Lower respiratory tract infections in the intensive care unit: consequences of antibiotic resistance for choice of antibiotic.

Pneumonia in the intensive care unit (ICU) has been associated with highly virulent pathogens that often exhibit resistance to multiple antibiotics and mortality rates of 30-70%. Pseudomonas aeruginosa and Enterobacteriaceae are the leading pathogens, followed by Staphylococcus aureus and polymicrobial etiologies. Recent clinical studies using monotherapy for nosocomial pneumonias resulted in low eradication rates for P. aeruginosa and staphylococci. An additional problem of these studies was the development of resistance by P. aeruginosa during the antibiotic treatment; also the selection of highly resistant strains like Xanthomonas maltophilia and Acinetobacter species was a major concern. However, several prospective studies comparing monotherapy versus combination therapy in nosocomial pneumonia of ICU patients have shown that a response rate of 60% is achievable, which is comparable to historic rates for combination therapy regimens. Only infections induced by P. aeruginosa, S. aureus, or other highly resistant pathogens (Acinetobacter, X. maltophilia, etc.) should be treated with well-defined antibiotic combinations.

Nosocomial pneumonia in the critical care unit.

Nosocomial pneumonia poses a major threat to the recovery of patients receiving mechanical ventilation. In addition, nosocomial pneumonia is often difficult to diagnose. This article examines the extent of the threat and some of the difficulties facing the critical care physician when diagnosing nosocomial pneumonia.

[BiPAP therapy of respiratory disorders in patients with congenital neuromuscular diseases]. / BiPAP-Therapie von Atmungsstörungen bei Patienten mit angeborenen neuromuskulären Erkrankungen.

BACKGROUND: Patients with hereditary generalized neuromuscular diseases develop respiratory failure and decreased maximal inspiratory pressure (Pi max) due to both, involvement of respiratory muscles in the disease and secondary spine- and thorax-deformity. In recent years mechanical respiratory support was done mostly by hyperbaric pressure ventilation when the patients become hypercapnic during daytime. However, polysomnographic investigations have shown that despite normal ventilation during daytime, severe respiratory failure might be detectable only during sleep. PATIENTS AND METHODS: Fourty patients with hereditary generalized neuromuscular diseases were analyzed using polysomnographic analyses and lung function tests (4-channel-ECG,2-channel-ECG, EOG, respiratory parameters, continuous oxygen saturation measurement and capillary blood gas analyses during sleep). Patients with need of ventilatory support during sleep were treated using bilevel positive airway pressure ventilation (BiPAP). RESULTS: Twenty patients revealed severe sleep related breathing disorders and were therefore treated by BiPAP. All showed normalisation or substantial improvement during BiPAP-therapy except two patients with persistent daytime symptoms. During follow-up (6 to 38 months) 3 patients died (cardiomyopathy, pulmonary embolism, pneumonia). The most important side effect of BiPAP-therapy was pressure marks due to the masks. CONCLUSIONS: BiPAP is useful for treatment of sleep related respiratory failure in patients with hereditary generalized neuromuscular diseases.

[Invasive and non-invasive home ventilation--changes between 1982 and 1996]. / Invasive und nichtinvasive intermittierende Selbstbeatmung--Wandel zwischen 1982 und 1996.

PATIENTS AND METHODS: In our centre, 111 patients with chronic ventilatory insufficiency (33 females, 78 males, age 48 +/- 18 years, range 3 to 76 years) were treated by intermittent positive pressure ventilation between 1982 and 1996. Underlying diseases were neuromuscular diseases in 29%, sleep-related hypoventilation in 26%, kyphoscoliosis in 15%, chronic obstructive airway disease in 15%, and post-tuberculosis syndromes in 12%. Singular indications were 1 bronchiectasis, 1 lung fibrosis and 1 cystic fibrosis. RESULTS: Until 1991, most patients were ventilated via tracheostoma (10 of 16), in the following years 87 of 95 patients could be ventilated via a nasal or facial mask. Ventilation mode was a controlled one in 80 patients and an assisted one in 31 patients, average ventilation time during night was 6 to 8 hours. In the majority of patients hypercapnia was not only removed during ventilation but also at daytime as an indicator of improvement of ventilatory insufficiency accomplished by a clearly better quality of life and daytime activity. Ten patients (9%) died due to their underlying diseases, 5 of them in the first year of intermittent ventilation.

Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care.

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality. Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1+/-5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1-229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia. These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.

[Standardised antibiotic therapy in major lung surgery (author's transl)]. / Standardisierte antibiotische Therapie in der grossen Lungenchirurgie.

Sputum and bronchial biopsies and smears were obtained from 221 patients who had undergone partial pneumonectomy without preceding antibiotic therapy. The results of 343 sputum examinations and of 126 bacteriological examinations of biopsies and smears were evaluated. Pathogenic bacteria were demonstrated in about 50% of the sputa and in about 25% of the biopsies and swabs. Anaerobic micro-organisms were extremely rare. Treatment was with tetracycline. Before antibiotic therapy Haemophilus influenzae, staphylococci and E. coli predominated, afterwards there were practically only staphylococci and Esch. coli. The incidence of primary resistance to the usual antibiotics was high, especially in respect of gram-negative organisms. The difference in incidence between primary and secondary resistance was one of degree. The least effective agents were ampicillin and amoxicillin, the most active were the aminoglycosides. Erycin proved satisfactory in infections with grampositive organisms while the cephalosporins were active against both gram-positive and gram-negative bacteria. The development of resistance and the clinical picture suggest that "eradication" of the infection during the postoperative stage is not advisable as it causes the selection of more or less drug-resistant organisms. A more satisfactory approach is gradually to reduce the infection until the immediate postoperative stage is over. Macroscopic and microscopic examination of the sputum is important, as the choice of the appropriate antibiotic is determined by the result of gram-staining.

[Results of thoracoscopy in localized lung and chest wall diseases]. / Ergebnisse der Thorakoskopie bei lokalisierten Lungen- und Brustwandkrankheiten.

On the basis of 109 thoracoscopic examinations--out of a total number of 1,014 thoracoscopies performed between 1981 and 1986 at our Department--carried out to investigate localised disorders of the lungs and wall of the chest, the diagnostic effectiveness of the method for this indication has been examined. The lesions involved were 59 pulmonary foci, and 50 localised changes involving the wall of the chest, thoracic spine or diaphragm. With the aid of thoracoscopy, the diagnosis proved possible in 83% of the disorders of the chest wall, in comparison with only 46% in the case of the pulmonary lesions, since the focus is often not sufficiently sub-pleural in location, or else pleural adhesions that presented impaired the view. On the basis of the high diagnostic yield in localised diseases of the thoracic wall, thoracoscopy should be considered for this indication in particular, when clarification of the situation is not possible with radiological procedures, and surgery appears unnecessary or not feasible.

Monotherapy of nosocomial pneumonia.

Nosocomial pneumonia remains a common problem and is the leading cause of death among patients with nosocomial infection. However, the initial empiric therapy of nosocomial pneumonia is directed at the leading organisms common to all patients, and for many patients monotherapy is adequate for at least 48 hours, at which time the microbiological results of appropriate diagnostic procedures should be known and the treatment can be focused. The currently available antimicrobial agents such as third- and fourth-generation cephalosporins, piperacillin plus tazobactam, carbapenems, and some fluoroquinolones are highly active and bactericidal. They should be used in consideration of current pharmacodynamic knowledge, which will lead to convincing clinical results. Combination of antibiotics is necessary only in specific situations or for the amelioration of special pathogens, such as Pseudomonas aeruginosa, Acinetobacter spp., and against mixed aerobic and anaerobic infections.

Clinical results in the treatment of respiratory infections with moxifloxacin.

Respiratory infections are a common source of morbidity and mortality, with pneumonia being the number one cause of death from infectious disease in Western industrialized countries. Initial antibiotic therapy of upper and lower respiratory infections is often empiric, being directed at the pathogens that are most likely to be present. Leading pathogens in respiratory infections are S. pneumoniae, H. influenzae and M. catarrhalis, which have developed considerable resistance problems against previous standard antibiotics like beta-lactams, macrolides and tetracyclines in the last decade. Newly developed quinolones such as moxifloxacin combine enhanced in vitro activity against Gram-positive bacteria with maintenance of activity against Gram-negative organisms. Three comparative, prospective, randomized, double-blind studies in the treatment of community acquired sinusitis, AECB and CAP demonstrated equal or higher efficacy of moxifloxacin in comparison to standard antibiotic therapies.

