Efficacy and safety of higher-dose intravenous ciprofloxacin in severe hospital-acquired infections.

In an open prospective study, 54 patients in an interdisciplinary, operative, anesthesiologic intensive care unit were treated with intravenous ciprofloxacin for life-threatening infections. Secondary nosocomial pneumonias were the predominant infection in most patients. A total of 88 causative pathogens were isolated from 50 patients. The most commonly isolated organism was Pseudomonas aeruginosa; Serratia marcescens, Staphylococcus aureus, and Enterobacter sp. were also isolated. Pathogens could not be detected in four patients (three patients with pneumonia, one patient with urinary tract infection). Ciprofloxacin was administered intravenously, either 400 mg every 12 hours or, after a loading dose of 600 mg every 12 hours on Day 1, 400 mg every 12 hours on successive treatment days. A total of 44 patients were treated parenterally, four orally. An additional six patients received ciprofloxacin in both dosage forms as sequential therapy. Serum ciprofloxacin levels were determined by high-performance liquid chromatography in 17 patients. The serum concentrations and the elimination half-life were in accordance with values already published for parenteral doses of 200 and 500 mg ciprofloxacin. Ciprofloxacin clearance was linear even at the high dose (600 mg every 12 hours loading dose) and no cumulative effect was observed. Clinical outcome was very good. Cure was achieved in 21 patients, and clinical improvement occurred in 23 (favorable clinical response rate, 82 percent). Two patients did not respond to therapy, and eight patients were not evaluable. Adverse effects occurred in 12 patients: transient elevation of liver enzymes (seven patients), temporary increase in serum creatinine levels (two), convulsions (two), and exanthem (one). The treatment of severe infections in intensive care patients with higher doses of parenteral ciprofloxacin appears to be considerably more effective than therapy with the doses of intravenous ciprofloxacin recommended to date. Therefore, these preliminary results are the subject of an ongoing double-blind study.

Outbreaks of Staphylococcus aureus infections during treatment of late onset pneumonia with ciprofloxacin in a prospective, randomized study.

We carried out a prospective, randomized four-center study in nosocomial pneumonia to evaluate the clinical and microbiological efficacy and safety of different treatment regimens in adult intensive care patients. During the randomized treatment of 18 patients with late onset pneumonia, ciprofloxacin (CIP) was compared to ceftazidim plus gentamicin (CAZ/GM), outbreaks of Staphylococcus aureus infections occurred in center 1. This article reports the unexpected findings. In the CIP group six out of ten patients were superinfected or reinfected with ciprofloxacin-resistant pathogens at the follow-up on day 5 after treatment. Four out of these six patients were superinfected with methicillin-susceptible or methicillin-resistant S. aureus (MRSA). Four superinfected patients died with pneumonia during treatment or before the follow-up. In the CAZ/GM group one out of eight patients was superinfected with MRSA. One patient died with pneumonia during treatment. There was no problem with multiresistant S. aureus or MRSA before the study period in center 1. In conclusion, we observed outbreaks of S. aureus infections during the treatment of late onset pneumonia with ciprofloxacin, which were associated with a high mortality. These superinfections occurred in mechanically ventilated, postoperative cardiac surgical patients after 13 days in the intensive care unit (ICU). We recommend combining ciprofloxacin with an antibiotic agent active against gram-positive bacteria in ventilator-associated pneumonia after a prolonged ICU stay. Selective pressure of ciprofloxacin could have played a role in these superinfections.

Asymptomatic carriage of Klebsiella pneumoniae producing extended-spectrum beta-lactamase by patients in a neurological early rehabilitation unit: management of an outbreak.

During 11 months 58 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) isolates were grown from 10 patients on a neurological early rehabilitation unit. The patients had no signs of infection but were colonized in the nose and trachea, and unusually only one had colonization in the gut. A single clone of ESBL-Kp was identified by pulse field gel electrophoresis. Strong hygienic precautions similar to those for Methicillin-resistant Staphylococcus aureus patients prevented spread of the bacteria to other wards. However, rehabilitation for patients with severe neurological failures made it very difficult to follow hygienic requirements. Disinfection of mucous membranes was difficult. Eventually the application of a nasal spray containing povidone-iodine proved to be successful.

Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma.

