Ciprofloxacin is one of a new generation of fluorinated quinolones structurally related to nalidixic acid. The primary mechanism of action of ciprofloxacin is inhibition of bacterial DNA gyrase. It is a broad spectrum antibacterial drug to which most Gram-negative bacteria are highly susceptible in vitro and many Gram-positive bacteria are susceptible or moderately susceptible. Unlike most broad spectrum antibacterial drugs, ciprofloxacin is effective after oral or intravenous administration. Ciprofloxacin has been most extensively studied following oral administration. It attains concentrations in most tissues and body fluids which are at least equivalent to the minimum inhibitory concentration designated as the breakpoint for bacterial susceptibility in vitro. The results of clinical trials with orally and intravenously administered ciprofloxacin have confirmed the potential for its use in a wide range of infections, which was suggested by its in vitro antibacterial and pharmacokinetic profiles. It has proven an effective treatment for many types of systemic infections as well as for both acute and chronic infections of the urinary tract. Ciprofloxacin generally appeared to be at least as effective as alternative orally administered antibacterial drugs in the indications in which they were compared, and in some indications, to parenterally administered antibacterial therapy. However, further studies are needed to fully clarify the comparative efficacy of ciprofloxacin and standard antibacterial therapies. Bacterial resistance to ciprofloxacin develops infrequently, both in vitro and clinically, except in the setting of pseudomonal respiratory tract infections in cystic fibrosis patients. The drug is also well tolerated. Thus, as an orally active, broad spectrum and potent antibacterial drug, ciprofloxacin offers a valuable alternative to broad spectrum parenterally administered antibacterial drugs for use in a wide range of clinical infections, including difficult infections due to multiresistant pathogens.

Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers9 diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous system toxicities occurring most commonly, but only rarely necessitating discontinuance of therapy. In 17 of 18 prospective, randomized, double-blind comparisons with another agent or placebo, fluoroquinolones were tolerated as well as or better than the comparison regimen. Bacterial resistance has been uncommonly documented but occurs, most notably with P. aeruginosa and Staphylococcus aureus and occasionally other species for which the therapeutic ratio is less favorable. Fluoroquinolones offer an efficacious, well-tolerated, and cost-effective alternative to parenteral therapies of selected infections.

Fluoroquinolone antimicrobial agents.

Synergy resulting from the combination of ciprofloxacin and an antipseudomonal penicillin has been reported for 20%-50% of isolates of Pseudomonas aeruginosa. A similar effect has also been reported for the combination of ciprofloxacin and fosfomycin. In contrast, the combination of quinolones and aminoglycosides rarely showed synergy when tested against P. aeruginosa. Most studies have shown that the combination of beta-lactams or aminoglycosides with quinolones is indifferent against Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, and Serratia species. The combination of ciprofloxacin and chloramphenicol can be antagonistic against E. coli. In general, the combination of quinolone antibiotics with other drugs tested against staphylococci, enterococci, and anaerobic species has shown indifference. The neutropenic mouse model of infection has demonstrated the synergistic effect of ciprofloxacin plus antipseudomonal penicillins; the combination of ciprofloxacin and rifampin has been superior to single agents in experimental Staphylococcus aureus osteomyelitis. Ciprofloxacin has been the quinolone studied most thoroughly, and few data are available about the combination of other quinolones with other antimicrobial agents. Overall, the occurrence of synergy when quinolones are combined with other antimicrobial agents is infrequent, and clinical studies that demonstrate the clinical relevance of data from in vitro and animal models of infection are not available. However, data from in vitro and animal model studies indicate that the combination of a quinolone with other antimicrobial agents rarely results in antagonism.

