Bacteriological Response Research Articles

Effectiveness of anti-tuberculosis treatment among patients receiving highly active antiretroviral therapy at Vihiga District Hospital in 2007

Purpose: In Kenya there is need for proper co-ordination of antiretroviral therapy (ART) and tuberculosis (TB) treatment as most (60%) of the TB patients are also human immunodeficiency virus (HIV) positive. This study aims to determine the difference in response to TB treatment among HIV-negative TB patients and HIV-positive TB patients receiving delayed highly active antiretroviral therapy (HAART) at Vihiga District Hospital. Materials andMethods: A total of 116 patients were diagnosed using direct smears from sputum prepared and stained using the Ziehl-Neelsen procedure. The patients were offered HIV testing and counselling, and then categorized into category A (PTB with HIV n =50) and category B (PTB without HIV co-infection n =66). They were put on the same TB chemotherapy of a short course comprising of: Two months of Rifampicin-R, Isoniazid-H, Pyrazinamide-Z and plain Ethambutal-E, followed by six months of Ethambutal and Isoniazid. The main outcome measured was the sputum conversion rate from positive sputum to negative sputum. One way analysis of variance (ANOVA) was used to test the null hypothesis. Results: Fifty patients (43%) were found to be HIV positive and were put on HAART. The other 66 patients (57%) were HIV negative. The sputum conversion rate for HIV positive TB patients after two months and five months was 88 and 94%, respectively. The sputum conversion rate for HIV negative TB patients at two months and after five months was 92 and 97%, respectively. However, there was no significant difference in the bacteriological outcome responses to TB chemotherapy between the two groups. Conclusion: The high sputum conversion rates in the two groups indicated good control and management of TB. Findings in this study indicated that delayed use of HAART during TB treatment leads to better outcome in TB treatment. The study recommends more concerted efforts to provide TB treatment to HIV positive TB patients in Kenya.

Effect of Mercurius solubilis on the bacteriological response in the alveolitis process in rats

The purpose of this study was to assess the bacteriological response in alveolitis in rats treated with the homeopathic medicine Merc solubilis (Merc sol.) 12 cH. The study was randomized and observer blind. The animals were anesthetized and the upper right incisor extracted resulting in alveolitis. Animals were randomly assigned to groups (n=18/group): Water control, Alcohol control and Merc sol. 12 cH. These groups were subsequently divided into 3 subgroups (n=6/subgroup): Early Euthanasia (EE), Mid Euthanasia (ME) and Late Euthanasia (LE), killed at the 6th, 15th and 21st days respectively. The perialveolar microbiota was collected by swab in Brain Heart Infusion (BHI) for seeding and bacterioscopy. After seeding, the Petri dishes were incubated at 37 degrees C for 48 h. Quantitative and qualitative changes were observed in the perialveolar microbiota when the groups were compared. Water control and Alcohol control had the highest counts of pathogenic bacteria, the microbiotica of the Merc sol. group remained closer to normal. Merc sol. 12 cH did not reduce bacterial growth, but the microbiotica remained within the parameters of normality, obtaining the best results at 21 days after treatment.

Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion

Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients. To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months. This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or to stop treatment. Patients were followed for relapse for 30 months after beginning treatment. Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10). Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.

Carbapenems versus other beta-lactams in the treatment of hospitalised patients with infection: a mixed treatment comparison

