Table 3.

Pseudomonas aeruginosa Eradication Studies

Investigators	Pt. No.	Method of detection	Type of study	Regimen (drug/duration)	Success of eradication; Duration of eradication	Other comments/ conclusions
Littlewood42	7	OP or Sp	Case study	INH colistin	NANA	Decreased frequency of Pa+ after initiation of drug
Steinkamp58	14	OP or Sp	Open, no control	INH tobramycin, variable time (mean 20 months)	NANA	Efficacious and safe Patients were chronically infected.
Steinkamp57	28	OP or Sp	Open, no control	IV tobramycin + IV azlocillin × 14 days	Pa-: 64% 2 d after tx end. Pa-: 35%–3mo, 18%–6mo, 47% 14 mo. to study end.	Safe; some still Pa+ at tx end, most Pa+ by 3–6 months after therapy.
Valerius43	26	Sp	RCT with untreated control	INH colistin + PO ciprofloxacin × 21 days	NA; Not chronically colonized: 86% of tx, 42% of ctrl group mean 17.4 months	Endpoint: time to chronic colonization using the Copenhagen criteria*
Vazquez44	16	OP or Sp	Historic control group	INH colistin and INH tobramycin + PO Ciprofloxacin × 14 days	NA Mean follow up: 27.4 months (tx), 24.2 months (ctrl)	Based on number of Pa+ cultures, not patients, Pa+ in 4.6% tx vs. 86% ctrl group (p<0.001)
Frederiksen45	91	OP or Sp	Historic control group	INH colistin + PO ciprofloxacin × 3 weeks-3 months	Pa- (until onset of chronic Pa): 86% tx vs. 75% ctrl; Not chronically colonized: 84% of tx, 28% of ctrl group at 3.5 years	Endpoint: time to chronic colonization using the Copenhagen criteria*
Wiesemann46	22	OP or Sp	RCT with placebo control	INH tobramycin × 1 year	NANA	Analyzed by “time to event” (conversion to Pa- culture); only assessed in tx group: 1.89 months (mean); Large pt. dropout rate.
Ratjen47	15	OP or Sp (very specifically defined-no Ab hx, no Pa+ hx)	Open, no control	INH tobramycin × 1 year	Pa-: 93%Pa- AND Ab-: 93% at 1 year, 60% still Pa- and Ab- at 2 years	Early Pa+ patients, also supported with serological data.
Munck64	19	OP or Sp(also <2 precipitin antibodies)	Open, no control	IV ceftazidime or imipenem × 2–3 wk then INH colistin × at least 2 months	Pa-: 100% at end of tx Pa-: 3–25 months	Unrelated strains of Pa seen in all pts, though 5 pts. had some isolates with identical genotypes.
Nixon30	24	BAL/Sp, tracheal aspirate	Prospective, observational cohort (Patients identified by newborn screening)	IV timentin/tobramycin (or other) × 2 weeks, then PO ciprofloxacin and/or INH tobra × 3 months	NA at >12 mos, 25% still Pa-.	Following Pa acquisition prospectively with BAL, tx undertaken when Pa+.
Heinzl65	28	OP/Sp	Retrospective analysis of prophylaxis policy for “high-risk” CF Patients	INH gentamycin: continuous vs. intermittent tx Mean: 6.5 years	NAPa-: 100% in continuous tx group, 44% in intermittent group within 9–53 months	Endpoint: time to Pa acquisitionθ
Gibson48	21	BAL	RCT with placebo control	INH Tobramycin × 28 days	Pa-: 100% tx, 7% ctrl Pa- at 2 mo: 75% tx	First RCT showing eradication in lower airways
Taccetti**50	47	“respiratory secretions”	Sequential cohort study with historical control group	INH colistin + PO ciprofloxacin ×3 wks (extended to 3 months if still Pa+)	81%*18 month eradication (median)	51% recolonised (and retreated) during the 7 year study period; new strains in 73% of strains genotyped
Gibson49	31	BAL	Open label, sequential cohort, multicenter	INH tobramycin × 28 or 56 days, variable follow up	75% in 28/56 cohort, 63% in 28/84 cohort; 82% in 56/112 cohort; 75% in 28/112 cohort	Of patients with negative exotoxin A titres, ALL had successful eradication. Inhaled tobramycin more robust anti-microbial effect on lower airway Pa.
Hansen51	146	LRT/sputum	Descriptive, retrospective cohort study, historical controls	INH colistin + PO ciprofloxacin × 21 or 90 days	Pa- at 6 months: 21 day tx: 50%; 90 day tx: 81% Time to Pa+: 21 day tx: 5 months, 90 day tx: 10.4 months, ctrl: 1.9 months Time to chronic infection: 3.7 years in 12% of Pa+ 80% protected from chronicity up to 15 years	Endpoints: time to Pa acquisition and time to chronic colonization by both Copenhagen* and Leeds** criteria

^*Copenhagen criteria²⁴;

^**Leeds criteria²⁶;

^θDefined as 2 or more Pa+ bacterial cultures from respiratory secretions obtained within a 3 month time span.

OP-oropharyngeal, Sp-sputum, BAL-bronchoalveolar lavage, LRT-obtained by endolaryngeal suctioning, RCT-randomized controlled trial, INH-inhaled, IV-intravenous, PO-oral, Pa-Pseudomonas aeruginosa, NA-not available, tx-treatment, ctrl-control.