Synergy of Fluoroquinolones with Other Antimicrobial Agents

Antimicrobial synergy resulting from antibiotic combination therapy is often important in the treatment of serious bacterial infections. Previous studies have demonstrated synergy between an aminoglycoside and beta-lactam antibiotics in the treatment of Pseudomonas aeruginosa infections. The present paper investigates the synergic effects of aminoglycosides (amikacin and netilmicin) and fluoroquinolones (ciprofloxacin, ofloxacin and pefloxacin) in combination with third-generation cephalosporins (cefoperazone, ceftriaxone and ceftazidime) against 18 clinical isolates of Pseudomonas spp. The effects of these drugs were examined by three methods (disc diffusion, 'chequerboard' titration and the time-killing method), to evaluate the activities of the antibiotics alone and in combination against selected isolates. Fractional inhibitory concentration indices were calculated for all isolates with all combinations. Use of the disc diffusion method revealed that amikacin and netilmicin in combination with the three cephalosporins exhibited synergy against 7-12 isolates, whereas the combinations of quinolones and ceftazidime displayed synergic effects only in the case of 3-5 isolates. On 'chequerboard' titration, amikacin and ceftriaxone exerted synergy against seven of the isolates. The other combinations showed synergy against fewer isolates, but every combination demonstrated synergic effect against some of the isolates. The tested combinations had different effects against various Pseudomonas spp. With the time-killing method, the 1/2 x MIC of amikacin or ciprofloxacin in combination with the 1/2 x MIC of third-generation cephalosporins proved to be most effective. No antagonism was found with these combinations. Discrepancies in the detection of synergy were observed for the different methods.

Investigation of the synergic effects of aminoglycoside- fluoroquinolone and third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp.

Since December 2019, when a cluster of pneumonia cases due to SARS-CoV-2 initially emerged in Wuhan city and then rapidly spread throughout the world, the necessity for data concerning the clinical and para-clinical features of Iranian patients with COVID-19 was highlighted. Therefore, we aimed to compare the clinical, para-clinical and laboratory evidences of deceased patients with survival group. We extracted data regarding 233 patients with laboratory-confirmed COVID-19 from Buali Hospital in Iran; clinical/para-clinical and inflammatory indexes data were collected and analyzed. The data of laboratory examinations and chest CT findings were compared between deceased and survived patients. The mean age of the patients was 49.8 years and 64% of our patients were male. The acute respiratory distress syndrome occurred in 64 patients, 52 who were admitted to the ICU, which all of them underwent invasive mechanical ventilation, and 28 who died. Lymphopenia (79%), neutrophilia (79%), and thrombocytopenia (21%) were the most frequently observed laboratory findings of the deceased group on admission. Most patients (68%) had a high systematic immune-inflammation (SII) index of > 500 and increased C-reactive protein level (88%). Levels of inflammatory indexes such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and SII were documented to be significantly elevated in the deceased group when compared with the patients who survived (P < 0.0001, P < 0.001, P < 0.0001, respectively). The most commonly presented symptoms were fever (70%) and cough (63%) on admission. Headache was uncommon (11%). Ground-glass opacity with consolidation (mixed) was the most common radiologic finding on chest CT (51%). No radiographic or CT abnormality was found in 15 of 204 patients (7%). Small fraction of patients with COVID-19 may present without fever and abnormal radiologic findings. Elevated NLR, PLR and SII can be considered as prognostic and risk stratifying factor of severe form of disease.

/pdf/comparison-of-clinical-para-clinical-and-laboratory-findings-1w9d0x1gjj.pdf

Comparison of clinical, para-clinical and laboratory findings in survived and deceased patients with COVID-19: diagnostic role of inflammatory indications in determining the severity of illness.

Combinations of ciprofloxacin with azlocillin, piperacillin and ticarcillin were tested in vitro against clinical isolates. Azlocillin plus ciprofloxacin showed synergy against 30% ofPseudomonas aeruginosaisolates; it was either synergistic or additive against 78% of all isolates tested even those resistant to the beta-lactam. Synergism was rarely noted forKlebsiella pneumoniae, Escherichia coli, Enterobacterspp. orBranhamellaspp. isolates. Minimum inhibitory concentrations of ciprofloxacin plus azlocillin, plus piperacillin and plus ticarcillin againstPseudomonasspp. were reduced 4 or 2 fold, respectively. However, the combination azlocillin plus ciprofloxacin showed primarily indifference against gram-positive strains. Neutropenic mice infected with a lethal challenge ofPseudomonasspp. were protected by a combination of azlocillin and ciprofloxacin. Its additive and/or synergistic effects and expanded spectrum of activity against streptococci, methicillin-resistant staphylococci and JK corynebacteria may provide an alternative to traditional therapy.

Synergy of ciprofloxacin and azlocillin in vitro and in a neutropenic mouse model of infection.

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Synergy of ciprofloxacin and azlocillin in vitro and in a neutropenic mouse model of infection.