ABSTRACTObjective: To compare the effectiveness of meropenem with cefepime and piperacillin/tazobactam in the absence of direct comparisons in randomised controlled trials.Data sources: Two previously conducted systematic reviews, one comparing the carbapenems (ertapenem and imipenem/cilastatin) versus 4th-generation cephalosporins (cefepime) or antipseudomonal penicillins (piperacillin/tazobactam), and the other comparing the carbapenems (imipenem/cilastatin versus meropenem), were updated to provide the basis for this mixed treatment comparison. Searching was completed in April 2007. No restriction was placed on language of publication.Study selection and data extraction: Randomised controlled trials of adult patients hospitalised with infection and treated with a carbapenem or cefepime or piperacillin/tazobactam. Two reviewers independently assessed the papers against the inclusion/exclusion criteria and for methodological quality with any differences in opinion adjudicated by a third party. Two reviewers independently extracted data on clinical response, bacteriological response, mortality, and adverse events.Data synthesis: A mixed treatment comparison meta-analysis using Bayesian Markov Chain Monte Carlo simulation was used to perform the indirect comparison. The dataset comprised 34 trials: four comparing ertapenem versus piperacillin/tazobactam, one imipenem/cilastatin versus cefepime, 26 imipenem/cilastatin versus meropenem, three imipenem/cilastatin versus piperacillin/tazobactam. We calculated odds ratios (OR) using imipenem/cilastatin as the common comparator. Meropenem was associated with the highest probability of being the most effective treatment for clinical response (OR 1.52, 95% credible interval [CrI] 1.23–1.87) and bacteriological response (OR 1.45, 95% CrI 1.15–1.80) with a reduced risk of serious adverse events (overall: OR 0.88, 95% CrI 0.76–1.02; serious adverse events leading to withdrawal: OR 0.73, 95% CrI 0.42–1.20; and GI-related: OR 0.76, 95% CrI 0.55–1.02). There was little difference between the three carbapenems and cefepime on all-cause mortality.Conclusions: This mixed treatment comparison suggests meropenem has substantial advantages over cefepime, ertapenem, imipenem/cilastatin and piperacillin/tazobactam in the treatment of hospitalised patients with infection.

Update on the Efficacy and Tolerability of Meropenem in the Treatment of Serious Bacterial Infections

Meropenem is a carbapenem antibiotic approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and pediatric bacterial meningitis (in patients >or=3 months of age). In clinical trials, it also has shown efficacy as initial empirical therapy for the treatment of nosocomial pneumonia. Unlike other beta-lactam antibiotics, including third-generation cephalosporins, carbapenems have shown activity against extended-spectrum beta-lactamase-producing and AmpC chromosomal beta-lactamase-producing bacteria. Compared with imipenem, meropenem is more active against gram-negative pathogens and somewhat less active against gram-positive pathogens, and it does not require coadministration of a renal dehydropeptidase inhibitor. In most comparative trials, clinical and bacteriological response rates with imipenem and meropenem were similar. Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections. Meropenem is well tolerated by children and adults and has an acceptable safety profile. Alternative meropenem dosing strategies for the optimization of outcomes are under investigation.

Intramammary infusion of a live culture ofLactococcus lactisfor treatment of bovine mastitis: comparison with antibiotic treatment in field trials

A treatment containing a live food-grade organism, Lactococcus lactis DPC3147, was compared with conventional antibiotic therapy for its potential to treat bovine chronic subclinical or clinical mastitis in two separate field trials. Effects on disease symptoms and bacteriology were monitored in response to infusion with the culture in each trial. In the first trial, the live culture treatment was compared with an intramammary antibiotic (n=11 quarters for each treatment). Results from this small trial demonstrated that the live culture had potential to be as effective at eliminating chronic subclinical infections as an antibiotic treatment. By day 12, 7 of the 11 quarters treated with the live culture were pathogen-free compared with 5 of the 11 antibiotic-treated infected quarters. Somatic cell counts (SCC) remained relatively unchanged regardless of treatment: average log SCC pre- and post-treatment in the lactococci-treated group were 6.33+/-0.41 (day 0) and 6.27+/-0.43 cells/ml (day 12) and average log SCC pre- and post-treatment in the antibiotic-treated group were 6.34+/-0.37 and 6.22+/-0.46 cells/ml on day 0 and on day 12, respectively. In the second trial, the live culture was compared with an intramammary antibiotic for the treatment of naturally occurring clinical mastitis cases (n=25 quarters for each treatment). Following a 14-d experimental period, similar bacteriological responses were observed in 7 out of 25 live culture treated quarters and 9 out of 25 antibiotic-treated quarters. Additionally, 15 of 25 cases treated with the culture and 18 of 25 cases treated with the antibiotic did not exhibit clinical signs of the disease following treatment. The results of these trials suggest that live culture treatment with Lc. lactis DPC3147 may be as efficacious as common antibiotic treatments in some instances.

