Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery

Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery

Int J Immunopathol Pharmacol. 2009 April-June

Macchi A, Castelnuovo P.
Department of Otorhinolaryngology University of Insubria, Varese, Azienda Ospedaliero Universitaria Ospedale di Circolo e Fondazione Macchi, Varese, Italy.

Tonsillectomy and adenoidectomy remain the first choice treatment of chronic or recurrent acute infections of the upper respiratory tract in children. The aim of this study is to investigate the efficacy of the combination of thiamphenicol glycinate acetylcysteinate plus beclomethasone, administered as aerosol, in children awaiting tonsillectomy and/or adenoidectomy. The study comprised 204 children, aged 1 to 12 years, with chronic adenotonsillitis who had been listed for surgery due to obstructive symptoms and recurrent acute infections. Patients were randomized to treatment with thiamphenicol glycinate acetylcysteinate, dosage 250 mg/day in 2 administrations plus beclomethasone with a dosage of 400 μg/day in 2 administrations, or no treatment, control group, unless required. The drugs were administered by aerosol for 10 days/month over a period of 6 months. Clinical visits were at 4, 7 and 12 months after the start of treatment. The primary efficacy outcome was the reduction in the number of patients requiring surgery. Secondary efficacy measures were the reduction of nasal obstruction, the decrease in the number of infectious episodes and the tolerability of the treatment. Aerosol treatment with thiamphenicol glycinate acetylcysteinate plus beclomethasone resulted in a significantly lower proportion of patients requiring surgery (29 of 101; 29 percent) compared to patients in the control group (100 of 103; 97 percent) (p < 0.0001). Treatment was also associated with a reduction of nasal obstruction and a decrease in the number of infectious episodes. No treatment-related adverse events were reported and the aerosol therapy proved easy to administer to children. The aerosol therapy with the combination of thiamphenicol glycinate acetylcysteinate plus beclomethasone was able to prevent or postpone surgery in a substantial percentage of patients, without adverse events. These preliminary results suggest that this novel approach could play a role in the antibiotic prophylaxis of chronic infectious diseases of the upper airways.

PubMed

Current topical and systemic approaches to treatment of rosacea

Current topical and systemic approaches to treatment of rosacea
J Eur Acad Dermatol Venereol. 2009 Jun

Korting H, Schöllmann C.
Department of Dermatology and Allergology, Ludwig-Maximilians-Universität, Munich, Germany.

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline.

Conventionally, 100-200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

PubMed

Antibiotics and probiotics in inflammatory bowel disease: why, when, and how

Antibiotics and probiotics in inflammatory bowel disease: why, when, and how
Curr Opin Gastroenterol. 2009 May 11

Prantera C, Scribano ML.
Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.

PURPOSE OF REVIEW: To summarize recent evidence on the role of intestinal bacteria in inflammatory bowel diseases, and of antibiotics and probiotics in their treatment. The implications connected with the use of antibiotics are also examined.

RECENT FINDINGS: The hypothesis that Mycobacterium paratuberculosis could be a causative agent of Crohn's disease has not been confirmed by a large trial on symptomatic patients treated by a combination of antibiotics active against this bacterium. An increased number of adherent-invasive Escherichia coli have been found in the intestinal tissue of patients with Crohn's disease, but their role in the pathogenesis of this condition remains to be defined. The combination of metronidazole and azathioprine, associating the effects of a reduced bacterial load with immunosuppression, appears to be a therapeutic option to decrease the recurrence of postoperative Crohn's disease in high-risk patients. However, concerns are raised by the possibility that antibiotics may induce disease relapse due to Clostridium difficile infection.

SUMMARY: Recent literature provides increasing support for the use of antibiotics in Crohn's disease, although the side effects limit their long-term use. The efficacy of antibiotics in ulcerative colitis is not confirmed by the available literature, except in severe colitis. More trials are needed to support the use of probiotics as therapy in inflammatory bowel disease.

PMID: 19444096 [PubMed - as supplied by publisher]

Antibiotic Use in Premature Infants After Discharge From the Neonatal Intensive Care Unit.

