The place of antibiotic therapy in the management of chronic acute exacerbations of chronic bronchitis.

In the USA, more than 16 million adults are affected by chronic obstructive pulmonary disease, and chronic bronchitis has been estimated to affect up to 13 million individuals or approximately 4-6% of adults. Chronic bronchitis is an increasing cause of significant morbidity and mortality. During acute exacerbations of chronic bronchitis, subjects experience a worsening of bronchitic symptoms, with an increase from baseline in one or more or the following; dyspnoea, cough and/or sputum volume, purulence or viscosity. The severity of an exacerbation can be graded by how many of these symptoms are present. Antibiotic therapy should be initiated based on patient history and severity of the exacerbation.

A retrospective review of 228 episodes of infective endocarditis where rheumatic valvular disease is still common.

Two hundred and twenty-eight episodes of infective endocarditis in adult patients (mean age 36 years) were reviewed retrospectively. There were 183 episodes (80%) of native valve, 15 (7%) early prosthetic valve and 30 (13%) late prosthetic valve endocarditis. The most common predisposing factor was rheumatic valvular disease (65%). None of the patients were intravenous drug users. According to the Duke criteria, the number of definite, probable and rejected episodes were 121 (53%), 94 (41%) and 13 (6%), respectively. Additional minor criteria increased the number of definite endocarditis to 82%. The Duke criteria are not primarily intended to influence treatment decisions but are helpful in standardising research activities. The choice of the level of sensitivity or specificity of the criteria may be adjusted according to the aim of the study and prevalence of disease in a particular area. More sensitive criteria may be valuable in those countries where the prevalence of rheumatic valvular disease is still high.

Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish University Hospital.

A total of 101 episodes of Staphylococcus aureus bacteraemia were evaluated for the factors influencing prognosis. The overall episode mortality rate and the mortality rate due to bacteraemia were 43.6 and 21.8%, respectively. Episodes with methicillin-resistant S. aureus (MRSA) bacteraemia had a significantly higher overall mortality rate (58.7 vs. 30.9%, P<0.01) and mortality rate due to bacteraemia (32.6 vs. 12.7%, P=0.02) when compared with episodes caused by methicillin-sensitive S. aureus (MSSA). The multivariate analysis revealed that the underlying disease, presence of infective endocarditis, septic shock and central intravascular catheter and methicillin resistance of S. aureus were the five independent risk factors associated with a higher mortality rate.

Quinolones in the treatment of typhoid fever.

Typhoid fever is a severe systemic disease. Treatment with appropriate antibiotics is essential for enteric fever. Development and rapid dissemination of resistance to chloramphenicol, ampicillin, and cotrimoxazole have complicated the treatment of enteric fever. Therapeutic options for the treatment of multidrug-resistant strains are limited to third generation cephalosporins or fluoroquinolone antibiotics. Recent clinical experiences have shown that quinolones are the drugs of choice for treatment of enteric fever. Studies have shown that shorter courses may be sufficient to cure uncomplicated typhoid fever.

The role of beta-lactam/beta-lactamase inhibitors in the management of mixed infections.

Microbiological studies show that the in vitro antimicrobial activity of sulbactam-ampicillin encompasses not only gram-positive and gram-negative aerobes, but also anaerobes. Such a broad spectrum of activity suggests its suitability as monotherapy for the empiric management of polymicrobial infections. Typical mixed infections, which are frequently life-threatening, include those occurring in the abdomen or pelvis, diabetic foot infections, and brain abscess. Numerous comparative clinical studies have revealed the clinical and bacteriological efficacy of sulbactam-ampicillin to be comparable to that of imipenem cilastatin and the second-generation cephalosporins cefoxitin and cefotetan. In addition, other studies have demonstrated that sulbactam-ampicillin monotherapy is cost-beneficial. A reduction in the duration of hospitalization, the lack of potentially toxic side-effects, and lower drug costs associated with monotherapy all contribute to the cost-effectiveness of sulbactam-ampicillin.

In vitro activities of antibiotics alone and in combination against Brucella melitensis at neutral and acidic pHs.