OBJECTIVES: Recently published data suggest a prognostic value of immunohistochemical proliferation markers for limited laryngeal carcinoma. Previous studies have reported contrasting findings on this issue. In this context, different treatment modalities may be responsible for contradictory findings. To study the relationship between proliferative activity--expressed by the immunohistochemical labeling index of proliferation-associated markers Ki-67 (MIB1), Lewis-X (LeuM1), and proliferating cell nuclear antigen (PCNA) and by p53 status--and treatment failure in a matched-pair study on recurrent and nonrecurrent T1 and T2 glottic carcinoma having received primary transoral laser surgery. METHODS: Twenty-one patients with tumor recurrence were randomly selected and matched with 26 patients with nonrecurrent disease regarding histopathological grading and age. MIB1 staining was used to determine the Ki-67 labeling index, and LeuM1 staining for detecting the Lewis-X antigen; immunohistochemistry determined the p53 status and PCNA labeling index. RESULTS: The Ki-67 labeling index was significantly (P = .001) higher in tumors from patients who had treatment failure (mean = 20.02%) than in patients who did not fail treatment ("nonfailures") (mean = 9.95%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (15%) of the general study population showed a mean time to relapse of 23 months (n = 21), compared with 50 months for cases (n = 26) below the median (P = .016). PCNA labeling index correlated less impressively with tumor recurrence (mean = 28.59% for treatment failures, mean = 21.75% for nonfailures, P = .022). Positive detection of the Lewis-X antigen was significantly associated with recurrence (P = .015) and time to relapse (P = .006). Status of p53 was not a significant prognostic factor. CONCLUSION: The Ki-67 (MIB1) labeling index may be associated with early relapse of limited laryngeal carcinoma treated with transoral laser surgery. Since the prognostic relevance of Ki-67 seems to be different for radiological and surgical concepts of treatment, Ki-67 might become useful as criterion of therapy selection. The Lewis-X antigen, for the first time used on laryngeal carcinoma, seems to be a strong prognostic marker deserving further investigations.

[Development of ultrasonography in a radiological university department from 1994 to 2001]. / Entwicklung der sonographischen Diagnostik in einer Radiologischen Universitätsklinik von 1994 bis 2001.

BACKGROUND: In 1994, 5 % of a total of 25 718 examinations and 7 % of all 4630 B-mode sonograms performed in the Radiology Department, University of Cologne was classified as not indicated. In light of these results, the health care policy guidelines for sonographic indications have been amended. PURPOSE: The aim of this study was to establish the current rate of non-indicated sonographic examinations performed in routine diagnostics by radiology departments at university hospitals, to determine the reasons for such over-diagnosis and identify which regulatory mechanisms can be implemented to prevent his. METHOD: We counted the number of 1) B-mode and 2) color-flow Doppler ultrasound imaging procedures carried out in patients who had had no change in symptoms within the previous 4 weeks or who were scheduled without reference to an existing sonogram (double examinations). 3) The reasons for over-diagnosis were analyzed. 4) The 1994 survey was repeated in 2000 with an identical protocol and 5) additionally, a modified survey of the diagnostic questions was conducted. RESULTS: 1) Out of 4,119 patients presenting for the first time to receive a B-mode sonogram, 443 prior sonograms (11 %), 305 CT scans (7 %) and 57 MRI scans (1 %) were documented. 2) Double sonograms were carried out in 6 % of the 1,118 patients presenting for the first time for color-flow Doppler ultrasounds and in 16 % of the 651 patients assigned to receive catheter angiographies with arterial color-flow Doppler. 2) 41 out of 55 (75 %) prior sonograms from non-university settings stated by 94 surgery patients were listed in the medical records. 36 out of 43 (84 %) prior sonograms from the university hospital were repeated in the same patients despite the fact that the medical report with the findings was available. None of the 48 sonograms indicated to confirm a plausible finding yielded any information that was additionally relevant to therapy. 4) In the period April - June, 2000, 12 % of all 15,921 tests and interventions, 26 % of 3,569 B-mode sonograms and 58 % of 1,033 abdominal sonograms performed in adults were classified as having not been indicated. 5) Staging and follow-up were stated as the most common reasons that a sonography was carried out in 46 % of the 1,017 adults who were given B-mode sonograms conducted from Jan - Mar, 2000 and comprised 62 % of the 410 sonograms classified as not or probably not medically indicated. CONCLUSION: The results showed that a multidisciplinary consensus was required to establish the diagnostic value of sonographic procedures. Therefore, this research group drafted a hospital-internal interdisciplinary guideline for "abdominal transcutaneous B-mode sonography in oncological questions".

