Severe community-acquired legionella pneumonia: treatment, complications and outcome

Legionella pneumophila is the second most common cause of severecommunity-acquired pneumonia requiring treatment with intermittentpositive pressure ventilation. The prognosis of this conditionand its complications have not been well documented. Erythromycinis the first-line antibiotic of choice based on clinical experience.Rifampicin has been recommended as an additional agent, thoughclinical experience has not been reported. We have retrospectivelyexamined 30 cases of severe community-acquired legionella pneumonia.The mean age of the patients was 53 years, 24 were male andeight died (27%, mean age 57 years). During admission 26 patientsreceived erythromycin (eight died) and 15 received rifampicinin addition (five died); four received neither drug and survived.Mean duration of intermittent positive pressure ventilationwas 15.9 days for survivors and 14.1 days for fatal cases. Acuterenal failure requiring dialysis developed in 13 (43%), of whomfive died (38%). Positive inotropic drugs were used in 10 patientsand of these six died. Jaundice occurred in 11 patients andwas significantly more common (p = 0.028) in patients who receivedrifampicin (60%) than in those who did not (17%). Excess bilirubinwas largely conjugated when measured and there was no consistenthepatitic or obstructive change in the liver enzymes. Severecommunity-acquired legionella pneumonia has a relatively goodoutcome with a mortality of 27%, though prolonged intermittentpositive pressure ventilation may be required. Acute renal failureis common but reversible in survivors, and jaundice is morecommon in those who receive rifampicin.     

军团菌肺炎11例误诊分析

军团菌肺炎是一种由革兰阴性杆菌引起的细菌性肺炎 ,其临床表现复杂 ,容易误诊。我院 1991年 12月～1999年 4月收治军团菌肺炎 11例均误诊。现报告如下。1　临床资料1.1　一般资料　 11例均为住院病人 ,男 9例 ,女 2例 ,男∶女为 4 .5∶ 1;年龄 2 9～ 85岁 ,平均 6 4 .7岁 ,6 0     

Failure of prolonged treatment with ciprofloxacin in acute infections due to Brucella melitensis

A randomized prospective, pilot study was performed to compare the efficacy of oral ciprofloxacin (750 mg or 1000 mg bd) with standard oral antimicrobial therapy (rifampicin plus doxycycline) in the treatment of acute infection with Brucella melitensis. All antimicrobial drugs were administered for 42 days. Although all patients responded rapidly, five of the six patients receiving ciprofloxacin relapsed following cessation of therapy. There were no relapses among the patients who received doxycycline/rifampicin. Despite its in-vitro activity against B. melitensis (MIC 0.5 mg/l), ciprofloxacin, administered twice daily, does not appear to constitute adequate therapy for acute brucellosis.     

Usefulness of the Legionella Score for differentiating from COVID-19 pneumonia to legionella pneumonia

Legionella pneumophila is a major causative pathogen of community-acquired pneumonia (CAP), but recently the novel coronavirus disease 2019 (COVID-19) became the most common causative pathogen of CAP. Because L. pneumophila CAP is clinically distinct from bacterial CAPs, the Japan Society for Chemotherapy (JSC) developed a simple scoring system, the Legionella Score, using six parameters for the presumptive diagnosis of L. pneumophila pneumonia. We investigated the clinical and laboratory differences of L. pneumophila CAP and COVID-19 CAP and validated the Legionella Score in both CAP groups. We analyzed 102 patients with L. pneumophila CAP and 956 patients with COVID-19 CAP. Dyspnea and psychiatric symptoms were more frequently observed and cough was less frequently observed in patients with L. pneumophila CAP than those with COVID-19 CAP. Loss of taste and anosmia were observed in patients with COVID-19 CAP but not observed in those with L. pneumophila CAP. C-reactive protein and lactate dehydrogenase levels in L. pneumophila CAP group were significantly higher than in the COVID-19 CAP group. In contrast, sodium level in the L. pneumophila CAP group was significantly lower than in the COVID-19 CAP group. The median Legionella Score was significantly higher in the L. pneumophila CAP group than the COVID-19 CAP group (score 4 vs 2, p < 0.001). Our results demonstrated that the JSC Legionella Score had good diagnostic ability during the COVID-19 pandemic. However, physicians should consider COVID-19 CAP when loss of taste and/or anosmia are observed regardless of the Legionella Score.     

