used in the future.


Bacteriophage therapy in children: Facts and prospects

Bacteriophage therapy in children: Facts and prospects

Med Sci Monit. 2008 Aug

Fortuna W, Miedzybrodzki R, Weber-Dabrowska B, Gorski A.
Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland and Phage Therapy Unit, Healthcare Center, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

Data from the World Health Organization confirm a decrease in the effectiveness of antibiotic therapy. The spread of bacteria resistant to several groups of antibiotics creates more problems in the treatment of various diseases, especially in children. It is possible that pharmacological agents may prove to be ineffective in curing infections caused by resistant pathogens, and this could lead to a post-antibiotic era. It is necessary to extend the arsenal of the available therapeutic tools. Bacteriophages have long been used therapeutically and prophylactically in children. In the beginnings of phage therapy, enthusiasm prevailed over the rational methods used in contemporary controlled studies. Many people dealing with phages described cases of successful therapy, but did not conduct comparative studies. Nevertheless, phage administration seems to be safe, even in children after intravenous administration. The therapeutic and prophylactic application of phages is now experiencing a renaissance of interest. The authors' own recent analysis demonstrated the cost effectiveness of phages over antibiotic especially in the treatment of infections caused by multidrug-resistant bacteria. It can be concluded that the results of the therapeutic and prophylactic application of phages against multi-drug resistant pathogens are encouraging. It seems clear that bacteriophages need further evaluation regarding the control of bacterial infection in children.


A new lipoglycopeptide: telavancin.

A new lipoglycopeptide: telavancin.

Expert Opin Pharmacother. 2008 Aug

Nannini EC, Stryjewski ME.
Sanatorio Parque, Division of Infectious Diseases, Argentina.

The increase in infections caused by resistant Gram-positive organisms has led to an urgent need for new antibiotics. Telavancin is a rapidly bactericidal lipoglycopeptide with multiple mechanisms of action, including concentration-dependent inhibition of bacterial cell wall synthesis and disruption of the functional integrity of the cell membrane. Telavancin is active against a wide variety of Gram-positive organisms including Staphylococcus aureus with resistance to methicillin, reduced susceptibility to vancomycin, and full resistance to vancomycin. Telavacin is approximately 90% protein bound; it has a serum half-life of around 8 h and a prolonged postantibiotic effect, allowing once daily administration. Telavancin is eliminated principally through the urine, requiring dose adjustment in patients with renal impairment. The efficacy and safety of telavancin was demonstrated in a large program of patients with complicated skin and skin structure infections. Development of resistance has not been detected in clinical strains. Adverse events include taste disturbance, nausea and vomiting; a small proportion of patients experienced reversible increase in serum creatinine. Two large Phase III studies in patients with healthcare associated pneumonia were recently completed. Telavancin has the potential to become an important therapeutic option to treat serious infections produced by resistant Gram-positive cocci, particularly those caused by methicillin-resistant S. aureus.

Expert Opinion

Thursday, July 17, 2008

Ciprofloxacin-induced acute cholestatic liver injury and associated renal failure. Case report and review.

Ciprofloxacin-induced acute cholestatic liver injury and associated renal failure. Case report and review.
Minerva Gastroenterol Dietol. 2008 Sep

Dichiara AJ, Atkinson M, Goodman Z, Sherman KE.
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

Ciprofloxacin, a commonly prescribed fluoroquinolone antibiotic, has generally been well-tolerated; however, there are rare reports of associated hepatic failure or renal failure. We describe a case of a 65 year-old man with a history of ischemic cardiomyopathy who was treated with ciprofloxacin 500 mg twice daily for cellulitis. Six days into his treatment course, he developed acute cholestatic jaundice and acute anuric renal failure. Clinical, laboratory, and pathologic data suggest that the patient had developed reversible, severe ciprofloxacin-induced cholestatic liver injury and acute tubular necrosis requiring hemodialysis. Within two months of stopping the ciprofloxacin, the patient was off dialysis and back to his baseline creatinine in three months. Liver tests normalized by five months.

This report illustrates a case of cholestatic liver injury and renal failure involving ciprofloxacin use.

We review the literature regarding hepatic and renal injury as it relates to ciprofloxacin. To our knowledge, this represents the first case report of simultaneous acute cholestatic liver injury and renal failure secondary to ciprofloxacin.


Sunday, July 13, 2008

Tigecycline for the Treatment of Acinetobacter Infections: A Case Series September

Tigecycline for the Treatment of Acinetobacter Infections: A Case Series September
Ann Pharmacother. 2008 Jul 9

Gallagher JC, Rouse HM.
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, ILClinical Assistant Professor; Clinical Specialist, Infectious Diseases, Temple University School of Pharmacy, Philadelphia, PA.

BACKGROUND: Acinetobacter infections resistant to multiple classes of antibiotics have become prevalent in many institutions. Tigecycline has in vitro activity against Acinetobacter spp. and has been suggested as a therapeutic option in these infections.