Risk Factors and Mortality Associated with Default from Multidrug‐Resistant Tuberculosis Treatment

Completing treatment for multidrug-resistant (MDR) tuberculosis (TB) may be more challenging than completing first-line TB therapy, especially in resource-poor settings. The objectives of this study were to (1) identify risk factors for default from MDR TB therapy (defined as prolonged treatment interruption), (2) quantify mortality among patients who default from treatment, and (3) identify risk factors for death after default from treatment. We performed a retrospective chart review to identify risk factors for default from MDR TB therapy and conducted home visits to assess mortality among patients who defaulted from such therapy. Sixty-seven (10.0%) of 671 patients defaulted from MDR TB therapy. The median time to treatment default was 438 days (interquartile range, 152-710 days), and 27 (40.3%) of the 67 patients who defaulted from treatment had culture-positive sputum at the time of default. Substance use (hazard ratio, 2.96; 95% confidence interval, 1.56-5.62; P = .001), substandard housing conditions (hazard ratio, 1.83; 95% confidence interval, 1.07-3.11; P = .03), later year of enrollment (hazard ratio, 1.62, 95% confidence interval, 1.09-2.41; P = .02), and health district (P = .02) predicted default from therapy in a multivariable analysis. Severe adverse events did not predict default from therapy. Forty-seven (70.1%) of 67 patients who defaulted from therapy were successfully traced; of these, 25 (53.2%) had died. Poor bacteriologic response, <1 year of treatment at the time of default, low education level, and diagnosis with a psychiatric disorder significantly predicted death after default in a multivariable analysis. The proportion of patients who defaulted from MDR TB treatment was relatively low. The large proportion of patients who had culture-positive sputum at the time of treatment default underscores the public health importance of minimizing treatment default. Prognosis for patients who defaulted from therapy was poor. Interventions aimed at preventing treatment default may reduce TB-related mortality.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8) were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study--EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.

Vaccination of European badgers ( Meles meles) with BCG by the subcutaneous and mucosal routes induces protective immunity against endobronchial challenge with Mycobacterium bovis

Mycobacterium bovis is endemic in badger (Meles meles) populations of Ireland and the United Kingdom and infected badgers are a potential source of infection for cattle. In domestic livestock tuberculosis causes economic losses from lost production and the costs associated with eradication programmes, and in addition there is a risk of zoonotic infection. Whereas culling is currently used to control tuberculous badger populations in Ireland, vaccination, if it were available, would be preferred. A study was undertaken to examine the protective responses of badgers vaccinated either by the subcutaneous or mucosal (intranasal and conjunctival) routes with bacille Calmette-Guérin (BCG), when challenged with M. bovis by the endobronchial route. Three groups of badgers were used. The first group (n=4) was vaccinated with approximately 5 x 10(5) colony forming units (cfu) of BCG by subcutaneous injection. In the second group (n=5) badgers were vaccinated via the mucosal route by instilling 1.0 x 10(5)cfu into each conjunctival sac and spraying 1.0 x 10(5)cfu into each nostril (final vaccine dose of 4 x 10(5)cfu). The control (n=5) badgers served as a non-vaccinated group. Twelve weeks post-vaccination all badgers in the three groups were challenged with approximately 10(4)cfu of M. bovis by endobronchial inoculation. At 12 weeks post-infection all badgers were examined post-mortem to assess the pathological and bacteriological responses to challenge. Gross and histological lesions of tuberculosis were seen in all challenged badgers and M. bovis was recovered from all challenged badgers. However, across six of the eight parameters used to measure disease severity, the infection in the vaccinated badgers was significantly less severe than in the control group. The BCG vaccine induced a significant protective effect in the badgers and the protective immunity was generated by subcutaneous and mucosal vaccination.