Efficacy of liposome-encapsulated ciprofloxacin compared with ciprofloxacin and ceftriaxone in a rat model of pneumococcal pneumonia

Encapsulation of ciprofloxacin in sterically stabilized liposomes results in a prolonged circulation time and improved pharmacokinetics. Liposome-encapsulated ciprofloxacin was compared with conventional ciprofloxacin and ceftriaxone in a rat model of pneumococcal pneumonia. Male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae and then treated with intravenous ceftriaxone (100 mg/kg), ciprofloxacin (40 or 80 mg/kg) or liposomal ciprofloxacin (40 or 80 mg/kg) administered once or twice daily for 3 days. White blood counts, development of bacteraemia and mortality were measured for 10 days. Antibiotic concentrations in serum, lung lavage fluid and white blood cells recovered from lung lavage fluid were determined. Liposomal ciprofloxacin concentrations were significantly higher in serum and lavage fluid compared with conventional ciprofloxacin, resulting in greater area under the serum concentration-time curve and maximum serum concentration. Despite these higher concentrations, survival rates were similar between groups treated with equivalent doses of liposomal ciprofloxacin versus ciprofloxacin. When antibiotics were given once daily, ceftriaxone was more effective than either form of ciprofloxacin.     

Clinical effect of intravenous ciprofloxacin on hospital-acquired pneumonia

The effect of intravenous ciprofloxacin (CPFX) on hospital-acquired pneumonia was examined. The subjects were 32 patients with hospital-acquired pneumonia classified as being in group I, group II, and group III, based on The Japanese Respiratory Society Guidelines for management of hospital-acquired pneumonia. None of the patients had received antibiotic treatment for the pneumonia. CPFX 300mg was intravenously infused twice daily for 3–14 days, and its clinical effect, bacterological effect, and side effects were examined. Intravenous CPEX was clinically effective in 21 of the 32 patients, with an efficacy rate of 65.6%. With regard to bacteriological efficacy, 4 of 5 strains of methicillin-sensitive Staphylococcus aureus, 2 of 3 strains of Klebsiella pneumoniae, 1 of 2 strains of Streptococcus pneumoniae, 1 of 2 strains of Streptococcus agalactiae, 1 of 2 strains of Pseudomonas aeruginosa, 1 of 2 strains of Serratia marcescens, and the 1 strain of Klebsiella oxytoca were eradicated, with an eradication rate of 42.3% (11 of 26 strains whose fate was confirmed eradicated). Abnormal laboratory findings (side effects) were observed in 11 of the 32 patients (34.4%), but all side effects were mild. Based on the above data, intravenous CPFX may be the drug which should be recommended as the first choice for hospital-acquired pneumonia.     

Comparative efficacies of ciprofloxacin, ampicillin and chloramphenicol in treatment of experimental Haemophilus influenzae pneumonia

An experimental murine model of bacteraemic Haemophilus influenzae pneumonia was used to evaluate the therapeutic efficacy of ciprofloxacin, as compared with ampicillin and chloramphenicol. An ampicillin-sensitive (AS) and an ampicillin-resistant (AR) challenge strain were employed. Ciprofloxacin treatment produced intrapulmonary killing of H. influenzae which was superior to that achieved with ampicillin (P less than 0.001, both strains) and chloramphenicol (P less than 0.001, strain AS; P less than 0.005, strain AR). Likewise, survival from strain AS pneumonia was 61% in the ciprofloxacin-treated animals, as compared with 43% for the chloramphenicol-treated, and 22% for the ampicillin-treated groups. We conclude that ciprofloxacin may be an effective agent in treating pneumonia caused by either ampicillin-sensitive or ampicillin-resistant strains of H. influenzae.     