Antibiotic Use in Premature Infants After Discharge From the Neonatal Intensive Care Unit.
Clin Pediatr (Phila). 2009 May 15

Lorch SA, Wade KC, Bakewell-Sachs S, Medoff-Cooper B, Silber JH, Escobar GJ.

Using a retrospective cohort of premature infants, we constructed multivariable Poisson models to determine factors associated with the receipt of antibiotics during the first year after discharge, N = 891. Black race (incidence rate ratio 1.80 compared with White infants, P = .008), male gender (incidence rate ratio 1.44; P = .007), bronchopulmonary dysplasia (incidence rate ratio 1.47; P = .04), and each additional child at home (incidence rate ratio 1.21, P = .002) increased the receipt of antibiotics for any reason. Male gender and additional children at home increased the receipt of nonrecommended antibiotics, while Black infants received care at facilities that prescribed more nonrecommended antibiotics. Even in a high-risk population of children, factors other than the medical history and presentation of the child may alter antibiotic prescription patterns and result in variations in care.

PMID: 19448131 [PubMed - as supplied by publiusher]

Antimicrobial and antibiofilm efficacy of triclosan and DispersinB(R) combination

Antimicrobial and antibiofilm efficacy of triclosan and DispersinB(R) combination
Antimicrob Chemother. 2009 May 14

Darouiche RO, Mansouri MD, Gawande PV, Madhyastha S.
Center for Prostheses Infections and Infectious Disease Section, Michael E. Debakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.

Objectives: The objectives of this study were to examine: (i) synergy of the combination of triclosan and DispersinB((R)) (DspB); (ii) in vitro efficacy and durability of triclosan + DspB-coated vascular catheters; and (iii) in vivo efficacy of triclosan + DspB-coated catheters compared with chlorhexidine-silver sulfadiazine (CH-SS)-coated and uncoated (control) vascular catheters in preventing colonization by Staphylococcus aureus.

Methods: We investigated the potential synergistic antimicrobial and antibiofilm activity of triclosan and DspB by biofilm assays. The in vitro antimicrobial efficacy of triclosan + DspB-coated catheters was determined by microbial colonization assays. Antimicrobial durability of the coated catheters was tested by soaking segments in bovine serum for 7 days and determining antimicrobial activity, and by a serial plate transfer method. The in vivo efficacy of triclosan + DspB-coated catheters compared with CH-SS-coated and uncoated catheters was assessed by subcutaneous implantation of segments in a rabbit model of S. aureus infection.

Results: The combination of triclosan and DspB showed synergistic antimicrobial and antibiofilm activity against S. aureus, Staphylococcus epidermidis and Escherichia coli, significantly reduced bacterial colonization (P less then 0.05) and generally demonstrated a prolonged superior antimicrobial activity against clinical pathogens compared with CH-SS-coated catheters. Triclosan + DspB-coated and CH-SS-coated catheters exhibited equal in vivo efficacy (P less then/= 0.05) in reducing colonization by S. aureus compared with uncoated catheters.

Conclusions: Catheters coated with the triclosan + DspB combination showed synergistic, broad-spectrum and durable antimicrobial activity. Furthermore, the in vivo efficacy of catheters coated with this unique antimicrobial/antibiofilm composition prompts clinical evaluation of such an innovative approach.

PMID: 19447791 [PubMed - as supplied by publisher]

Maintaining a Sterile Urinary Tract: The Role of Antimicrobial Peptides

Maintaining a Sterile Urinary Tract: The Role of Antimicrobial Peptides
Urol. 2009 May 16

Ali AS, Townes CL, Hall J, Pickard RS.
Newcastle University, Newcastle upon Tyne, United Kingdom.

PURPOSE: The normally sterile urinary tract is constantly challenged by microbial invasion leading to a high prevalence of isolated, recurrent and catheter associated urinary tract infection. The continuous emergence of bacterial resistance following overuse of traditional antibiotics requires the urgent development of alternative treatment strategies. The involvement of innate immune mechanisms in host defense is an emerging field of microbiological research with recent work focusing on the urinary tract. We performed a comprehensive literature review to establish the current level of knowledge concerning the role of innate immunity and specifically antimicrobial peptides within the human urinary tract.

MATERIALS AND METHODS: A systematic review of the literature was performed by searching PubMed(R) from January 1988 to September 2008. Electronic searches were limited to the English language using the key words antimicrobial, peptide and urinary. Reference lists from relevant reviews were hand searched and appropriate articles were retrieved. The proceedings of conferences held in the last 2 years by the American Urological Association, European Association of Urology and British Association of Urological Surgeons were also searched.

RESULTS: Several defensive mechanisms have evolved in response to the threat of urinary infection, comprising physical factors and innate immune responses characterized by the expression of antimicrobial peptides. Antimicrobial peptides are small (less than 10 kDa), cationic and amphipathic peptides of variable length, sequence and structure with broad spectrum killing activity against a wide range of microorganisms including gram-positive and gram-negative bacteria. Several antimicrobial peptides have been identified in the urinary tract, and the amount and type of antimicrobial peptides expressed vary according to tissue source and disease state. These differences may reflect altered levels of innate response and, hence, susceptibility to infection. Antimicrobial peptides are already being exploited therapeutically for skin and endovascular catheter infection, and prospects for useful application in the urinary tract are emerging.

CONCLUSIONS: Although investigation of antimicrobial peptide function in the human urinary tract is at an early stage, it is clear that there is considerable potential for the future design of novel therapeutic strategies. More knowledge is needed concerning the pathway of involvement of antimicrobial peptides in the maintenance of urinary tract sterility and the ways in which this is altered during active infection.

PMID: 19447447 [PubMed - as supplied by publisher]

Prospective analysis of central venous catheter colonization and related factors

Prospective analysis of central venous catheter colonization and related factors
Enferm Clin. 2009 May 14

Pérez Castro I, Iborra Obiols MI, Comas Munar MD, Yrurzun Andreu R, Sanz Moncusí M, Lahoz Simón C, Gómez Montoya MI, Comallonga Bartomeu T, Navasa Anadón M.
Institut de Malalties Digestives i Metabóliques, Hospital Clínic de Barcelona, Barcelona, España.

OBJECTIVE: To evaluate the incidence of central venous catheter (CVC) colonization in inpatient units of the Institut de Malalties Digestives i Metabòliques (IMDiM) of Hospital Clinic (Barcelona, Spain) with a view to reducing the risk of infection.

METHOD: A 4-month descriptive, prospective and longitudinal study was performed. A total of 230 patients admitted to the IMDiM with CVC were included during the study period. At catheter removal, the tip was cultured and, if the patient had fever, two blood cultures were also obtained. A database was created. Data were analyzed using SPSS v.11.0. Variables were compared with the Chi-square and Student's t-tests and a multivariate analysis was performed using Cox logistic regression. A value of P 0.05

RESULTS: Catheter tip culture was positive in 45.2%. The rate of catheter-related bloodstream infections was 2.9 per thousand catheter-days, which was clinically significant. The probability of catheter tip contamination 10 days after placement was 25%. Multivariate analysis revealed that the independent variables associated with a higher risk of infection were catheter type, changes of dressing, and infected bacterial stopcocks.

CONCLUSIONS: These results suggest that: 1) the protocol for catheter insertion and care should be reviewed and updated, 2) catheter removal should be considered after the 10th day, 3) the appropriate type of catheter should be selected, the catheter with the lowest number of lumens should be used, and changes of catheter dressing should be reduced.

PMID: 19447058 [PubMed - as supplied by publisher]

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. andrew.seaton@ggc.scot.nhs.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]

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.

PubMed

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. KMK@otc.isu.edu

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.

ScienceDirect

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. william.martone@cubist.com

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

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.

Springerlink

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.

Objective.

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.

Subjects.

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

Results.

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.

Conclusion.

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.

Informaworld

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. Wagenlehner@AOL.com

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]

Paromomycin.

Paromomycin

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

Elsevier

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]