Carbapenems versus other beta-lactams in treating severe infections in intensive care: a systematic review of randomised controlled trials

Carbapenems have not been comprehensively compared in clinical trials with fourth-generation cephalosporins (4GC) and antipseudomonal penicillins (APP) in the treatment of severe infections (SI) and febrile neutropenia (FN). A systematic review of CENTRAL, EMBASE, MEDLINE and JICST-EPlus for randomised controlled trials was conducted to establish the currently available evidence. Database searching was supplemented by hand searching and contacting conference organisers. Searching was completed in November 2006 and no restriction was placed on the language of publication. Data were extracted on clinical response, bacteriologic response, all-cause mortality and adverse events. Of the 265 papers identified, 12 were appropriate for meta-analysis (four 4GC and eight APP). The results showed that carbapenems are associated with a significant reduction in all-cause mortality (relative risk 0.62, 95% confidence interval: 0.41 to 0.95; p=0.03) compared to APP in the treatment of SI, and withdrawals due to adverse events (RR 0.65, 95% CI: 0.45 to 0.96; p=0.03) are also less common. When compared in the treatment of FN, carbapenems are associated with a significant increase in clinical response during the initial 72 h of treatment (RR 1.37, 95% CI: 1.09 to 1.74; p=0.008) and bacteriologic response (RR 1.73, 95% CI: 1.03 to 2.89; p=0.04). For all other outcomes, including all comparisons with 4GC, there were no significant differences between treatments. The use of carbapenems rather than APP could reduce mortality and, by simplifying treatment decisions, reduce the time before patients receive appropriate antibiotic treatment. The currently available evidence is insufficient for distinguishing between carbapenems and 4GC.

Doripenem

Doripenem, a parenteral, broad-spectrum antibacterial agent of the carbapenem family, is indicated as empirical therapy in serious bacterial infections in adults. Doripenem is indicated in Japan for use as a single agent in intra-abdominal infections (IAIs), lower respiratory tract infections (including nosocomial pneumonia), complicated urinary tract infections (cUTIs) and a variety of other bacterial infections, such as complicated skin and skin structure infections (cSSSIs), obstetric and gynaecological infections, serious ear, nose and throat infections, sepsis and endocarditis, dental and oral surgical infection, and ophthalmic infection caused by various susceptible strains of Gram-negative, Gram-positive or anaerobic bacteria. Doripenem is indicated in the US for the treatment of complicated IAIs (cIAIs) or cUTIs, including pyelonephritis, caused by susceptible strains of designated pathogens, and in the EU for the treatment of nosocomial pneumonia (including ventilator-associated pneumonia [VAP]), cIAIs or cUTIs.Doripenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, and anaerobic pathogens. The drug also has a low propensity to select for resistance and is suitable for the prolonged infusions that may be required to achieve pharmacodynamic/pharmacokinetic targets for bactericidal activity (and therefore efficacy) against pathogens with increased MICs (minimum concentrations required to inhibit the pathogens). Doripenem is no less effective than other antibacterial agents, including meropenem, imipenem/cilastin, piperacillin/tazobactam or levofloxacin in a wide range of serious bacterial infections, such as complicated lower respiratory infections, nosocomial pneumonia (including VAP), cIAIs and cUTIs, and is well tolerated. Thus, doripenem is a valuable addition to the options available for the empirical treatment of serious bacterial infections in hospitalized patients.

Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant Gram-negative bacteria: A prospective study

Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens. To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin. Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin was 2.2 (+/-0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.