[Perioperative use of ampicillin/sulbactam, cefoxitin and piperacillin/ metronidazole in elective colon and rectal surgery. A prospective randomized quality assurance study of 422 patients]. / Perioperative Anwendung von Ampicillin/Sulbactam, Cefoxitin und Piperacillin/Metronidazol in der elektiven Colon- und Rectumchirurgie. Eine prospektive randomisierte Qualitätssicherungsstudie bei 422 Patienten.

As has been proved before, antibiotic prophylaxis is highly effective in lowering wound infection rates in colorectal surgery. In order to establish quality control, we checked the effectiveness of three different prophylactic antibiotic regimes in 422 patients in a prospective and randomized trial. Between the three groups were no significant differences as regards age, type of operation and risk factors like adipositas and diabetes. The wound infection rate according to CDC-criteria was from 7.0 to 9.5%. We did not find a significant difference between the three antibiotic regimes. It is therefore our conclusion, that in our setting each of the three different types of antibiotics is of equal value. This means, on the other hand, that the cheapest one is enough.

[Ceftazidime with and without tobramycin versus azlocillin plus tobramycin in the therapy of bronchopulmonary infections in intensive care patients]. / Ceftazidim mit und ohne Tobramycin versus Azlocillin plus Tobramycin in der Therapie bronchopulmonaler Infektionen bei Intensivpatienten.

In a still ongoing open, randomized prospective trial the preliminary data of 50 intensive care patients on artificial ventilation were analysed. The evaluation included clinical and bacteriological efficacy and tolerance of ceftazidime alone or in combination with tobramycin versus azlocillin plus tobramycin. Artificially ventilated patients who had been treated in an intensive care unit for at least five days were selected to enter the study because of a high probability of colonisation with gram-negative bacteria. 16 patients were treated for bronchopulmonary infection with ceftazidime alone, and 17 each were treated with ceftazidime plus tobramycin or with azlocillin plus tobramycin. In the ceftazidime group nine patients were cured and three were improved (75% clinical success). Of the patients treated with ceftazidime plus tobramycin, 11 were cured and one was improved (75% clinical success); one patient died from very severe multiple trauma. In the azlocillin-tobramycin group, six patients were cured and two were improved (57% clinical success). Two patients from this group died from their underlying disease and another died from multiple organ failure due to septicemia.

[First appearance of penicillinase-producing gonococci at Bremen (author's transl)]. / Erstmaliges Auftreten penicillinasebildender Gonokokken in Bremen.

Three cases of penicillin-resistant gonorrhoea were detected at Bremen during a period of 3 months: in a tourist and 2 sailors. The infections had been acquired in Thailand, Africa, and USA, respectively. In all 3 cases penicillinase-producing strains of gonococci were isolated, resistant to penicillin in concentrations of 20 micrograms/ml and more. Patients were successfully treated with spectinomycin. The identification of penicillinase-producing strains of gonococci is of major epidemiological importance. Therefore, bacteriological investigations including sensitivity tests and, if necessary, penicillinase-tests should be done in each case of penicillin-resistant gonorrhoea. Relevant cases should be reported to the Venereal Diseases and Treponematoses Unit at Geneva, Switzerland.

[Value of monoclonal antibodies (PC 10, MIB1, p53 and LeuM 1) for assessing the prognosis of patients with squamous epithelial carcinoma of the larynx after partial laser resection]. / Wertigkeit monoklonaler Antikörper (PC 10,MIB 1,p53 und LeuM 1) für die Abschätzung der Prognose von Patienten mit Plattenepithelkarzinomen des Larynx nach Laserteilresektion.