Diagnostic problems in lower respiratory tract infections.

The main problems of diagnosis in lower respiratory tract infection are the differentiation of infection from colonization or contamination, and the isolation of a reliable and true pathogen. The clinical findings and differentiation of patients into those with pneumonia or infective exacerbations of chronic bronchitis should provide a definitive early diagnosis. Expectorated sputum may be unreliable in pneumonia, because of contamination by oropharyngeal flora. Although blood cultures may be negative, they provide a precise diagnosis and should be obtained in all pneumonias admitted to hospital. Other more invasive procedures are transtracheal needle aspiration, fibrebronchoscopic techniques including protected specimen brush and bronchoalveolar lavage with quantitative culturing and cytological analysis, transthoracic needle aspiration, thoracoscopy--guided biopsy and open lung biopsy. Any invasive procedure in a severely ill patient should be carefully directed weighing the risks as well as the benefits, whilst taking the underlying disease and expected survival into consideration.

[Incompatibility of tuberculosis therapy in a patient with AIDS]. / Unverträglichkeit der Tuberkulosetherapie bei AIDS.

A man with advanced HIV infection (CD4 lymphocytes 90/microliter, CD4/CD8 ratio 0.2) was admitted to hospital with fever, cough and weight loss. The radiological and bronchoscopic findings, together with the presence of acid-fast bacilli in the sputum, pointed to open pulmonary tuberculosis caused by Mycobacterium tuberculosis, a diagnosis confirmed by histological examination and culture. Quadruple antibiotic therapy with isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and amikacin was immediately begun and was at first clinically successful. Ten days later, however, a rash appeared; it was ascribed to RMP (anaphylactoid reaction after re-exposure). All the other first-line drugs tried during the ensuing eight months evoked severe adverse reactions (INH: rash and itching; amikacin: hearing impairment and tinnitus; EMB, pyrazinamide, prothionamide, p-aminosalicylic acid: rash and itching). Treatment was nevertheless clinically and microbiologically successful, and the patient insisted upon a 2 1/2 months' rest without therapy. This period was followed by extrapulmonary spread (severe arthritis of the elbow) and recurrence of pulmonary tuberculosis. The tubercle bacilli were sensitive to all the drugs so far employed. Renewed and lasting control of the infection was achieved only by continuous administration of steroids (prednisolone 10 mg twice daily) in conjunction with an unconventional antibiotic regimen consisting of amikacin, protionamide, terizidone, clarithromycin and sparfloxacin for some five months. Because of an episode of cerebral convulsions during treatment of cytomegalovirus retinitis with ganciclovir, the terizidone was discontinued (it was suspected of interacting with ganciclovir). The patient has had no more fits and sputum culture has remained negative for six months.

[Intermittent nasal positive pressure ventilation with a ventilator in accordance with the Medical Device Regulation III (MedGV III). Clinical experiences with the BREAS PV 201 in 19 patients]. / Intermittierende nasale Uberdruckbeatmung (nIPPV) mit einem Beatmungsgerät nach der Medizinischen Geräteverordnung III (MedGV III). Klinische Erfahrungen mit dem BREAS PV 201 bei 19 Patienten.

UNLABELLED: During the period from January to September 1995, 19 patients suffering from ventilatory insufficiency were adjusted to nocturnal nasal intermittent positive pressure ventilation (nIPP) therapy with a new ventilatory apparatus conforming to German regulations governing medical equipment (MedGV III). This equipment had not been available previously. 5 patients were suffering from obstructive ventilatory disorder, 5 patients from an underlying neurological disease and 3 patients from thoracic restriction. In 6 patients the reason for their ventilatory disorder was obesity hypoventilation or disorder of central ventilatory regulation. The average age was 54 years (15-73 years). Whereas 14 patients were suffering from global respiratory insufficiency already during the day, the others had marked respiratory disorder only at night. In all cases ventilation was carried out during the whole night. RESULTS: nIPPV achieved normoxia in all patients whereas in 10 patients hypercapnia was not completely eliminated. In all cases, however, the previously elevated pCO2 could be reduced. Hence, sufficient nIPPV can be achieved also with a respirator complying with the new German MedGV III regulations.

Pneumocystis carinii pneumonia as a complication of immunosuppressive therapy.