Repuesta serológica y bacteriológica a la exposición al biovar 1 de Brucella abortus en búfalos de agua (Bubalus bubalis) vacunados con la cepa RB51 de Brucellus abortus

Serological and bacteriological responses to Brucella abortus biovar 1 following vaccination with B. abortus strain RB51 (RB51) were evaluated in thirty domestic water buffalo (Bubalus bubalis) randomly divided into five treatment groups. Groups I to V received, respectively, the recommended dose (RD) of RB51 vaccine once, RD twice 4 weeks apart, double RD once, double RD twice 4 weeks apart, and saline once (control). Vaccination did not result in a serological response. Experimental animals released 27 weeks post initial inoculation (27 PIIW) into a brucellosis-positive herd failed to seroconvert after 29 weeks. Experimental challenge commenced at 57 PIIW. All animals received B. abortus biovar 1 intraconjunctivally at 0, 5 and 9 weeks post experimental exposure (PEEW). Serum samples collected at 4, 8 and 13 PEEW were negative. At 16 PEEW all animals received B. abortus biovar 1 subcutaneously (SC), and all seroconverted by 20 PEEW. Five of twenty-six animals were positive for Brucella infection on bacterial culture. Brucella abortus biovar 1 was isolated from three animals; B. abortus RB51 was isolated from two. Treatment group, age and sex had no effect on the isolation of Brucellae (P>0.05).

A Randomized Study of Sequential Intravenous/Oral Moxifloxacin in Comparison to Sequential Intravenous Ceftriaxone/Oral Cefuroxime Axetil in Patients with Hospital-Acquired Pneumonia

Empiric treatment of hospital-acquired pneumonia (HAP) should be focused on the suspected pathogens. We evaluated the efficacy and safety of moxifloxacin vs ceftriaxone in patients with HAP without risk of infections with Pseudomonas aeruginosa and other non-fermentative Gram-negative bacteria. We performed a prospective, randomized, non-blind, multicentric and multinational study to compare the efficacy and safety of moxifloxacin 400 mg IV once daily followed by oral moxifloxacin 400 mg once daily to ceftriaxone 2 g IV once daily followed by oral cefuroxime axetil 500 mg twice daily to treat mild-to-moderate HAP in adult patients requiring initial parenteral therapy. The primary efficacy variable was clinical response 7-10 days after the end of a 7-14-day treatment period, secondary endpoints included clinical and bacteriologic response at different intervals for up to 31 days after treatment. The trial was terminated prematurely due to slow patient recruitment. A total of 161 subjects (87 men, 74 women) between 18 and 95 years of age were enrolled, 120 of whom were eligible for per protocol efficacy analyses (60 each in the moxifloxacin and the comparator groups). Clinical success rates were 87% for moxifloxacin and 83% for the comparator [95% CI (-9.77 to 15.96%)]. The results for secondary endpoints were comparable between groups. Both treatments were safe and well tolerated. Moxifloxacin IV/oral can be considered as a possible alternative for the antibiotic treatment of patients with mild-to-moderate nosocomial pneumonia without risk factors for highly resistant microorganisms.

Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining Fluid

In spite of the development and wide use of antibiotics, pneumonia is still the leading cause of infection-related mortality worldwide (101), and antibiotic resistance in the major pathogens of pneumonia has become more frequent during the past several decades. In order to defeat and prevent antibiotic resistance, antibiotics need to be used based on pharmacokinetics (PK) and pharmacodynamics (PD) (6, 10, 35). With regard to the PK/PD of antibiotics, considerable effort has been devoted to directly measure the concentrations of antibiotics at infection sites, because the distributions of antibiotics may be different among a variety of tissues. However, even beyond the fact that these measurements are carried out in normal tissues, the techniques used for the measurement are variable in accuracy and reproducibility and the interpretation of their results is hindered by many confounding factors (74, 75). For pulmonary infections, concentrations of antibiotics in epithelial lining fluid (ELF) for extracellular pathogens and in alveolar macrophage (AM) cells for intracellular pathogens are thought to reflect antibiotic activity in pneumonia. Antibiotics whose concentrations are high at these extravascular sites, such as macrolides and fluoroquinolones, tend to be promoted for treatment of pulmonary infection over antibiotics like betalactams and aminoglycosides, even though clinical trials do not show differences in clinical outcome or even bacteriological response. In fact, it is less clear why the ratios of ELF to plasma concentrations are diverse between antibiotics and even between members of the same antibiotic class. The measured ELF-to-plasma concentration ratios may differ based on physicochemical characteristics intrinsic to the molecules. And also, as the ELF concentration of antibiotics is commonly measured by bronchoalveolar lavage (BAL), technical factors or errors in the method of measurement may create these differences. It is believed that these factors need to be clarified before the concept of ELF concentration should be connected to antibiotic outcomes such as bacterial eradication or clinical response. In the current review, data from published human studies were extracted and analyzed to interpret ELF concentrations of antibiotics measured by BAL, considering possible confounding factors.