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. Received: 4 August 1998 Accepted: 27 August 1998     

Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated liposomes for treatment of Klebsiella pneumoniae pneumonia in rats

Animal and clinical data show that high ratios of the area under the concentration-time curve and the peak concentration in blood to the MIC of fluoroquinolones for a given pathogen are associated with a favorable outcome. The present study investigated whether improvement of the therapeutic potential of ciprofloxacin could be achieved by encapsulation in polyethylene glycol (PEG)-coated long-circulating sustained-release liposomes. In a rat model of unilateral Klebsiella pneumoniae pneumonia (MIC = 0.1 microg/ml), antibiotic was administered at 12- or 24-h intervals at twofold-increasing doses. A treatment period of 3 days was started 24 h after inoculation of the left lung, when the bacterial count had increased 1,000-fold and some rats had positive blood cultures. The infection was fatal within 5 days in untreated rats. Administration of ciprofloxacin in the liposomal form resulted in delayed ciprofloxacin clearance and increased and prolonged ciprofloxacin concentrations in blood and tissues. The ED(50) (dosage that results in 50% survival) of liposomal ciprofloxacin was 3.3 mg/kg of body weight/day given once daily, and that of free ciprofloxacin was 18.9 mg/kg/day once daily or 5.1 mg/kg/day twice daily. The ED(90) of liposomal ciprofloxacin was 15.0 mg/kg/day once daily compared with 36.0 mg/kg/day twice daily for free ciprofloxacin; 90% survival could not be achieved with free ciprofloxacin given once daily. In summary, the therapeutic efficacy of liposomal ciprofloxacin was superior to that of ciprofloxacin in the free form. PEG-coated liposomal ciprofloxacin was well tolerated in relatively high doses, permitting once daily administration with relatively low ciprofloxacin clearance and without compromising therapeutic efficacy.     

Comparison of ciprofloxacin and rifampicin in experimental Legionella pneumophila pneumonia

We evaluated intraperitoneal ciprofloxacin and rifampicin alone and as combination therapy in experimentally induced Legionella pneumophila pneumonia in guinea pigs. Intraperitoneal treatment began 48 h after intratracheal inoculation of 3 X 10(6) L. pneumophila and consisted of sterile saline (0.3 ml bid), ciprofloxacin (30 mg/kg bid), rifampicin (10 mg/kg/bid), or ciprofloxacin plus rifampicin (same doses). Animals were treated for five days and survivors killed after 11 days. Quantitative lung cultures were done post mortem. Respective mean and median days of animal survival were increased by treatment with ciprofloxacin plus rifampicin (8.4 and 9.5 days), ciprofloxacin (8.2 and 7.5 days), or rifampicin (8.3 and 7.5 days), compared with controls (5.5 and 5.0 days). Compared with control animals (log rank test) survival was improved by treatment with ciprofloxacin plus rifampicin (P less than or equal to 0.047) ciprofloxacin (P less than or equal to 0.047) or rifampicin (P less than or equal to 0.047). Quantitative lung cultures (cfu/g) were also decreased by treatment with ciprofloxacin plus rifampicin (2.0 X 10(4)), ciprofloxacin (5.4 X 10(4)), or rifampicin (1.7 X 10(4)) compared with controls (3.2 X 10(8)). No differences in survival, quantitative lung cultures, or animal weights were noted between treatment groups. This study demonstrates that ciprofloxacin is as effective as rifampicin in the treatment of experimentally induced L. pneumophila pneumonia and that the combination of ciprofloxacin plus rifampicin has no advantages over single agent therapy in this model.     