Brucellae survive acidic pHs in phagolysosomes. Azithromycin, streptomycin, and quinolones were active against Brucella melitensis at pH 7.0 but not at pH 5.0; rifampin and doxycycline retained activity at pH 5.0. Regardless of pH, azithromycin-rifampin and ofloxacin-rifampin showed less synergy than established streptomycin-doxycycline and rifampin-doxycycline combinations.

Septic shock as a predictor of mortality in bacteremia caused by coagulase-negative staphylococci.

Fifty episodes of bacteremia caused by coagulase-negative staphylococci at Hacettepe University Hospital over a five-year period were reviewed to evaluate the factors influencing the prognosis. Overall mortality and mortality due to bacteremia were 36% and 24%, respectively. Septic shock was determined to be the only factor adversely influencing mortality in both univariate and multivariate analyses. Age, sex, duration of hospitalization, origin of infection, underlying disease, presence of central intravascular or urinary catheters, and prior antibiotic therapy were not statistically significant parameters in predicting septic shock.

Treatment of enteric fever with pefloxacin for 7 days versus 5 days: a randomized clinical trial.

In this prospective study of enteric fever, 22 patients received 400 mg of pefloxacin twice daily for 5 days (group A) and 24 received 400 mg of pefloxacin twice daily for 7 days (group B). Causative microorganisms were Salmonella typhi (8 in group A, 11 in group B) and Salmonella paratyphi B (14 in group A, 13 in group B). The clinical cure and bacterial eradication rates were 96% (21 of 22) in group A and 100% in group B. In conclusion, 5-day oral administration of pefloxacin was as effective as 7-day treatment of enteric fever caused by Salmonella spp.

Efficacy of sulbactam-ampicillin for the treatment of severe diabetic foot infections.

Diabetic foot infections, a frequent and serious cause of morbidity in patients with diabetes mellitus, are caused by anaerobic and aerobic bacteria. Given the fact that seriously impaired host defense factors are almost always present in these patients, bactericidal agents with a broad spectrum of antimicrobial activity are required for their treatment. Seventy-four patients with diabetic foot infections were treated with parenteral sulbactam-ampicillin (1.5 g, q.i.d.). All patients were followed-up prospectively in order to determine the efficacy and safety of sulbactam-ampicillin. The mean duration (+/- SD) of treatment in patients with osteomyelitis (n = 49) and soft tissue infections (n = 25) was 41 +/- 5 and 14 +/- 3 days, respectively. Infected limbs were amputated at various levels in 14 patients (19%). Clinical cure rates were 86% and 100% in patients with osteomyelitis and with soft tissue infection, respectively. The most frequent side effect was diarrhea and observed in 10 patients (14%). The results of the present study indicate that sulbactam-ampicillin is safe and effective in the treatment of diabetic foot infections.

Clinical implications of aminopenicillins with beta-lactamase inhibitors.

Aminopenicillin/beta-lactamase inhibitor combinations (ampicillin/sulbactam and amoxicillin/clavulanic acid) are well established in the therapy of a wide range of infections in both hospital and primary-care settings as a result of their very broad-spectrum activity and good tolerability. These agents are particularly suited to the prophylaxis and treatment of polymicrobial infections. Clinical studies have demonstrated their efficacy in the treatment of diabetic foot infections, intra-abdominal infections, aspiration-related lung infections, brain abscesses and pelvic inflammatory disease, and in the prophylaxis of infections following abdominal, pelvic and head and neck surgery. Recent studies have also revealed that aminopenicillin/beta-lactamase inhibitors may provide therapy or prophylaxis which is more cost-effective than with comparative antimicrobial agents.

Resistance patterns in Turkey.

Resistance to antimicrobial agents in Gram-positive and Gram-negative bacteria is common in Turkey. In this review, resistance to several antimicrobial agents in this country is discussed for bacteria which have gained clinical importance in recent years. Among Gram-positives, staphylococci are of major importance because of their high level of resistance to many agents in the hospital and the community. Methicillin resistance in different hospitals ranges from 13% to 37%. High-level resistance to gentamicin occur in enterococci and resistance to glycopeptides have not been reported in these isolates. S. pneumoniae resistance to penicillin have been observed in Turkey as 47% in Hacettepe University and most of the resistant isolates were from children with severe underlying diseases. In reports from other hospitals, the level of resistance was lower because of a different patient population. In Gram-negative bacilli, aminoglycoside resistance is a significant problem in the treatment of severe infections in our country. The most common mechanism of resistance in our isolates is the plasmid-mediated enzymatic modification of these agents. Extended-broad spectrum beta-lactamases have been detected in Klebsiella spp. and Salmonella spp. in Turkey. In a Pseudomonas strain, an extended-spectrum variant of OXA-10 was identified. Some isolates were also shown to produce plasmid mediated PER-1 enzymes. Due to resistance problems encountered in many hospitals, restriction control measures have been started in some hospitals in order to limit the antibiotic use and our hope is the country-wide application of these precautions as soon as possible.