Clinical and bacteriological response to treatment of clinical mastitis with one of three intramammary antibiotics

AIM: To compare the proportions of clinical and bacteriological cure of glands of dairy cows diagnosed with clinical mastitis, following treatment with one of three different intramammary antibiotic preparations. METHODS: Cows from dairy cow herds (n=28) across New Zealand which were diagnosed with clinical mastitis in one or more glands at any stage of lactation were randomly assigned at the cow level within sequentially presented groups of three animals to be treated with one of three intramammary antibiotics. The treatments were 1 g procaine penicillin, 0.25 g cefuroxime, and a combination of 1 g procaine penicillin and 0.5 g dihydrostreptomycin (DHS). All treatments were infused on three occasions at 12-hourly intervals. Duplicate milk samples were collected for bacteriology before initial treatment, and 21–42 days later. Logistic regression or generalised linear mixed models were used to analyse the proportion of cows or quarters retreated for mastitis within 30 days of initial treatment (‘eclinical treatment failure’), and the proportion of glands from which bacteria were isolated initially but from which the same bacterial species was not re-isolated (‘bacteriological cure’). RESULTS: The annual herd average cumulative incidence rate of clinical mastitis was 12.7 cases/100 cows. The incidence rate was higher in young (2-year-old) and old (≥9-year-old) cows relative to 3- and 4-year-old cows, and was higher in Friesian than Jersey or crossbred cows. Streptococcus uberis was the pathogen most commonly isolated, and its relative prevalence declined with time postpartum. Cows treated with cefuroxime were more likely (p<0.01) to be re-treated for clinical mastitis in the 30 days after initial treatment than cows treated with procaine penicillin or procaine penicillin and DHS. Bacteriological cure occurred in 74% of treated glands and there was no difference in the proportion of cures among the treatments (p=0.4). The proportion of cures was lower when treatment occurred 28–72 days after calving (p<0.01) and if a major pathogen was isolated (p<0.001). CONCLUSIONS AND CLINICAL RELEVANCE: There was no benefit in terms of clinical or bacteriological cure rate in treating clinical mastitis cases with the combination of procaine penicillin and DHS compared to treatment with procaine penicillin alone. The proportion of clinical mastitis cases re-treated differed among herds, and more cows treated with cefuroxime were retreated within 30 days of initial treatment. However, the bacteriological cure proportion was the same among the treatments. Cure proportions were lower in cows from which major mastitis pathogens were isolated and when treatment commenced 28–72 days after calving.

Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study

Short-course therapy has been advocated for the treatment of community-acquired pneumonia (CAP). We compared the efficacy and safety of 5 and 7 day courses of gemifloxacin for outpatient treatment of mild-moderate CAP. In a multicentre, double-blind, parallel group study, patients were randomized to receive 320 mg of oral gemifloxacin once daily for 5 or 7 days. Over 95% of all patients in each cohort had a Fine score of <or=III. The primary efficacy endpoint was clinical cure at follow-up (days 24-30). Secondary outcomes were clinical and bacteriological responses at the end of therapy (days 7-9) and bacteriological and radiological responses at follow-up. Adverse events (AEs) were also monitored. In a total of 469 per protocol (PP) patients, clinical resolution at follow-up was 95% and 92% for 5 and 7 day treatments, respectively [95% confidence interval (CI) -1.48, 7.42], indicating non-inferiority of 5 day treatment. Clinical resolution at the end of therapy was 96% for both regimens (95% CI -3.85, 3.42). Bacteriological response rates in PP patients at the end of therapy were 94% and 96% for 5 and 7 day groups, respectively (95% CI -8.27, 3.25) and 91% for both groups at follow-up (95% CI -6.89, 7.93). Radiological success in PP patients at follow-up was 98% and 93% in 5 and 7 day groups, respectively (95% CI 0.35, 7.91). Pre-therapy pathogens were identified in 242 (47.3%) patients, most commonly Streptococcus pneumoniae. Frequency of treatment-related AEs was 21% in both cohorts with discontinuation rates of 1.2% and 2% in the 5 and 7 day groups, respectively. A lower incidence of rash was observed in the 5 day cohort (0.4%) versus the 7 day cohort (2.8%) (P=0.04). Gemifloxacin once daily for 5 days is not inferior to 7 days in the PP population with respect to clinical, bacteriological and radiological efficacy. Further work is needed, however, to explore whether fewer treatment days would improve patient compliance and reduce the incidence of AEs.