OBJECTIVE: To describe the clinical and microbiologic outcomes of patients who received tigecycline for the treatment of infections caused by Acinetobacter spp. at our institution.

METHODS: A retrospective review was conducted of the medical records of 29 sequential patients who received tigecycline for treatment of Acinetobacter infections. The outcomes assessed for efficacy were clinical improvement or cure and microbiologic cure in evaluable patients.

RESULTS: Patients received tigecycline a median of 30 days into hospitalization for a median of 11 days. Common indications were pneumonia (15 pts.), bacteremia (6), and urinary tract infection (3). Positive clinical outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of the 25 microbiologically evaluable patients, 11 (44%) had resolution of their cultures. Eleven patients had susceptibility testing performed, and the median minimum inhibitory concentration was 4 microg/mL (range 3-8).

CONCLUSIONS: In this case series, most patients did not have clinically or microbiologically favorable outcomes with tigecycline therapy. No patient had an isolate that was fully susceptible to tigecycline. Data from more studies are needed before tigecycline can be recommended for the treatment of Acinetobacter infections.

Annals of Pharmacotherapy (PubMed)

Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?

Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?
Curr Opin Crit Care. 2008 Aug

Roberts JA, Lipman J, Blot S, Rello J.
Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia.

PURPOSE OF REVIEW: Increasing interest is being directed toward possible benefits associated with continuous infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed.

RECENT FINDINGS: One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing continuous infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics.

SUMMARY: Continuous infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for continuous infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.

Lippincott, Williams & Wilkins

Sunday, June 29, 2008

Reduction of unnecessary IV antibiotic days using general criteria for antibiotic switch.

Reduction of unnecessary IV antibiotic days using general criteria for antibiotic switch.

Scand J Infect Dis. 2008

Waagsbø B, Sundøy A, Quist Paulsen E.
From the Medisinsk avdeling, Sørlandet Sykehus Kristiansand, Norway.

This study was designed to help physicians consider change from intravenous to oral antibiotic therapy for any infection from d 3 of hospital stay, by implementing guidelines for antibiotic switch. A 2-centre intervention study was conducted at Sorlandet Hospital HF Kristiansand and Arendal. All patients admitted to the Medical Clinic at these hospitals prescribed with intravenous antibiotics at hospitalization, were included. After collecting data in an observation period, antibiotic switch guidelines were launched in the respective departments of both hospitals. The length of unnecessary intravenous d, duration of hospital stay and outcome of treatment were compared before (observation group) and after (intervention group) the guidelines were implemented. Antibiotic switch was considered from d 3 and onward. The effect of switch guidelines implementation was measured as a reduction of unnecessary intravenous d. Duration of unnecessary intravenous antibiotic therapy was significantly reduced from 3.4 d in the observation group to 1.4 d in the intervention group. Unnecessary intravenous d were found to constitute 83% of total intravenous therapy duration in the observation group and 48% in the intervention group. Duration of hospital stay was significantly reduced from 7.0 to 6.3 d. There was no statistically significant difference in mortality rate, re-prescription of intravenous antibiotic therapy or re-admittance to the hospital. In conclusion, implementing antibiotic switch guidelines significantly reduces the duration of unnecessary intravenous antibiotic therapy. The switch guidelines were based on general criteria for antibiotic switch for any infection.


Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs.

Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs.

Scand J Infect Dis. 2008

Erlandsson M, Gill H, Nordlinder D, Giske CG, Jonas D, Nilsson LE, Walther S, Hanberger H.
From the Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping.

Pseudomonas aeruginosa is 1 of the bacteria most adaptive to anti-bacterial treatment. Previous studies have shown nosocomial spread and transmission of clonal strains of P. aeruginosa in European hospitals. In this study we investigated antibiotic susceptibility and clonality in 101 P. aeruginosa isolates from 88 patients admitted to 8 Swedish ICUs during 2002. We also compared phenotypes and genotypes of P. aeruginosa and carried out cluster analysis to determine if phenotypic data can be used for surveillance of clonal spread. All isolates were collected on clinical indication as part of the NPRS II study in Sweden and were subjected to AFLP analysis for genotyping. 68 isolates with unique genotypes were found. Phenotyping was performed using MIC values for 5 anti-pseudomonal agents. Almost 6% of the isolates were multi-drug resistant (MDR), and this figure rose to almost 8% when intermediate isolates were also included. We found probable clonal spread in 9 cases, but none of them was found to be an MDR strain. Phenotypical cluster analysis produced 40 clusters. Comparing partitions did not demonstrate any significant concordance between the typing methods. The conclusion of our study is that cross-transmission and clonal spread of MDR P. aeruginosa does not present a clinical problem in Swedish ICUs, but probable cross-transmission of non-MDR clones indicate a need for improved hygiene routines bedside. The phenotype clusters were not concordant with genotype clusters, and genotyping is still recommended for epidemiological tracking.