BACKGROUND: Patients receiving immunosuppressive therapy with corticosteroids and cytotoxic agents may develop opportunistic infections such as Pneumocystis carinii pneumonia (PCP). This indicates a severe T-cell defect, but so far there are no established criteria for identifying patients at risk. PATIENTS AND METHODS: CD4+ and CD8+ T-lymphocyte counts were determined by flow cytometry in seven HIV-negative patients who developed PCP as a complication of immunosuppressive treatment. RESULTS: CD4+ T-lymphocyte counts (T-helper phenotype) were less than 200/microl in all seven patients (mean 90.6/microl). The markedly reduced CD4 counts measured in these patients are similar to those observed in organ transplant recipients who developed PCP during immunosuppressive therapy for prevention of graft rejection and in HIV-positive patients with PCP as an AIDS-defining illness. CONCLUSION: Measuring CD4+ T-lymphocyte counts may be helpful in determining the risk of PCP not only in HIV-positive patients, but also in patients receiving immunosuppressive therapy. The risk of acquiring PCP seems to increase when CD4+ lymphocyte counts drop below 200/microl, regardless of the underlying disease.

[Infections caused by Stenotrophomonas maltophilia (SMA) in intensive care patients--a prospective case-control study]. / Infektionen durch Stenotrophomonas maltophilia (SMA) bei Intensivpatienten--eine prospektive Fall-Kontrollstudie.

BACKGROUND AND OBJECTIVE: The importance of Stenotrophomonas maltophilia (SMA) as an etiologic frequently polyresistant pathogen in severe nosocomial infections has increased. METHODS: In our prospective study we evaluated the risk factors of nosocomial infections by SMA in our internal intensive care unit (ICU) over a one year period from July 1997 to June 1998. RESULTS: 111 patients (80 men, 31 women, mean age +/- SD: 58.0 +/- 13.3 years) were treated for more than 5 days in the ICU. SMA were cultured in 16/111 patients (13 men, three women, mean age 57.8 +/- 3.4 years) out of bronchial secretions (68%), sputum (19%) and pleural fluid (13%). Univariate analysis resulted in 15 different risk factors (p < 0.05); however, multivariate analysis provided three independent risk factors: chronic obstructive pulmonary disease (OR 95% CI [1.91; infinity]), length of stay in the ICU (OR 95% CI [1.07; 1.26]) and therapy with carbapenems before admittance to ICU (OR 95% CI [0.56; 153]). Four of 16 patients died due to an SMA-infection, two by purulent exacerbations of a chronic bronchitis and two by sepsis. Molecular typing of 18 SMA isolates in 15 patients resulted in 9 different genetic types and a clonal dissemination could only be confirmed in three patients. CONCLUSIONS: In respiratory ICU SMA infections are favored by severe COPD, length of stay in the ICU and by selection pressure of applicated antibiotics, especially carbapenems.

Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis.

The diagnostic significance of procalcitonin concentrations in lower respiratory tract infections and tuberculosis is not known. A prospective analysis was, therefore, performed in patients with acute exacerbation of chronic bronchitis (AECB), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and tuberculosis and their procalcitonin levels compared with those of patients with noninfectious lung diseases (controls). In addition, standard inflammatory parameter data were collected. A prospective clinical study was performed with four different groups of patients and a control group that consisted of patients with noninfectious lung diseases. A total of 129 patients were included: 25 with HAP, 26 CAP, 26 AECB, 27 tuberculosis, and 25 controls. C-reactive protein level, blood cell counts and procalcitonin concentration were evaluated on the first day after onset of clinical and inflammatory symptoms prior to treatment. The median procalcitonin concentrations in HAP, CAP, AECB and tuberculosis were not elevated in relation to the cut-off level of 0.5 ng x mL(-1). In the HAP group, in four of five patients who subsequently died, procalcitonin concentrations of >0.5 ng x mL(-1) were found. In acute lower respiratory infections, such as HAP, CAP and AECB, significantly elevated levels were found in comparison to the control group, but below the usual cut-off level. No differences were observed between tuberculosis and the control group. Relative to the current cut-off level of 0.5 ng x mL(-1), procalcitonin concentration is not a useful parameter for diagnosis of lower respiratory tract infections. However, compared to the control group, there were significantly elevated levels in patients with hospital-acquired pneumonia, community-acquired pneumonia and acute exacerbation of chronic bronchitis below the current cut-off level, which should be further investigated.