Tuberculosis and HIV in India

Tuberculosis is the most common HIV-related opportunistic infection in India, and caring for patients with both diseases is a major public health challenge. India has about 1.8 million new cases of tuberculosis annually, accounting for a fifth of new cases in the world — a greater number than in any other country (see pie chart).1 Patients with latent Mycobacterium tuberculosis infection are at higher risk for progression if they are coinfected with HIV. Patients with HIV infection have a similar bacteriologic response to tuberculosis treatment as those who are not infected but have higher risks of recurrence and death. The influence . . .

Role of oral extended-spectrum cephems in the treatment of acute exacerbation of chronic bronchitis

Risk stratification is the recommended approach for treatment of acute exacerbation of chronic bronchitis (AECB) to optimize the chances of clinical success. The suggested oral therapy for “simple or uncomplicated” AECB, which is predominantly a result of infection due to Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, includes advanced macrolides and 2nd- or 3rd-generation cephalosporins, in addition to the older 1st-line agents (aminopenicillins, doxycycline, trimethoprim/sulfamethoxazole, and erythromycin). In light of increasing resistance of H. influenzae and S. pneumoniae to the older agents, the specific directed structural modification of the cephalosporin nucleus resulted in the development of extended-spectrum 3rd-generation oral cephems with enhanced β-lactamase stability and improved activity against Gram-positive pathogens (penicillin-susceptible S. pneumoniae and oxacillin-susceptible Staphylococcus aureus). Analysis of results of double-blind randomized clinical trials assessing efficacy of the extended-spectrum oral cephems published since 2000 demonstrates that both cefdinir and cefditoren have similar point estimates of success in comparison to their comparators (cefuroxime, cefprozil, or Locarbacef), when either the clinical cure or the bacteriologic response was analyzed. Thus, oral extended-spectrum 3rd-generation cephems, which retain antimicrobial efficacy against the traditional respiratory pathogens despite changing resistance patterns, offer excellent coverage against the key pathogens involved in simple or uncomplicated AECB.

Moxifloxacin vs amoxicillin/clavulanate in the treatment of acute sinusitis

Purpose The aim of this study was to compare the efficacy and safety of moxifloxacin with that of amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults. Materials and methods Five hundred seventy-five patients from Latin American countries were randomized to receive oral moxifloxacin 400 mg once daily for 7 days, or oral amoxicillin/clavulanate 500/125 mg 3 times daily for 10 days, in a prospective, open study. Results At the test-of-cure visit (7-14 days after the end of therapy), the clinical success rate in the moxifloxacin group was 93.4% similar to that in the amoxicillin/clavulanate group (92.7%). Documented bacteriological eradication plus presumed eradication rates in the moxifloxacin (96.5%) and the amoxicillin/clavulanate (96.7%) groups were also similar. Drug-related adverse events were recorded in 32.2% of patients in the moxifloxacin group and 29.7% in the amoxicillin/clavulanate group. Patient discontinuation in the trial due to adverse events occurred for 10 patients in the moxifloxacin group and 6 in the amoxicillin/clavulanate group. Conclusions Overall, in terms of clinical and bacteriological response, moxifloxacin was equivalent to amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults.