Hospital-acquired respiratory tract infections: clinical experience with beta-lactam/beta-lactamase inhibitors

The treatment of nosocomial pneumonia presents a major treatment challenge and one complicated by the rising prevalence of multidrug resistance among nosocomial pathogens. Contemporary treatment strategies for nosocomial pneumonia, which is most often attributable to Gram-negative bacilli or Staphylococcus aureus, mandate early empiric therapy with broad-spectrum antibacterial agents. The choice of agents for empiric therapy is fundamental to outcome, and the selection of inappropriate agents, to which pathogens are resistant, contributes significantly to morbidity and mortality. The adoption of practice guidelines, such as those proposed by the American Thoracic Society, can help to guide antibiotic selection, especially when combined with knowledge of local patterns of infection and antimicrobial susceptibility. Beta-Lactam/beta-lactamase inhibitor combinations, particularly those with activity against Pseudomonas aeruginosa, are among the core antibiotic agents considered suitable for empiric therapy of nosocomial pneumonia. They are particularly suited to use in hospitals with high rates of beta-lactamase-mediated resistance, especially resistance due to extended-spectrum beta-lactamases, infections with Acinetobacter spp. and those of mixed aetiology.     

Treatment of lower respiratory tract infections with cefoperazone

Fifteen patients with documented bacterial lower respiratory tract infections were treated with cefoperazone (2 gm every 12 hours, administered parenterally) as the single antibiotic therapy. Pulmonary infections included pneumonia (10), anaerobic lung abscess (2), bronchitis (2), and exacerbation of bronchiectasis (1); most of the patients had concomitant illnesses that compromised their host-immune status. Bacteria recovered from respiratory tract cultures included aerobic gram-negative bacilli (17), anaerobes (6), and aerobic gram-positive cocci (3). After therapy, lasting 5 to 28 days, nine patients had complete resolution of their infection, and the remaining six patients had significant clinical improvement. Diarrhea was the adverse reaction most commonly noted; others included an unusual reaction resembling serum sickness, and, in one patient treated for 24 days, hypotension and a subsequent decrease in renal function. Drug-related abnormalities in blood and serum values were few and mild. Cefoperazone was found to be effective in the treatment of lower respiratory tract infections.     

Enoxacin in lower respiratory tract infections

In this open, non-comparative study 45 lower respiratory tract infections were treated with the new 4-quinolone, enoxacin. Special attention was paid to infections caused by Pseudomonas aeruginosa. Pseudomonas infections were treated with 600 mg bd. whereas infections caused by other bacteria were treated with 400 mg enoxacin bd. In 43 cases efficacy could be assessed. In six out of 23 cases Pseudomonas spp. were eradicated from the sputum. In 12 of the remaining 17 cases a clear reduction in bacterial numbers and a decrease of sputum volume and purulence were obtained. Clinical improvement or cure was obtained in 20 out of the 23 cases. Most of the causative microorganisms in the other infections were eradicated. In two patients Staphylococcus aureus persisted. Overgrowth with streptococci occurred in three patients. Adverse reactions were frequent and occurred in 29 out of 45 treatment periods. They were mainly related to the gastrointestinal tract and the central nervous system. In 25 out of 30 patients on concomitant treatment with theophylline an elevation of plasma theophylline concentrations occurred. Twelve of these patients developed signs and symptoms possibly related to theophylline toxicity. After treatment with enoxacin the MICs of most persisting Pseudomonas strains were two to four times higher than pre-treatment values.     

Community-acquired respiratory tract infections caused by resistant pneumococci: clinical and bacteriological efficacy of the ketolide telithromycin