Oral treatment of Pseudomonas-induced urinary tract infections with ciprofloxacin

In an open study, a group of 11 patients with asymptomatic urinary tract infections, caused by resistant Pseudomonas strains, were given 200 mg of ciprofloxacin per day for 1 week. All strains displayed an in vitro sensitivity to the drug. Complete clinical resolution was obtained in 8 patients and long-term eradication in 3. No adverse reactions and only minor and reversible laboratory changes were recorded. Ciprofloxacin could be a valuable oral drug in the treatment of severe urinary infections. However, more clinical studies on the development of resistance under therapy and with other dose schedules are indicated.     

The antimicrobial activity of ciprofloxacin against Legionella species and the treatment of experimental Legionella pneumonia in guinea pigs

The antimicrobial activity of ciprofloxacin was tested against 15 standard reference strains, and 37 clinical and environmental strains of Legionella pneumophila by an agar dilution method, using a new growth medium (B-SYE agar) which we devised. The minimal inhibitory concentrations of ciprofloxacin were found to be inoculum dependent, and ranged from 0.02 to 0.06 mg/l at 10(4) cfu inoculum and 0.02 by 0.125 mg/l at 10(6) cfu inoculum. The most potent antibacterial activity was shown by rifampicin, followed by ofloxacin, ciprofloxacin, enoxacin, norfloxacin, erythromycin and pipemidic acid in that order. The therapeutic efficacy of ciprofloxacin in experimental guinea pig pneumonia due to L. pneumophila was fairly good with a survival rate of 80%. From other data of ours, its effectiveness in experimental pneumonia was equal to or greater than that of erythromycin. Further studies would be appropriate to investigate the possibility of using ciprofloxacin for the treatment of human L. pneumophila infection.     

Use of ciprofloxacin in the treatment of hospitalized patients with intra-abdominal infections

BACKGROUND: Numerous combination and single-agent antimicrobial regimens are available for the treatment of intra-abdominal infections. Selection of empiric agents must be directed at providing reliable activity against endotoxin-generating Escherichia coli, other gram-negative facultative bacteria, and anaerobes such as Bacteroides fragilis. Safety profiles, pharmacokinetic profiles, and cost-effectiveness must also be considered. Use of fluoroquinolones for the treatment of intra-abdominal infections has recently been advocated. METHODS: We review 2 prospective, comparative clinical trials conducted between 1992 and 2002 that evaluated the efficacy and safety of IV ciprofloxacin in patients with intra-abdominal infections. Separate pharmacoeconomic analyses conducted for each study are also reviewed. RESULTS: A total of 4 ciprofloxacin studies (2 clinical, 2 pharmacoeconomic) comprise the database. The combination of ciprofloxacin plus metronidazole was at least as effective as imipenem/cilastatin and clinically more effective than piperacillin/tazobactam therapy, based on clinical success end points. In 1 trial, treatment success for the clinically valid population was reported for 84% (93/111) of patients treated with IV ciprofloxacin/metronidazole, 86% (91/106) of those treated with IV/oral ciprofloxacin/metronidazole, and 81% of those treated with IV imipenem/cilastatin (91/113). The IV/oral ciprofloxacin/metronidazole regimen had a statistically significant lower mean infection-related cost than the IV only ciprofloxacin/metronidazole plus imipenem groups (difference of approximately 1100 US dollars; P = 0.029). In the second clinical trial, clinical resolution rates were statistically different for patients receiving IV/oral ciprofloxacin/metronidazole (74%) versus IV piperacillin/tazobactam therapy (63%; P = 0.047). Ciprofloxacin/metronidazole was more cost-effective compared with piperacillin/tazobactam (2200 US dollars-3600 US dollars lower cost-effective ratios per patient) regardless of whether the patient had a diagnosis of appendicitis or whether a switch to an oral drug was permissible. CONCLUSIONS: In the studies reviewed herein, the combination of ciprofloxacin plus metronidazole was an effective and safe regimen for the treatment of intra-abdominal infections. This regimen has potential advantages over exclusively IV regimens, including the option of sequential IV/oral therapy, patient convenience, cost savings, and reduced hospital stay.