Transferable production of PER-1 beta-lactamase in Pseudomonas aeruginosa.

PER-1, an extended-spectrum class A beta-lactamase, has been described only from Pseudomonas aeruginosa RNL-1, which was obtained in France in 1991. During studies on ceftazidime-resistant P. aeruginosa collected from December 1991 to July 1993 in Ankara, Turkey, we found 14 further isolates with PER-1 enzyme, as recognised by isoelectric point (pI 5.4), hydrolytic activity, gene hybridization and DNA sequence. Five of these isolates also had OXA-10 (PSE-2)-related enzymes and one hyper-produced ampC beta-lactamase, whereas eight had PER-1 enzyme alone. The last group, from four wards, appeared to be identical, giving the same DNA restriction patterns and carrying the PER-1 gene on an 8.5 kb HincII fragment. Two more producers were related but the other four were unique. In several representatives of the group of eight replicates, the PER-1 gene was shown to be encoded on a plasmid, larger than 154 kb in size, which transferred to P. aeruginosa PU21. A further isolate had the gene on an even larger conjugative plasmid. By contrast, the PER-1 gene reportedly was chromosomally-inserted in strain RNL-1. The PER-1 producers and their transconjugants were highly resistant to ceftazidime and aztreonam (MIC > or = 128 mg/L) but not to carbapenems or latamoxet. Piperacillin insusceptibility was marginal (MIC 8 mg/L). Clavulanate 4 mg/L, but not tazobactam 4 mg/L, reversed resistance to ceftazidime and carbenicillin. Purification of the enzyme to homogeneity was achieved by three ion exchanges and one gel filtration. We found much lower Vmax rates for aminothiazolyl cephalosporins than reported previously for PER-1 enzyme. This reflected the present assays being in 0.1 M phosphate buffer pH 7.0, whereas the previous were pH-stat-regulated; concentrated phosphate reduced enzyme activity against ceftazidime, but not against cephaloridine.

Role of quinolones in the treatment of diarrhoeal diseases.

Diarrhoeal diseases are still an important health problem in both developing and developed countries, and resistance to commonly used antibiotics among enteric pathogens is a major issue. Quinolones have become important agents in the treatment of diarrhoeal diseases because of their excellent in vitro activity against pathogens and their pharmacological features. In many clinical studies, they appeared to be effective in the treatment of shigellosis and the prevention and treatment of diarrhoea in travellers. Several studies have demonstrated that single-dose therapy with these agents is sufficient in many cases. Their role in the treatment of acute salmonellosis is still controversial, because of their lack of efficacy in eliminating salmonella from the faeces.

Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome.

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, < 500/microL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.

Efficacy of a three-day course of azithromycin in the treatment of community-acquired pneumococcal pneumonia. Preliminary report.

Azithromycin is an azalide antibiotic with activity against many of the respiratory pathogens and with marked tissue affinity. In a prospective study, the efficacy of a short-course of azithromycin was evaluated in 25 patients with community-acquired pneumococcal pneumonia. Gram-positive diplococci were abundant in the sputum smears of all patients, and Streptococcus pneumoniae was isolated in the sputum cultures of 15; one patient had pneumococcal bacteremia, as well. Azithromycin was administered at a single dose of 1,000 mg on day 1, and 500 mg on subsequent days for a total of three days in 19 patients, five days in four patients, two and four days in one patient each. Defervescence occurred within 24 hours after the first dose. The overall clinical cure and bacteriologic eradication rates were 96% and 93%, respectively. One patient with pneumococcal bacteremia failed to respond and died in respiratory failure. Side-effects were encountered in three (12%) patients. In conclusion, three-day therapy with a total azithromycin dose of 1,500 mg seems effective and safe in patients with community-acquired pneumococcal pneumonia and no underlying pulmonary condition.

Atypical pneumonias: therapeutic possibilities.

The atypical pneumonia syndrome is characterized by systemic complaints rather than respiratory symptoms. The causative pathogens include Mycoplasma, Chlamydia, Legionella and respiratory viruses (influenza, adenovirus, respiratory syncytial virus). The reported incidence of disease caused by these pathogens in community-acquired pneumonias varies from study to study. As most of these pathogens are intracellular, the antibiotics used in the treatment of atypical pneumonia are those able to penetrate into cells. Empirical antimicrobial therapy consists of macrolides (erythromycin or some of the newer agents such as roxithromycin, azithromycin or clarithromycin) or tetracyclines (e.g. doxycycline). In cases of severe legionellosis and in immunocompromised and critically-ill patients, the macrolides are sometimes given in combination with rifampicin. Promising alternatives are some of the newer fluoroquinolones (e.g. ofloxacin, pefloxacin) in the treatment of legionellosis.

Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin.

Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. Thirty patients received 200 mg of doxycycline plus 600 mg of rifampin once daily, and 31 patients were treated with 400 mg of ofloxacin plus 600 mg of rifampin once daily for 6 weeks. Nine patients in each group had complications of the disease. There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease.

OXA-11, an extended-spectrum variant of OXA-10 (PSE-2) beta-lactamase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa ABD, which was isolated in October 1991 from blood cultures of a burn patient in Turkey, was resistant to cephalosporins, particularly ceftazidime (MIC, 512 micrograms/ml), penicillins, aztreonam, and meropenem, but not to imipenem. Cephalosporin and penicillin resistance transferred to P. aeruginosa PU21 and was associated with a beta-lactamase with a pI of 6.4 encoded by a 100-MDa plasmid designated pMLH52. Like extended-spectrum TEM and SHV beta-lactamases, this enzyme hydrolyzed penicillins and newer cephalosporins but did not hydrolyze cefoxitin or carbapenems. However, it differed from TEM and SHV derivatives in being a potent oxacillinase, and its encoding gene did not hybridize with probes to TEM and SHV genes. To characterize the enzyme, libraries of total DNA were cloned into plasmid pUC19 and were transformed into Escherichia coli DH5 alpha. Recombinant plasmids that gave ceftazidime resistance all contained a 3.65-kb BamHI fragment. Deletions from this fragment allowed the beta-lactamase gene to be located on a 1.4-kb section of DNA, which contained an open reading frame of 798 bases. This encoded a protein that was deduced to differ from PSE-2 beta-lactamase only in having serine instead of asparagine at position 143 and aspartate instead of glycine at position 157. It is concluded that the resistance of isolate ABD dependent on an extended-spectrum variant of the PSE-2 enzyme. The ability of this enzyme to cause ceftazidime resistance dependent primarily on a low Km for the compound; Vmax remained low. It is proposed that PSE-2 should be transferred to the OXA group as OXA-10 and that the new enzyme be designated OXA-11.

Treatment of intracranial abscesses: experience with sulbactam/ampicillin.

In an open prospective study, the efficacy of sulbactam/ampicillin (50 and 100 mg/kg, respectively, qid) was evaluated in 21 patients with intracranial abscess(es). Sixteen patients had cerebral, 3 epidural, and 2 cerebellar abscesses. Multiple lesions were found in 7 patients. Sixteen patients underwent surgical intervention, others were treated with antibiotic alone. The mean duration of antibiotic therapy (+/- SD) was 48 +/- 10 days (range 26-65 days). The mean duration of follow-up after completion of therapy (+/- SD) was 6 +/- 2.4 months. All patients had at least some reduction in size of abscess(es) within 3 weeks of the initiation of therapy as monitored by computerized tomography. Seventeen patients were cured, three patients died due to causes unrelated to their infection. One patient was reoperated since no clear improvement either clinically or radiologically was observed 18 days after the first operation. Side effects of sulbactam/ampicillin were minor and transient. Results obtained in this study indicate that sulbactam/ampicillin can be used in the treatment of intracranial abscesses, alone or with surgical intervention.