An immunohistochemical analysis with monoclonal antibodies against Ki-67 (MIB 1), PCNA (PC10), p53 and Lewis X antigen was performed on 47 squamous carcinomas of the larynx after partial laser resection. Ki-67 index and expression of Lewis X antigen correlated significantly with both tumor recurrence rate and tumor-free interval. A much weaker relationship was found for the expression of proliferating cell nuclear antigen (PCNA), and no correlation existed with p53 expression. In conclusion, examination of Ki-67 and Lewis X antigen is thought to provide useful prognostic information concerning laser-resectable squamous carcinomas of the larynx.

[Reactions of different Enterobacteriaceae and Vibrionaceae species in BRILA-MUG (Fluorocult) bouillion]. / Reaktionen verschiedener Enterobacteriaceae- und Vibrionaceae-Spezies in BRILA-MUG (Fluorocult)-Bouillon.

In order to test the usefulness of BRILA-MUG (= Fluorocult) medium (Merck) for isolation and identification of total coliforms and faecal coliforms in surface water according to the EC guidelines for bathing waters a total of 969 strains of different Enterobacteriaceae and Vibrionaceae species was examined under different culture conditions. These included 486 E. coli (reference strains of O-groups 1-170, enterotoxin and Verotoxin-producing strains), 149 Salmonella (subspecies I-VI), 92 Yersinia, 44 Shigella, 64 Vibrio, 16 Aeromonas, and 118 strains of other Enterobacteriaceae species. After 48 h incubation at 36 degrees C 372 (82.0%) of 486 E. coli showed the typical reactions of gas formation, fluorescence (beta-glucuronidase activity), and indole production. Examination of fluorescence after addition of 1 N NaOH (0.5 ml), or testing of indole production after subculture in tryptophane containing broth improved the amount of typical reactions to 434 (95.4%). Incubation at 44 degrees C for 48 h gave less favourable results as compared with that at 36 degrees C. Out of 483 strains of other species 3.9% Salmonella strains of subspecies II-IV, 6.25% Citrobacter freundii, and 50% Edwardsiella tarda strains yielded reactions typical of E. coli. Shigella and Yersinia strains occasionally produced indole or fluorescence, but never visible gas.

[The determination of total coliform and fecal coliform bacteria for quality control of bathing waters using the EC guideline 76/160 most probable number and BRILA-MUG broth]. / Die Bestimmung der gesamtcoliformen und faekalcoliformen Bakterien zur Qualitätsüberwachung von Badegewässern nach der EG-Richtlinie 76/160 EWG mit Hilfe der BRILA-MUG-Bouillon.

In the monitoring of bathing waters according to EC Guideline 76/160 EWG, total coliform and faecal coliform bacteria have to be regularly determined by a quantitative method. This requirement can be fulfilled with sufficient reliability by the MPN method. Therefore, a procedure had to be developed which on the one hand is practical and not laborious, and on the other hand warrants a sufficiently specific, quantitative bacteriological diagnostic. The commercially available BRILA-MUG-broth appeared suitable for this purpose as it allows a direct determination of total as well as faecal coliform bacteria in the same assay. By this method, total coliform bacteria are recognized by gas production from lactose whereas faecal coliform bacteria additionally produce indole and liberate fluorochrome from MUG. Theoretical considerations and practical experiences showed that the rate of false-positive as well as false-negative results was within a range of 10% if compared with reactions described in the literature. Some factors which may influence the results are discussed.

[Comparative studies of fresh and seawater for the determination of total coliform and fecal coliform bacteria according to the European Economic Community guideline 76/160 (bathing water) by the use of the most-probable-number method with BRILA-MUG broth and differentiation according to the drinking water ordinance]. / Vergleichende Untersuchungen von Süss- und Seewasser zur Bestimmung der gesamtcoliformen und fäkalcoliformen Bakterien nach der E.G.-Richtlinie 76/160 EWG (Badegewässer) unter Anwendung des MPN-Verfahrens mit BRILA-MUG-Bouillon und Differenzierung nach der Trinkwasserverordnung.