The incidence of community-acquired respiratory tract infections caused by Streptococcus pneumoniae exhibiting antibacterial resistance has increased dramatically in recent years. Telithromycin is the first of a new class of antibacterials, the ketolides, which have been developed specifically to provide effective treatment for these infections. Data were analysed from 3935 patients who had participated in one Japanese Phase II study and 11 US/global Phase III studies in three indications: community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Patients received either telithromycin 800 mg once daily or a comparator antibacterial. S. pneumoniae isolates considered to be causative for infection were tested for susceptibility to penicillin G and erythromycin A. In per-protocol analyses, telithromycin showed a high level of clinical efficacy against S. pneumoniae, with clinical cure rates of 92.8% for all isolates, 91.7% for those with reduced susceptibility to penicillin G and 86.0% for those with reduced susceptibility to erythromycin A. Bacterial eradication rates were consistent with the clinical outcomes. High rates of clinical cure and bacterial eradication were also observed for infections caused by isolates demonstrating high-level resistance to erythro-mycin A [MICs >/= 512 mg/L: 100% (13/13) clinical cure, 100% (13/13) bacterial eradication]. These results support the use of telithromycin as a first-line oral therapy for the treatment of community-acquired respiratory tract infections caused by S. pneumoniae with reduced susceptibility to penicillin G and erythromycin A.     

Ampicillin/sulbactam in lower respiratory tract infections: a review.

The pathophysiology and microbiology of lower respiratory tract infections are outlined and diagnostic and therapeutic problems considered. The use of sulbactam/ampicillin in the treatment of these infections is evaluated. The two drugs have similar pharmacokinetic characteristics; predictable and dose-dependent peak serum concentrations of both agents are achieved after parenteral administration. More than 90% of strains of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella sp, Escherichia coli, and Acinetobacter sp were inhibited by ampicillin/sulbactam concentrations of 16/8 micrograms/ml. Serum concentrations of ampicillin and sulbactam were 18 to 28 micrograms/ml and 13 micrograms/ml, respectively, after intramuscular administration of 1 gm/0.5 gm of ampicillin/sulbactam and 58 micrograms/ml and 30 micrograms/ml, respectively, after intravenous administration of the same dose. Good distribution of ampicillin/sulbactam into lung tissue, sputum, and bronchial fluid has been demonstrated. In over 2,250 patients treated with ampicillin/sulbactam, the rate of discontinuance of treatment because of side effects was less than 1%. Satisfactory clinical and bacteriologic outcome has been reported in over 80% of patients treated with ampicillin/sulbactam. The cost of ampicillin/sulbactam treatment is generally lower than that of other comparable antibiotic regimens.     

Therapy of lower respiratory tract infections with moxalactam.

Moxalactam was evaluated in the therapy of lower respiratory tract infections in 40 patients. The most common organisms isolated were Streptococcus pneumoniae (37.2%) and Haemophilus influenzae (21.5%). Gram-negative enteric organisms were isolated from six patients. No patient was evaluated as a treatment failure; however, two patients died of unrelated causes either during therapy or in the immediate posttherapy period. We determined the comparative minimal inhibitory concentrations of moxalactam, cefamandole, and cephalothin for our aerobic clinical isolates. Susceptibilities of the anaerobic isolates were measured by the Kirby-Bauer method. All isolates were susceptible to moxalactam. Moxalactam was found to be highly effective in the therapy of lower respiratory tract infections.     

Clinical experience with moxifloxacin in patients with respiratory tract infections

BACKGROUND: Moxifloxacin is an advanced-generation fluoroquinolone used primarily for the treatment of respiratory tract infections. OBJECTIVE: To further investigate moxifloxacin's general and cardiac safety and evaluate its efficacy in the community practice setting in a large surveillance study. METHODS: A total of 18,409 outpatients with suspected bacterial episodes of acute sinusitis, acute exacerbation of chronic bronchitis, or community-acquired pneumonia of mild to moderate severity were enrolled at 3377 community practice sites. Patients with sinusitis or pneumonia received once-daily oral moxifloxacin 400 mg for 10 days; those with bronchitis received 5 days' treatment. At follow-up, within 48 hours after the end of treatment, adverse event information was collected. An external safety committee assessed possible cardiac-related events. Efficacy was also evaluated at follow-up via the degree of resolution of clinical signs and symptoms. RESULTS: Of 18,374 safety-valid patients, 17.7% experienced adverse events and 14.3% experienced drug-related adverse events. The most common drug-related adverse events were nausea (5.3%), diarrhea (2.2%), and dizziness (2.0%). There was no clinical evidence of increased risk of cardiac arrhythmias with moxifloxacin treatment. Of 17,137 patients included in the efficacy analysis, 92.9% overall experienced clinical cure or improvement (92.8% with sinusitis, 92.9% with bronchitis, 94.1% with pneumonia). CONCLUSIONS: Once-daily oral moxifloxacin 400 mg was shown to be safe and effective in this trial for the treatment of respiratory tract infections of suspected bacterial origin in the clinical practice setting.     

Efficacy of twice-daily amoxycillin/clavulanate in lower respiratory tract infections

In this double-blind, double-dummy study, 324 patients with clinical evidence of community-acquired pneumonia (CAP) or an acute exacerbation of chronic bronchitis were randomly assigned to receive 10 days' treatment with either amoxycillin/clavulanate 875/125 mg twice daily or amoxycillin/clavulanate 500/125 mg three times daily. At the end of therapy, clinical success rates were 92.4% for the twice daily regimen and 94.2% for the three times daily regimen. There was no statistically significant difference between treatments (p = 0.647) and the 95% confidence interval around the treatment difference indicated that the two treatments were equivalent. Treatment equivalence was also confirmed at follow-up, four weeks after the end of treatment. Both regimens were well tolerated. In conclusion, amoxycillin/clavulanate 875/125 mg twice daily is as effective as amoxycillin/clavulanate 500/125 mg three times daily for the treatment of community-acquired lower respiratory tract infections and could improve patient compliance.     

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

Evaluation of: Thussu A, Chattopadhyay A, Sawhney IS, Khandelwal N. Albendazole therapy for single small enhancing CT lesion (SSECTL) in brain in epilepsy. J. Neurol. Neurosurg. Psychiatry DOI: jnnp.2007.128058v1 (2007) (Epub ahead of print).

Neurocysticercosis is a major cause of neurologic disease worldwide. In India and other developing countries, single small enhancing computed tomographic lesions representing solitary cysticercus granuloma are a common cause of new-onset seizures. The interesting feature of these solitary enhancing lesions is their spontaneous disappearance within a few weeks. The modalities of treatment that have been evaluated in these patients include antituberculous drugs, albendazole and corticosteroids. In several series, patients received only antiepileptic therapy to control seizures. There is consensus among experts that these patients require antiepileptic therapy. Some experts think that antiepileptic drugs may be withdrawn safely after the lesion has resolved. In several studies, treatment with albendazole has been tried but, because of conflicting results, its role in management of solitary cysticercus granuloma is uncertain. The present study by Thussu et al. also could not establish the exact role of albendazole in the management of solitary cysticercus granuloma. The authors observed that albendazole treatment led to early resolution of the solitary cysticercus granuloma. However, significantly better radiological resolution of lesions did not result in improved seizure-related prognosis. To resolve the issue of effectiveness of albendazole, properly conducted multicentric randomized control studies are needed.     

Cefotiam therapy of lower respiratory tract infections.

Cefotiam, a new cephalosporin, was evaluated in the treatment of lower respiratory tract infections in 29 patients. The bacteria isolated from the sputum of these patients included Streptococcus pneumoniae (31%), Klebsiella pneumoniae (31%), and Haemophilus influenzae (28%). Satisfactory response was observed in 90% of the patients. There were three treatment failures, two superinfections, and four colonizations with gram-negative organisms resistant to the drug. Superficial phlebitis was noted in two patients. The results of this study suggest that cefotiam is an effective and well-tolerated antibiotic for the treatment of lower respiratory tract infections due to susceptible organisms.     

Role of fluoroquinolones in lower respiratory tract infections

Oral quinolones such as ciprofloxacin are promising agents in the treatment of serious bronchopulmonary infections due to susceptible gram-negative micro-organisms such as Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae and even Pseudomonas aeruginosa. Their moderative activity against Streptococcus pneumoniae may limit the use of these agents in the treatment of acute exacerbations of chronic bronchitis and in the empiric management of community-acquired bacterial pneumonia. Further prospectively designed studies are needed to address this issue. The ability of quinolones to effectively penetrate bronchial mucosa and to be concentrated within macrophages may afford additional advantage to these agents. They should not be used as a sole agent in the treatment of aspiration pneumonia nor anaerobic pleuropulmonary disease. Quinolones are very active in experimental models of Legionnaire's disease and deserve further clinical study. Ciprofloxacin is a promising alternative to standard parenteral drugs in the management of Pseudomonas aeruginosa infections in adults with cystic fibrosis. The potential for drug interactions with theophylline must be kept in mind for patients on both of these drugs.     

Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination

Piperacillin-tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity that includes Gram-positive and -negative aerobic and anaerobic bacteria. Piperacillin-tazobactam retains its in vitro activity against broad-spectrum beta-lactamase-producing and some extended-spectrum beta-lactamase-producing Enterobacteriaceae, but not against isolates of Gram-negative bacilli harboring AmpC beta-lactamases. Piperacillin-tazobactam has recently been reformulated to include ethylenediaminetetraacetic acid and sodium citrate; this new formulation has been shown to be compatible in vitro with the two aminoglycosides, gentamicin and amikacin, allowing for simultaneous Y-site infusion, but not with tobramycin. Multicenter, randomized, double-blinded clinical trials have demonstrated piperacillin-tazobactam to be as clinically effective as relevant comparator antibiotics. Clinical trials have demonstrated piperacillin-tazobactam to be effective for the treatment of patients with intra-abdominal infections, skin and soft tissue infections, lower respiratory tract infections, complicated urinary tract infections, gynecological infections and more recently, febrile neutropenia. Piperacillin-tazobactam has an excellent safety and tolerability profile and continues to be a reliable option for the empiric treatment of moderate-to-severe infections in hospitalized patients.     

Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections

Studies of beta-lactam pharmacodynamics in infected patients are sparse. In this study, classification and regression tree (CART) and logistic regression analyses were used to identify which pharmacodynamic indices and magnitudes were significant predictors of meropenem efficacy for 101 adult patients with lower respiratory tract infections (LRTI). Using demographic data, a validated population pharmacokinetic model was employed to predict pharmacokinetic parameters and free serum concentrations in the studied patients. Pharmacodynamic indices [percentage of the dosing interval that free drug concentrations remain above the MIC (% fT > MIC), f(maximum concentration of drug in serum) (fC(max))/MIC, fC(min)/MIC, and f(area under the concentration-time curve) (fAUC)/MIC] were calculated based on the baseline pathogen with the highest drug MIC for each patient. The median (range) of percent fT > MIC, fC(max)/MIC, fC(min)/MIC, and fAUC/MIC were 100% (0 to 100%), 728.8 (0.8 to 15,777), 19.9 (0.01 to 278), and 3,605.4 (2.7 to 60,865.9), respectively. CART identified the following breakpoints as significant predictors for microbiological response: >54% fT > MIC, a fC(max)/MIC > 383, and a fC(min)/MIC > 5; fC(min)/MIC > 5 was the only significant predictor of clinical response. Due to 100% fT > MIC achieved in the majority of LRTI patients, fC(min)/MIC was the statistically significant parameter associated with meropenem clinical and microbiological response in the adults with LRTI. The findings for LRTI patients can be applied to optimize meropenem dose regimens to achieve clinical success and microbiological eradication in clinical practice.     

Treatment of community-acquired lower respiratory tract infections with oral cefuroxime axetil

The subjects were adult hospitalized patients, 12 with pneumonia and eight with acute bronchitis. The patients with pneumonia received 500 mg of cefuroxime orally twice daily and the patients with bronchitis received 250 mg twice daily. Treatment lasted for ten days in responsive patients. The pathogens identified in the patients' sputum were Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Enterobacter aerogenes, Staphylococcus aureus, or Branhamella catarrhalis. Clinical and bacteriologic cures were achieved in 11 of the 12 patients with pneumonia and in seven of the eight patients with bronchitis. It is concluded that cefuroxime axetil is safe and effective in the treatment of community-acquired pneumonia or acute bronchitis.     

Effective management of lower respiratory tract infections in childhood

This article summarises the five most common lower respiratory tract infections seen in acute care, guiding the nurse in assessment and early recognition of signs of deterioration. A discussion on each condition is provided along with guidance on prevention, advice for parents and on managing patients. This article is intended for students or newly qualified children's nurses, however, it can also serve as a refresher for all professionals working with children.