During the summer season of 1989 about 222 samples of bathing water (Northsea, Baltic Sea and inland waters) were investigated, i.e. 2 times 1998 dilution tubes (1501 positive) were tested. Results with BRILA-MUG and lactose-bouillon were compared and additional 97 samples were tested with one respectively three colonies by confirmative tests. -- The BRILA-MUG one-tube-test (gas, fluorescence and indol) has as expected larger numbers of total coliforms (GC) and faecal coliforms (FC) in comparison with corresponding numbers for E. coli and coliform bacteria according to German law for drinking water (TrinkwV). -- BRILA-MUG and lactose-bouillon with the same identification mode according to "TrinkwV" has corresponding results concerning E. coli and coliform bacteria. -- Following the identification mode according to "TrinkwV" the total coliforms (GC/gas in BRILA-MUG) depending on the origin proved 60-80% as coliform bacteria. Additional API-tests showed that the other bacteria are coliform bacteria too or bacteria which can be considered as indicators for water pollution. -- Faecal coliforms (FC/fluorescence and indol-positive) depending on the origin proved 70-90% as E. coli, if following the identification mode according to "TrinkwV". Using 3 instead of 1 colony per positive dilution tube for identification the positive results increased approximately by 9%. 15% of negative results with the identification mode according to "TrinkwV" proved as E. coli-positive with identification according to API-system, i.e. the corresponding rate of E. coli-positive tubes will therefore be higher than shown above. The BRILA-MUG one-tube-test in connection with the MPN-method can be used successfully to determine the number of total and faecal coliforms according to the EEC-directive for bathing waters. The test needs only a minimum of material and also a minimum of laboratory staff. Differences between this test and other more extensive tests with several biochemical identification steps are negligible. The work load for bathing water tests would not be justified in this case.

[Growth behavior of Enterobacteriaceae in BRILA-MUG-broth and in different modifications of broth]. / Wachstumsverhalten von Enterobacteriaceae in BRILA-MUG-Bouillon und in verschiedenen Modifikationen der Bouillon.

Both substances, brilliant green and bile, inhibit the growth of gram-positive bacteria in culture media and selectively enrich gram-negative bacteria. Therefore, the brilliant green-lactose-bile broth (BRILA) and the BRLA broth supplemented with tryptophan and methyl-umbelliferyl-beta-D-glucuronide (BRILA-MUG) contain brilliant green as well as bile. Because BRILA-MUG broth as a selective enrichment and differentiating medium of faecal coliform and total coliform bacteria, E. coli and coliforms, respectively, is recommended for testing samples of surface water according to the EC guidelines for bathing waters (no. 76/160 EWG), the question arose of the optimal combination of components in the BRILA-MUG broth. As the described investigations show, the addition of buffer substances did not improve the culture properties of the BRILA-MUG broth. However, the original BRILA broth was improved by supplementing it with buffer substances such as CaCO3 or Na2HPO4. The same effect of culture improvement was obtained by removing brilliant green. This modification of BRILA broth is practically identic with the well-known MacConkey broth. On the other hand, the modification of omitting bile from the original BRILA broth causes a remarkable impairment of the culture properties lowering bacterial counts per ml by 3-5 log. The observations suggest that brilliant green inhibits both, gram-positive bacteria as well as the gram-negative Enterobacteriaceae. Therefore, it is a selective substance of doubtful usefulness.

[A comparison of BRILA-MUG and lauryl sulfate-MUG bouillon as detection media for total and fecal coliform bacteria in bathing waters in conformity with the Economic Community Guideline 76/160 EWG]. / Ein Vergleich von BRILA-MUG- und Laurylsulfat-MUG-Bouillon als Nachweismedien für gesamt- und fäkalcoliforme Bakterien in Badegewässern gemäss EG-Richtlinie 76/160 EWG.

The spectrum of gram-negative rods occurring in surface waters is wide and depending on the season, i.e. the water temperature. The concentration of bacteria is higher in summer than in winter. However, the seasonal difference of the concentration of Enterobacteriaceae is less than that of the Aeromonas spec. and of the non-fermenters. The comparison of yields of total and faecal coliforms determined in samples of surface water by using the brilliant green bile lactose 4-methylumbelliferyl-beta-D-glucuronide (BRI-LA-MUG) broth and the lauryl sulfate-MUG broth, respectively, shows that the BRILA-MUG broth is more sensitive and gives higher yields than the lauryl sulfate-MUG broth. On the other hand, the lauryl sulfate-MUG broth inhibits more the growth of gram-negative rods, especially that of Aeromonas spec. and non-fermenters, whereas the Enterobacteriaceae are less inhibited.